Updated on 2024/03/28

写真a

 
SONE, Hirohito
 
Organization
Academic Assembly Institute of Medicine and Dentistry IGAKU KEIRETU Professor
Faculty of Medicine School of Medicine Professor
Graduate School of Medical and Dental Sciences Biological Functions and Medical Control Homeostatic Regulation and Developments Professor
Title
Professor
Contact information
メールアドレス
External link

Degree

  • MD, PhD, FACP ( 1997.3   University of Tsukuba )

Research Interests

  • 身体運動科学・健康科学

  • 代謝内分泌・糖尿病・動脈硬化学

  • 栄養学・食品学

  • 健康診断医学・臨床検査医学

  • 肥満・脂質異常症・高血圧・メタボリックシンドローム

  • 人工知能(AI)

  • 疫学・臨床疫学・医療保健ビッグデータ解析学

  • 生活習慣病学

  • 大規模臨床研究・臨床試験

  • 内科学

  • 予防医学・公衆衛生学

Research Areas

  • Others / Others  / Laboratory medicine

  • Informatics / Life, health and medical informatics  / 医療ビッグデータ解析学

  • Life Science / Medical management and medical sociology  / 予防疫学、臨床疫学、臨床試験

  • Humanities & Social Sciences / Family and consumer sciences, and culture and living  / 栄養学、臨床栄養学、公衆栄養学、栄養疫学

  • Life Science / Genome biology  / バイオインフォマティクス、オミックス

  • Life Science / Hygiene and public health (laboratory)  / 地域医療学

  • Life Science / Nutrition science and health science  / 運動療法学、生涯スポーツ学

  • Life Science / Metabolism and endocrinology  / Endocrinilogy and Metabolism

  • Life Science / General internal medicine  / 総合診療学

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Research History (researchmap)

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control Homeostatic Regulation and Developments   Professor

    2012.10

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  • Department of Endocrinology and Metabolism, University of Tsukuba Mito Medical Center   Professor

    2009.4 - 2012.8

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  • The Open University of Japan

    2008.4 - 2014.4

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  • Department of Nutrition and Food Science, Faculty of Human Life and Environmental Sciences, Ochanomizu University   Associate Professor

    2006.4 - 2009.3

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  • The University of Tokyo   Faculty of Medicine

    2004.4

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  • University of Tsukuba   Lecturer

    1999.4 - 2006.3

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  • University of Michigan   Department of Endocrinology and Metabolism, School of Medicine of Endocrinology and Metabolism, School of Medicine

    1997.4 - 1999.3

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    Country:United States

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  • University of Tsukuba

    1996.4 - 1997.3

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  • Resident of Endocrinology and Metabolism, University of Tsukuba Hospital   Resident of Internal Medicine

    1990.6 - 1996.3

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Research History

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control Homeostatic Regulation and Developments   Professor

    2012.9

  • Niigata University   Faculty of Medicine School of Medicine   Professor

    2012.9

Education

  • University of Tsukuba   School of Medicine

    1984.4 - 1990.3

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    Country: Japan

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Professional Memberships

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Committee Memberships

  • 日本栄養・食糧学会   理事  

    2022.5   

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    Committee type:Academic society

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  • 日本臨床運動療法学会   副理事長  

    2021.9   

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    Committee type:Academic society

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  • 日本医学会連合   COVID expert opinion 実務担当者会議委員  

    2020.12   

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    Committee type:Academic society

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  • 日本糖尿病・妊娠学会   副理事長  

    2020.11   

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    Committee type:Academic society

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  • 厚生労働省 薬事・食品衛生審議会 食品衛生部会 新開発食品評価調査会   委員(座長)  

    2019.1 - 2024.4   

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    Committee type:Government

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  • 厚生労働省 薬事・食品衛生審議会 食品衛生分科会   委員  

    2019.1 - 2024.3   

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    Committee type:Government

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  • 厚生労働省 薬事・食品衛生審議会 食品衛生分科会 新開発食品調査部会   部会長  

    2019.1 - 2024.3   

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    Committee type:Government

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  • 日本臨床運動療法学会   理事  

    2018.4   

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    Committee type:Academic society

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  • 日本糖尿病生活習慣病ヒューマンデータ学会   理事  

    2017.4   

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    Committee type:Academic society

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  • 日本内分泌学会   幹事、評議員  

    2016.4   

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    Committee type:Academic society

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  • 日本臨床栄養学会   理事  

    2016.4   

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    Committee type:Academic society

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  • 新潟県医師会   代議員  

    2016   

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    Committee type:Academic society

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  • 日本糖尿病眼学会   理事  

    2014.4   

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    Committee type:Academic society

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  • 日本公衆衛生学会   代議員  

    2014.4   

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    Committee type:Academic society

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  • 日本糖尿病・妊娠学会   常任理事  

    2014.4   

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    Committee type:Academic society

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  • 日本糖尿病学会   評議員  

    2013.4   

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    Committee type:Academic society

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  • 日本疫学会   理事  

    2013.4   

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    Committee type:Academic society

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  • 厚生労働省 「日本人の食事摂取基準(2015 年版)」策定検討会   委員  

    2013.2 - 2014.3   

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    Committee type:Government

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  • 日本内科学会   評議員  

    2012.10   

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    Committee type:Academic society

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  • 厚生労働省 薬事・食品衛生審議会 食品衛生分科会 新開発食品評価調査会   臨時委員  

    2011.1 - 2019.1   

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    Committee type:Government

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  • 厚生労働省 薬事・食品衛生審議会 食品衛生分科会 新開発食品調査部会   臨時委員  

    2011.1 - 2019.1   

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    Committee type:Government

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  • 日本肥満学会   評議員  

    2010   

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    Committee type:Academic society

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  • 日本栄養・食糧学会   代議員・参与  

    2010   

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    Committee type:Academic society

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  • 日本臨床分子医学会   評議員  

    2010 - 2014   

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    Committee type:Academic society

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  • 日本栄養改善学会   評議員  

    2009.4   

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    Committee type:Academic society

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  • 日本病態栄養学会   評議員  

    2008.4   

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    Committee type:Academic society

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  • 日本未病システム学会   評議員  

    2008.4 - 2019.3   

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    Committee type:Academic society

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  • 日本生活習慣病(成人病)学会   評議員  

    2008 - 2020   

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    Committee type:Academic society

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  • 日本糖尿病合併症学会   評議員  

    2007.4   

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    Committee type:Academic society

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  • 日本動脈硬化学会   評議員  

    2002.4   

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    Committee type:Academic society

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Studying abroad experiences

  • Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan   Postdoctoral Research Fellow

    1997.4 - 1999.3

Qualification acquired

  • 日本内科学会 総合内科専門医・指導医

  • 日本糖尿病学会 専門医・指導医

  • 日本内分泌学会 専門医・指導医

  • 日本動脈硬化学会 専門医・指導医

  • 社会医学系専門医協会 社会医学系指導医

  • 日本臨床栄養学会 臨床栄養指導医

  • 日本医師会 認定産業医

  • 日本医師会 認定健康スポーツ医

  • 日本スポーツ協会 認定スポーツドクター

  • Fellow of American College of Physicians (FACP)

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Papers

  • A 52-week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N-ISM study. Reviewed International journal

    Masaru Kitazawa, Takashi Katagiri, Hiromi Suzuki, Satoshi Matsunaga, Mayuko H Yamada, Tomoo Ikarashi, Masahiko Yamamoto, Kazuo Furukawa, Midori Iwanaga, Mariko Hatta, Kazuya Fujihara, Takaho Yamada, Shiro Tanaka, Hirohito Sone

    Diabetes, obesity & metabolism   23 ( 3 )   811 - 821   2021.3

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    AIM: To compare the long-term efficacy of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors as second-line drugs after metformin for patients not at high risk of atherosclerotic cardiovascular disease (ASCVD). MATERIALS AND METHODS: In a 52-week randomized open-label trial, we compared ipragliflozin and sitagliptin in Japanese patients diagnosed with type 2 diabetes, without prior ASCVD and treated with metformin. The primary endpoint was a glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks. RESULTS: Of a total of 111 patients (mean age 59.2 years, mean body mass index [BMI] 26.6 kg/m2 , 61.3% men), 54 patients received ipragliflozin and 57 received sitagliptin. After 52 weeks, achievement of the primary endpoint was not significantly different (37.0% and 40.3%; P = 0.72). HbA1c reduction rate at 24 weeks was greater for sitagliptin (56.1%) than for ipragliflozin (31.5%; P = 0.01). From 24 to 52 weeks, the HbA1c reduction with sitagliptin was attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%; P = 0.10). Improvements in BMI, C-peptide and high-density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin. Adverse events occurred in 17 patients with ipragliflozin and in 10 patients with sitagliptin (P = 0.11). CONCLUSION: The HbA1c-lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin.

    DOI: 10.1111/dom.14288

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  • A Prospective Cohort Study of Muscular and Performance Fitness and Risk of Hearing Loss: The Niigata Wellness Study. Reviewed International journal

    Ryoko Kawakami, Susumu S Sawada, Kiminori Kato, Yuko Gando, Haruki Momma, Hideaki Oike, Motohiko Miyachi, I-Min Lee, Steven N Blair, Minoru Tashiro, Chika Horikawa, Yasuhiro Matsubayashi, Takaho Yamada, Kazuya Fujihara, Hirohito Sone

    The American journal of medicine   134 ( 2 )   235 - 242   2021.2

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Several cross-sectional studies have linked higher physical fitness with better hearing sensitivity but have not established a causal relation; none have used a prospective design that is less susceptible to bias. We used a prospective cohort study to investigate the association between muscular and performance fitness and the incidence of hearing loss. METHODS: A total of 21,907 participants without hearing loss received physical fitness assessments between April 2001 and March 2002. Muscular and performance fitness index, an age- and sex-specific summed z-score based on grip strength, vertical jump height, single-leg balance, forward bending, and whole-body reaction time was calculated. Participants were classified into quartiles according to the muscular and performance fitness index and each physical fitness test. They were followed up for the development of hearing loss, assessed by pure-tone audiometry at annual health examinations between April 2002 and March 2008. Hazard ratios and 95% confidence intervals for hearing loss incidence were estimated using Cox proportional hazards regression models. RESULTS: During follow-up, 2765 participants developed hearing loss. The hazard ratios (95% confidence intervals) for developing hearing loss across the muscular and performance fitness index quartiles (lowest to highest) were 1.00 (reference), 0.88 (0.79-0.97), 0.83 (0.75-0.93), and 0.79 (0.71-0.88) (Ptrend <.001). Among the various physical fitness components, a clear dose-response association with hearing loss incidence was observed for vertical jump height and single-leg balance (Ptrend <.001 for both). CONCLUSION: Higher muscular and performance fitness is associated with a lower incidence of hearing loss.

    DOI: 10.1016/j.amjmed.2020.06.021

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  • Machine Learning Approach to Decision Making for Insulin Initiation in Japanese Patients With Type 2 Diabetes (JDDM 58): Model Development and Validation Study. Reviewed International journal

    Kazuya Fujihara, Yasuhiro Matsubayashi, Mayuko Harada Yamada, Masahiko Yamamoto, Toshihiro Iizuka, Kosuke Miyamura, Yoshinori Hasegawa, Hiroshi Maegawa, Satoru Kodama, Tatsuya Yamazaki, Hirohito Sone

    JMIR medical informatics   9 ( 1 )   e22148   2021.1

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Applications of machine learning for the early detection of diseases for which a clear-cut diagnostic gold standard exists have been evaluated. However, little is known about the usefulness of machine learning approaches in the decision-making process for decisions such as insulin initiation by diabetes specialists for which no absolute standards exist in clinical settings. OBJECTIVE: The objectives of this study were to examine the ability of machine learning models to predict insulin initiation by specialists and whether the machine learning approach could support decision making by general physicians for insulin initiation in patients with type 2 diabetes. METHODS: Data from patients prescribed hypoglycemic agents from December 2009 to March 2015 were extracted from diabetes specialists' registries, resulting in a sample size of 4860 patients who had received initial monotherapy with either insulin (n=293) or noninsulin (n=4567). Neural network output was insulin initiation ranging from 0 to 1 with a cutoff of >0.5 for the dichotomous classification. Accuracy, recall, and area under the receiver operating characteristic curve (AUC) were calculated to compare the ability of machine learning models to make decisions regarding insulin initiation to the decision-making ability of logistic regression and general physicians. By comparing the decision-making ability of machine learning and logistic regression to that of general physicians, 7 cases were chosen based on patient information as the gold standard based on the agreement of 8 of the 9 specialists. RESULTS: The AUCs, accuracy, and recall of logistic regression were higher than those of machine learning (AUCs of 0.89-0.90 for logistic regression versus 0.67-0.74 for machine learning). When the examination was limited to cases receiving insulin, discrimination by machine learning was similar to that of logistic regression analysis (recall of 0.05-0.68 for logistic regression versus 0.11-0.52 for machine learning). Accuracies of logistic regression, a machine learning model (downsampling ratio of 1:8), and general physicians were 0.80, 0.70, and 0.66, respectively, for 43 randomly selected cases. For the 7 gold standard cases, the accuracies of logistic regression and the machine learning model were 1.00 and 0.86, respectively, with a downsampling ratio of 1:8, which were higher than the accuracy of general physicians (ie, 0.43). CONCLUSIONS: Although we found no superior performance of machine learning over logistic regression, machine learning had higher accuracy in prediction of insulin initiation than general physicians, defined by diabetes specialists' choice of the gold standard. Further study is needed before the use of machine learning-based decision support systems for insulin initiation can be incorporated into clinical practice.

    DOI: 10.2196/22148

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  • Higher dietary protein/energy ratio is associated with a lower risk for obesity in older women with type 2 diabetes: Cross-sectional analysis of Japanese patients with type 2 diabetes mellitus

    Efrem d'Ávila Ferreira, Mariko Hatta, Khin Laymon, Izumi Ikeda, Mizuki Takeuchi, Yasunaga Takeda, Sakiko Yoshizawa Morikawa, Chika Horikawa, Noriko Kato, Hiroshi Maegawa, Kazuya Fujihara, Hirohito Sone

    Human Nutrition &amp; Metabolism   200257 - 200257   2024.3

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.hnm.2024.200257

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  • Association between screen time, including that for smartphones, and overweight/obesity among children in Japan: NICE EVIDENCE Study 4

    Izumi Ikeda, Kazuya Fujihara, Sakiko Morikawa Yoshizawa, Yasunaga Takeda, Hajime Ishiguro, Mayuko Yamada Harada, Chika Horikawa, Yasuhiro Matsubayashi, Takaho Yamada, Yohei Ogawa, Hirohito Sone

    Endocrine Journal   2024

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    Publishing type:Research paper (scientific journal)   Publisher:Japan Endocrine Society  

    DOI: 10.1507/endocrj.ej23-0343

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  • isCGMとPHRスマートフォンアプリを用いた糖尿病発症予防プログラムの有効性検証のためのランダム化比較試験

    北澤 勝, 武田 安永, 治田 麻理子, 堀川 千嘉, 佐藤 隆明, 大澤 妙子, 石澤 正博, 鈴木 浩史, 松林 泰弘, 藤原 和哉, 山田 貴穂, 曽根 博仁

    日本先進糖尿病治療研究会雑誌   17 ( 3 )   152 - 152   2023.12

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    Language:Japanese   Publisher:日本先進糖尿病治療研究会  

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  • トリュフによる血糖上昇抑制効果

    鈴木 浩史, 渡辺 賢一, カク・アンジュ, ウー・シージャ, 石黒 創, 井口 晃徳, 小西 徹也, 曽根 博仁

    機能性食品と薬理栄養   17 ( 3 )   201 - 201   2023.12

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    Language:Japanese   Publisher:(株)インフォノーツパブリッシング  

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  • "Lifestyle Intervention with Smartphone app and isCGM for People at High Risk of Type 2 Diabetes: Randomized Trial". International journal

    Masaru Kitazawa, Yasunaga Takeda, Mariko Hatta, Chika Horikawa, Takaaki Sato, Taeko Osawa, Masahiro Ishizawa, Hiroshi Suzuki, Yasuhiro Matsubayashi, Kazuya Fujihara, Takaho Yamada, Hirohito Sone

    The Journal of clinical endocrinology and metabolism   2023.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    AIMS: Although conventional interventions for people at high risk of developing type 2 diabetes are usually conducted face-to-face, such interventions are burdensome for healthcare providers. We developed a lifestyle intervention program combining lifestyle coaching via a smartphone application augmented by intermittently scanned continuous glucose monitoring (isCGM) without burdening healthcare providers. Its effectiveness for glycemic control and body weight reduction in people at risk of type 2 diabetes was investigated. MATERIALS AND METHODS: For this 12-week randomized unblinded trial with offline recruitment, participants with HbA1c 5.6-6.4% or fasting blood glucose 110-125 mg/dl and body mass index (BMI) > 23 kg/m2 but <40 kg/m2 were randomly assigned to the Intervention group (App) and Control group (C). Primary endpoint was the difference in time in range (TIR) of blood glucose 70-140 mg/dL (3.9-7.8 mmol/L) before and after the study period between the two groups. RESULTS: Among 168 patients (mean age 48.1 y, mean BMI 26.6 kg/m2, and male 80.4%), 82 and 86 were assigned to the App group and C group, respectively. After 12 weeks, TIR of blood glucose 70-140 mg/dL significantly improved in the App group compared to the C group (-2.6 min/day vs. + 31.5 min/day, p = 0.03). Changes in time above range did not differ, whereas time below range (blood glucose <70 mg/dL;  + 23.5 min/day vs. -8.9 min/day, p = 0.02) improved in the App group. BMI (-0.26 vs. -0.59, p = 0.017) was reduced in the App group compared to the C group. CONCLUSION: Intervention with a smartphone app and isCGM increased glycemic control accompanied by decreased carbohydrate intake and weight loss. Further trials are needed to confirm whether these interventions can reduce incident type 2 diabetes.

    DOI: 10.1210/clinem/dgad639

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  • Single-cell transcriptome profiling of pancreatic islets from early diabetic mice identifies Anxa10 for Ca2+ allostasis toward β-cell failure. International journal

    Kaori Motomura, Takashi Matsuzaka, Shigeyuki Shichino, Tatsuro Ogawa, Hao Pan, Takuya Nakajima, Yasuhito Asano, Toshitsugu Okayama, Tomoyo Takeuchi, Hiroshi Ohno, Song-Iee Han, Takafumi Miyamoto, Yoshinori Takeuchi, Motohiro Sekiya, Hirohito Sone, Naoya Yahagi, Yoshimi Nakagawa, Tatsuya Oda, Satoshi Ueha, Kazuho Ikeo, Atsushi Ogura, Kouji Matsushima, Hitoshi Shimano

    Diabetes   2023.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    Type 2 diabetes (T2D) is a progressive disorder denoted by hyperglycemia and impaired insulin secretion. Although a decrease in β-cell function and mass is a well-known trigger for diabetes, the comprehensive mechanism is still unidentified. Here we carried out single-cell RNA sequencing (scRNA-seq) of pancreatic islets from prediabetic and diabetic db/db mice, an animal model of T2D. We discovered a diabetes-specific transcriptome landscape of endocrine and nonendocrine cell types with subpopulations of β and α cells. We recognized a new prediabetic gene, Anxa10, that was induced by, and regulated Ca2+ influx from metabolic stresses. Anxa10-overexpressed β cells displayed suppression of glucose-stimulated intracellular Ca2+ elevation and potassiuminduced insulin secretion. Pseudotime analysis of β cells predicted this Ca2+-surge responder-cluster proceeded to mitochondria dysfunction and also endoplasmic reticulum stress. Other trajectories comprised dedifferentiation and transdifferentiation, emphasizing acinar-like cells in diabetic islets. Altogether, our data provides a new insight into Ca2+ allostasis and β cell failure processes.

    DOI: 10.2337/db23-0212

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  • 妊娠糖尿病既往女性のフォローアップに関する診療ガイドライン

    平松 祐司, 杉山 隆, 安日 一郎, 曽根 博仁, 菊池 透, 瀧本 秀美, 安田 和基, 小川 佳宏, 荒田 尚子, 和栗 雅子, 橋本 貢士, 宮越 敬, 山下 洋, 鳴本 敬一郎, 青山 友子, 山本 周美, 川崎 麻紀, Obaidur Rahman, 川嵜 有紀, 大田 えりか, 内潟 安子, 川崎 英二, 守屋 達美, 上塘 正人, 田中 幹二, 増山 寿, 森川 守, 楠田 聡, 杉原 茂孝, 清水 一紀, 武田 純, 原島 伸一, 柳澤 慶香, 田中 佳代, 人見 麻美子, 板倉 敦夫, 寺内 康夫, 平成30年度日本医療研究開発機構日本医療研究開発機構女性の健康の包括的支援実用化研究事業「妊娠糖尿病女性における出産後の糖尿病・メタボリックシンドローム発症のリスク因子同定と予防介入に関する研究」研究班, 一般社団法人日本糖尿病・妊娠学会

    糖尿病と妊娠   23 ( 別冊 )   1 - 95   2023.10

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    Language:Japanese   Publisher:(一社)日本糖尿病・妊娠学会  

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  • 血糖コントロールと妊娠合併症リスクとの量反応関係メタ回帰分析

    児玉 暁, 山田 貴穂, 柳生田 紀子, 谷内 洋子, 堀川 千嘉, 大澤 妙子, 北澤 勝, 藤原 和哉, 西島 浩二, 曽根 博仁

    糖尿病と妊娠   23 ( 3 )   S - 109   2023.10

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    Language:Japanese   Publisher:(一社)日本糖尿病・妊娠学会  

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  • Associations among metabolic health, weight status, and various physical fitness components in Japanese adolescents: a cross-sectional study (NICE EVIDENCE study- Agano 3). International journal

    Sakiko Yoshizawa Morikawa, Yasunaga Takeda, Kazuya Fujihara, Izumi Ikeda, Ayako Kobayashi, Mariko Hatta, Yurie Mitsuma, Chika Horikawa, Hajime Ishiguro, Takaho Yamada, Yohei Ogawa, Hirohito Sone

    Journal of sports sciences   41 ( 13 )   1279 - 1289   2023.9

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    Aim was to examine associations among metabolic health, weight status, and various physical fitness (PF) components in 1744 Japanese adolescents aged 13-14. Anthropometric measurements and PF tests (20 m shuttle run test [20mSRT], handgrip strength/body mass [HG], standing long jump [SLJ], and sit ups [SU]) were administered. The bottom sex-specific quintile of PF indicated "low fit". Participants were classified as non-overweight (non-OW) or overweight/obese (OW) according to the International Obesity Task Force. Clustered metabolic risk was defined as the sum of Z scores for mean arterial pressure, non-high-density lipoprotein cholesterol, and HbA1c, divided by three, and ≥ 1 SD. Combination of weight status and scores for HG or SU were additively associated with clustered metabolic risk. Compared with the non-OW-moderate-high fit group, the OW-low HG group was 3.05 (95%CI: 1.88-4.97) times more likely to have clustered metabolic risk although risk was not significantly elevated in the OW-moderate-high HG group (1.52 [95%CI: 0.88-2.62]). A similar association was observed between OW and low SU scores but not between OW and low 20mSRT or SLJ scores. Adolescents with OW and moderate-high HG or SU scores had a lower prevalence of an unfavourable metabolic state than those with OW and low HG or SU results.

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  • Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity. International journal

    Suguru Tamura, Hajime Ishiguro, Tatsuya Suwabe, Takayuki Katagiri, Kaori Cho, Kyoko Fuse, Yasuhiko Shibasaki, Tadahisa Mikami, Takero Shindo, Hiroshi Kitagawa, Michihiro Igarashi, Hirohito Sone, Masayoshi Masuko, Takashi Ushiki

    Scientific reports   13 ( 1 )   13098 - 13098   2023.8

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    Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation.

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  • Relationship between the magnitude of body mass index reductions and remission in patients with type 2 diabetes in real world settings: Analysis of nationwide patient registry in Japan (JDDM74) Reviewed International journal

    Hirohito Sone

    Diabetes, Obesity and Metabolism   2023.7

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    AIMS: To determine the association between the magnitude of weight loss and incidence of remission according to baseline characteristics in patients with diabetes in clinical settings. METHODS: In total, 39 676 Japanese patients with type 2 diabetes aged ≥18 years with glycated haemoglobin (HbA1c) ≥6.5% and/or glucose-lowering drug prescription were identified from databases of specialists' clinics from 1989 and followed until September 2022. Remission was diagnosed as maintaining HbA1c <6.5% at least 3 months after cessation of a glucose-lowering drug. Factors associated with remission were evaluated by logistic regression analysis according to weight change in 1 year (i.e. ≥10%, 7.0-9.9%, 3.0-6.9% reduction, <3% change and ≥3.0% increase). RESULTS: During the study period, 3454 remissions occurred. The rates of remission were higher in the group with the greatest reduction of body mass index (BMI) in any category examined (i.e. baseline BMI, HbA1c, duration of diabetes and treatment). The incidences of remission per 1000 person-years were about 25 and 50, respectively, for those with BMI ≥22.5 and reductions in BMI of 7.0-9.9% and ≥10% in 1 year. Remissions per 1000 person-years were 99.2 and 91.8, respectively, for those with baseline HbA1c of 6.5-6.9 and a 10% BMI reduction and those not taking glucose-lowering drugs accompanied by a 10% BMI reduction. CONCLUSIONS: Modest weight losses of 3.0-7.9% were significantly associated with remission, but a minimum of 10% weight loss would be required in addition to an early diagnosis to achieve a 10% remission rate in clinical settings. Our results implied that remission may be expected with a relatively lower BMI in an Asian population compared with that was reported in Western populations if accompanied by weight loss.

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  • Retrospective cohort study to examine the association between serum amylase and the incidence of type 2 diabetes mellitus, Toranomon Hospital Health Management Center Study 23 (TOPICS 23). International journal

    Izumi Ikeda, Kazuya Fujihara, Taeko Osawa, Yasunaga Takeda, Mariko Hatta, Yasuhiro Matsubayashi, Satoru Kodama, Yasumichi Mori, Takashi Kadowaki, Ritsuko Honda, Yasuji Arase, Hirohito Sone

    BMJ open diabetes research & care   11 ( 4 )   2023.7

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    INTRODUCTION: Low serum amylase values are cross-sectionally associated with the prevalence of type 2 diabetes mellitus (T2DM) but have not been shown to be longitudinally associated with its incidence. This retrospective cohort (ie, historical cohort) study aimed to examine the association of previously lowered levels of serum amylase with incident T2DM. RESEARCH DESIGN AND METHODS: Examined were 8316 individuals who had annual health examinations for 6 years (ie, 7 times) at the Toranomon Hospital Health Management Center. The trajectory of serum amylase as the study exposure was classified into two elements: (1) serum amylase level at entry and (2) change in serum amylase, which was expressed as the annual change rate. The annual change rate was calculated by dividing the change in the amylase values according to follow-up periods. Regression analyses were performed to examine the association between low and decreased levels of serum amylase and the incidence of T2DM. RESULTS: Analyzed were 6917 individuals who had not developed T2DM within 1 year after cohort entry. T2DM thereafter occurred in 1021 patients. Cox regression indicated that the adjusted HR (95% CI) for incident T2DM for amylase ≤57 IU/L (quintile (Q) 1) was 0.97 (0.84 to 1.13) compared with amylase ≥58 IU/L (Q2-Q5). Logistic regression indicated that the adjusted OR (95% CI) for an annual change rate of amylase ≤-2.0% (Q1) vs ≥-1.9% (Q2-Q5) was 3.53 (3.00 to 4.16). The adjusted ORs were consistently significant throughout sensitivity analyses according to baseline amylase and the combination of age, body mass index, and hemoglobin A1c. CONCLUSIONS: Results showed that not low but previously decreased serum amylase was a risk factor for T2DM, suggesting the significance of periodic examinations of serum amylase values to detect individuals at high risk of T2DM.

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  • Enfortumab Vedotin-induced Hyperglycemia and Ileal Conduit Reconstruction-induced Metabolic Acidosis. International journal

    Takaaki Sato, Hiroshi Suzuki, Yuya Asashima, Hirohito Sone

    JCEM case reports   1 ( 4 )   luad092   2023.7

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    We report a 76-year-old man who was treated for hyperglycemia and metabolic acidosis after chemotherapy with enfortumab vedotin and pembrolizumab administered after his surgery for bladder cancer. He had an approximately 20-year history of diabetes. His body mass index was 18.6, and he received metformin 1000 mg/day, sitagliptin 50 mg/day, mitiglinide 30 mg/day, and voglibose 0.6 mg/day with hemoglobin A1c was approximately 7%. He underwent total cystectomy and ileal conduit reconstruction. After relapse, he received chemotherapy but later developed hyperglycemia and metabolic acidosis. His hyperglycemia was caused by enfortumab vedotin, and metabolic acidosis was attributable to the ileocecal canal. These symptoms should be remembered as important complications of this standard treatment, which prompted this case report.

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  • エンフォルツマブによる高血糖と回腸導管による代謝性アシドーシスをきたした1例

    浅島 雄弥, 佐藤 隆明, 佐々木 知佳, 鈴木 浩史, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    糖尿病   66 ( 7 )   568 - 568   2023.7

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  • 329-OR: Accuracy of Dietary Records (DR) Using a Smartphone App Is Greatly Improved by User’s Adjustments Compared with Artificial Intelligence (AI) Alone

    MASARU KITAZAWA, CHIKA HORIKAWA, IZUMI IKEDA, YASUNAGA TAKEDA, EFREM D. FERREIRA, MIZUKI TAKEUCHI, SAKIKO Y. MORIKAWA, KAZUYA FUJIHARA, SATORU KODAMA, HIROHITO SONE

    Diabetes   72 ( Supplement_1 )   2023.6

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    Although DR are important in managing diabetes, the traditional method, such as weighing foods and calculating nutrients, is burdensome to both patients and medical care providers. Although photo DR with smartphones using AI to identify the dish and calculate nutrients can be expected to reduce this burden, accuracy not been clarified. Furthermore, it is not clear to what extent accuracy improves when users and dietitians adjust the name of the dish and the portion consumed compared with AI only. In this study, photo DR taken with the smartphone app were analyzed by AI only, then adjusted by the users followed by further adjustments by a dietitian. We compared the nutrients calculated by AI, users, and dietitians to those by the traditional weighing method. Analyzed were 180 participants (mean age 58.7 y, BMI 26.7 kg/m2, 94/86 women/men, 22 with diabetes, energy intake [EI] 1640 kcal/day) The EIs (kcal/day) were calculated as 1502, 1619, and 1674 for AI, users, and dietitians, respectively, those were lower than that with the weighing method Spearman's rank correlation coefficients compared to the weighing method were 0.48, 0.88, and 0.88 for AI, users and dietitians, respectively, showing a weak correlation for AI and a strong correlation for users and dietitians. The user's adjustments greatly improved accuracy without increasing the burden on the dietitians.

    <p></p> Disclosure

    M.Kitazawa: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. C.Horikawa: None. I.Ikeda: None. Y.Takeda: None. E.D.Ferreira: None. M.Takeuchi: None. S.Y.Morikawa: None. K.Fujihara: None. S.Kodama: None.

    Funding

    Grants-in-Aid for Scientific Research (21K17637)

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  • Recent updates in factors associated with incidence and screening of diabetic eye disease

    Hirohito Sone

    Journal of Diabetes Investigation   2023.6

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    DOI: 10.1111/jdi.13991

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  • 中学生におけるスクリーンタイムがボディイメージの歪みと精神的健康度へ及ぼす影響

    池田 和泉, 藤原 和哉, 森川 咲子, 武田 安永, 石黒 創, 堀川 千嘉, 山田 貴穂, 小川 洋平, 曽根 博仁

    日本内分泌学会雑誌   99 ( 1 )   333 - 333   2023.5

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  • ヘパプラスチンテストを取り入れた出血原因鑑別の検査戦略 後天性第V因子欠乏症における経験

    松田 将門, 山田 隆, 古山 悠里, 柴崎 康彦, 関 義信, 星山 良樹, 寺井 崇二, 瀧澤 淳, 曽根 博仁, 増子 正義

    日本血栓止血学会誌   34 ( 2 )   262 - 262   2023.5

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  • The Reply

    Ryoko Kawakami, Kiminori Kato, Hirohito Sone

    The American Journal of Medicine   136 ( 5 )   e104 - e104   2023.5

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    DOI: 10.1016/j.amjmed.2022.12.027

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  • Incidence and predictors of remission and relapse of type 2 diabetes mellitus in Japan: Analysis of a nationwide patient registry Reviewed International journal

    Hirohito Sone

    Diabetes, Obesity and Metabolism   25 ( 8 )   2227 - 2235   2023.5

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    AIMS: To determine the incidence of remission and 1-year relapse from remission and associated factors in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 48 320 Japanese patients with type 2 diabetes aged ≥18 years, with glycated haemoglobin (HbA1c) levels ≥48 mmol/mol (6.5%) and/or glucose-lowering drug prescription, were identified from databases of specialist clinics from 1989 and followed until September 2022. Remission was defined as HbA1c <48 mmol/mol at least 3 months after cessation of a glucose-lowering drug. Relapse was defined as failure to maintain remission for 1 year. Factors associated with remission and relapse were evaluated by logistic regression analysis. RESULTS: The overall incidence of remissions per 1000 person-years was 10.5, and for those with HbA1c levels of 48 to 53 mmol/mol (6.5% to 6.9%), those taking no glucose-lowering drugs at baseline, and those with a ≥10% body mass index (BMI) reduction in 1 year, it was 27.8, 21.7 and 48.2, respectively. Shorter duration, lower baseline HbA1c, higher baseline BMI, higher BMI reduction at 1 year, and no glucose-lowering drugs at baseline were significantly associated with remission. Among 3677 persons with remission, approximately two-thirds (2490) relapsed within 1 year. Longer duration, lower BMI at baseline, and lower BMI reduction at 1 year were significantly associated with relapse. CONCLUSIONS: The results showed that the incidence of remission and predictors of relapse, especially baseline BMI, might differ greatly between East Asian and Western populations. Furthermore, the relationships of BMI reduction with remission and relapse may be greater in East Asian than in Western populations, implying ethnic differences in returning from overt hyperglycaemia to nearly normal glucose levels.

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  • Reduced incidence of cardiovascular disease in patients with type 2 diabetes through the integrated improvement of diabetes care by comparing two prospective observational cohorts in real-world clinical practice (JDDM 72) International journal

    Hirohito Sone

    Diabetes Research and Clinical Practice   202   110674 - 110674   2023.4

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    AIM: To investigate whether any reduction in all-cause mortality and cardiovascular disease morbidity was found over the decade in type 2 diabetes on real-world practice. METHODS: A prospective observational study was performed by following two independent cohorts recruited in 2004 (n = 3286, Cohort 1) and 2014 (n = 3919, Cohort 2). The primary outcome was a composite of onset of cardiovascular disease and death. Cox proportional hazards analysis was used to explore any difference between Cohort 2 and Cohort 1 for the composite endpoints and cardiovascular disease after adjustment for covariates and accumulation of five risks (smoking, HbA1c, blood pressure, lipids, and albuminuria) outside target ranges. RESULTS: During the 8-year follow-up, 391 (11.9%) and 270 (6.9%) primary outcomes, and 270 (8.2%) and 161 (4.1%) cardiovascular diseases occurred in Cohort 1 and Cohort 2, respectively. Cohort 2 (vs. Cohort 1) exhibited a significant risk reduction for composite endpoints (HR 0.73, 95% CI 0.62 to 0.86) and cardiovascular disease (HR 0.64, 95% CI 0.52 to 0.79), and similarly exhibited a significant reduction independent of the accumulation of the five risks. CONCLUSIONS: The significant reduction of Cohort 2 for cardiovascular disease independent of the baseline covariates suggests an integrated effect delivered by the recent treatment advances.

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  • 耐糖能や年齢で層別化した血清アミラーゼ低値およびその経時的減少が2型糖尿病発症に及ぼす影響の縦断的検討

    池田 和泉, 藤原 和哉, 大澤 妙子, 武田 安永, 治田 麻里子, 松林 泰弘, 児玉 暁, 森 保道, 本田 律子, 門脇 孝, 荒瀬 康司, 曽根 博仁

    糖尿病   66 ( Suppl.1 )   S - 215   2023.4

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  • Network meta-analysis of glucose-lowering drug treatment regimens with the potential risk of hypoglycemia in patients with type 2 diabetes mellitus in terms of glycemic control and severe hypoglycemia Reviewed

    Hirohito Sone

    Journal of Investigative Medicine   2023.4

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    DOI: 10.1177/10815589221149188

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  • 写真撮影とAIを活用した食事記録スマートフォンアプリによる日常の食事記録の妥当性検証

    北澤 勝, 堀川 千嘉, 長谷川 美代, 武田 安永, 治田 麻理子, 松林 泰弘, 山田 貴穂, 児玉 暁, 藤原 和哉, 曽根 博仁

    糖尿病   66 ( Suppl.1 )   S - 230   2023.4

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  • Utility of a Physical Fitness Score in Screening for Chronic Diseases International journal

    Hirohito Sone

    Journal of Sports Science and Medicine   22 ( 1 )   98 - 110   2023.3

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    We developed a new Physical Score (PS) consisting of comprehensive physical fitness indicators and elucidated the association between the resultant PS and metabolic diseases, i.e., diabetes, hypertension, dyslipidemia, fatty liver, and metabolic syndrome (MetS), among Japanese. Analyzed were 49,850 persons (30,039 men) aged 30 to 69 y who underwent physical fitness tests. Principal component analysis was performed on the correlation matrix of the physical fitness test results (relative grip strength, single-leg balance with eyes closed, and forward bending) according to sex and age. We defined the PS as the first principal component score. A formula was developed for various age groups comprised of men and women from 30 to 69 years of age from which the PS for each age and sex was calculated. The PS for both men and women was normally distributed with a value of 0 ± 1.15-1.16. Multivariate logistic regression analysis showed that the risk of metabolic diseases increased approximately 1.1-1.6 times per each 1-point reduction in the PS. The association between PS and MetS was particularly strong in that a 1-point reduction in the PS increased the risk of MetS by 1.54 times (95% confidence interval 1.46 to 1.62) in men and by 1.21 times (1.15 to 1.28) in women. The association between a lower PS and disease risk was stronger in younger men for fatty liver and in older men for MetS. Conversely, in women, the association between a lower PS and disease risk was stronger in older women for fatty liver and in younger women for MetS. For diabetes, hypertension, and dyslipidemia, the change in the impact of PS reductions across age groups was small. The PS is a useful and simple non-invasive tool for screening Japanese people for metabolic diseases.

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  • 炭水化物エネルギー比率の算出方法の違いは、糖尿病患者の炭水化物エネルギー比率と心血管疾患発症リスクの関係に影響しうるか

    堀川 千嘉, 高原 充佳, 片上 直人, 武田 安永, 竹内 瑞希, 藤原 和哉, 鈴木 浩明, 津田 謹輔, 吉岡 成人, 押田 芳治, 島野 仁, 佐藤 譲, 林野 泰明, 田嶼 尚子, 西村 理明, 山崎 義光, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   77回   314 - 314   2023.3

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  • Risk of fetal undergrowth in the management of gestational diabetes mellitus in Japan

    Hirohito Sone

    Journal of Diabetes Investigation   2023.2

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1111/JDI.13977

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  • 妊娠初期における母体のヘモグロビン値・赤血球恒数と低出生体重児出産との関連の検討

    谷内 洋子, 坂本 莉菜, 柴崎 康彦, 山田 貴穂, 生魚 薫, 柳生田 紀子, 龍野 一郎, 曽根 博仁

    Journal of Epidemiology   33 ( Suppl.1 )   146 - 146   2023.2

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  • ソフトドリンクケトーシス治療中に腎性尿崩症が指摘された一例

    日向 裕大, 矢口 雄大, 砂田 大介, 川井 千尋, 山本 正彦, 石黒 創, 北澤 勝, 石澤 正博, 鈴木 浩史, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   98 ( 4 )   856 - 856   2023.2

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  • エンフォルツマブによる高血糖と回腸導管による代謝性アシドーシスの1例

    浅島 雄弥, 佐藤 隆明, 佐々木 知佳, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曾根 博仁

    新潟医学会雑誌   137 ( 2 )   71 - 71   2023.2

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  • Combined effects of blood pressure and glycemic status on risk of heart failure: a population-based study

    Hirohito Sone

    Journal of Hypertension   Publish Ahead of Print   2023.1

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    DOI: 10.1097/HJH.0000000000003362

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  • Association of the estimated glomerular filtration rate (eGFR) and/or proteinuria to predict the risk of initiation of dialysis in people with and without diabetes

    Hirohito Sone

    Diabetology International   14 ( 1 )   86 - 93   2023.1

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    AIMS: To determine the associations between combined urinary protein (UP) and a reduced estimated glomerular filtration rate (eGFR) and the risk of starting dialysis with or without diabetes mellitus (DM). METHODS: A nationwide database with claims data on 335,778 people with and without DM aged 19-72 years in Japan was used to elucidate the impact of the severities of UP and eGFR on starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modeling, we investigated the severities of UP and eGFR to predict the initiation of dialysis with and without DM. RESULTS: Both eGFR < 60 and UP(+) were independent predictors for starting dialysis with and without DM, and their values exhibited a synergistic risk of dialysis. eGFR < 60 presented a nearly twofold risk for starting dialysis compared to UP(+) regardless of DM. Risk of starting dialysis was increased with UP(+) and eGFR ≥ 60 accompanied by DM although this association was not observed without DM. Those who had UP(-) and eGFR < 60 had a high risk of starting dialysis regardless of DM. Compared with DM(-)UP(-)eGFR ≥ 60, HRs for starting dialysis for DM(+)UP(+)eGFR ≥ 60, DM(+)UP(-)eGFR < 60 and DM(+)UP(+)eGFR < 60 significantly increased 17.7 (10.6-29.7), 25.5 (13.8-47.1) and 358.1 (239.1-536.5) times, respectively. CONCLUSIONS: eGFR < 60 and UP(+) together presented an extremely high risk of dialysis especially with DM. UP( +) increased the risk of starting dialysis regardless of the eGFR with DM. Both patient education and a treatment strategy by physicians might be helpful to avoid the progression of renal failure.

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  • オンライン予防歯科教育動画による企業従業員のヘルスリテラシー向上と行動変容における有効性の検証

    植木 麻有子, 田村 浩平, 木村 大地, 木村 美樹, 曽根 博仁, 小川 祐司

    口腔衛生学会雑誌   73 ( 1 )   64 - 64   2023.1

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  • Hypoglycemic Hemiplegia Associated with Reversible Narrowing of the Contralateral Middle Cerebral Artery in a Patient with Adrenal Insufficiency

    Hirohito Sone

    Internal Medicine   2023

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    DOI: 10.2169/INTERNALMEDICINE.0038-22

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  • Machine Learning Approach to Drug Treatment Strategy for Diabetes Care

    Hirohito Sone

    Diabetes & Metabolism Journal   2023

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    DOI: 10.4093/DMJ.2022.0349

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  • Prediction and prevention of the onset of hypertension from the viewpoint of estimated 24-hour salt excretion and physical fitness test

    Hirohito Sone

    Journal of Hypertension   2023

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  • Relationship between changes in blood pressure from summer to winter and estimated 24-hour salt excretion using spot urine: the Niigata Wellness Study

    Hirohito Sone

    Hypertension Research   2023

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    DOI: 10.1038/S41440-022-01049-1

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  • Effect of dietary fiber-enriched brown rice crackers on suppressing elevation of blood glucose level

    Hiroshi Suzuki, Kenichi Watanabe, Izumi Ikeda, Yasunaga Takeda, Mariko Hatta, Chika Horikawa, Efrem D’Avila Ferreira, Wu Sijia, Khin Laymon, Hirohito Sone

    Functional Foods in Health and Disease   13 ( 11 )   595 - 604   2023

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    Background: Rice crackers are composed of carbohydrates refined from rice and enjoyed as a snack in Japan. Most rice crackers are crafted from white rice, and the potential postprandial blood glucose rise following their consumption may pose a clinical concern. Brown rice contains more dietary fiber than white rice and has been reported to suppress elevations of blood glucose. Dietary fiber-enhanced brown rice crackers have a significantly higher dietary fiber content than regular brown rice crackers and can be expected to suppress blood glucose elevations more reliably. Methods: We conducted a crossover trial in humans using white rice crackers and dietary fiber-enhanced brown rice crackers to investigate the effect of dietary fiber-enhanced brown rice crackers on postprandial blood glucose elevations. Participants ingested the 100 g rice crackers with 200 mL water for 10 min, and blood was collected from the fingertip at 7 time points: baseline, and at 15, 30, 45, 60, 90, and 120 min after ingestion of the rice cracker. The primary outcome measure was the blood glucose levels, and the secondary outcome measure was the incremental area under curve of blood glucose. Results: Glucose levels and incremental areas under curve at 60 min and 120 min after intake were significantly lower with dietary fiber-enhanced brown rice crackers than with white rice crackers. Incremental area under curves at 60 min and 120 min after intake of rice crackers were also significantly lower in dietary fiber-enhanced brown rice crackers than white rice crackers. Conclusions: Ingesting dietary fiber-enhanced brown rice crackers instead of white rice crackers could be useful for achieving better glycemic control.

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  • Machine learning approach to predict body weight in adults International journal

    Hirohito Sone

    Frontiers in Public Health   11   1090146 - 1090146   2023

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    BACKGROUND: Obesity is an established risk factor for non-communicable diseases such as type 2 diabetes mellitus, hypertension and cardiovascular disease. Thus, weight control is a key factor in the prevention of non-communicable diseases. A simple and quick method to predict weight change over a few years could be helpful for weight management in clinical settings. METHODS: We examined the ability of a machine learning model that we constructed to predict changes in future body weight over 3 years using big data. Input in the machine learning model were three-year data on 50,000 Japanese persons (32,977 men) aged 19-91 years who underwent annual health examinations. The predictive formulas that used heterogeneous mixture learning technology (HMLT) to predict body weight in the subsequent 3 years were validated for 5,000 persons. The root mean square error (RMSE) was used to evaluate accuracy compared with multiple regression. RESULTS: The machine learning model utilizing HMLT automatically generated five predictive formulas. The influence of lifestyle on body weight was found to be large in people with a high body mass index (BMI) at baseline (BMI ≥29.93 kg/m2) and in young people (<24 years) with a low BMI (BMI <23.44 kg/m2). The RMSE was 1.914 in the validation set which reflects ability comparable to that of the multiple regression model of 1.890 (p = 0.323). CONCLUSION: The HMLT-based machine learning model could successfully predict weight change over 3 years. Our model could automatically identify groups whose lifestyle profoundly impacted weight loss and factors the influenced body weight change in individuals. Although this model must be validated in other populations, including other ethnic groups, before being widely implemented in global clinical settings, results suggested that this machine learning model could contribute to individualized weight management.

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  • Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis

    Nurani Istiqamah, Takashi Matsuzaka, Momo Shimizu, Kaori Motomura, Hiroshi Ohno, Shiho Hasebe, Rahul Sharma, Yuka Okajima, Erika Matsuda, Song-Iee Han, Yuhei Mizunoe, Yoshinori Osaki, Yuichi Aita, Hiroaki Suzuki, Hirohito Sone, Yoshinori Takeuchi, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Hitoshi Shimano

    BBA Advances   3   100078 - 100078   2023

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  • Citrate synthase insufficiency leads to specific metabolic adaptations in the heart and skeletal muscles upon low-carbohydrate diet feeding in mice(vol 9, 925908, 2022)

    Hirohito Sone

    Frontiers in Nutrition   9   2023

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    A decrease in TCA cycle activity may lead to impaired nutrition metabolism and cellular energy shortage. Herein, we aimed to characterize the detailed metabolic changes that compensate for energy shortages in energy-consuming organs (heart and skeletal muscles) in mice with knockout of citrate synthase (CS), an important enzyme in the TCA cycle. CS hetero knockout (CS +/−) mice and wild-type mice were fed a low-carbohydrate ketogenic diet (LCKD) or high-fat, high-carbohydrate diet (HFHCD) to induce metabolic changes. Body weight, blood serum parameters, metabolic gene expression, and adenosine triphosphate (ATP) levels were measured in the heart and skeletal muscles. Glycogen content, anabolic and catabolic biomarkers, and morphological changes were also assessed in the skeletal muscles. After diet feeding, there were no differences observed in the body weight and blood serum parameters between wild-type and CS +/− mice. The cardiac expression of genes related to the utilization of fatty acids, monocarboxylates, and branched amino acids increased in LCKD-fed CS +/− mice. In contrast, no significant differences in gene expression were observed in the muscles of LCKD-fed mice or the heart and muscles of HFHCD-fed mice. ATP levels decreased only in the skeletal muscles of LCKD-fed CS +/− mice. Additionally, the decrease in glycogen content, suppression of p70 S6 kinase, and presence of type I fiber atrophy were observed in the muscles of LCKD-fed CS +/− mice. These results suggest that the energy-consuming organs with CS insufficiency may undergo tissue-specific adaption to compensate for energy shortages when the carbohydrate supply is limited.

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  • Hepatocyte- or macrophage-specific SREBP-1a deficiency in mice exacerbates methionine- and choline-deficient diet-induced nonalcoholic fatty liver disease. International journal

    Masaya Araki, Yoshimi Nakagawa, Hodaka Saito, Yasunari Yamada, Song-Iee Han, Yuhei Mizunoe, Hiroshi Ohno, Takafumi Miyamoto, Motohiro Sekiya, Takashi Matsuzaka, Hirohito Sone, Hitoshi Shimano

    American journal of physiology. Gastrointestinal and liver physiology   323 ( 6 )   G627-G639   2022.12

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    Sterol regulatory element-binding proteins (SREBPs) are master transcription factors for lipid synthesis, and SREBP-1 is important for fatty acid and triglyceride synthesis. SREBP-1 has two isoforms, SREBP-1a and SREBP-1c, which are splicing variants transcribed from the Srebf1 gene. Although SREBP-1a exhibits stronger transcriptional activity than SREBP-1c, hepatic SREBP-1c is considered more physiologically important. We generated SREBP-1a flox mice using the CRISPR/Cas9 system and hepatocyte- and macrophage-specific SREBP-1a knockout (KO) mice (LKO, liver-knockout; and mΦKO, macrophage-knockout). There were no significant differences among all the mouse genotypes upon feeding with a normal diet. However, feeding with a methionine- and choline-deficient (MCD) diet resulted in exacerbated liver injury in both KO mice. In LKO mice, fatty liver was unexpectedly exacerbated, leading to macrophage infiltration and inflammation. In contrast, in mΦKO mice, the fatty liver state was similar to that in flox mice, but the polarity of the macrophages in the liver was transformed into a proinflammatory M1 subtype, resulting in the exacerbation of inflammation. Taken together, we found that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in MCD diet-induced hepatitis.NEW & NOTEWORTHY Hepatocyte- and macrophage-specific SREBP-1a knockout mice were generated for the first time. This study reveals that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in methionine- and choline-deficient diet-induced hepatitis.

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  • 乳酸醗酵酒粕の非アルコール性脂肪性肝炎の進行抑制効果

    鈴木 浩史, 渡辺 賢一, Arumugam Somasundaram, Afrin Rejina, 松林 泰弘, 曽根 博仁

    機能性食品と薬理栄養   16 ( 3 )   191 - 191   2022.12

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  • デキサメタゾン投与後に周期性四肢麻痺を呈したバセドウ病の一例

    浅島 雄弥, 佐藤 隆明, 滝澤 大輝, 日向 裕大, 今西 明, 橋本 浩平, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   98 ( 2 )   583 - 583   2022.10

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  • Wogonin, a Compound in Scutellaria baicalensis, Activates ATF4–FGF21 Signaling in Mouse Hepatocyte AML12 Cells

    Yasunari Yamada, Hodaka Saito, Masaya Araki, Yuhei Tsuchimoto, Shin-ichi Muroi, Kyohei Suzuki, Kazufumi Toume, Jun-Dal Kim, Takashi Matsuzaka, Hirohito Sone, Hitoshi Shimano, Yoshimi Nakagawa

    Nutrients   14 ( 19 )   3920 - 3920   2022.9

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    Fibroblast growth factor 21 (FGF21), which is mainly synthesized and secreted by the liver, plays a crucial role in systemic glucose and lipid metabolism, ameliorating metabolic diseases. In this study, we screened the WAKANYAKU library derived from medicinal herbs to identify compounds that can activate Fgf21 expression in mouse hepatocyte AML12 cells. We identified Scutellaria baicalensis root extract and one of its components, wogonin, as an activator of Fgf21 expression. Wogonin also enhanced the expression of activating transcription factor 4 (ATF4) by a mechanism other than ER stress. Knockdown of ATF4 by siRNA suppressed wogonin-induced Fgf21 expression, highlighting its essential role in wogonin’s mode of action. Thus, our results indicate that wogonin would be a strong candidate for a therapeutic to improve metabolic diseases by enhancing hepatic FGF21 production.

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  • YAP1/TAZ activity maintains vascular integrity and organismal survival. International journal

    Shun Uemura, Masayuki Yamashita, Kazumasa Aoyama, Takako Yokomizo-Nakano, Motohiko Oshima, Miki Nishio, Masayoshi Masuko, Jun Takizawa, Hirohito Sone, Yasuhiro Yamada, Akira Suzuki, Atsushi Iwama

    Biochemical and biophysical research communications   619   117 - 123   2022.9

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    Radiation therapy is one of the major treatment modalities for patients with cancers. However, ionizing radiation (IR) damages not only cancer cells but also the surrounding vascular endothelial cells (ECs). Hippo pathway effector genes Yap1 and Taz are the two transcriptional coactivators that have crucial roles in tissue homeostasis and vascular integrity in various organs. However, their function in adult ECs at the steady state and after IR is poorly understood. Here, we report sex- and context-dependent roles of endothelial YAP1/TAZ in maintaining vascular integrity and organismal survival. EC-specific Yap1/Taz deletion compromised systemic vascular integrity, resulting in lethal circulation failure preferentially in male mice. Furthermore, EC-specific Yap1/Taz deletion induced acute lethality upon sublethal IR that was closely associated with exacerbated systemic vascular dysfunction and circulation failure. Consistent with these findings, RNA-seq analysis revealed downregulation of tight junction genes in Yap1/Taz-deleted ECs. Collectively, our findings highlight the importance of endothelial YAP1/TAZ for maintaining adult vascular function, which may provide clinical implications for preventing organ injury after radiation therapy.

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  • 耐糖能およびHDL-C値によるLDL-C値が冠動脈疾患発症に及ぼす影響の検討

    山田 万祐子, 藤原 和哉, 大澤 妙子, 北澤 勝, 松林 泰弘, 矢口 雄大, 山本 正彦, 佐藤 隆明, 三ツ間 友里恵, 岩永 みどり, 山田 貴穂, 児玉 暁, 曽根 博仁

    糖尿病合併症   36 ( Suppl.1 )   173 - 173   2022.9

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  • 尿細管障害を伴う低カリウム血症の加療中にデノスマブによる著明な低Ca血症をきたした1例

    砂田 大介, 矢口 雄大, 川井 千尋, 日向 裕大, 山本 正彦, 石黒 創, 北澤 勝, 石澤 正博, 鈴木 浩史, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    新潟医学会雑誌   136 ( 9 )   303 - 303   2022.9

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  • 糖尿病性ケトアシドーシス治療中に腎性尿崩症が指摘された一例

    日向 裕大, 矢口 雄大, 砂田 大介, 川井 千尋, 山本 正彦, 石黒 創, 北澤 勝, 石澤 正博, 鈴木 浩史, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    新潟医学会雑誌   136 ( 9 )   303 - 303   2022.9

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  • Predictors of hemoglobin and its changes focusing on anemia and polycythemia after administration of the SGLT2 inhibitor, tofogliflozin. International journal

    Yasuhiro Matsubayashi, Akihiro Yoshida, Hideki Suganami, Momoko Oe, Takaaki Sato, Yuta Yaguchi, Kazuya Fujihara, Takaho Yamada, Shiro Tanaka, Kohei Kaku, Hirohito Sone

    Diabetes, obesity & metabolism   24 ( 12 )   2469 - 2473   2022.8

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  • Fast walking and physical activity are independent contributors to improved physical function. International journal

    Haruka Shiozaki, Kazuya Fujihara, Mayuko Yamada-Harada, Masahiko Yamamoto, Yurie Mitsuma, Masaru Kitazawa, Yuta Yaguchi, Yasuhiro Matsubayashi, Midori Iwanaga, Takaho Yamada, Satoru Kodama, Hirohito Sone

    Family practice   2022.8

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    BACKGROUND AND OBJECTIVES: To clarify whether the presence or absence of fast walking and habitual physical activity are independently associated with the incidence of functional disability. METHODS: This historical cohort study was comprised of 9,652 (4,412 men, mean age 65 years) individuals aged 39-98 years without functional disability at baseline. Functional disability was determined based on the Japanese long-term care insurance system, which specified requirements for assistance in the activities of daily living. The impact of fast walking and habitual physical activity on the incidence of functional disability was analysed by Cox proportional hazards models. RESULTS: The follow-up period was a median of 3.7 years during which 165 patients were newly certified as having functional disability. In the multivariate analysis, baseline age in 5-year increments (hazard ratio 2.42 [95% confidence interval 2.18-2.69]), no habitual physical activity (1.56 [1.07-2.27]), and not fast walking (1.89 [1.32-2.69]) significantly increased the risk of functional disability after adjustment for covariates. The stratified analysis showed that compared with physical activity (+), the impact of physical activity (-) on the incidence of functional disability was observed in those aged ≥75 years regardless of fast walking (+). Fast walking (-) significantly increased the risk of disability compared with fast walking (+) in those aged <75 years regardless of a physical activity habit. CONCLUSION: In Japanese, slow walking speed and lack of a physical activity habit were shown to be independent risk factors for incident functional disability, with their impact differing according to age.

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  • Two cases of 22q11.2 deletion syndrome with decreased serum calcium during recovery following thyrotoxicosis. International journal

    Shota Hiroshima, Chihiro Taniguchi, Mika Inoue, Hirohito Sone, Keisuke Nagasaki

    Congenital anomalies   2022.8

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  • Effect of heat-moisture treated brown rice crackers on postprandial flow-mediated dilation in adults with mild endothelial dysfunction. International journal

    Kenichi Watanabe, Masao Hirayama, Somasundaram Arumugam, Masayoshi Sugawara, Hisanori Kato, Sumiko Nakamura, Ken'ichi Ohtsubo, Hitoshi Matsumoto, Yuri Nomi, Noriyuki Homma, Yoshifumi Fujii, Naoto Murohashi, Rajarajan A Thandavarayan, Hiroshi Suzuki, Kazuya Fujihara, Satoru Kodama, Hirohito Sone

    Heliyon   8 ( 8 )   e10284   2022.8

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    Background: Endothelial dysfunction is an early pathophysiological feature and independent predictor of a poor prognosis in most forms of cardiovascular disease. We evaluated the effect of brown rice crackers (BR-C) on endothelial function. Methods: Effect of heat-moisture treated (HMT) -BR-C on postprandial flow-mediated dilation (FMD) in adults with mild endothelial dysfunction was compared with that of BR-C and white rice crackers (WR-C) in 12 adults with mild endothelial dysfunction (less than 7.0% of FMD) by a randomized, single-blind, three-treatment three-period crossover trial (UMIN 000034898). Since we considered that the FMD increase was associated with the treatment of HMT-BR-C, we examined the effect of three possible factors: postprandial glucose levels, polyphenol content, and polyphenol release from the food matrix. Results: Mean pre-intake baseline FMD values of HMT-BR-C, BR-C, and WR-C were 4.9%, 5.1%, and 4.9%, respectively, and those values 1 h post-intake were 6.3%, 5.1%, and 4.8%, respectively. There was no difference in intergroup comparisons of FMD using Dunnett's multiple comparison test. There was a significant increase in FMD only in HMT-BR-C in intragroup comparisons (P = 0.042 by paired-t test). In comparison with BR-C, no significant difference was noted in the postprandial glucose level nor in the content of total polyphenols and ferulic acid derivatives in HMT-BR-C. However, the 70% ethanol extracted from HMT-BR-C contained a significantly larger amount of free and bound ferulic acids than from BR-C. Conclusion: HMT-BR-C intake increased the postprandial FMD response.

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  • Association between Obesity and Intake of Different Food Groups among Japanese with Type 2 Diabetes Mellitus—Japan Diabetes Clinical Data Management Study (JDDM68) International journal

    Mariko Hatta, Chika Horikawa, Yasunaga Takeda, Izumi Ikeda, Sakiko Yoshizawa Morikawa, Noriko Kato, Mitsutoshi Kato, Hiroki Yokoyama, Yoshio Kurihara, Hiroshi Maegawa, Kazuya Fujihara, Hirohito Sone

    Nutrients   14 ( 15 )   2022.7

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    BACKGROUND: We investigated the association between various food groups and obesity in Japanese patients with type 2 diabetes. METHODS: 2070 patients with type 2 diabetes who attended 26 diabetes clinics throughout Japan were analyzed and were divided into obese and non-obese groups. Intakes of food groups determined by a food frequency questionnaire were compared. Odds ratios for obesity for quartiles of individual food groups were calculated using a logistic regression model. RESULTS: Non-obese patients consumed a larger variety of food groups than obese patients, with the diets of non-obese individuals closer to the traditional Japanese diet characterized by fish, seaweed, and soybeans/soy products. Among 21 food groups, low vegetable intake and high sweets intake were the most strongly associated with obesity in both men and women. Low intake of both fruits and vegetables and the combination of high intake of sweets and low intake of fruits were associated with obesity. CONCLUSIONS: Food groups and their combinations that were strongly associated with obesity in Japanese patients with type 2 diabetes were identified. Our findings also suggested an inverse association between the traditional Japanese diet and obesity.

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  • 生活習慣・栄養分野におけるガイドライン2022のトピックスと今後の課題 脂質改善・動脈硬化予防のための運動・身体活動

    木庭 新治, 曽根 博仁, 児玉 暁, 藤原 和哉, 横田 裕哉, 宮下 政司, 井上 茂

    日本動脈硬化学会総会プログラム・抄録集   54回   151 - 151   2022.7

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  • Impact of metabolic syndrome and metabolic dysfunction-associated fatty liver disease on cardiovascular risk by the presence or absence of type 2 diabetes and according to sex. International journal

    Yasuhiro Matsubayashi, Kazuya Fujihara, Mayuko Yamada-Harada, Yurie Mitsuma, Takaaki Sato, Yuta Yaguchi, Taeko Osawa, Masahiko Yamamoto, Masaru Kitazawa, Takaho Yamada, Satoru Kodama, Hirohito Sone

    Cardiovascular diabetology   21 ( 1 )   90 - 90   2022.6

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    BACKGROUND: To determine the impact of metabolic syndrome (MetS) and/or metabolic dysfunction-associated fatty liver disease (MAFLD), which are pathophysiologically similar and include insulin resistance, on the development of new-onset cardiovascular disease with and without type 2 diabetes and according to sex. METHODS: This study included 570,426 individuals without a history of cardiovascular disease who were enrolled in a nationwide claims database from 2008 to 2016 and were classified by the presence or absence of MetS and/or MAFLD stratified by the presence or absence of type 2 diabetes and sex. The fatty liver index was used to determine the presence or absence of fatty liver that required a diagnosis of MAFLD. Risks of developing coronary artery disease (CAD) and cerebrovascular disease (CVD) in each category were analyzed using a multivariate Cox proportional hazard model. RESULTS: During a median follow-up of 5.2 years, 2252 CAD and 3128 CVD events occurred. Without type 2 diabetes the hazard ratio (HR) (95% CI) for CAD/CVD compared with neither MAFLD nor MetS was 1.32 (1.17-1.50)/1.41(1.28-1.57) for MAFLD only (without MetS), 1.78 (1.22-2.58)/1.66 (1.34-2.06) for MetS only (without MAFLD), and 2.10 (1.84-2.39)/1.73 (1.54-1.95) for MAFLD + MetS. For those with type 2 diabetes, the HR for CAD for MAFLD only (compared with neither MAFLD nor MetS) was 1.29 (1.06-1.58), for MetS only 1.34 (0.84-2.13), and for MAFLD + MetS 1.22 (1.02-1.47). For CVD, there was a significant increase in HR only in MAFLD + MetS [1.44 (1.18-1.76)]. The results of the analysis stratified by sex showed that MAFLD had a greater impact in men, and MetS had a greater impact in women regarding the development of CAD. CONCLUSIONS: Distinguishing between MetS and/or MAFLD in the presence or absence of type 2 diabetes and according to sex may aid in accurately identifying patients at high risk of cardiovascular disease.

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  • 【健康食品・機能性食品による健康障害の防止】わが国の健康食品やサプリメントによる重篤な有害事象 内科学会症例報告データベースにおける検討

    鈴木 浩史, 渡辺 賢一, 山本 正彦, 武田 安永, 治田 麻理子, 堀川 千嘉, 藤原 和哉, 曽根 博仁

    機能性食品と薬理栄養   15 ( 6 )   297 - 303   2022.6

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  • J-EDIT・JDCSの合同解析による、年代別に見た日本人2型糖尿病患者の食塩摂取量と心血管疾患発症の縦断的検討

    堀川 千嘉, 池田 和泉, 相田 麗, 田中 司朗, 鎌田 智恵実, 吉村 幸雄, 藤原 和哉, 井藤 英喜, 赤沼 安夫, 守屋 達美, 荒木 厚, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   76回   231 - 231   2022.5

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  • Differences in occupational stress by smoking intensity and gender in cross-sectional study of 59 355 Japanese employees using the Brief Job Stress Questionnaire (BJSQ): the Niigata Wellness Study

    Shigemi Tashiro, Kiminori Kato, Masaru Kitazawa, Kazuya Fujihara, Satoru Kodama, Minoru Tashiro, Kazuhiro Matsuda, Masato Otsuka, Koji Sato, Hirohito Sone

    BMJ Open   2022.4

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  • 青少年におけるスマートフォンを含むスクリーンタイムと肥満との関連

    池田 和泉, 藤原 和哉, 森川 咲子, 武田 安永, 石黒 創, 山田 万祐子, 堀川 千嘉, 松林 泰弘, 山田 貴穂, 曽根 博仁

    日本内分泌学会雑誌   98 ( 1 )   296 - 296   2022.4

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  • 小児における睡眠時間およびソーシャルジェットラグと過体重・肥満の関連

    塩崎 悠香, 藤原 和哉, 山田 万祐子, 大澤 妙子, 北澤 勝, 松林 泰弘, 矢口 雄大, 山本 正彦, 佐藤 隆明, 山田 貴穂, 曽根 博仁

    日本内分泌学会雑誌   98 ( 1 )   296 - 296   2022.4

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  • 新たな総合体力指標を用いたメタボリックシンドロームの発症予測能の検討

    佐藤 隆明, 藤原 和哉, 山田 万祐子, 張 かおり, 矢口 雄大, 山本 正彦, 北澤 勝, 石黒 創, 大澤 妙子, 山田 貴穂, 加藤 公則, 曽根 博仁

    糖尿病   65 ( Suppl.1 )   S - 155   2022.4

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  • 耐糖能およびHDLコレステロール値別にみたLDLコレステロールが冠動脈疾患に及ぼす影響の検討

    山田 万祐子, 藤原 和哉, 大澤 妙子, 北澤 勝, 松林 泰弘, 矢口 雄大, 山本 正彦, 佐藤 隆明, 三ツ間 友里恵, 岩永 みどり, 山田 貴徳, 児玉 暁, 曽根 博仁

    糖尿病   65 ( Suppl.1 )   S - 186   2022.4

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  • HDLコレステロール値別にみたLDLコレステロールと冠動脈疾患との関連

    山田 万祐子, 藤原 和哉, 大澤 妙子, 北澤 勝, 松林 泰弘, 矢口 雄大, 山本 正彦, 佐藤 隆明, 三ツ間 友里恵, 岩永 みどり, 山田 貴穂, 児玉 暁, 曽根 博仁

    日本内分泌学会雑誌   98 ( 1 )   322 - 322   2022.4

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  • AHA Life's simple 7に基づく腎透析導入リスクの予測

    大澤 妙子, 藤原 和哉, 山田 万祐子, 矢口 雄大, 佐藤 隆明, 北澤 勝, 松林 泰弘, 山田 貴穂, 曽根 博仁

    糖尿病   65 ( Suppl.1 )   S - 142   2022.4

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  • Dietary intake and physical activity in Japanese patients with type 2 diabetes: the Japan Diabetes Complication and its Prevention prospective study (JDCP study 8).

    Chika Horikawa, Kinsuke Tsuda, Yoshiharu Oshida, Jo Satoh, Yasuaki Hayashino, Naoko Tajima, Rimei Nishimura, Hirohito Sone

    Diabetology international   13 ( 2 )   344 - 357   2022.4

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    Medical nutrition therapy and exercise therapy are the cornerstones of treatment for patients with type 2 diabetes; however, there has not been a nationwide study on the actual dietary intake and physical activity status of patients since the 2000s. We aimed to clarify this in Japanese patients with type 2 diabetes using data from the Japan Diabetes Complication and its Prevention prospective (JDCP), a nationwide study launched in 2007. A total of 1992 patients with type 2 diabetes, aged 40-75 years, completed either the Brief-type, self-administered Diet History Questionnaire (1643 patients) or International Physical Activity Questionnaire (1834 patients), and their data were analyzed in this study. Mean daily energy intake for all participants was 1686.8 kcal/day, and the mean proportions of carbohydrate, protein, and fat comprising total energy intake were 60.2, 16.2, and 23.6%, respectively. The patients in this study had similar energy and nutrient intake status to patients in the 1996 Japan Diabetes Complications Study; however, Japanese patients still had higher carbohydrate and lower fat consumption than patients with diabetes in Western countries. The physical activity questionnaire reported that 31.0% of patients did not have exercise habits; this was particularly noticeable in female patients and patients under the age of 65. BMI increased from 22.7 to 24.1 kg/m2 in men and 23.2 to 24.8 kg/m2 in women from 1996 to 2007, respectively. Further research is required to investigate how dietary intake and physical activity associates with the risk of developing complications in type 2 diabetes patients.

    DOI: 10.1007/s13340-022-00575-0

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  • 肥満における各野菜摂取頻度と遺伝子・環境相互作用の検討

    藤原 和哉, 野川 駿, 齋藤 憲司, 堀川 千嘉, 武田 安永, 張 かおり, 石黒 創, 児玉 暁, 曽根 博仁

    糖尿病   65 ( Suppl.1 )   S - 160   2022.4

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  • 日本人2型糖尿病患者における、年齢層別に見た食塩摂取量と心血管疾患発症との関係 J-EDIT・JDCSの解析から

    堀川 千嘉, 相田 麗, 田中 司朗, 鎌田 智英実, 田中 佐知子, 吉村 幸雄, 小寺 玲美, 藤原 和哉, 守屋 達美, 井藤 英喜, 赤沼 安夫, 荒木 厚, 曽根 博仁

    糖尿病   65 ( Suppl.1 )   S - 142   2022.4

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  • 日本人2型糖尿病患者における食品群摂取量と肥満の関連 JDDMにおける検討

    治田 麻理子, 堀川 千嘉, 武田 安永, 池田 泉, 森川 咲子, 加藤 則子, 加藤 光敏, 横山 宏樹, 栗原 義夫, 前川 聡, 藤原 和哉, 曽根 博仁, 糖尿病データマネジメント研究会

    糖尿病   65 ( Suppl.1 )   S - 131   2022.4

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  • 妊娠中期における糖代謝状態と低出生体重児出産との関連の検討

    谷内 洋子, 山田 貴穂, 藤原 和哉, 生魚 薫, 堀川 千嘉, 田中 康弘, 龍野 一郎, 曽根 博仁

    糖尿病   65 ( Suppl.1 )   S - 214   2022.4

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  • 肥満傾向または肥満を合併した2型糖尿病高リスクを有する男性に対する血糖自己測定SMBGと栄養教育ツールを併用した栄養教育の効果

    長谷川 美代, 堀川 千嘉, 田代 稔, 鈴木 沙織, 藤原 和哉, 北澤 勝, 加藤 公則, 田中 司朗, 曽根 博仁

    日本栄養士会雑誌   65 ( 3 )   159 - 168   2022.3

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    肥満傾向または肥満を合併した2型糖尿病高リスク者において、摂取した食事の全体量、食べ方を振り返り、食後血糖との関連を把握できるための栄養教育とSMBGとの併用効果が血糖コントロールやBMIの改善に有効であるかを検討した。対象は、医療機関未受診の20〜69歳男性でHbA1c5.6%以上6.5%未満かつBMI24kg/m2以上の者31人を介入群15人、対照群16人に無作為化クラスター割り付けした。介入群には半年間週2回夕食2時間後にSMBGを行い、食事摂取と食後血糖の関係を認識するよう促し、その間管理栄養士と保健師が3回の栄養教育を実施し、対照群には3回の栄養教育のみ行った。解析条件を満たした者は介入群11人、対照群10人であった。介入群と対照群のHbA1cとBMIは、介入前後の変化量に有意差は認められなかった(p=0.09、0.44)。炭水化物エネルギー比は、介入群のみ介入後の比率が増える傾向にあった(p=0.06)。介入群では、内的誘惑に対する統制感が有意に改善した(p=0.01)。また、「食事量」の行動において介入群、対照群共に有意な改善が見られた(p=0.02、p=0.01)。SMBGと本栄養教育の併用が、1食における3大栄養素や食品群の適量を把握し、「栄養素が血糖に変わる速度と割合」の理解につながること、行動の振り返りと問題点の改善が自己効力感を高め、前向きな行動変容につながることが示唆された。(著者抄録)

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  • Leisure-time physical activity and incidence of objectively assessed hearing loss: The Niigata Wellness Study. International journal

    Ryoko Kawakami, Susumu S Sawada, Kiminori Kato, Yuko Gando, Haruki Momma, Hideaki Oike, Motohiko Miyachi, I-Min Lee, Minoru Tashiro, Chika Horikawa, Hajime Ishiguro, Yasuhiro Matsubayashi, Kazuya Fujihara, Hirohito Sone

    Scandinavian journal of medicine & science in sports   32 ( 2 )   435 - 445   2022.2

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    Previous cohort study reported that high physical activity was associated with a low risk of self-reported hearing loss in women. However, no studies have examined the association between physical activity and the development of hearing loss as measured using an objective assessment of hearing loss in men and women. Here, we used cohort data to examine the association between leisure-time physical activity and incidence of objectively assessed hearing loss in men and women. Participants included 27 537 Japanese adults aged 20-80 years without hearing loss, who completed a self-administered physical activity questionnaire between April 2001 and March 2002. The participants were followed up for the development of hearing loss as measured by audiometry between April 2002 and March 2008. During follow-up, 3691 participants developed hearing loss. Compared with the none physical activity group, multivariable adjusted hazard ratios (HRs) for developing hearing loss were 0.93 (95% confidence interval (CI), 0.86-1.01) and 0.87 (0.81-0.95) for the medium (<525 MET-min/week) and high (≥525 MET-min/week) physical activity groups, respectively (p for trend = 0.001). The magnitude of risk reduction was slightly greater in vigorous-intensity activity than in moderate-intensity activity (p for interaction = 0.01). Analysis by sound frequency showed that the amount of physical activity was inversely associated with high frequency hearing loss development (p for trend <0.001), but not with low frequency hearing loss development (p for trend = 0.19). Higher level of leisure-time physical activity was associated with lower incidence of hearing loss, particularly for vigorous-intensity activities and high sound frequencies.

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  • Morphological and functional adaptation of pancreatic islet blood vessels to insulin resistance is impaired in diabetic db/db mice. International journal

    Yuka Okajima, Takashi Matsuzaka, Shun Miyazaki, Kaori Motomura, Hiroshi Ohno, Rahul Sharma, Takuya Shimura, Nurani Istiqamah, Song-Iee Han, Yuhei Mizunoe, Yoshinori Osaki, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Hirohito Sone, Takafumi Miyamoto, Yuichi Aita, Yoshinori Takeuchi, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Tsutomu Tomita, Hitoshi Shimano

    Biochimica et biophysica acta. Molecular basis of disease   1868 ( 4 )   166339 - 166339   2022.1

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    The pancreatic islet vasculature is of fundamental importance to the β-cell response to obesity-associated insulin resistance. To explore islet vascular alterations in the pathogenesis of type 2 diabetes, we evaluated two insulin resistance models: ob/ob mice, which sustain large β-cell mass and hyperinsulinemia, and db/db mice, which progress to diabetes due to secondary β-cell compensation failure for insulin secretion. Time-dependent changes in islet vasculature and blood flow were investigated using tomato lectin staining and in vivo live imaging. Marked islet capillary dilation was observed in ob/ob mice, but this adaptive change was blunted in db/db mice. Islet blood flow volume was augmented in ob/ob mice, whereas it was reduced in db/db mice. The protein concentrations of total and phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 were increased in ob/ob islets, while they were diminished in db/db mice, indicating decreased eNOS activity. This was accompanied by an increased retention of advanced glycation end-products in db/db blood vessels. Amelioration of diabetes by Elovl6 deficiency involved a restoration of capillary dilation, blood flow, and eNOS phosphorylation in db/db islets. Our findings suggest that the disability of islet capillary dilation due to endothelial dysfunction impairs local islet blood flow, which may play a role in the loss of β-cell function and further exacerbate type 2 diabetes.

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  • Higher Iron Intake Is Independently Associated with Obesity in Younger Japanese Type-2 Diabetes Mellitus Patients International journal

    Efrem d'Ávila, Mariko Hatta, Yasunaga Takeda, Chika Horikawa, Mizuki Takeuchi, Noriko Kato, Hiroki Yokoyama, Yoshio Kurihara, Koichi Iwasaki, Kazuya Fujihara, Hiroshi Maegawa, Hirohito Sone

    Nutrients   14 ( 1 )   2022.1

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    We aimed to analyze the association between dietary iron intake and obesity assessed by BMI after adjustment for nutrient intake (macronutrients and fiber) and food groups. The study design was cross-sectional. Patients with type-2 diabetes (n = 1567; 63.1% males; mean age 62.3 ± 11.6 years) were included in the study. To assess diet, consumption of typical food groups was determined by a food frequency questionnaire. Obesity was defined as BMI ≥ 25 kg/m2. We performed a binary regression analysis between quartiles of iron intake and obesity by quartiles of age group. A direct linear association was found for the highest quartile of iron intake and obesity in the younger age group of 30 to 54 years (OR = 3.641, 95% CI = 1.020-12.990; p trend = 0.011). Multivariate analysis using food groups as opposed to nutrients revealed a positive trend for obesity in the younger age group after adjusting for lifestyle factors, energy intake and bean and vegetable intake (p trend = 0.023). In all participants, an inverse association was observed before adjustment by vegetable intake (OR = 0.453, 95% CI = 0.300-0.684; p trend = 0.001). Higher iron intake was associated with obesity independent of macronutrient and fiber intake but only in the youngest quartile of age group examined.

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  • 耐糖能別おける収縮期血圧と冠動脈疾患(CAD)/脳血管疾患発症(CVD)の関連

    藤原 和哉, 山田 万祐子, 山本 正彦, 松林 泰弘, 北澤 勝, 石澤 正博, 堀川 千嘉, 児玉 暁, 曽根 博仁

    Journal of Epidemiology   32 ( Suppl.1 )   128 - 128   2022.1

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  • 妊娠中期における母体のインスリン値と低出生体重児出産との関連の検討

    谷内 洋子, 藤原 和哉, 堀川 千嘉, 生魚 薫, 山本 正彦, 石澤 正博, 山田 貴穂, 児玉 暁, 曽根 博仁

    Journal of Epidemiology   32 ( Suppl.1 )   142 - 142   2022.1

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  • Evaluation of a Comprehensive Physical Fitness Index to Predict Future Prediabetes and Metabolic Syndrome (MetS)

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-539-P

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  • Impact of Health Factors on Incident Cardiovascular Disease (CVD) According to Glucose Tolerance Status

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-1098-P

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  • Impact of Medication Adherence (MA) to Oral Glycemic Agents (OHAs) on Initiation of Dialysis in Patients with Moderately Impaired Renal Function

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-529-P

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  • Combined Severe Diabetic Complications: The New Life-Altering Outcome

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-1165-P

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  • Breadth of the Human Leukocyte Antigens Class I Immunopeptidome in Allogenic Hematopoietic Stem Cell Transplantation Outcomes for Myeloid Malignancy

    Hirohito Sone

    Blood   2022

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    DOI: 10.1182/BLOOD-2022-168616

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  • HLA-B Leader Mismatch Positively Correlates with Survival Rate in Haplo and Cord Blood Transplantation for Acute Leukemia in Japanese Patients

    Hirohito Sone

    Blood   2022

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    DOI: 10.1182/BLOOD-2022-165740

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  • Associations of Systolic Blood Pressure (SBP) with the Incidence of Heart Failure (HF) According to Glucose Tolerance Status (GTS)

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-325-OR

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  • Network Meta-analysis of Hypoglycemic Treatment Regimens with Potential Risk of Hypoglycemia in Terms of Glycemic Control and Severe Hypoglycemia

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-378-P

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  • Sex Differences in the Effect of High Serum Uric Acid on the Incidence of Vision-Threatening Retinopathy in Those with Type 2 Diabetes

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-472-P

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  • Impact of Metabolic Syndrome and Metabolic Dysfunction-Associated Fatty Liver Disease on Cardiovascular Risk in People with and without Type 2 Diabetes

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-1091-P

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  • Meal Ingestion of Ceraceomyces tessulatus Strain BDM-X (Agaricomycetes) Protects against Nonalcoholic Steatohepatitis in Mice

    Hirohito Sone

    International Journal of Medicinal Mushrooms   2022

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    DOI: 10.1615/INTJMEDMUSHROOMS.2021041928

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  • Association between Sleep Duration, Bedtime, and Hyperglycemia or Overweight/Obesity among Japanese Children

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-1439-P

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  • Use of American Heart Association's "Life's Simple 7" as a Predictor for Initiation of Dialysis

    Hirohito Sone

    Diabetes   2022

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    DOI: 10.2337/DB22-1214-P

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  • Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice

    Hirohito Sone

    Frontiers in Nutrition   2022

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    DOI: 10.3389/FNUT.2022.925908

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  • Predictive ability of current machine learning algorithms for type 2 diabetes mellitus: A meta-analysis.

    Satoru Kodama, Kazuya Fujihara, Chika Horikawa, Masaru Kitazawa, Midori Iwanaga, Kiminori Kato, Kenichi Watanabe, Yoshimi Nakagawa, Takashi Matsuzaka, Hitoshi Shimano, Hirohito Sone

    Journal of diabetes investigation   13 ( 5 )   900 - 908   2021.12

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    AIMS/INTRODUCTION: Recently, an increasing number of cohort studies have suggested using machine learning (ML) to predict type 2 diabetes mellitus. However, its predictive ability remains inconclusive. This meta-analysis evaluated the current ability of ML algorithms for predicting incident type 2 diabetes mellitus. MATERIALS AND METHODS: We systematically searched longitudinal studies published from 1 January 1950 to 17 May 2020 using MEDLINE and EMBASE. Included studies had to compare ML's classification with the actual incidence of type 2 diabetes mellitus, and present data on the number of true positives, false positives, true negatives and false negatives. The dataset for these four values was pooled with a hierarchical summary receiver operating characteristic and a bivariate random effects model. RESULTS: There were 12 eligible studies. The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.81 (95% confidence interval [CI] 0.67-0.90), 0.82 [95% CI 0.74-0.88], 4.55 [95% CI 3.07-6.75] and 0.23 [95% CI 0.13-0.42], respectively. The area under the summarized receiver operating characteristic curve was 0.88 (95% CI 0.85-0.91). CONCLUSIONS: Current ML algorithms have sufficient ability to help clinicians determine whether individuals will develop type 2 diabetes mellitus in the future. However, persons should be cautious before changing their attitude toward future diabetes risk after learning the result of the diabetes prediction test using ML algorithms.

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  • Impact of prior cerebrovascular disease and glucose status on incident cerebrovascular disease in Japanese International journal

    Momoko Oe, Kazuya Fujihara, Mayuko Harada-Yamada, Taeko Osawa, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaaki Sato, Yuta Yaguchi, Midori Iwanaga, Hiroyasu Seida, Takaho Yamada, Hirohito Sone

    Cardiovascular Diabetology   20 ( 1 )   174 - 174   2021.12

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    <title>Abstract</title><sec>
    <title>Background</title>
    Although both a history of cerebrovascular disease (CVD) and glucose abnormality are risk factors for CVD, few large studies have examined their association with subsequent CVD in the same cohort. Thus, we compared the impact of prior CVD, glucose status, and their combinations on subsequent CVD using real-world data.


    </sec><sec>
    <title>Methods</title>
    This is a retrospective cohort study including 363,627 men aged 18–72 years followed for ≥ 3 years between 2008 and 2016. Participants were classified as normoglycemia, borderline glycemia, or diabetes defined by fasting plasma glucose, HbA1c, and antidiabetic drug prescription. Prior and subsequent CVD (i.e. ischemic stroke, transient ischemic attack, and non-traumatic intracerebral hemorrhage) were identified according to claims using ICD-10 codes, medical procedures, and questionnaires.


    </sec><sec>
    <title>Results</title>
    Participants’ mean age was 46.1 ± 9.3, and median follow up was 5.2 (4.2, 6.7) years. Cox regression analysis showed that prior CVD + conferred excess risk for CVD regardless of glucose status (normoglycemia: hazard ratio (HR), 8.77; 95% CI 6.96–11.05; borderline glycemia: HR, 7.40, 95% CI 5.97–9.17; diabetes: HR, 5.73, 95% CI 4.52–7.25). Compared with normoglycemia, borderline glycemia did not influence risk of CVD, whereas diabetes affected subsequent CVD in those with CVD- (HR, 1.50, 95% CI 1.34–1.68). In CVD-/diabetes, age, current smoking, systolic blood pressure, high-density lipoprotein cholesterol, and HbA1c were associated with risk of CVD, but only systolic blood pressure was related to CVD risk in CVD + /diabetes.


    </sec><sec>
    <title>Conclusions</title>
    Prior CVD had a greater impact on the risk of CVD than glucose tolerance and glycemic control. In participants with diabetes and prior CVD, systolic blood pressure was a stronger risk factor than HbA1c. Individualized treatment strategies should consider glucose tolerance status and prior CVD.


    </sec>

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  • マウスにおける越後白雪茸の摂取による非アルコール性脂肪性肝炎の進行抑制効果

    鈴木 浩史, 渡辺 賢一, Arumugam Somasundaram, Yellurkar Manoj Limbraj, Sreedhar Remya, Afrin Rejina, 曽根 博仁

    機能性食品と薬理栄養   15 ( 3 )   184 - 184   2021.12

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  • Impact of Medication Adherence and Glycemic Control on the Risk of Micro- and Macrovascular Diseases in Patients with Diabetes. International journal

    Yuta Yaguchi, Kazuya Fujihara, Mayuko Harada Yamada, Yasuhiro Matsubayashi, Takaho Yamada, Midori Iwanaga, Masaru Kitazawa, Masahiko Yamamoto, Hiroyasu Seida, Satoru Kodama, Hirohito Sone

    The American journal of medicine   135 ( 4 )   461 - 470   2021.11

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    PURPOSE: Our purpose in the research was to clarify the impact of medication adherence to oral hypoglycemic agents during a 1-year period and subsequent glycemic control on the risk of micro- and macrovascular diseases. METHODS: Examined was a nationwide claims database on 13,256 individuals with diabetic eye disease without requiring prior treatment, 7,862 without prior initiation of dialysis, 15,556 without prior coronary artery disease, 16,243 without prior cerebrovascular disease, and 19,386 without prior heart failure from 2008 to 2016 in Japan. Medication adherence was evaluated by the proportion of days covered. Patients were considered to have poor adherence if the proportion of days covered was <80%. Multivariate Cox regression model identified risks of micro- and macrovascular diseases. RESULTS: In each group, mean age was 53 to 54 years, HbA1c was 7.1% to 7.2%, and median follow-up period was 4.6 to 5.1 years, and the percentage of poor adherence was approximately 30%. During the study period, 532 treatment-requiring diabetic eye disease, 75 dialysis, 389 coronary artery disease, 316 cerebrovascular disease, and 144 heart failure events occurred. Multivariate Cox regression model revealed that the hazard ratio (95% confidence interval) of dialysis in the poor adherence group was 2.04 (1.27-3.30) compared with the good adherence group. The hazard ratios in the poor adherence/poor glycemic control group were 3.34 (2.63-4.24) for treatment-requiring diabetic eye disease, 4.23 (2.17-8.26) for dialysis, 1.69 (1.23-2.31) for coronary artery disease, and 2.08 (1.25-3.48) for heart failure compared with the good adherence/good glycemic control group. CONCLUSIONS: Poor medication adherence was an independent risk factor for the initiation of dialysis, suggesting that clinicians must pay close attention to these patients.

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  • イノツズマブによる再寛解導入に引き続いてブリナツモマブを投与し再移植できたB-ALLの1例

    米澤 穂高, 布施 香子, 水戸部 正樹, 武田 るい, 諏訪部 達也, 片桐 隆幸, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   62 ( 10 )   1526 - 1526   2021.10

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  • Comparing Associations of Dietary Energy Density and Energy Intake, Macronutrients with Obesity in Patients with Type 2 Diabetes (JDDM 63). International journal

    Yasunaga Takeda, Kazuya Fujihara, Rina Nedachi, Izumi Ikeda, Sakiko Yoshizawa Morikawa, Mariko Hatta, Chika Horikawa, Mitsutoshi Kato, Noriko Kato, Hiroki Yokoyama, Yoshio Kurihara, Kazuhiro Miyazawa, Hiroshi Maegawa, Hirohito Sone

    Nutrients   13 ( 9 )   2021.9

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    To investigate the association between dietary energy density (DED) and obesity in people with type 2 diabetes mellitus. Moreover, we compared the strength of the associations of DED with intake of energy and macronutrients in terms of obesity as well as nutritional factors that have long been used for medical nutritional therapy. Cross-sectionally investigated were 1615 outpatients with type 2 diabetes who attended 26 clinics nationwide with diabetes specialists. Odds ratios (ORs) were calculated for the association between obesity and DED, energy, and macronutrients by quintile categories and a 1 SD increment with adjustment for potential confounders. β coefficients were calculated for the association between body mass index (BMI) and each nutritional factor by 1 SD increments in nutritional values. Multi-adjusted OR for obesity between extreme quintiles of DED was 2.99 (95% confidence interval (95% CI): 2.01-3.12). Conversely, the ORs did not differ significantly according to the quintiles of other nutrient factors. Multi-adjusted β coefficient of BMI per 1 SD according to DED was far higher than those of other nutrient factors (β coefficient 0.65, 95% CI: 0.41-0.88). These findings indicated that DED in persons with type 2 diabetes was positively associated with BMI and the prevalence of obesity. DED was also much more potently associated with obesity and BMI than nutritional indicators such as intake of energy or macronutrients.

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  • Altered Microbiota by a High-Fat Diet Accelerates Lethal Myeloid Hematopoiesis Associated with Systemic Socs3 Deficiency International journal

    Kaori Cho, Takashi Ushiki, Hajime Ishiguro, Suguru Tamura, Masaya Araki, Tatsuya Suwabe, Takayuki Katagiri, Mari Watanabe, Yoko Fujimoto, Riuko Ohashi, Yoichi Ajioka, Ippei Shimizu, Shujiro Okuda, Masayoshi Masuko, Yoshimi Nakagawa, Hideyo Hirai, Warren S. Alexander, Hitoshi Shimano, Hirohito Sone

    iScience   24 ( 10 )   103117 - 103117   2021.9

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    The suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling required to prevent excessive cellular responses. In particular, SOCS3 is involved in the regulation of metabolic syndromes, such as obesity and diabetes, by suppressing leptin and insulin signals. SOCS3 also suppresses the inflammatory response associated with metabolic stress, but this specific role remains undefined. Wild-type mice on a high-fat diet (HFD) exhibited only fatty liver, whereas systemic deletion of SOCS3 resulted in excessive myeloid hematopoiesis and hepatic inflammation. In addition, depletion of the gut microbiota resulted in considerable improvement in excess granulopoiesis and splenomegaly, halting the progression of systemic inflammation in SOCS3KO mice on the HFD. This result suggests that intestinal dysbiosis is involved in inflammation associated with SOCS3KO. Although contributing to diet-induced obesity and fatty liver, SOCS3 is nevertheless critical to suppress excess myeloid hematopoiesis and severe systemic inflammation associated with intestinal dysbiosis on HFD.

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  • Carrot Consumption Frequency Associated with Reduced BMI and Obesity through the SNP Intermediary rs4445711 International journal

    Kazuya Fujihara, Shun Nogawa, Kenji Saito, Chika Horikawa, Yasunaga Takeda, Kaori Cho, Hajime Ishiguro, Satoru Kodama, Yoshimi Nakagawa, Takashi Matsuzaka, Hitoshi Shimano, Hirohito Sone

    Nutrients   13 ( 10 )   2021.9

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    It is unclear whether genetic interactions are involved in the association between vegetable intake and reduced body mass index (BMI) or obesity. We conducted a comprehensive search for single nucleotide polymorphisms (SNPs) which are associated with the interaction between vegetable intake frequency and BMI or obesity. We performed a genome-wide association analysis to evaluate the genetic interactions between self-reported intake of vegetables such as carrot, broccoli, spinach, other green vegetables (green pepper and green beans), pumpkin, and cabbage with BMI and obesity, which is defined as a BMI ≥ 25.0 kg/m2 in the Japanese population (n = 12,225). The mean BMI and prevalence of obesity was 23.9 ± 3.4 kg/m2 and 32.3% in men and 22.1 ± 3.8 kg/m2 and 17.3% in in women, respectively. A significant interaction was observed between rs4445711 and frequency of carrot intake on BMI (p = 4.5 × 10-8). This interaction was slightly attenuated after adjustment for age, sex, alcohol intake, smoking, physical activity and the frequency of total vegetable intake (p = 2.1 × 10-7). A significant interaction was also observed between rs4445711 and frequency of carrot intake on obesity (p = 2.5 × 10-8). No significant interactions that were the same as the interaction between frequency of carrot intake and rs4445711 were observed between the intake frequency of broccoli, spinach, other green vegetables, pumpkin or cabbage and BMI or obesity. The frequency of carrot consumption is implicated in reducing BMI by the intermediary of rs4445711. This novel genetic association may provide new clues to clarify the association between vegetable intake and BMI or obesity.

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  • Secular Trends in Dietary Intake over a 20-Year Period in People with Type 2 Diabetes in Japan: A Comparative Study of Two Nationwide Registries; Japan Diabetes Complications Study (JDCS) and Japan Diabetes Clinical Data Management Study (JDDM) International journal

    Mizuki Takeuchi, Chika Horikawa, Mariko Hatta, Yasunaga Takeda, Rina Nedachi, Izumi Ikeda, Sakiko Yoshizawa Morikawa, Noriko Kato, Hiroki Yokoyama, Rei Aida, Shiro Tanaka, Chiemi Kamada, Yukio Yoshimura, Toshiko Saito, Kazuya Fujihara, Atsushi Araki, Hirohito Sone

    Nutrients   13 ( 10 )   2021.9

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    BACKGROUND: In order to provide effective dietary guidance, it is necessary to consider dietary intake, which can change over time. This study analyzed changes in the diet of Japanese patients with type 2 diabetes over a 20-year period. METHODS: We compared the results of two dietary surveys that used the food frequency questionnaire format. The first was conducted in 1996 by the Japan Diabetes Complications Study (JDCS) (n = 1509; males 53.3%), and the second in 2014-2018 by the Japan Diabetes Clinical Data Management Study (JDDM) (n = 1145; males 65.6%). Both are nationwide representative registries of outpatients with type 2 diabetes in Japan. RESULTS: Over a 20-year period, both men and women with type 2 diabetes had a significant increase in body mass index (BMI). Nonetheless, there was only a small change in energy intake. Conversely, there was a significant increase in fat intake and thus in the fat-to-energy ratio. With regard to food groups, there was a significant increase in meat intake and a decrease in the intake of fish, soybeans/soy products, vegetables, and fruits, with a particularly significant decrease in vegetables. CONCLUSIONS: Even in Japan, an industrialized country with a stable socioeconomic environment, there were many significant changes in the dietary intake of patients with type 2 diabetes over the 20-year period.

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  • WT1ペプチドワクチン投与後のCML患者におけるWT1特異的CTLの持続性と多様性(Persistence and diversity of WT1-specific CTLs in a CML patient vaccinated WT1 peptide)

    諏訪部 達也, 柴崎 康彦, 田村 秀, 片桐 隆幸, 布施 香子, 牛木 隆志, 曽根 博仁, 成田 美和子, 増子 正義

    日本血液学会学術集会   83回   PS - 1   2021.9

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  • ドナーリンパ球のコンドロイチン硫酸合成低下はGVHDを軽減する(Genetic manipulation resulting in decreased donor chondroitin sulfate mitigates GVHD in mice)

    田村 秀, 牛木 隆志, 諏訪部 達也, 片桐 隆幸, 石黒 創, 布施 香子, 柴崎 康彦, 進藤 岳郎, 五十嵐 道弘, 曽根 博仁, 増子 正義

    日本血液学会学術集会   83回   OS3 - 1   2021.9

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  • AMLにおける造血幹細胞移植後1年未満の再発は高い死亡率と相関する(Post-transplant relapse of AML within one year is associated with a high mortality rate)

    片桐 隆幸, 本宮 奈津子, 武田 ルイ, 水戸部 正樹, 米沢 穂高, 諏訪部 達也, 布施 香子, 柴崎 康彦, 瀧澤 淳, 曽根 博仁, 増子 正義

    日本血液学会学術集会   83回   PS - 10   2021.9

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  • Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at ER monitoring and regulating fatty acids

    Hirohito Sone

    BioRxiv   2021.8

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    DOI: 10.1101/2021.08.24.457590

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  • Developing a health economic model for Asians with type 2 diabetes based on the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial. International journal

    Shiro Tanaka, Jakob Langer, Tim Morton, Nicki Hoskins, Lars Wilkinson, Sachiko Tanaka-Mizuno, Ryo Kawasaki, Tatsumi Moriya, Chika Horikawa, Rei Aida, Atsushi Araki, Kazuya Fujihara, Hirohito Sone

    BMJ open diabetes research & care   9 ( 1 )   2021.8

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    INTRODUCTION: Cost-effectiveness analyses are becoming increasingly important in Japan following the introduction of a health technology assessment scheme. The study objective was to develop an economic model to evaluate the cost-effectiveness of two interventions for type 2 diabetes in a Japanese population. RESEARCH DESIGN AND METHODS: The Japan Diabetes Complications Study/Japanese Elderly Diabetes Intervention Trial risk engine (JJRE) Cost-Effectiveness Model (JJCEM) was developed, incorporating validated risk equations in Japanese patients with type 2 diabetes from the JJRE. Weibull regression models were developed for progression of the model outcomes, and a targeted literature review was performed to inform default values for utilities and costs. To illustrate outcomes, two simulated analyses were performed in younger (aged 40 years) and older (aged 80 years) Japanese populations, comparing a hypothetical treatment with placebo. RESULTS: The model considers a population based on user-defined values for 11 baseline characteristic parameters and simulates rates of diabetic complications over a defined time horizon. Costs, quality-adjusted life years, and an incremental cost-effectiveness ratio are estimated. The model provides disaggregated results for two competing interventions, allowing visualization of the key drivers of cost and utility. A scatterplot of simulations and cost-effectiveness acceptability curve are generated for each analysis. CONCLUSIONS: This is the first cost-effectiveness model for East Asian patients with type 2 diabetes, developed using Japan-specific risk equations. This population constitutes the largest share of the global population with diabetes, making this model highly relevant. The model can be used to evaluate the cost-effectiveness of anti-diabetic interventions in patients with type 2 diabetes in Japan and other East Asian populations.

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  • Intensive oral care can reduce bloodstream infection with coagulase-negative staphylococci after neutrophil engraftment in allogeneic hematopoietic stem-cell transplantation. International journal

    Tatsuya Suwabe, Kyoko Fuse, Kouji Katsura, Marie Soga, Takayuki Katagiri, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer   30 ( 1 )   475 - 485   2021.7

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    PURPOSE: Bloodstream infection (BSI) is a major complication of allogeneic hematopoietic stem-cell transplantation (allo-SCT). There are several causes of BSI; in particular, severe oral mucositis (OM) can induce BSI due to coagulase-negative staphylococci (CoNS). The OM severity may be reduced with intensive oral care. Thus, we evaluated whether the type of oral care affects the BSI incidence eventually. METHOD: We performed retrospective analysis on 206 recipients who underwent allo-SCT from 2006 to 2017 at our institute. Intensive oral care by a dental specialist was performed for 111 recipients (intensive-care group) and self-oral care was performed by 95 recipients (self-care group). Incidence of BSI was assessed by type of the oral care, before neutrophil engraftment (pre-E-BSI) and after neutrophil engraftment (post-E-BSI) period until 180 days after allo-SCT. RESULT: A total of 112 BSI occurred in 90 of the 206 recipients and 120 bacteria were identified, with CoNS being the most prevalent. There was no significant difference in the incidence of pre-E-BSI between the self-care and intensive-care groups (30.8% and 30.6%, respectively; P = 0.508). Meanwhile, the incidence of post-E-BSI was significantly lower in the intensive-care group than in the self-care group (14.3% and 28.6%; P = 0.008). In addition, the intensive-care group had significantly lower incidence of post-E-BSI with CoNS than the self-care group (8.5% and 21.5%, respectively; P = 0.009). CONCLUSION: Intensive oral care through the period of allo-HCT can significantly reduce the post-E-BSI occurrence, especially due to CoNS.

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  • Central diabetes insipidus after syndrome of inappropriate antidiuretic hormone secretion with severe hyponatremia in a patient with Rathke's cleft cyst.

    Yudai Hinata, Nobumasa Ohara, Takeshi Komatsu, Yuki Sakurai, Yuichiro Yoneoka, Yasuhiro Seki, Katsuhiko Akiyama, Hirohito Sone

    Internal medicine (Tokyo, Japan)   61 ( 2 )   197 - 203   2021.7

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    A 49-year-old man developed severe hyponatremia associated with transient headache and was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction and sodium supplementation corrected the hyponatremia. However, several days later, the patient exhibited hypernatremia with thirst and polyuria. A detailed examination indicated central diabetes insipidus (CDI) with an intrasellar cystic lesion indicative of Rathke's cleft cyst (RCC). A case of RCC exhibiting headache, hyponatremia, and subsequent hypernatremia has been reported. Our case shows that CDI may appear after SIADH in patients with RCC, especially in those with serum sodium levels that unexpectedly increase rapidly beyond the reference range.

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  • Meta-analytic research of the dose-response relationship between salt intake and risk of heart failure. Reviewed International journal

    Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Mariko Hatta, Yasunaga Takeda, Rena Nedachi, Kiminori Kato, Kenichi Watanabe, Hirohito Sone

    Hypertension research : official journal of the Japanese Society of Hypertension   44 ( 7 )   885 - 887   2021.7

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  • Association of estimated plasma volume and weight loss after long-term administration and subsequent discontinuation of the sodium-glucose cotransporter-2 inhibitor tofogliflozin. International journal

    Yasuhiro Matsubayashi, Akihiro Yoshida, Hideki Suganami, Momoko Oe, Takaaki Sato, Yuta Yaguchi, Kazuya Fujihara, Takaho Yamada, Shiro Tanaka, Kohei Kaku, Hirohito Sone

    Diabetes, obesity & metabolism   23 ( 7 )   1660 - 1665   2021.7

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    Sodium-glucose cotransporter-2 inhibitors (SGLT2) are drugs that have been reported to have several effects through the regulation of plasma volume, for example, antihypertensive effects. This study aimed to clarify the impact of long-term administration and subsequent discontinuation of the SGLT2 inhibitor tofogliflozin on estimated plasma volume (ePV), brain natriuretic peptide (BNP) and the relationship between changes in ePV, BNP and body weight (BW). Data from 157 participants with type 2 diabetes receiving tofogliflozin monotherapy in a phase 3 study were analysed. Changes in variables or correlations among them during a 52-week administration and a 2-week post-treatment period were investigated. Percent change in ePV was calculated using the Strauss formula. Significant decreases in BW, ePV and ln-transformed BNP (ln-BNP) were noted by week 52. %ΔBW was not significantly correlated with %ΔePV and Δln-BNP, while %ΔePV was significantly correlated with Δln-BNP. Two weeks after discontinuation of tofogliflozin, BW, ePV and ln-BNP were significantly increased. %ΔBW was significantly correlated with %ΔePV and Δln-BNP. Furthermore, ePV and BNP were significantly higher than baseline levels.

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  • Author Correction: Meta-analytic research of the dose-response relationship between salt intake and risk of heart failure. International journal

    Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Mariko Hatta, Yasunaga Takeda, Rena Nedachi, Kiminori Kato, Kenichi Watanabe, Hirohito Sone

    Hypertension research : official journal of the Japanese Society of Hypertension   44 ( 7 )   894 - 894   2021.7

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  • 粘液水腫性昏睡に急性膵炎を合併した一例

    齋藤 啓輔, 矢口 雄大, 滝澤 祥子, 西井 郁生, 竹内 亮, 山本 正彦, 川田 亮, 石黒 創, 北澤 勝, 松林 泰弘, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( Suppl.Update )   38 - 40   2021.7

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  • Starvation-induced transcription factor CREBH negatively governs body growth by controlling GH signaling. International journal

    Yoshimi Nakagawa, Kae Kumagai, Song-Iee Han, Yuhei Mizunoe, Masaya Araki, Seiya Mizuno, Hiroshi Ohno, Kazuya Matsuo, Yasunari Yamada, Jun-Dal Kim, Takafumi Miyamoto, Motohiro Sekiya, Morichika Konishi, Nobuyuki Itoh, Takashi Matsuzaka, Satoru Takahashi, Hirohito Sone, Hitoshi Shimano

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   35 ( 6 )   e21663   2021.6

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    cAMP responsive element-binding protein H (CREBH) is a hepatic transcription factor to be activated during fasting. We generated CREBH knock-in flox mice, and then generated liver-specific CREBH transgenic (CREBH L-Tg) mice in an active form. CREBH L-Tg mice showed a delay in growth in the postnatal stage. Plasma growth hormone (GH) levels were significantly increased in CREBH L-Tg mice, but plasma insulin-like growth factor 1 (IGF1) levels were significantly decreased, indicating GH resistance. In addition, CREBH overexpression significantly increased hepatic mRNA and plasma levels of FGF21, which is thought to be as one of the causes of growth delay. However, the additional ablation of FGF21 in CREBH L-Tg mice could not correct GH resistance at all. CREBH L-Tg mice sustained GH receptor (GHR) reduction and the increase of IGF binding protein 1 (IGFBP1) in the liver regardless of FGF21. As GHR is a first step in GH signaling, the reduction of GHR leads to impairment of GH signaling. These data suggest that CREBH negatively regulates growth in the postnatal growth stage via various pathways as an abundant energy response by antagonizing GH signaling.

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  • 陰茎・陰嚢病変を合併した精巣原発DLBCL

    水戸部 正樹, 武田 ルイ, 米沢 穂高, 田村 秀, 諏訪部 達也, 片桐 隆幸, 河本 啓介, 布施 香子, 柴崎 康彦, 増子 正義, 井上 佳菜子, 三好 寛明, 大島 孝一, 曽根 博仁, 瀧澤 淳

    臨床血液   62 ( 6 )   668 - 668   2021.6

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  • 同種造血幹細胞移植後の慢性GVHDとしての類上皮肉芽腫および多発筋炎

    諏訪部 達也, 布施 香子, 水戸部 正樹, 武田 ルイ, 米沢 穂高, 片桐 隆幸, 河本 啓介, 牛木 隆志, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 大島 孝一, 増子 正義

    臨床血液   62 ( 6 )   675 - 675   2021.6

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  • Associations of Systolic Blood Pressure and Diastolic Blood Pressure With the Incidence of Coronary Artery Disease or Cerebrovascular Disease According to Glucose Status. International journal

    Mayuko Harada Yamada, Kazuya Fujihara, Satoru Kodama, Takaaki Sato, Taeko Osawa, Yuta Yaguchi, Masahiko Yamamoto, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Hiroyasu Seida, Wataru Ogawa, Hirohito Sone

    Diabetes care   44 ( 9 )   2124 - 2131   2021.5

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    OBJECTIVE: To determine associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with new-onset coronary artery disease (CAD) or cerebrovascular disease (CVD) according to glucose status. RESEARCH DESIGN AND METHODS: Examined was a nationwide claims database from 2008 to 2016 on 593,196 individuals. A Cox proportional hazards model identified risks of CAD and CVD events among five levels of SBP and DBP. RESULTS: During the study period 2,240 CAD and 3,207 CVD events occurred. Compared with SBP ≤119 mmHg, which was the lowest quintile of SBP, hazard ratios (95% CI) for CAD/CVD in the 4 higher quintiles (120-129, 130-139, 140-149, ≥150 mmHg) gradually increased from 2.10 (1.73-2.56)/1.46 (1.27-1.68) in quintile 2 to 3.21 (2.37-4.34)/4.76 (3.94-5.75) in quintile 5 for normoglycemia, from 1.39 (1.14-1.69)/1.70 (1.44-2.01) in quintile 2 to 2.52 (1.95-3.26)/4.12 (3.38-5.02) in quintile 5 for borderline glycemia, and from 1.50 (1.19-1.90)/1.72 (1.31-2.26) in quintile 2 to 2.52 (1.95-3.26)/3.54 (2.66-4.70) in quintile 5 for diabetes. A similar trend was observed for DBP across 4 quintiles (75-79, 80-84, 85-89, and ≥90 mmHg) compared with ≥74 mmHg, which was the lowest quintile. CONCLUSIONS: Results indicated that cardiovascular risks gradually increased with increases in SBP and DBP regardless of the presence of and degree of a glucose abnormality. Further interventional trials are required to apply findings from this cohort study to clinical practice.

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  • Accuracy of Japanese claims data in identifying diabetes-related complications. Reviewed International journal

    Kazuya Fujihara, Mayuko Yamada-Harada, Yasuhiro Matsubayashi, Masaru Kitazawa, Masahiko Yamamoto, Yuta Yaguchi, Hiroyasu Seida, Satoru Kodama, Kohei Akazawa, Hirohito Sone

    Pharmacoepidemiology and drug safety   30 ( 5 )   594 - 601   2021.5

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    PURPOSE: To evaluate the accuracy of various claims-based definitions of diabetes-related complications (coronary artery disease [CAD], heart failure, cerebrovascular disease and dialysis). METHODS: We evaluated data on 1379 inpatients who received care at the Niigata University Medical & Dental Hospital in September 2018. Manual electronic medical chart reviews were conducted for all patients with regard to diabetes-related complications and were used as the gold standard. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each claims-based definition associated with diabetes-related complications based on Diagnosis Procedure Combination (DPC), International Classification of Diseases, Tenth Revision (ICD-10) codes, procedure codes and medication codes were calculated. RESULTS: DPC-based definitions had higher sensitivity, specificity, and PPV than ICD-10 code definitions for CAD and cerebrovascular disease, with sensitivity of 0.963-1.000 and 0.905-0.952, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. Sensitivity, specificity, and PPV were high using procedure codes for CAD and dialysis, with sensitivity of 0.963 and 1.000, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. DPC and/or ICD-10 codes + medication were better for heart failure than the ICD-10 code definition, with sensitivity of 0.933, specificity of 1.000, and PPV of 1.000. The PPVs were lower than 60% for all diabetes-related complications using ICD-10 codes only. CONCLUSION: The DPC-based definitions for CAD and cerebrovascular disease, procedure codes for CAD and dialysis, and DPC or ICD-10 codes with medication codes for heart failure could accurately identify these diabetes-related complications from claims databases.

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  • WT1-specific CD8 + cytotoxic T cells with the capacity for antigen-specific expansion accumulate in the bone marrow in MDS. Reviewed

    Tatsuya Suwabe, Yasuhiko Shibasaki, Hiroyuki Sato, Suguru Tamura, Takayuki Katagiri, Hiroki Nemoto, Takuya Kasami, Takashi Kozakai, Ayako Nanba, Toshiki Kitajima, Kyoko Fuse, Takashi Ushiki, Hirohito Sone, Miwako Narita, Masayoshi Masuko

    International journal of hematology   113 ( 5 )   723 - 734   2021.5

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    Wilms' tumor 1 (WT1) is a tumor-associated antigen and immunotherapy target in myelodysplastic syndrome (MDS). Further information is needed on the characteristics of WT1-specific CD8 + T cells to develop immunotherapeutic strategies for MDS. To clarify the frequency, distribution, and phenotype of WT1-specific CD8 + T cells, which occur innately in MDS patients, we analyzed paired peripheral blood (PB) and bone marrow (BM) samples from 39 patients with MDS or acute myeloid leukemia with myelodysplasia-related changes. The median frequency of WT1 tetramer-binding CD8 + T cells in the CD8 + T cell population was 0.11% in PB and 0.18% in BM. A further tetramer assay combined with mixed lymphocyte peptide culture (MLPC assay) was used to detect functional WT1-specific CD8 + T cells that could respond to the WT1 peptide. Functional WT1-specific CD8 + T cells were detected in BM in 61% of patients, which was significantly higher than in PB (23%, p = 0.001). The frequency of these cells estimated by the MLPC assay was tenfold higher in BM than in PB. The majority of WT1 tetramer-binding CD8 + T cells in BM had a unique phenotype with co-expression of CD39 and CXCR4. These findings will facilitate the development of novel immunotherapeutic strategies for MDS.

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  • 乾燥人フィブリノゲン製剤の継続輸注で着床・妊娠継続・出産をし得た先天性低フィブリノゲン血症

    関 義信, 牛木 隆志, 増子 正義, 瀧澤 淳, 曽根 博仁, 奥村 伸生

    日本血栓止血学会誌   32 ( 2 )   214 - 214   2021.5

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  • GB療法施行中にHigh-grade B-cell lymphoma with MYC and BCL2 rearrangementsで再燃したFollicular lymphoma(Grade 3A)の2症例

    水戸部 正樹, 本宮 奈津子, 武田 ルイ, 米沢 穂高, 鈴木 隆晴, 諏訪部 達也, 片桐 隆幸, 河本 啓介, 布施 香子, 柴崎 康彦, 増子 正義, 井上 佳菜子, 三好 寛明, 大島 孝一, 曽根 博仁, 瀧澤 淳

    日本リンパ網内系学会会誌   61   114 - 114   2021.5

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  • 腎障害を有する高悪性度B細胞リンパ腫症例にDA-EPOCH-Rを施行した1例

    水戸部 正樹, 河本 啓介, 鈴木 隆晴, 米沢 穂高, 田村 秀, 諏訪部 達也, 根本 洋樹, 布施 香子, 柴崎 康彦, 増子 正義, 三好 寛明, 大島 孝一, 曽根 博仁, 瀧澤 淳

    臨床血液   62 ( 5 )   532 - 532   2021.5

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  • ルキソルチニブ・ヒドロキシウレア併用療法が奏効した慢性好中球性白血病(CNL)の1例

    武田 ルイ, 布施 香子, 片桐 隆幸, 河本 啓介, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 野本 信彦, 曽根 博仁, 増子 正義

    臨床血液   62 ( 5 )   529 - 530   2021.5

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  • 乾燥人フィブリノゲン製剤の継続輸注で着床・妊娠継続・出産をし得た先天性低フィブリノゲン血症

    関 義信, 牛木 隆志, 増子 正義, 瀧澤 淳, 曽根 博仁, 奥村 伸生

    日本血栓止血学会誌   32 ( 2 )   214 - 214   2021.5

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  • The Japanese Medical Science Federation COVID-19 Expert Opinion English Version.

    Masaomi Nangaku, Takashi Kadowaki, Hiroshi Yotsuyanagi, Norio Ohmagari, Moritoki Egi, Junichi Sasaki, Tetsuya Sakamoto, Yoshinori Hasegawa, Takashi Ogura, Shigeru Chiba, Koichi Node, Ryo Suzuki, Yasuhiro Yamaguchi, Atsuko Murashima, Norihiko Ikeda, Eriko Morishita, Kenji Yuzawa, Hiroyuki Moriuchi, Satoshi Hayakawa, Daisuke Nishi, Atsushi Irisawa, Toshiaki Miyamoto, Hidetaka Suzuki, Hirohito Sone, Yuuji Fujino

    JMA journal   4 ( 2 )   148 - 162   2021.4

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    In 2020, the COVID-19 pandemic has had unprecedented impacts on various aspects of the world. Each academic society has published a guide and/or guidelines on how to cope with COVID-19 separately. As the one and only nationwide association of academic societies that represent medical science in Japan, JMSF has decided to publish the expert opinion to help patients and care providers find specifically what they want. This expert opinion is a summary of recommendations by many academic societies and will be updated when necessary. Patients that each academic society targets differ even though they suffer from the same COVID-19, and recommendations can be different in a context-dependent manner. Readers are supposed to be flexible and adjustable when they use this expert opinion.

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  • Rates and risk factors for amputation in people with diabetes in Japan: a historical cohort study using a nationwide claims database. International journal

    Masanori Kaneko, Kazuya Fujihara, Mayuko Yamada Harada, Taeko Osawa, Masahiko Yamamoto, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Hiroyasu Seida, Satoru Kodama, Hirohito Sone

    Journal of foot and ankle research   14 ( 1 )   29 - 29   2021.4

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    BACKGROUND: The prevalence of diabetes is rising, and diabetes develops at a younger age in East Asia. Although lower limb amputation negatively affects quality of life and increases the risk of cardiovascular events, little is known about the rates and predictors of amputation among persons with diabetes from young adults to those in the "young-old" category (50-72 y). METHODS: We analyzed data from a nationwide claims database in Japan accumulated from 2008 to 2016 involving 17,288 people with diabetes aged 18-72 y (mean age 50.2 y, HbA1c 7.2%). Amputation occurrence was determined according to information from the claims database. Cox regression model identified variables related to lower limb amputation. RESULTS: The mean follow-up time was 5.3 years, during which time 16 amputations occurred (0.17/1000 person-years). Multivariate Cox regression analysis showed that age (hazard ratio [HR] 1.09 [95% confidence intervals] 1.02-1.16, p = 0.01) and HbA1c (HR 1.46 [1.17-1.81], p < 0.01) were independently associated with amputations. Compared with those aged < 60 years with HbA1c < 8.0%, the HR for amputation was 27.81 (6.54-118.23) in those aged ≥60 years and HbA1c ≥8.0%. CONCLUSIONS: Age and HbA1c were associated with amputations among diabetic individuals, and the rates of amputation were significantly greater in those ≥60 years old and with HbA1c ≥8.0%.

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  • Physical Fitness and Dyslipidemia Among Japanese: A Cohort Study From the Niigata Wellness Study. Reviewed

    Haruki Momma, Kiminori Kato, Susumu S Sawada, Yuko Gando, Ryoko Kawakami, Motohiko Miyachi, Ryoichi Nagatomi, Minoru Tashiro, Yasuhiro Matsubayashi, Satoru Kodama, Midori Iwanaga, Kazuya Fujihara, Hirohito Sone

    Journal of epidemiology   31 ( 4 )   287 - 296   2021.4

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    BACKGROUND: Grip strength reflects systemic muscle strength and mass and is reportedly associated with various metabolic variables. However, its prognostic association with dyslipidemia is unknown. We examined the association of grip strength and other physical fitness markers with the incidence of dyslipidemia among Japanese adults. METHODS: A total of 16,149 Japanese (6,208 women) individuals aged 20-92 years who underwent a physical fitness test between April 2001 and March 2002 were included in this cohort study. Grip strength, vertical jump, single-leg balance with eyes closed, forward bending, and whole-body reaction time were evaluated at baseline. Dyslipidemia was annually determined based on fasting serum lipid profiles and self-reported dyslipidemia from April 2001 to March 2008. RESULTS: During the follow-up period, 4,458 (44.9%) men and 2,461 (39.6%) women developed dyslipidemia. A higher relative grip strength (grip strength/body mass index) was associated with a lower incidence of dyslipidemia among both men and women (P for trend <0.001). Compared with those for the first septile, the hazards ratios and 95% confidence intervals (CIs) for the seventh septile were 0.56 (95% CI, 0.50-0.63) for men and 0.69 (95% CI, 0.58-0.81) for women. Moreover, relative vertical jump (vertical jump strength/body mass index) was also inversely associated with the incidence of dyslipidemia among both men and women (P for trend <0.001). There was no association between other physical fitness and dyslipidemia among both men and women. CONCLUSION: Relative grip strength and vertical jump may be useful risk markers of the incidence of dyslipidemia.

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  • Distinct effects of chondroitin sulfate on hematopoietic cells and the stromal microenvironment in bone marrow hematopoiesis. Reviewed International journal

    Takayuki Katagiri, Shun Uemura, Takashi Ushiki, Yaeko Nakajima-Takagi, Motohiko Oshima, Tadahisa Mikami, Asami Kawasaki, Hajime Ishiguro, Tomoyuki Tanaka, Hirohito Sone, Hiroshi Kitagawa, Michihiro Igarashi, Atsushi Iwama, Masayoshi Masuko

    Experimental hematology   96   52 - 62   2021.4

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    The bone marrow (BM) microenvironment, known as the BM niche, regulates hematopoiesis but is also affected by interactions with hematopoietic cells. Recent evidence indicates that extracellular matrix components are involved in these interactions. Chondroitin sulfate (CS), a glycosaminoglycan, is a major component of the extracellular matrix; however, it is not known whether CS has a physiological role in hematopoiesis. Here, we analyzed the functions of CS in hematopoietic and niche cells. CSGalNAcT1, which encodes CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, was highly expressed in hematopoietic stem and progenitor cells (HSPCs) and endothelial cells (ECs), but not in mesenchymal stromal cells (MSCs) in BM. In T1 knockout (T1KO) mice, a greater number of HSPCs existed compared with the wild-type (WT), but HSPCs from T1KO mice showed significantly impaired repopulation in WT recipient mice on serial transplantation. RNA sequence analysis revealed the activation of IFN-α/β signaling and endoplasmic reticulum stress in T1KO HSPCs. In contrast, the number of WT HSPCs repopulated in T1KO recipient mice was larger than that in WT recipient mice after serial transplantation, indicating that the T1KO niche supports repopulation of HSPCs better than the WT niche. There was no obvious difference in the distribution of vasculature and MSCs between WT and T1KO BM, suggesting that CS loss alters vascular niche functions without affecting its structure. Our results revealed distinct roles of CS in hematopoietic cells and BM niche, indicating that crosstalk between these components is important to maintain homeostasis in BM.

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  • DA-EPOCH-R therapy for high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements in a patient with renal dysfunction. Reviewed

    Masaki Mitobe, Keisuke Kawamoto, Takaharu Suzuki, Tatsuya Suwabe, Yasuhiko Shibasaki, Masayoshi Masuko, Kanako Inoue, Hiroaki Miyoshi, Koichi Ohshima, Hirohito Sone, Jun Takizawa

    Journal of clinical and experimental hematopathology : JCEH   61 ( 1 )   42 - 47   2021.3

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    High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, also known as double-hit lymphoma, has been reported as refractory to R-CHOP therapy and requires more intensive regimens. However, intensive and safe regimens for patients with renal dysfunction are unknown. Herein, we report the successful use of DA-EPOCH-R therapy for double-hit lymphoma in a 64-year-old man with renal dysfunction. The patient had lymphoma-induced bilateral ureteral obstruction. Although renal dysfunction remained after removing the obstruction using R-CHOP therapy, we completed six cycles of DA-EPOCH-R therapy without any major adverse events. DA-EPOCH-R therapy may be a safe regimen for renal dysfunction patients.

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  • Dipeptidyl peptidase-4 inhibitor, anagliptin, alters hepatic insulin clearance in relation to the glycemic status in Japanese individuals with type 2 diabetes.

    Takahiro Abe, Yasuhiro Matsubayashi, Sayaka Muragishi, Akihiro Yoshida, Hideki Suganami, Kenichi Furusawa, Kazuya Fujihara, Shiro Tanaka, Kohei Kaku, Hirohito Sone

    Journal of diabetes investigation   12 ( 10 )   1805 - 1815   2021.3

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    AIMS/INTRODUCTION: This study investigated the impact of the dipeptidyl peptidase-4 inhibitor, anagliptin, on hepatic insulin clearance (HIC) in Japanese type 2 diabetes patients and explored its relationship to glycemic status. MATERIALS AND METHODS: Data on 765 participants in anagliptin phase 2 and 3 studies were analyzed. Adjusted changes in variables during 12 weeks of anagliptin therapy were compared with a placebo. HIC was calculated as the ratio, C-peptide area under the curve 0-120 min to insulin area under the curve 0-120 min, after a meal tolerance test. To explore the effects of baseline HIC levels on variables, participants receiving anagliptin were divided according to quartiles of baseline HIC. Furthermore, multivariate analysis investigated the association between baseline HIC levels and glycemic status. RESULTS: Anagliptin significantly reduced glycosylated hemoglobin levels (P < 0.001 vs placebo) and HIC levels (P < 0.01). Longer duration of diabetes, lower body mass index, higher glycosylated hemoglobin and lower insulin secretion capacity were observed with increases in baseline HIC levels. Improvements in glycosylated hemoglobin, glycoalbumin and 1,5-anhydroglucitol levels were greater in the relatively higher HIC group (baseline HIC levels ≥median) than in the lower HIC group (<median). CONCLUSIONS: Anagliptin affected HIC levels according to HIC baseline levels. Higher baseline HIC values might result in improved hyperglycemia through reduced HIC.

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  • Body flexibility and incident hypertension: The Niigata wellness study. Reviewed International journal

    Yuko Gando, Susumu S Sawada, Haruki Momma, Ryoko Kawakami, Motohiko Miyachi, I-Min Lee, Steven N Blair, Minoru Tashiro, Chika Horikawa, Yasuhiro Matsubayashi, Takaho Yamada, Kazuya Fujihara, Kiminori Kato, Hirohito Sone

    Scandinavian journal of medicine & science in sports   31 ( 3 )   702 - 709   2021.3

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    A high level of physical fitness, especially cardiorespiratory fitness, is associated with lower incidence of hypertension. However, the relationship between flexibility, which is a component of physical fitness, and the incidence of hypertension is unknown. The purpose of this study was to investigate the relationship between flexibility and the incidence of hypertension in a cohort study. A total of 22,972 (14,805 men and 8167 women; median age 49 years) normotensive participants were included in this study. Between April 2001 and March 2002, flexibility (standing forward bending) was measured using a standing trunk flexion meter. The participants were divided into quartiles of flexibility by sex and age group. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90 mm Hg, or a self-reported history of previously diagnosed hypertension or current medication for hypertension at a health examination between April 2002 and March 2008. Hazard ratios and 95% confidence intervals (95% CI) for the incidence of hypertension were estimated using Cox proportional hazards models after adjusting for age, sex, body mass index, exercise habits, smoking status, and drinking status. During 102,948 person years of follow-up (median 5.6 years), 4235 participants developed hypertension. Compared with the lowest flexibility (quartile 1), hazard ratios and 95% CI were 0.96 (0.88 - 1.04) for quartile 2, 0.94 (0.86 - 1.03) for quartile 3, and 0.83 (0.76 - 0.91) for quartile 4. A high level of flexibility was associated with lower incidence of hypertension, independent of other confounding factors.

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  • Severity of hypertension as a predictor of initiation of dialysis among study participants with and without diabetes mellitus. Reviewed International journal

    Taeko Osawa, Kazuya Fujihara, Mayuko Harada Yamada, Masahiko Yamamoto, Masaru Kitazawa, Yasuhiro Matsubayashi, Midori Iwanaga, Takaho Yamada, Hiroyasu Seida, Satoru Kodama, Yoshimi Nakagawa, Hitoshi Shimano, Hirohito Sone

    Journal of investigative medicine : the official publication of the American Federation for Clinical Research   69 ( 3 )   724 - 729   2021.3

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    To determine associations between severity of hypertension and risk of starting dialysis in the presence or absence of diabetes mellitus (DM). A nationwide database with claims data on 258 874 people with and without DM aged 19-72 years in Japan was used to elucidate the impact of severity of hypertension on starting dialysis. Initiation of dialysis was determined from claims using International Classification of Diseases-10 codes and medical procedures. Using multivariate Cox modeling, we investigated the severity of hypertension to predict the initiation of dialysis with and without DM. Hypertension was significantly associated with the initiation of dialysis regardless of DM. The incidence of starting dialysis in those with systolic blood pressure (SBP) ≤119 mm Hg and DM (DM+) was almost the same as in those with SBP ≥150 mm Hg and absence of DM (DM-). In comparison with SBP ≤119 mm Hg, SBP ≥150 mm Hg significantly increased the risk of the initiation of dialysis about 2.5 times regardless of DM+ or DM-. Compared with DM- and SBP ≤119 mm Hg, the HR for DM+ and SBP ≥150 mm Hg was 6.88 (95% CI 3.66 to 12.9). Although the risks of hypertension differed only slightly regardless of the presence or absence of DM, risks for starting dialysis with DM+ and SBP ≤119 mm Hg were equivalent to DM- and SBP ≥150 mm Hg, indicating more strict blood pressure interventions in DM+ are needed to avoid dialysis. Future studies are required to clarify the cut-off SBP level to avoid initiation of dialysis considering the risks of strict control of blood pressure.

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  • Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan

    Ryosuke Tateishi, Takeshi Matsumura, Takeshi Okanoue, Toshihide Shima, Koji Uchino, Naoto Fujiwara, Takafumi Senokuchi, Kazuyoshi Kon, Takayoshi Sasako, Makiko Taniai, Takumi Kawaguchi, Hiroshi Inoue, Hirotaka Watada, Naoto Kubota, Hitoshi Shimano, Shuichi Kaneko, Etsuko Hashimoto, Sumio Watanabe, Goshi Shiota, Kohjiro Ueki, Kosuke Kashiwabara, Yutaka Matsuyama, Hideo Tanaka, Masato Kasuga, Eiichi Araki, Kazuhiko Koike, Yoshiyasu Karino, Shuhei Hige, Masatomo Sekiguchi, Koji Ogawa, Hideaki Miyoshi, Kyu Yong Cho, Masaru Baba, Atsushi Inoue, Kazuobu Aso, Mitsuyoshi Okada, Yasuhiro Takikawa, Kei Endo, Yasushi Ishigaki, Hirobumi Togashi, Michiaki Unno, Takanori Morikawa, Hideki Katagiri, Shojiro Sawada, Hiromasa Ohira, Atsushi Takahashi, Michio Shimabukuro, Akihiro Kudo, Naomi Tanaka, Junko Mitsuhashi, Toshifumi Tokai, Yasushi Matsuzaki, Tadashi Ikegami, Masato Imai, Kou Nishikawa, Sadao Takahashi, Sumiko Nagoshi, Kosuke Maezawa, Masafumi Matsuda, Tetsuhiro Chiba, Masayuki Yokoyama, Koutaro Yokote, Yoko Hidetaka, Mitsuhiko Moriyama, Hitomi Nakamura, Midori Fujishiro, Tadakazu Hisamatsu, Kaori Nishikawa, Toshihiko Nouchi, Yuki Sakurai, Harumi Daikoku, Michinori Murayama, Yoshinori Saigusa, Takashi Matsui, Ryosuke Tateishi, Hidenari Nagai, Takanori Mukozu, Takahisa Hirose, Masahiko Miyagi, Hiroaki Sato, Akira Mizuki, Masanori Miura, Yuzuru Sato, Rena Kaneko, Kumiko Hamano, Hiroko Kato, Kentaro Kikuchi, Yusuke Kajiyama, Makoto Chuma, Hiroko Ito, Hiroshi Yasuda, Nobuyuki Matsumoto, Yasushi Tanaka, Yoshio Nagai, Kento Imajo, Yasuo Terauchi, Yuzuru Ito, Shuji Terai, Hirohito Sone, Satoshi Matsunaga

    Journal of Gastroenterology   56 ( 3 )   261 - 273   2021.3

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    Background: Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates. Methods: The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected. Results: The mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%. Conclusion: A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology.

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  • Sodium Intake and Incidence of Diabetes Complications in Elderly Patients with Type 2 Diabetes-Analysis of Data from the Japanese Elderly Diabetes Intervention Study (J-EDIT). Reviewed International journal

    Chika Horikawa, Rei Aida, Shiro Tanaka, Chiemi Kamada, Sachiko Tanaka, Yukio Yoshimura, Remi Kodera, Kazuya Fujihara, Ryo Kawasaki, Tatsumi Moriya, Hidetoshi Yamashita, Hideki Ito, Hirohito Sone, Atsushi Araki

    Nutrients   13 ( 2 )   2021.2

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    This study investigates the associations between sodium intake and diabetes complications in a nationwide cohort of elderly Japanese patients with type 2 diabetes aged 65-85. Data from 912 individuals regarding their dietary intake at baseline is analyzed and assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes are times to diabetic retinopathy, overt nephropathy, cardiovascular disease (CVD), and all-cause mortality during six years. We find that mean sodium intake in quartiles ranges from 2.5 g to 5.9 g/day. After adjustment for confounders, no significant associations are observed between sodium intake quartiles and incidence of diabetes complications and mortality, except for a significant trend for an increased risk of diabetic retinopathy (p = 0.039). Among patients whose vegetable intake was less than the average of 268.7 g, hazard ratios (HRs) for diabetic retinopathy in patients in the second, third, and fourth quartiles of sodium intake compared with the first quartile were 0.87 (95% CI, 0.31-2.41), 2.61 (1.00-6.83), and 3.70 (1.37-10.02), respectively. Findings indicate that high sodium intake under conditions of low vegetable intake is associated with an elevated incidence of diabetic retinopathy in elderly patients with type 2 diabetes.

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  • Ability of Current Machine Learning Algorithms to Predict and Detect Hypoglycemia in Patients With Diabetes Mellitus: Meta-analysis. Reviewed International journal

    Satoru Kodama, Kazuya Fujihara, Haruka Shiozaki, Chika Horikawa, Mayuko Harada Yamada, Takaaki Sato, Yuta Yaguchi, Masahiko Yamamoto, Masaru Kitazawa, Midori Iwanaga, Yasuhiro Matsubayashi, Hirohito Sone

    JMIR diabetes   6 ( 1 )   e22458   2021.1

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    BACKGROUND: Machine learning (ML) algorithms have been widely introduced to diabetes research including those for the identification of hypoglycemia. OBJECTIVE: The objective of this meta-analysis is to assess the current ability of ML algorithms to detect hypoglycemia (ie, alert to hypoglycemia coinciding with its symptoms) or predict hypoglycemia (ie, alert to hypoglycemia before its symptoms have occurred). METHODS: Electronic literature searches (from January 1, 1950, to September 14, 2020) were conducted using the Dialog platform that covers 96 databases of peer-reviewed literature. Included studies had to train the ML algorithm in order to build a model to detect or predict hypoglycemia and test its performance. The set of 2 × 2 data (ie, number of true positives, false positives, true negatives, and false negatives) was pooled with a hierarchical summary receiver operating characteristic model. RESULTS: A total of 33 studies (14 studies for detecting hypoglycemia and 19 studies for predicting hypoglycemia) were eligible. For detection of hypoglycemia, pooled estimates (95% CI) of sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 0.79 (0.75-0.83), 0.80 (0.64-0.91), 8.05 (4.79-13.51), and 0.18 (0.12-0.27), respectively. For prediction of hypoglycemia, pooled estimates (95% CI) were 0.80 (0.72-0.86) for sensitivity, 0.92 (0.87-0.96) for specificity, 10.42 (5.82-18.65) for PLR, and 0.22 (0.15-0.31) for NLR. CONCLUSIONS: Current ML algorithms have insufficient ability to detect ongoing hypoglycemia and considerate ability to predict impeding hypoglycemia in patients with diabetes mellitus using hypoglycemic drugs with regard to diagnostic tests in accordance with the Users' Guide to Medical Literature (PLR should be ≥5 and NLR should be ≤0.2 for moderate reliability). However, it should be emphasized that the clinical applicability of these ML algorithms should be evaluated according to patients' risk profiles such as for hypoglycemia and its associated complications (eg, arrhythmia, neuroglycopenia) as well as the average ability of the ML algorithms. Continued research is required to develop more accurate ML algorithms than those that currently exist and to enhance the feasibility of applying ML in clinical settings. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020163682; http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42020163682.

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  • Le Carbone prevents liver damage in non-alcoholic steatohepatitis-hepatocellular carcinoma mouse model via AMPKα-SIRT1 signaling pathway activation. Reviewed International journal

    Mst Rejina Afrin, Somasundaram Arumugam, Vigneshwaran Pitchaimani, Vengadeshprabhu Karuppagounder, Rajarajan Amirthalingam Thandavarayan, Meilei Harima, Chowdhury Faiz Hossain, Kenji Suzuki, Hirohito Sone, Yasuhiro Matsubayashi, Kenichi Watanabe

    Heliyon   7 ( 1 )   e05888   2021.1

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    Le Carbone (LC), a fiber-enriched activated charcoal dietary supplement, claimed to be effective against inflammation associated with colitis, trimethylaminuria, and sclerosis. The study aimed to investigate the underlying mechanisms of LC to protect liver damage and its progression in non-alcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mice. To induce this model, C57BL/6J male baby mice were injected with a low-dose of streptozotocin and fed with a high-fat diet (HFD) 32 during 4 weeks-16 weeks of age. The LC suspension was administered orally at a dose of 5 mg/mouse/day started at the age of 6 weeks and continued until 16 weeks of age along with HFD32 feeding. At the end of the experiment, serum and liver tissues were collected for the biochemical, histological, and molecular analysis. We found that LC suspension improved the histopathological changes, serum aminotransferases in NASH mice. The hepatic expression of metabolic proteins, p-AMPKα and sirtuin 1, and proteins responsible for β-oxidation of fatty acids, peroxisome proliferator-activated receptor (PPAR) γ coactivator-α, PPARα were significantly repressed in NASH mice. LC treatment markedly restored these expressions. LC treatment significantly reduced the hepatic proteins expressions of PPARγ, tissue inhibitor of metalloproteinases 4, p47phox, p-JNK, p-ERK1/2, glypican-3, and prothrombin in NASH mice. Our findings demonstrate that LC prevents the liver damage and progression of NASH, possibly by enhancing the AMPK-SIRT1 signaling pathway.

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  • Difference in Glycemic Control between Ipragliflozin (Ipr) and Sitagliptin (Sit) According to Changes in Energy Intake (El) and Physical Activity (PA): Post -hoc Analysis of the NISM Study

    Hirohito Sone

    Diabetes   2021

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  • Easix-1yearas a Prognostic Index for Late Non-Relapse Mortality after Allogenichematopoietic Cell Transplantation

    Hirohito Sone

    Blood   2021

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    DOI: 10.1182/BLOOD-2021-147888

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  • YAP/TAZ Promote Hematopoietic Regeneration Via Accelerating the Recovery of Bone Marrow Niche

    Hirohito Sone

    Blood   2021

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  • Large Quantity of Alcohol Intake per Occasion was Positively Associated with Vision-Threatening Eye Diseases in Japanese Men with Type 2 Diabetes

    Hirohito Sone

    Diabetes   2021

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  • The Diversity of Long-Term Persistent WT1-Specific Cytotoxic T Lymphocytes after Wilms' Tumor 1 Peptide Vaccination

    Hirohito Sone

    Blood   2021

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  • Stratification of Intermediate-Risk Acute Myeloid Leukemia According to the Expression Level of WT1 mRNA at Diagnosis

    Hirohito Sone

    Blood   2021

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  • Impact of Medication Adherence and Glycemic Control on the Risk of Micro/Macrovascular Diseases in Patients with DiabetesY

    Hirohito Sone

    Diabetes   2021

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  • Predictors of Hemoglobin (Hb) and Its Changes Focusing on Anemia and Polycythemia after Administration of the SGLT2 Inhibitor Tofogliflozin

    Hirohito Sone

    Diabetes   2021

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  • Enterohepatic Transcription Factor CREB3L3 Protects Atherosclerosis via SREBP Competitive Inhibition. International journal

    Yoshimi Nakagawa, Yunong Wang, Song-Iee Han, Kanako Okuda, Asayo Oishi, Yuka Yagishita, Kae Kumagai, Hiroshi Ohno, Yoshinori Osaki, Yuhei Mizunoe, Masaya Araki, Yuki Murayama, Hitoshi Iwasaki, Morichika Konishi, Nobuyuki Itoh, Takashi Matsuzaka, Hirohito Sone, Nobuhiro Yamada, Hitoshi Shimano

    Cellular and molecular gastroenterology and hepatology   11 ( 4 )   949 - 971   2021

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    BACKGROUND & AIMS: cAMP responsive element-binding protein 3 like 3 (CREB3L3) is a membrane-bound transcription factor involved in the maintenance of lipid metabolism in the liver and small intestine. CREB3L3 controls hepatic triglyceride and glucose metabolism by activating plasma fibroblast growth factor 21 (FGF21) and lipoprotein lipase. In this study, we intended to clarify its effect on atherosclerosis. METHODS: CREB3L3-deficifient, liver-specific CREB3L3 knockout, intestine-specific CREB3L3 knockout, both liver- and intestine-specific CREB3L3 knockout, and liver CREB3L3 transgenic mice were crossed with LDLR-/- mice. These mice were fed with a Western diet to develop atherosclerosis. RESULTS: CREB3L3 ablation in LDLR-/- mice exacerbated hyperlipidemia with accumulation of remnant APOB-containing lipoprotein. This led to the development of enhanced aortic atheroma formation, the extent of which was additive between liver- and intestine-specific deletion. Conversely, hepatic nuclear CREB3L3 overexpression markedly suppressed atherosclerosis with amelioration of hyperlipidemia. CREB3L3 directly up-regulates anti-atherogenic FGF21 and APOA4. In contrast, it antagonizes hepatic sterol regulatory element-binding protein (SREBP)-mediated lipogenic and cholesterogenic genes and regulates intestinal liver X receptor-regulated genes involved in the transport of cholesterol. CREB3L3 deficiency results in the accumulation of nuclear SREBP proteins. Because both transcriptional factors share the cleavage system for nuclear transactivation, full-length CREB3L3 and SREBPs in the endoplasmic reticulum (ER) functionally inhibit each other. CREB3L3 promotes the formation of the SREBP-insulin induced gene 1 complex to suppress SREBPs for ER-Golgi transport, resulting in ER retention and inhibition of proteolytic activation at the Golgi and vice versa. CONCLUSIONS: CREB3L3 has multi-potent protective effects against atherosclerosis owing to new mechanistic interaction between CREB3L3 and SREBPs under atherogenic conditions.

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  • Skipping breakfast, late-night eating and current smoking are associated with medication adherence in Japanese patients with diabetes. Reviewed International journal

    Yuta Yaguchi, Kazuya Fujihara, Mayuko Harada Yamada, Yasuhiro Matsubayashi, Masaru Kitazawa, Taeko Osawa, Masahiko Yamamoto, Masanori Kaneko, Nauta Yamanaka, Hiroyasu Seida, Satoru Kodama, Hirohito Sone

    Primary care diabetes   14 ( 6 )   753 - 759   2020.12

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    AIMS: Little is known about the relationship between medication adherence for oral hypoglycemic agents (OHAs) and glycemic control after adjusting healthy adherer effect in large scale study. Thus, adjusting for health-related behaviors, we investigated the clinical variables associated with medication adherence and the relationship between medication adherence and glycemic control using a large claims database. METHODS: Analyzed were 8805 patients with diabetes whose medication records for OHA were available for at least 1year. Medication adherence was evaluated by the proportion of days covered (PDC). Multivariate logistic regression model was used to identify clinical variables significantly associated with non-adherence. Multiple regression analysis evaluated the relationship between PDC and HbA1c after adjusting for health-related behaviors. RESULTS: Mean PDC was 80.1% and 32.8% of patients were non-adherence. Logistic analysis indicated that older age and taking concomitant medications were significantly associated with adherence while skipping breakfast (odds ratio 0.66 [95% CI 0.57-0.76]), late-night eating (0.86 [0.75-0.98]), and current smoking (0.89 [0.80-0.99]) were significantly associated with non-adherence. CONCLUSIONS: Skipping breakfast, late-night eating and current smoking were significantly associated with medication adherence, suggesting that clinicians pay attention to those health-related behaviors to achieve good medication adherence.

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  • Marker chromosome is a strong poor prognosis factor after allogeneic HSCT for adverse-risk AML patients. Reviewed International journal

    Kyoko Fuse, Tomoyuki Tanaka, Yasuhiko Shibasaki, Tatsuo Furukawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    European journal of haematology   105 ( 5 )   616 - 625   2020.11

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    INTRODUCTION: Chromosome analysis is necessary for the risk classification of acute myeloid leukemia (AML). Marker chromosome (MC) is a fragmented chromosome whose origin cannot be identified from other chromosomes and originates from marked genomic instability. Although AML with MC (MC+) has a poor prognosis even after intensive chemotherapy, its influence on the outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. OBJECTIVE AND METHODS: We retrospectively analyzed 162 AML patients after allo-HSCT. To evaluate the significance of MC, we compared it with other chromosomal abnormalities. RESULT: Marker chromosome was detected in 14 (8.6%, MC+) patients (vs MC-, n = 158). The 2-year overall survival (OS) in MC+ vs MC- was 26.8% vs 62.2% (P = .0098). The 2-year cumulative incidence of relapse (CIR) in MC+ vs MC- was 80.4% vs 35.5% (P = .0004). Among adverse-risk AML (AD-AML, n = 36), AD-AML/MC+ (n = 11) demonstrated a poorer 2-year OS (9.1%, vs AD-AML/MC- n = 25, 58.3%, P = .0031) and higher 2-year CIR (89.6%, vs AD-AML/MC- 44.7%, P = .002). In multivariate analysis, MC (HR 3.08, 95% CI; 1.02-9.29, P = .046) and HCT-CI (HR 3.23, 95% CI; 1.00-10.4, P = .049) were independent risk factors for CIR among AD-AML. CONCLUSION: Our study suggests MC as a new independent factor for chromosome risk classification to further classify AD-AML.

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  • Network Meta-Analysis of Drug Therapies for Lowering Uric Acid and Mortality Risk in Patients with Heart Failure. Reviewed International journal

    Satoru Kodama, Kazuya Fujihara, Chika Horikawa, Mayuko Yamada, Takaaki Sato, Yuta Yaguchi, Masahiko Yamamoto, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Kenichi Watanabe, Hirohito Sone

    Cardiovascular drugs and therapy   35 ( 6 )   1217 - 1225   2020.10

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    PURPOSE: This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF). METHODS: Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%). RESULTS: Nine studies, which included seven different types of groups, were eligible for analysis. The "untreated uricemia" group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the "no uricemia" group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08-1.89)). The "start-allo" group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the "untreated uricemia" group (RR (95% CI), 0.68 (0.45-1.01)). However, in the "start-allo" group the SUCRA value was comparable to that in the "no uricemia" group (SUCRA: 65.4% for "start-allo"; 64.1% for "no uricemia"). CONCLUSIONS: Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.

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  • A Prospective Cohort Study of Muscular and Performance Fitness and Incident Glaucoma: The Niigata Wellness Study. Reviewed International journal

    Ryoko Kawakami, Yuko Gando, Kiminori Kato, Susumu S Sawada, Haruki Momma, Motohiko Miyachi, I-Min Lee, Steven N Blair, Minoru Tashiro, Chika Horikawa, Yasuhiro Matsubayashi, Takaho Yamada, Kazuya Fujihara, Hirohito Sone

    Journal of physical activity & health   17 ( 11 )   1171 - 1178   2020.10

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    BACKGROUND: To examine the association between muscular and performance fitness (MPF) and the incidence of glaucoma. METHODS: A total of 27,051 glaucoma-free participants aged 20-87 years underwent physical fitness tests between April 2001 and March 2002. The MPF index was calculated using an age- and sex-specific summed z-score from grip strength, vertical jump, single-leg balance, forward bending, and whole-body reaction time. The participants were divided into quartiles according to the MPF index and each physical fitness test. Participants were followed up for the development of glaucoma, which was defined based on physician-diagnosed glaucoma at an annual health examination between April 2002 and March 2008. Hazard ratios for the incidence of glaucoma were estimated using Cox proportional hazards models. RESULTS: During follow-up, 303 participants developed glaucoma. Compared with the lowest MPF index group, hazard ratio (95% confidence interval) of developing glaucoma was 0.64 (0.46-0.89) for the highest MPF index group (P for trend = .001). Vertical jump and whole-body reaction time were associated with incident glaucoma (P for trend = .01 and <.001, respectively). There were no associations between the other physical fitness tests and the incidence of glaucoma. CONCLUSION: Higher MPF is associated with lower incidence of glaucoma.

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  • Diabetes mellitus and risk of new-onset and recurrent heart failure: a systematic review and meta-analysis. Reviewed International journal

    Satoru Kodama, Kazuya Fujihara, Chika Horikawa, Takaaki Sato, Midori Iwanaga, Takaho Yamada, Kiminori Kato, Kenichi Watanabe, Hitoshi Shimano, Tohru Izumi, Hirohito Sone

    ESC heart failure   7 ( 5 )   2146 - 2174   2020.10

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    Despite mounting evidence of the positive relationship between diabetes mellitus (DM) and heart failure (HF), the entire context of the magnitude of risk for HF in relation to DM remains insufficiently understood. The principal reason is because new-onset HF (HF occurring in participants without a history of HF) and recurrent HF (HF re-occurring in patients with a history of HF) are not discriminated. This meta-analysis aims to comprehensively and separately assess the risk of new-onset and recurrent HF depending on the presence or absence of DM. We systematically searched cohort studies that examined the relationship between DM and new-onset or recurrent HF using EMBASE and MEDLINE (from 1 Jan 1950 to 28 Jul 2019). The risk ratio (RR) for HF in individuals with DM compared with those without DM was pooled with a random-effects model. Seventy-four and 38 eligible studies presented data on RRs for new-onset and recurrent HF, respectively. For new-onset HF, the pooled RR [95% confidence interval (CI)] of 69 studies that examined HF as a whole [i.e. combining HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF)] was 2.14 (1.96-2.34). The large between-study heterogeneity (I2 = 99.7%, P < 0.001) was significantly explained by mean age [pooled RR (95% CI) 2.60 (2.38-2.84) for mean age < 60 years vs. pooled RR (95% CI) 1.95 (1.79-2.13) for mean age ≥ 60 years] (P < 0.001). Pooled RRs (95% CI) of seven and eight studies, respectively, that separately examined HFpEF and HFrEF risk were 2.22 (2.02-2.43) for HFpEF and 2.73 (2.71-2.75) for HFrEF. The risk magnitudes between HFpEF and HFrEF were not significantly different in studies that examined both HFpEF and HFrEF risks (P = 0.86). For recurrent HF, pooled RR (95% CI) of the 38 studies was 1.39 (1.33-1.45). The large between-study heterogeneity (I2 = 80.1%, P < 0.001) was significantly explained by the proportion of men [pooled RR (95% CI) 1.53 (1.40-1.68) for < 65% men vs. 1.32 (1.25-1.39) for ≥65% men (P = 0.01)] or the large pooled RR for studies of only participants with HFpEF [pooled RR (95% CI), 1.73 (1.32-2.26) (P = 0.002)]. Results indicate that DM is a significant risk factor for both new-onset and recurrent HF. It is suggested that the risk magnitude is large for new-onset HF especially in young populations and for recurrent HF especially in women or individuals with HFpEF. DM is associated with future HFpEF and HFrEF to the same extent.

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  • Association of treatment-achieved HbA<sub>1c</sub> with incidence of coronary artery disease and severe eye disease in diabetes patients Reviewed

    Hirohito Sone

    Diabetes & Metabolism   46 ( 4 )   331 - 334   2020.9

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  • Association of treatment-achieved HbA1c with incidence of coronary artery disease and severe eye disease in diabetes patients Reviewed

    M. Harada, K. Fujihara, T. Osawa, M. Yamamoto, M. Kaneko, M. Ishizawa, Y. Matsubayashi, T. Yamada, N. Yamanaka, H. Seida, S. Kodama, W. Ogawa, H. Sone

    Diabetes & Metabolism   46 ( 4 )   331 - 334   2020.9

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  • Applications of physical performance measures to routine diabetes care for frailty prevention concept: fundamental data with grip strength, gait speed, timed chair stand speed, standing balance, and knee extension strength. Reviewed International journal

    Hiroki Yokoyama, Toshihiko Shiraiwa, Mitsuyoshi Takahara, Masahiro Iwamoto, Nobuichi Kuribayashi, Takuo Nomura, Minoru Yamada, Hirohito Sone, Shin-Ichi Araki

    BMJ open diabetes research & care   8 ( 1 )   2020.9

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    INTRODUCTION: Progression of muscle strength weakening will lead to a poor physical performance and disability. While this is particularly important in patients with diabetes, the associations of reduced muscle strength measured by grip strength with clinical features and physical performance remain unclear. We investigated clinical features and physical performance measures in association with grip strength in elderly people with diabetes in a primary care setting. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted enrolling 634 male and 323 female Japanese patients with type 2 diabetes aged 60 years or older. First, grip strength was measured and the associations of gender-specific grip strength with clinical features were evaluated. Second, in patients with a grip strength below the gender-specific median, physical performance measures, including gait speed, timed chair stand speed, knee extension strength, standing balance, and short physical performance battery scores, were investigated. Patients with and without a low performance defined by Asian Working Group for Sarcopenia were compared in terms of clinical features and physical performance measures. RESULTS: Grip strength decreased according to aging and longer duration of diabetes and was independently related to body mass index, glycated hemoglobin A1c (HbA1c), serum albumin, albuminuria, neuropathy, and stroke in male patients, and to body mass index and albuminuria in female patients. The physical performance measures became worse proportionally to a decrease in the grip strength. Patients with a low performance exhibited a significantly older age, lower grip strength and serum albumin, higher albuminuria, and poorer physical performance measures than those without. CONCLUSIONS: Reduced grip strength was associated with glycemic exposure indicators of age-related duration, HbA1c, and vascular complications. The physical performance measures became worse with decreasing grip strength. Measurements of grip strength and physical performance in patients with diabetes may help promote intervention to prevent frailty in future studies.

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  • Family Support for Medical Nutritional Therapy and Dietary Intake among Japanese with Type 2 Diabetes (JDDM 56). Reviewed International journal

    Chika Horikawa, Mariko Hatta, Sakiko Yoshizawa Morikawa, Yasunaga Takeda, Mizuki Takeuchi, Kazuya Fujihara, Noriko Kato, Hiroki Yokoyama, Yoshio Kurihara, Koichi Iwasaki, Shiro Tanaka, Hiroshi Maegawa, Hirohito Sone

    Nutrients   12 ( 9 )   2020.8

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    The aim of this study was to investigate the association between habitual dietary intake for patients with diabetes and the content of family support for medical nutritional therapy (MNT). Analyzed were 289 Japanese with type 2 diabetes (men, 58.5%; mean age, 62.0 years; mean HbA1c, 53.4 mmol/mol) who completed the Food Frequency Questionnaire and Diabetes Family Behavior Checklist (DFBC). Relationships of mean values for food group intake to DFBC responses regarding MNT were examined using multivariate analysis of covariance. Positive response to "Praise for following diet" was associated with lower sweets intake (none: 60.1 g/day; ≥once monthly: 50.9 g/day, p = 0.038) and higher seasoning intake (none: 21.6 g/day, ≥once monthly: 24.1 g/day, p = 0.046). Energy intake was higher with positive responses to "Eat at the same time that you do" (none: 1636 kcal/day, ≥once monthly: 1818 kcal/day, p = 0.038). "Nags about not following diet" was associated with higher fish (none: 68.7 g/day, ≥once monthly: 78.7 g/day, p = 0.042) and salt intake (none: 8.3 g/day, ≥once monthly: 9.0 g/day, p = 0.014). Eating foods not part of the diabetic diet (none: 218.4 g/day, ≥once monthly: 246.9 g/day, p = 0.014) resulted in a higher vegetable intake. In females, significant differences in relationships in the overall analysis were reversed. Our results clarified relationships between types of family support of patients with type 2 diabetes and their dietary intake and the importance of sex differences for more effective MNT.

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  • Successful Treatment with Edoxaban for Disseminated Intravascular Coagulation in a Case of Aortic Dissection Complicated with Immune Thrombocytopenic Purpura. Reviewed

    Shun Uemura, Hironori Kobayashi, Yoshinobu Seki, Yuki Okoshi, Hirohito Sone, Nobuhiko Nomoto

    Internal medicine (Tokyo, Japan)   59 ( 16 )   2035 - 2039   2020.8

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    A 70-year-old woman was hospitalized for exacerbation of chronic idiopathic thrombocytopenic purpura (ITP) and disseminated intravascular coagulation (DIC) from old aortic dissection. Initially, we increased the dose of prednisolone for ITP. However, her bleeding tendency caused by DIC worsened despite the rapid recovery of her platelet count, and the required amount of fresh-frozen plasma for transfusion increased. The administration of edoxaban for atrial fibrillation led to the marked improvement of her DIC status without serious adverse events. This case suggests that a direct oral anticoagulant may be an effective treatment for DIC caused by aortic dissection.

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  • Influence of an SGLT2 inhibitor, tofogliflozin, on the resting heart rate in relation to adipose tissue insulin resistance

    T. Nojima, Y. Matsubayashi, A. Yoshida, H. Suganami, T. Abe, M. Ishizawa, K. Fujihara, S. Tanaka, K. Kaku, H. Sone

    Diabetic Medicine   2020.8

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  • ガイドラインからみた糖尿病の食事療法における課題 高齢者糖尿病の食事療法

    荒木 厚, 大村 卓也, 山岡 巧弥, 田村 嘉章, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 83   2020.8

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  • 1型糖尿病に対して膵腎同時移植を施行し透析およびインスリンを離脱した1例

    岸 裕太郎, 竹内 亮, 山本 正彦, 松林 泰弘, 藤原 和哉, 岩永 みどり, 山田 高穂, 曽根 博仁, 三浦 宏平, 小林 隆, 若井 俊文

    糖尿病   63 ( 8 )   558 - 558   2020.8

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  • Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice. Reviewed International journal

    Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Mst Rejina Afrin, Remya Sreedhar, Meilei Harima, Masahiko Nakamura, Kenichi Watanabe, Satoru Kodama, Kazuya Fujihara, Hirohito Sone

    Neurochemistry international   137   104745 - 104745   2020.7

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    AIM AND OBJECTIVE: Insulin-induced moderate or severe hypoglycemia (MH or SH) impairs cognition and SH causes neuronal death. On the contrary, alternate day fasting (ADF) protects the brain during excitotoxic stress and improves cognitive function. Unlike the scenario in the periphery, insulin and its relationship towards brain glucose uptake and metabolism are considered to be less significant. Yet, the hypoglycemia associated brain metabolism is not clearly understood. The authors broadly investigated the brain metabolism in various hypoglycemic models such as insulin-induced MH, SH, SH with glucose reperfusion, 24 h fasting and ADF in the cortex or hippocampus of C57BL6/J mice. The authors analyzed the protein expression of insulin signaling kinases (plays a key role in neuronal survival and memory), Bcl-2 associated death promoter (p-BADser155) (dephosphorylation inhibits glucokinase activity and reduces glucose or increases ketone body metabolism in the brain), neuronal-specific glucose transporter 3 (GLUT 3) and nitrotyrosine (marker of nitric oxide which is involved in neuronal glucose uptake via GLUT 3) using western blotting analysis. RESULTS: Insulin-induced MH or SH differentially regulated the brain insulin signaling kinases. The expression of p-BADser155 decreased in all hypoglycemic models except the insulin-induced MH in hippocampus. The trended higher GLUT 3 and increased nitrotyrosine expression of insulin-induced SH were restored after glucose reperfusion. The trended higher or increased GLUT 3 and nitrotyrosine expression of ADF were positively correlated with serum beta-hydroxybutyrate levels. CONCLUSION: During hypoglycemia, it can be suggested that the brain might decrease glucose metabolism via glycolysis or prefer ketone body metabolism (except the insulin-induced MH in hippocampus) by modifying the p-BADser155 expression. In addition to the ketone body metabolism, the brain might adapt to uptake glucose in insulin-induced SH or ADF by modifying the GLUT 3 or nitrotyrosine expression.

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  • Hypertrophic pachymeningitis associated with myelodysplastic syndrome

    Akane Kaihatsu, Kyoko Fuse, Hirohito Sone, Masayoshi Masuko

    eJHaem   1 ( 1 )   12 - 13   2020.7

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    DOI: 10.1002/jha2.68

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  • Prevention of postprandial hypotension-related syncope by caffeine in a patient with long-standing diabetes mellitus. Reviewed

    Kazuo Furukawa, Tatsuro Suzuki, Hajime Ishiguro, Hiroshi Morikawa, Keiko Sonoda, Kenichi Iijima, Masahiro Ito, Osamu Hanyu, Hirohito Sone

    Endocrine journal   67 ( 6 )   585 - 592   2020.6

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    A 74-year-old man who had type 2 diabetes mellitus of a duration of 20 years was admitted for syncope after eating a high carbohydrate meal. Although he had had episodes of pallor or syncope after carbohydrate-rich meals, such as with large amounts of white rice, several times within a year and he had been taken to hospitals emergently, the etiology of these episodes had remained unclear despite his undergoing several studies. Studies did show severe orthostatic hypotension during the head-up tilt test and a decrease in the coefficient of variation of the R-R interval (CVR-R) on resting electrocardiogram, suggesting severe autonomic nervous dysfunction. Because of the episodes of syncope after eating a carbohydrate-rich meal, we investigated whether he had postprandial hypotension (PPH). The 75 g oral glucose tolerance test revealed a significant decrease in his postprandial blood pressure by about 40 mmHg, leading to the diagnosis of PPH. The carbohydrate-rich meal test induced syncope with systolic blood pressure under 40 mmHg. Then 150 mg caffeine was administered before a second carbohydrate-rich meal. The marked decline in postprandial blood pressure was suppressed and plasma noradrenaline levels were gradually increased over a period of 60 minutes. Caffeine could be useful for prevention of postprandial hypotension-related syncope.

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  • Association between Low Protein Intake and Mortality in Patients with Type 2 Diabetes. Reviewed International journal

    Takuya Yamaoka, Atsushi Araki, Yoshiaki Tamura, Shiro Tanaka, Kazuya Fujihara, Chika Horikawa, Rei Aida, Chiemi Kamada, Yukio Yoshimura, Tatsumi Moriya, Yasuo Ohashi, Yasuo Akanuma, Hideki Ito, Hirohito Sone

    Nutrients   12 ( 6 )   2020.6

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    The aim of this study was to investigate the association between protein intake and mortality risk in patients with type 2 diabetes. We analyzed a pooled data of 2494 diabetic patients from two prospective longitudinal studies. Nutritional intake was assessed using a Food Frequency Questionnaire at baseline. Protein intake per body weight (kg) per day was categorized into quartile groups. Adjusted hazard ratios (HRs) and 95% confidence interval (CI) were calculated using Cox regression analysis. During the six-year follow-up, there were 152 incidents of all-cause mortality. The HR for mortality in the lowest quartile of protein intake per body weight compared with the highest quartile was 2.26 (95% CI: 1.34-3.82, p = 0.002) after adjustment for covariates. Subgroup analyses revealed significant associations between low protein intake and mortality in patients aged over 75 years or under 65 years. After further adjustment of the total energy intake, a significant association between protein intake and mortality remained in patients aged ≥ 75 years, whereas the association was attenuated in those aged < 65 years. Our results suggest that adequate protein intake is necessary in older diabetic patients over 75 years, whereas with diabetes, whereas whole optimal total energy intake is required in younger patients with type 2 diabetes.

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  • Association of increased hepatic insulin clearance and change in serum triglycerides or β-hydroxybutyrate concentration via the sodium/glucose-cotransporter 2 inhibitor tofogliflozin. Reviewed International journal

    Yasuhiro Matsubayashi, Akihiro Yoshida, Hideki Suganami, Taeko Osawa, Kazuo Furukawa, Hiroshi Suzuki, Kazuya Fujihara, Shiro Tanaka, Kohei Kaku, Hirohito Sone

    Diabetes, obesity & metabolism   22 ( 6 )   947 - 956   2020.6

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    AIMS: Obesity and hepatic fat accumulation diminish hepatic insulin clearance, which can cause hyperinsulinaemia. Sodium/glucose-cotransporter 2 inhibitors (SGLT2-is) improve insulin resistance and hyperinsulinaemia by weight loss via increased urinary glucose excretion in type 2 diabetes. However, there are few reports of the influence of SGLT2-is on hepatic insulin clearance. We examined the impact of an SGLT2-i on hepatic insulin clearance and explored the clinical influence associated with changes in hepatic insulin clearance via an SGLT2-i and the mechanism of the effects of SGLT2-i. MATERIALS AND METHODS: Data were analysed from 419 patients with type 2 diabetes controlled by diet and exercise. Patients received a placebo or the SGLT2-i tofogliflozin (TOFO) (placebo: n = 56; TOFO: n = 363) orally once daily for ≥24 weeks. Hepatic insulin clearance was calculated from the ratio of areas under the curve (AUC) of C-peptide and insulin levels derived from oral meal tolerance test data (C-peptide AUC0-120 min /insulin AUC0-120 min : HICCIR ). The correlation of HICCIR via the SGLT2-i with other clinical variables was analysed using multivariate analysis. RESULTS: HICCIR was significantly increased via TOFO at week 24. Furthermore, with TOFO insulin and triglyceride (TG) levels were significantly reduced (P < 0.001) and β-hydroxybutyrate (BHB) was significantly elevated (P < 0.001). Changes in HICCIR were significantly correlated with changes in TG and BHB via TOFO. CONCLUSIONS: Increased HICCIR was significantly associated with reduced TG via TOFO and contributed to the greater increase in BHB compared with placebo in addition to the correction of hyperinsulinaemia.

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  • Vitamin B6 intake and incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: analysis of data from the Japan Diabetes Complications Study (JDCS). Reviewed International journal

    Chika Horikawa, Rei Aida, Chiemi Kamada, Kazuya Fujihara, Shiro Tanaka, Sachiko Tanaka, Atsushi Araki, Yukio Yoshimura, Tatsumi Moriya, Yasuo Akanuma, Hirohito Sone

    European journal of nutrition   59 ( 4 )   1585 - 1594   2020.6

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    PURPOSE: Although vitamin B6 has been suspected to prevent the progression of diabetic retinopathy, evidence of this in patients with type 2 diabetes based on longitudinal studies is sparse. This study investigated the relationship between vitamin B6 intake and the incidence of diabetic retinopathy in Japanese patients with type 2 diabetes. METHODS: The study was part of an examination of a nationwide cohort of patients with type 2 diabetes aged 40-70 years with HbA1c ≥ 48 mmol/mol. After excluding nonresponders to a dietary survey using the Food Frequency Questionnaire based on food groups, 978 patients were analyzed. Primary outcome was the 8-year risk of a diabetic retinopathy event, and Cox regression analyses estimated hazard ratios (HRs) for retinopathy according to vitamin B6 intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. RESULTS: Mean vitamin B6 intake in quartiles ranged from 1.1 to 1.6 mg/day, and half of the participants had vitamin B6 intake below the recommended daily dietary allowance according to dietary reference intakes in Japanese adults (men 1.4 mg/day; women 1.2 mg/day). After adjusting for confounders, HRs for diabetic retinopathy in the 2nd, 3rd, and 4th quartile groups of vitamin B6 intake compared with the 1st quartile group were 1.17 (95% confidence interval 0.81-1.69, p = 0.403), 0.88 (0.58-1.34, p = 0.550), and 0.50 (0.30-0.85, p = 0.010), respectively. CONCLUSIONS: Findings suggested that high vitamin B6 intake was associated with a lower incidence of diabetic retinopathy in Japanese with type 2 diabetes.

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  • Association of Higher Baseline BNP Levels with a Greater Reduction in Plasma Volume and Increase in Beta-Hydroxybutyrate via the SGLT2 Inhibitor Tofogliflozin in Type 2 Diabetes Reviewed

    Akihiro Yoshida, Yasuhiro Matsubayashi, Toshiaki Nojima, Hideki Suganami, Momoko Oe, Kazuya Fujihara, Shiro Tanaka, Kohei Kaku, Hirohito Sone

    DIABETES   69   2020.6

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  • Hepatocyte ELOVL Fatty Acid Elongase 6 Determines Ceramide Acyl-Chain Length and Hepatic Insulin Sensitivity in Mice. Reviewed International journal

    Takashi Matsuzaka, Motoko Kuba, Saori Koyasu, Yuta Yamamoto, Kaori Motomura, Sundaram Arulmozhiraja, Hiroshi Ohno, Rahul Sharma, Takuya Shimura, Yuka Okajima, Song-Iee Han, Yuichi Aita, Yuhei Mizunoe, Yoshinori Osaki, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Hirohito Sone, Yoshinori Takeuchi, Naoya Yahagi, Takafumi Miyamoto, Motohiro Sekiya, Yoshimi Nakagawa, Masatsugu Ema, Satoru Takahashi, Hiroaki Tokiwa, Hitoshi Shimano

    Hepatology (Baltimore, Md.)   71 ( 5 )   1609 - 1625   2020.5

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    BACKGROUND AND AIMS: Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. ELOVL fatty acid elongase 6 (Elovl6) is responsible for converting C16 saturated and monounsaturated fatty acids (FAs) into C18 species. We have previously shown that Elovl6 contributes to obesity-induced insulin resistance by modifying hepatic C16/C18-related FA composition. APPROACH AND RESULTS: To define the precise molecular mechanism by which hepatic Elovl6 affects energy homeostasis and metabolic disease, we generated liver-specific Elovl6 knockout (LKO) mice. Unexpectedly, LKO mice were not protected from high-fat diet-induced insulin resistance. Instead, LKO mice exhibited higher insulin sensitivity than controls when consuming a high-sucrose diet (HSD), which induces lipogenesis. Hepatic patatin-like phospholipase domain-containing protein 3 (Pnpla3) expression was down-regulated in LKO mice, and adenoviral Pnpla3 restoration reversed the enhancement in insulin sensitivity in HSD-fed LKO mice. Lipidomic analyses showed that the hepatic ceramide(d18:1/18:0) content was lower in LKO mice, which may explain the effect on insulin sensitivity. Ceramide(d18:1/18:0) enhances protein phosphatase 2A (PP2A) activity by interfering with the binding of PP2A to inhibitor 2 of PP2A, leading to Akt dephosphorylation. Its production involves the formation of an Elovl6-ceramide synthase 4 (CerS4) complex in the endoplasmic reticulum and a Pnpla3-CerS4 complex on lipid droplets. Consistent with this, liver-specific Elovl6 deletion in ob/ob mice reduced both hepatic ceramide(d18:1/18:0) and PP2A activity and ameliorated insulin resistance. CONCLUSIONS: Our study demonstrates the key role of hepatic Elovl6 in the regulation of the acyl-chain composition of ceramide and that C18:0-ceramide is a potent regulator of hepatic insulin signaling linked to Pnpla3-mediated NAFLD.

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  • Clinicopathological analysis of splenic red pulp low-grade B-cell lymphoma. Reviewed International journal

    Takaharu Suzuki, Hiroaki Miyoshi, Joji Shimono, Keisuke Kawamoto, Fumiko Arakawa, Takuya Furuta, Kyohei Yamada, Eriko Yanagida, Mai Takeuchi, Masao Seto, Hirohito Sone, Jun Takizawa, Koichi Ohshima

    Pathology international   70 ( 5 )   280 - 286   2020.5

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    Primary splenic low-grade B-cell lymphoma of the red pulp comprises hairy cell leukemia (HCL) and splenic B-cell lymphoma/leukemia, unclassifiable (SPLL-U). SPLL-U is a rare disease that includes subtypes of a hairy cell leukemia-variant (HCL-v), splenic diffuse red pulp small B-cell lymphoma (SDRPL) and other types that are known as narrow sense SPLL-U (SPLL-U-NS). Notably, limited information is available regarding the BRAF mutation (V600E) and cyclin D3 expression in subtypes of SPLL-U. Therefore, we performed a pathological analysis of the BRAF mutation (V600E) and characterized pathological features of SPLL-U. We reviewed the pathological findings of 12 SPLL-U cases. The 12 cases considered included two cases of HCL-v, six cases of SPLL-U-NS and four undetermined cases. The BRAF mutation (V600E) was detected in three cases, which were all SPLL-U-NS. Cases with the BRAF mutation (V600E) have increased levels of CD103 expression and decreased cyclin D3 and cyclin D1 expression compared with cases that lacked the BRAF mutation. These findings suggest that the BRAF mutation might play a significant role in SPLL-U. Therefore, the significance of the BRAF mutation should be evaluated via genomic or transcriptional analyses of a large cohort of SPLL-U patients.

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  • CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms. Reviewed International journal

    Aoi Satoh, Song-Iee Han, Masaya Araki, Yoshimi Nakagawa, Hiroshi Ohno, Yuhei Mizunoe, Kae Kumagai, Yuki Murayama, Yoshinori Osaki, Hitoshi Iwasaki, Motohiro Sekiya, Morichika Konishi, Nobuyuki Itoh, Takashi Matsuzaka, Hirohito Sone, Hitoshi Shimano

    iScience   23 ( 3 )   100930 - 100930   2020.3

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    Mice overexpressing the nuclear form of CREBH mainly in the liver (CREBH-Tg) showed suppression of high-fat high-sucrose (HFHS) diet-induced obesity accompanied by an increase in plasma fibroblast growth factor 21 (FGF21) levels. CREBH overexpression induced browning in inguinal white adipose tissue (WAT) and whole-body energy expenditure, which was canceled in Fgf21-/- mice. Deficiency of FGF21 in CREBH-Tg mice mostly canceled the improvement of obesity, but the suppression of inflammation of epidermal WAT, amelioration of insulin resistance, and improvement of glucose metabolism still sustained. Kisspeptin 1 (Kiss1) was identified as a novel hormone target for CREBH to explain these FGF21-independent effects of CREBH. Knockdown of Kiss1 in HFHS-fed CREBH-Tg Fgf21-/- mice showed partially canceled improvement of glucose metabolism. Taken together, we propose that hepatic CREBH pleiotropically improves diet-induced obesity-mediated dysfunctions in peripheral tissues by improving systemic energy metabolism in FGF21-dependent and FGF21-independent mechanisms.

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  • Efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Reviewed International journal

    Hirohito Sone, Tatsuroh Kaneko, Kosuke Shiki, Yoshifumi Tachibana, Egon Pfarr, Jisoo Lee, Naoko Tajima

    Diabetes, obesity & metabolism   22 ( 3 )   417 - 426   2020.3

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    AIM: To assess the efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, double-blind, parallel-group study randomized Japanese patients with T2D insufficiently controlled with insulin (1:1:1) to empagliflozin 10 mg (n=89), empagliflozin 25 mg (n=90) or placebo (n=90) for 52 weeks. The primary endpoint was change from baseline in glycated haemoglobin (HbA1c) at 16 weeks. RESULTS: At 16 weeks, empagliflozin 10 mg and 25 mg significantly decreased HbA1c: adjusted mean difference -0.92% (95% confidence interval [CI] -1.11, -0.73) and -1.00% (95% CI -1.18, -0.82; both P<0.0001) compared with placebo. This difference was maintained up to 52 weeks: adjusted mean difference at 52 weeks -0.90% (95% CI -1.09, -0.70) and -0.96% (95% CI -1.15, -0.77; both P<0.0001). At 52 weeks, significant improvements in fasting plasma glucose (adjusted mean difference -27.62 mg/dL [95% CI -36.15, -19.08] and -31.99 mg/dL [95% CI -40.35, -23.62]) and in body weight (-1.78 kg [95% CI -2.46, -1.10] and -1.92 kg [95% CI -2.58, -1.25]) were also seen with empagliflozin 10 mg and 25 mg compared with placebo (all P<0.0001). At 52 weeks, the frequency of adverse events (AEs) and serious AEs was similar in the three treatment groups; confirmed hypoglycaemia was reported slightly more in participants in the empagliflozin 10 mg and 25 mg groups (23.3% and 22.2% vs 14.4%). All hypoglycaemic events were mild in severity; no episodes required assistance. CONCLUSIONS: In Japanese patients with insufficiently controlled T2D, adding empagliflozin 10 mg or 25 mg to insulin treatment was associated with clinically meaningful reductions in HbA1c at 16 weeks and was generally well tolerated.

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  • The Glasgow prognostic score divides high-risk hematopoietic cell transplantation-specific comorbidity index patients into stratified subgroups in allogeneic hematopoietic cell transplantation. Reviewed International journal

    Yasuhiko Shibasaki, Tatsuya Suwabe, Takayuki Katagiri, Kyoko Fuse, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    Annals of hematology   99 ( 3 )   671 - 673   2020.3

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  • Combination of diabetes mellitus and lack of habitual physical activity is a risk factor for functional disability in Japanese. Reviewed International journal

    Kazuya Fujihara, Yasuhiro Matsubayashi, Mayuko Harada Yamada, Masaru Kitazawa, Masahiko Yamamoto, Masanori Kaneko, Satoru Kodama, Takuya Yahiro, Ayumu Tsutsui, Kiminori Kato, Hirohito Sone

    BMJ open diabetes research & care   8 ( 1 )   2020.1

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    OBJECTIVE: Declining healthy life expectancy due to functional disability is relevant and urgent because of its association with decreased quality of life and also for its enormous socioeconomic impact. The aim of this study is to examine the impact of diabetes, hypertension, dyslipidemia and physical activity habits on functional disability among community-dwelling Japanese adults. RESEARCH DESIGN AND METHODS: This is a population-based retrospective cohort study including 9673 people aged 39-98 years in Japan (4420, men). Functional disability was defined as a condition meeting Japan's new long-term care insurance certification requirements for the need of assistance in the activities of daily living whether by caregivers or assistive devices. Cox proportional-hazards regression model identified variables related to functional disability. RESULTS: Median follow-up was 3.7 years. During the study period, 165 disabilities occurred in the overall study population. Multivariate analysis showed that diabetes (HR 1.74 (95% CI 1.12 to 2.68)) and no physical activity habit (HR 1.83 (1.27 to 2.65)) presented increased risks for disability. HR for disability increased with the number of risk factors (HR of individuals with four conditions, 3.96 (1.59 to 9.99) vs individuals with none of those conditions as a reference). HR for disability among patients with diabetes with and without a physical activity habit was 1.68 (0.70 to 4.04) and 3.19 (1.79 to 5.70), respectively, compared with individuals without diabetes with a physical activity habit. CONCLUSIONS: The combination of diabetes and lack of habitual physical activity is predictive of functional disability in Japanese. Habitual physical activity attenuates the risk of functional disability in patients with diabetes.

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  • 副甲状腺癌の全身骨転移と鑑別が困難でありBrown腫瘍が疑われた一例

    山本 正彦, 種村 聡, 石黒 創, 松林 泰弘, 藤原 和哉, 岩永 みどり, 山田 貴穂, 曽根 博仁

    日本内分泌学会雑誌   95 ( 3 )   998 - 998   2020.1

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  • Combination of Diabetes Mellitus and Lack of Habitual Physical Activity Is a Risk Factor for Functional Disability in Japanese

    Hirohito Sone

    Diabetes   2020

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    DOI: 10.2337/DB20-1553-P

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  • Severity of Hypertension (HT) as a Predictor of Initiation of Dialysis among Study Participants with and without Diabetes Mellitus (DM)

    Hirohito Sone

    Diabetes   2020

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  • Weight and cardiometabolic risk among adolescents in Agano city, Japan: NICE EVIDENCE Study-Agano 1. Reviewed International journal

    Sakiko Yoshizawa Morikawa, Kazuya Fujihara, Yasunaga Takeda, Mariko Hatta, Chika Horikawa, Masahiro Ishizawa, Masahiko Yamamoto, Tomonobu Shiraishi, Hajime Ishiguro, Takaho Yamada, Yohei Ogawa, Hirohito Sone

    Asia Pacific journal of clinical nutrition   29 ( 4 )   856 - 866   2020

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    BACKGROUND AND OBJECTIVES: Pediatric obesity is associated with clustered cardiometabolic risk and the future incidence of cardiovascular disease. However, few studies have determined the effect of pediatric obesity in Asia, where obesity is less common than in Western countries. We aimed to clarify whether weight status including underweight and slightly overweight is associated with metabolic risk factors in Japanese adolescents. METHODS AND STUDY DESIGN: We performed a cross-sectional analysis of 2241 adolescents aged 13-14 years. Participants were classified as underweight, normal weight, slightly overweight, overweight, or obese according to the International Obesity Task Force. The clustered cardiometabolic risk (Z-CMR) was estimated by summing standardized sex-specific Z scores of mean arterial pressure (MAP), non-high-density lipoprotein cholesterol (non-HDLC), and HbA1c. RESULTS: Linear regression analysis showed that MAP, non-HDL-C, and Z-CMR were higher in the slightly overweight, overweight, and obese groups than in the normal weight group after adjusting for confounders. Compared with the normal weight group, the slightly overweight, overweight, and obese groups had higher prevalence of high BP [odds ratios (ORs): 1.38 (95% CI, 1.03, 1.85); 2.63 (1.77, 3.91); and 2.39 (1.57, 3.64), respectively]. Compared with the normal weight group, underweight boys, but not girls, had a lower prevalence of high Z-CMR [OR=0.20 (0.05, 0.84)]. CONCLUSIONS: Adolescents classified as slightly overweight had higher levels of BP, serum lipids, and clustered cardiometabolic risk than those classified as normal weight. This observation showed significant associations between weight status and cardiometabolic risk factors during adolescence even in East Asians.

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  • Medication Adherence (MA) Is an Independent Predictor for Glycemic Control Even after Adjustment for Lifestyle Confounders in Japanese Patients with Type 2 Diabetes

    Hirohito Sone

    Diabetes   2020

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  • Impact of Body Mass Index (BMI) and Waist Circumference (WC) on Coronary Artery Disease (CAD) in Japanese with and without Diabetes Mellitus (DM)

    Hirohito Sone

    Diabetes   2020

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  • Predictive Ability of Incident Type 2 Diabetes Mellitus (T2DM) Using Machine Learning Algorithms: A Meta-analysis

    Hirohito Sone

    Diabetes   2020

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  • Association between Plasma Metabolites in the Urea Cycle and Diabetic Kidney Disease (DKD) in a Japanese Population

    Hirohito Sone

    Diabetes   2020

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  • Ability for Detecting or Predicting Hypoglycemia with the Aid of Machine Learning Techniques: A Meta-analysis

    Hirohito Sone

    Diabetes   2020

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  • Blood Pressure as Predictor of Coronary Artery Disease (CAD)/Cerebrovascular Disease (CVD) According to Glucose Tolerance Status (GTS): Implications for Updated Guidelines

    Hirohito Sone

    Diabetes   2020

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  • Difference between Comprehensive Physical Fitness Age and Calendar Age Is a Potent Predictor of Incident Metabolic Syndrome (MetS)

    Hirohito Sone

    Diabetes   2020

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  • Low Level of and Decrease in Serum Amylase (AMY) Increases the Risk of Type 2 Diabetes Mellitus (T2DM)

    Hirohito Sone

    Diabetes   2020

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  • Physical Fitness (PF), Weight Status, and Metabolic Risk in Japanese Adolescents

    Hirohito Sone

    Diabetes   2020

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  • Randomized Controlled Trial of Ipragliflozin or Sitagliptin Combined with Metformin in Type 2 Diabetes: NISM Study

    Hirohito Sone

    Diabetes   2020

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  • Association between Screen Time Including Smartphone Use and Obesity and Its Associated Lifestyles in School Children in Japan

    Hirohito Sone

    Diabetes   2020

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  • Association of Plasma Volume with Body Weight and BNP after Long-Term Administration and Subsequent Withdrawal of the SGLT2 Inhibitor Tofogliflozin

    Hirohito Sone

    Diabetes   2020

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  • Isolated Adrenocorticotropic Hormone Deficiency Presenting with Severe Hyponatremia and Rhabdomyolysis: A Case Report and Literature Review. Reviewed International journal

    Takeshi Komatsu, Nobumasa Ohara, Naoko Hirota, Yuichiro Yoneoka, Takashi Tani, Keishi Terajima, Tetsutaro Ozawa, Hirohito Sone

    The American journal of case reports   20   1857 - 1863   2019.12

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    BACKGROUND Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder characterized by central adrenal insufficiency (AI) but normal secretion of pituitary hormones other than adrenocorticotropic hormone. IAD usually presents with unspecific symptoms of AI, such as anorexia and fatigue, but some patients present with a variety of atypical manifestations. Rhabdomyolysis is a potentially life-threatening clinical syndrome caused by skeletal muscle injury with the release of muscle cell contents into the circulation. A wide variety of disorders can cause rhabdomyolysis. Herein, we report an unusual case of IAD presenting with hyponatremia and rhabdomyolysis. CASE REPORT A 67-year-old Japanese woman with a 2-month history of anorexia and fatigue was diagnosed with severe hyponatremia (serum sodium, 118 mEq/L) and rhabdomyolysis (serum creatine phosphokinase, 6968 IU/L), after 2 days of vomiting and muscle weakness. Physical and laboratory findings did not show dehydration or peripheral edema. Her rhabdomyolysis resolved with normalization of serum sodium levels during administration of sodium chloride. However, her anorexia and fatigue remained unresolved. After reducing the amount of sodium chloride administered, the patient still had hyponatremia. Detailed endocrinological examinations indicated IAD; her hyponatremia was associated with inappropriately high plasma arginine vasopressin levels. The patient received corticosteroid replacement therapy, which resolved her anorexia, fatigue, excessive arginine vasopressin, and hyponatremia. CONCLUSIONS This case highlights the importance of considering the possibility of central AI in patients with hyponatremia and excessive arginine vasopressin levels. In addition, rhabdomyolysis associated with hyponatremia can be an important manifestation of IAD.

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  • Risk of coronary artery disease according to glucose abnormality status and prior coronary artery disease in Japanese men. Reviewed International journal

    Masaru Kitazawa, Kazuya Fujihara, Taeko Osawa, Masahiko Yamamoto, Mayuko Harada Yamada, Masanori Kaneko, Yasuhiro Matsubayashi, Takaho Yamada, Nauta Yamanaka, Hiroyasu Seida, Hirohito Sone

    Metabolism: clinical and experimental   101   153991 - 153991   2019.12

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    OBJECTIVE: Although glucose abnormality status (GAS), prior coronary artery disease (CAD), and other traditional risk factors affect the incidence of subsequent CAD, their impact in the same cohort has been scantly studied. RESEARCH DESIGN AND METHODS: We analyzed data from a nationwide claims database in Japan that was accumulated during 2008-2016 involving 138,162 men aged 18-72 years. Participants were classified as having normoglycemia, borderline glycemia, or diabetes mellitus (DM) with prior CAD (CAD+) or without prior CAD (CAD-). Cox regression model identified variables related to the incidence of CAD. RESULTS: Among CAD-, management of traditional risks differed from those with and without subsequent CAD events. On the other hand, such differences were weaker in borderline glycemia and DM CAD+, and the influence of traditional risk factors on subsequent CAD was not observed. Cox regression model showed that borderline glycemia and DM confer approximately 1.2- and 2.8-fold excess risks of CAD, respectively, compared with CAD- with normoglycemia. CAD+ confers approximately a 5- to 8-fold increased risk. The impacts of DM and prior CAD additively reached a hazard ratio (HR) of 15.74 (95% confidence interval [CI]: 11.82-21.00). However, the HR in those with borderline glycemia and CAD+ was 7.20 (95% CI: 5.01-10.34), which was not different from those with normoglycemia and CAD+. CONCLUSION: Control status of traditional risk factors and impact on subsequent CAD differ among categories of glycemic status with and without prior CAD. Individualizing treatment strategies is needed in consideration of risk factors, such as GAS and CAD+.

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  • Relationship Between Number of Multiple Risk Factors and Coronary Artery Disease Risk With and Without Diabetes Mellitus. Reviewed International journal

    Mayuko Yamada-Harada, Kazuya Fujihara, Taeko Osawa, Masahiko Yamamoto, Masanori Kaneko, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Nauta Yamanaka, Hiroyasu Seida, Wataru Ogawa, Hirohito Sone

    The Journal of clinical endocrinology and metabolism   104 ( 11 )   5084 - 5090   2019.11

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    PURPOSE: To determine the degree of control of multiple risk factors under real-world conditions for coronary artery disease (CAD) according to the presence or absence of diabetes mellitus (DM) and to determine whether reaching multifactorial targets for blood pressure (BP), low-density lipoprotein-cholesterol (LDL-C), HbA1c, and current smoking is associated with lower risks for CAD. METHODS: We investigated the effects on subsequent CAD of the number of controlled risk factors among BP, LDL-C, HbA1c, and current smoking in a prospective cohort study using a nationwide claims database of 220,894 individuals in Japan. Cox regression examined risks over a 4.8-year follow-up. RESULTS: The largest percentage of participants had two risk factors at target in patients with DM (39.6%) and subjects without DM (36.4%). Compared with those who had two targets achieved, the risks of CAD among those who had any one and no target achieved were two and four times greater, respectively, regardless of the presence of DM. The effect of composite control was sufficient to bring CAD risk in patients with DM below that for subjects without DM with any two targets achieved, whereas the risk of CAD in the DM group with all four risk factors uncontrolled was 9.4 times more than in the non-DM group who had achieved two targets. CONCLUSIONS: These findings show that composite control of modifiable risk factors has a large effect in patients with and without DM. The effect was sufficient to bring CAD risk in patients with DM below that in the non-DM group who had two targets achieved.

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  • 2型糖尿病発症予防のための妊娠糖尿病妊婦への非薬物的強化介入の試み

    川崎 麻紀, 荒田 尚子, 和栗 雅子, 飯村 祐子, 山本 周美, 川嵜 有紀, 牧 尉太, 玉田 祥子, 青山 友子, 田中 茂穂, 秦 健一郎, 宮越 敬, 橋本 貢士, 杉山 隆, 安日 一郎, 曽根 博仁, 菊池 透, 瀧本 秀美, 安田 和基, 小川 佳宏, 大田 えりか, 井上 永介, 平松 祐司

    糖尿病と妊娠   19 ( 3 )   S - 96   2019.11

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  • Patient-based prediction algorithm of relapse after allo-HSCT for acute Leukemia and its usefulness in the decision-making process using a machine learning approach. Reviewed International journal

    Kyoko Fuse, Shun Uemura, Suguru Tamura, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Yasuhiko Shibasaki, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Tatsuo Furukawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    Cancer medicine   8 ( 11 )   5058 - 5067   2019.9

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    Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for high-risk acute leukemia (AL), some patients still relapse. Since patients simultaneously have many prognostic factors, difficulties are associated with the construction of a patient-based prediction algorithm of relapse. The alternating decision tree (ADTree) is a successful classification method that combines decision trees with the predictive accuracy of boosting. It is a component of machine learning (ML) and has the capacity to simultaneously analyze multiple factors. Using ADTree, we attempted to construct a prediction model of leukemia relapse within 1 year of transplantation. With the model of training data (n = 148), prediction accuracy, the AUC of ROC, and the κ-statistic value were 78.4%, 0.746, and 0.508, respectively. The false positive rate (FPR) of the relapse prediction was as low as 0.134. In an evaluation of the model with validation data (n = 69), prediction accuracy, AUC, and FPR of the relapse prediction were similar at 71.0%, 0.667, and 0.216, respectively. These results suggest that the model is generalized and highly accurate. Furthermore, the output of ADTree may visualize the branch point of treatment. For example, the selection of donor types resulted in different relapse predictions. Therefore, clinicians may change treatment options by referring to the model, thereby improving outcomes. The present results indicate that ML, such as ADTree, will contribute to the decision-making process in the diversified allo-HSCT field and be useful for preventing the relapse of leukemia.

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  • Attenuation of Weight Loss Through Improved Antilipolytic Effect in Adipose Tissue Via the SGLT2 Inhibitor Tofogliflozin Reviewed International journal

    Akihiro Yoshida, Yasuhiro Matsubayashi, Toshiaki Nojima, Hideki Suganami, Takahiro Abe, Masahiro Ishizawa, Kazuya Fujihara, Shiro Tanaka, Kohei Kaku, Hirohito Sone

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   104 ( 9 )   3647 - 3660   2019.9

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    Context: Although calorie loss from increased urinary glucose excretion continues after long-term treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is), the mechanisms of the attenuated weight loss due to SGLT2is are not well known.Objective: To examine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2i, tofogliflozin, focusing on the antilipolytic effect of insulin on adipose tissue.Design and Participants: An integrated analysis was performed using data from two phase 3 studies of 52 weeks of tofogliflozin administration. The antilipolytic effect was evaluated using adipose tissue insulin resistance (Adipo-IR) calculated from the product of the levels of fasting insulin (f-IRI) and fasting free fatty acids (f-FFAs).Results: Data from 774 patients with type 2 diabetes (mean age, 58.5 years; glycosylated hemoglobin, 8.1%; body mass index, 25.6 kg/m(2); estimated glomerular filtration rate, 83.9 mUmin/1.73m(2); 66% men) were analyzed. Weight loss plateaued between weeks 24 and 52 after decreasing significantly. f-IRI levels decreased significantly from baseline to week 24, and the decrease was maintained until Week 52. f-FFA levels significantly increased, peaked at week 24, then declined from weeks 24 to 52. Adipo-IR levels declined progressively throughout the 52 weeks (-3.6 mmol/L.pmol/L and -6.2 mmol/L.pmol/L at weeks 24 and 52, respectively; P < 0.001 baseline vs weeks 24 and 52 and week 24 vs week 52). Higher baseline Adipo-IR levels were independently associated with greater weight loss at week 52.Conclusion: The improved antilipolytic effect in adipose tissue may attenuate progressive lipolysis, leading to attenuating future weight loss induced by an SGLT2i in patients with type 2 diabetes.

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  • Association between Helicobacter pylori infection, eradication and diabetes mellitus. Reviewed

    Masayuki Kato, Akiko Toda, Ritsuko Yamamoto-Honda, Yasuji Arase, Hirohito Sone

    Journal of diabetes investigation   10 ( 5 )   1341 - 1346   2019.9

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    AIMS/INTRODUCTION: It is suspected that Helicobacter pylori is associated with extradigestive diseases including diabetes. So far, a number of studies have examined the association between H. pylori and diabetes, and the results were conflicting. The aim of the present study was to examine the association between H. pylori infection, eradication and diabetes. MATERIALS AND METHODS: The present cross-sectional study was carried out using data from annual health checkups carried out at the Toranomon Hospital Health Management Center. The status of H. pylori infection, determined by serum antibodies and history of eradication, was categorized into three groups as "never," "current" and "past." The association between H. pylori infection and diabetes was examined using logistic regression. RESULTS: Of 21,634 participants, 6,530 (30.2%) had a current or past history of H. pylori infection, and 1,184 (5.5%) were identified as having diabetes. Multivariate adjusted odds ratios for diabetes compared with the "never" group were 1.36 (95% confidence interval 1.10-1.67) for the "current" group and 0.92 (95% confidence interval 0.79-1.07) for the "past" group. The association between H. pylori infection and diabetes was also observed among participants without a history of eradication. CONCLUSIONS: We found that current H. pylori infection was associated with an increased risk of diabetes, and the increased risk was not observed among participants after eradication. The results were concordant with the hypothesis that H. pylori infection increases the risk of diabetes. Further studies are necessary to validate the present results.

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  • 大血管障害 耐糖能状態及び心血管疾患既往の有無で層別化した、心血管疾患発症リスクの検討 Reviewed

    北澤 勝, 藤原 和哉, 山田 万祐子, 大澤 妙子, 山本 正彦, 矢口 雄大, 金子 正儀, 松林 泰弘, 山田 貴穂, 清田 浩康, 曽根 博仁

    糖尿病合併症   33 ( Suppl.1 )   242 - 242   2019.9

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  • 眼科処置を要する重症糖尿病性眼疾患発生リスクと血液学的因子の関係についての検討 Reviewed

    山本 正彦, 藤原 和哉, 大澤 妙子, 山田 万祐子, 石澤 正博, 石黒 創, 鈴木 浩史, 松林 泰弘, 児玉 暁, 長谷部 日, 曽根 博仁

    糖尿病合併症   33 ( Suppl.1 )   263 - 263   2019.9

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  • 大血管障害 糖尿病、非糖尿患者における血糖・血圧・脂質・喫煙の管理目標の達成状況と冠動脈疾患発症の関連 Reviewed

    山田 万祐子, 藤原 和哉, 大澤 妙子, 山本 正彦, 石澤 正博, 金子 正儀, 松林 泰弘, 清田 浩康, 山田 貴穂, 曽根 博仁

    糖尿病合併症   33 ( Suppl.1 )   241 - 241   2019.9

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  • 青少年期の体格と代謝指標の関連 Reviewed

    森川 咲子, 治田 麻理子, 平澤 玲子, 谷内 洋子, 堀川 千嘉, 曽根 博仁

    New Diet Therapy   35 ( 2 )   151 - 151   2019.9

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  • Effect of family-oriented diabetes programs on glycemic control: A meta-analysis. Reviewed International journal

    Satoru Kodama, Sakiko Morikawa, Chika Horikawa, Dai Ishii, Kazuya Fujihara, Masahiko Yamamoto, Taeko Osawa, Masaru Kitazawa, Takaho Yamada, Kiminori Kato, Shiro Tanaka, Hirohito Sone

    Family practice   36 ( 4 )   387 - 394   2019.7

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    BACKGROUND: Efficacy of programs for patients with diabetes mellitus (DM) that have promoted family members to help with patients' self-care activities has been largely inconsistent. This meta-analysis aims to assess the effect of family-oriented diabetes programs for glycemic control (GC). METHODS: Electronic literature searches were conducted for clinical trials with a parallel design wherein there were two groups according to whether family members were included (intervention group) or not included (control group) and changes in glycohemoglobin A1C (A1C) were assessed as a study outcome. Each effect size (i.e. difference in A1C change between the intervention and control group) was pooled with a random-effects model. RESULTS: There were 31 eligible trials consisting of 1466 and 1415 patients in the intervention and control groups, respectively. Pooled A1C change [95% confidence interval (CI)] was -0.45% (-0.64% to -0.26%). Limiting analyses to 21 trials targeted at patients with type 1 DM or 9 trials targeted at patients with type 2 DM, the pooled A1C changes (95% CI) were -0.35% (-0.55% to -0.14%) and -0.71% (-1.09% to -0.33%), respectively. CONCLUSION: This meta-analysis suggests that focusing on the family as well as the individual patient in self-management diabetes programs to improve the performance of self-care activities of patients with DM is effective in terms of proper GC.

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  • Blake's pouch cystに伴う水頭症の治療により若年性認知症の改善を認めた糖尿病の1例 Reviewed

    種村 聡, 山本 正彦, 石黒 創, 岩永 みどり, 松林 泰弘, 山田 貴穂, 藤原 和哉, 渡邊 賢一, 曽根 博仁

    糖尿病   62 ( 7 )   441 - 441   2019.7

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  • Overt Proteinuria, Moderately Reduced eGFR and Their Combination Are Predictive of Severe Diabetic Retinopathy or Diabetic Macular Edema in Diabetes. Reviewed International journal

    Masahiko Yamamoto, Kazuya Fujihara, Masahiro Ishizawa, Taeko Osawa, Masanori Kaneko, Hajime Ishiguro, Yasuhiro Matsubayashi, Hiroyasu Seida, Nauta Yamanaka, Shiro Tanaka, Satoru Kodama, Hiruma Hasebe, Hirohito Sone

    Investigative ophthalmology & visual science   60 ( 7 )   2685 - 2689   2019.6

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    Purpose: Since the combined effects of proteinuria and a moderately decreased eGFR on incident severe eye complications in patients with diabetes are still largely unknown, these associations were determined in a large historical cohort of Japanese patients with diabetes mellitus. Methods: We evaluated the effects of overt proteinuria (OP) (dipstick 1+ and over) and/or moderately reduced estimated glomerular filtration rate (eGFR) (MG) (baseline eGFR 30.0-54.9 mL/min/1.73 m2) on the incidence of treatment-required diabetic eye diseases (TRDED). We divided 7709 patients into four groups according to the presence or absence of OP and MG: no OP without MG (NP[MG-]), OP without MG (OP[MG-]), no OP with MG (NP[MG+]), and OP with MG (OP[MG+]). Multivariate Cox analyses were performed to calculate hazard ratios (HRs) with 95% confidence intervals for combinations of the presence and/or absence of OP and MG on the risk of developing TRDED. Results: During the median follow-up period of 5.6 years, 168 patients developed TRDED. HRs for OP and MG for incident TRDED were 1.91 (95% confidence interval, 1.27-2.87) and 1.90 (1.11-3.23), respectively. HRs for incident TRDED were 1.73 (1.11-2.69) and 5.57 (2.40-12.94) for OP(MG-) and OP(MG+), respectively, in comparison with NP(MG-). Conclusions: In Japanese patients with diabetes, OP and MG were separately as well as additionally associated with higher risks of TRDED. Results indicate the necessity of the simultaneous assessment of proteinuria and eGFR for appropriate evaluation of risks of severe eye complications in patients with diabetes.

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  • Combined Effects of Energy Intake and Physical Activity on Obesity in Japanese Patients with Type 2 Diabetes (JDDM 50): A Cross-Sectional Study. Reviewed International journal

    Mariko Hatta, Kazuya Fujihara, Sakiko Yoshizawa Morikawa, Yasutake Takeda, Dai Ishii, Chika Horikawa, Mitsutoshi Kato, Hiroki Yokoyama, Yoshio Kurihara, Koichi Iwasaki, Kazuhiro Miyazawa, Katsuya Yamazaki, Shiro Tanaka, Hiroshi Maegawa, Hirohito Sone

    Diabetes therapy : research, treatment and education of diabetes and related disorders   10 ( 3 )   1133 - 1138   2019.6

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    INTRODUCTION: The combined effects of energy intake (EI) and physical activity (PA) on obesity have been poorly investigated. We have investigated the combined effects of EI and PA quantitatively in Japanese men and women with type 2 diabetes. METHODS: Data on 1395 patients with type 2 diabetes who attended 25 diabetes clinics located throughout Japan, obtained by questionnaire, were analyzed. A logistic regression model was used to calculate the odds ratio for obesity. RESULTS: Multi-adjusted odds ratios for the top versus the bottom tertile of EI and the bottom versus the top tertile of PA were 1.39 (95% confidence interval [CI] 1.02-1.89) and 1.64 (95% CI 1.22-2.22), respectively. The combination of EI (kcal/day) ≥ 1967 and PA (metabolic equivalents [METs] h/week) ≤ 9.9 for men and of EI ≥ 1815 and PA ≤ 8.3 for women were significantly associated with obesity. CONCLUSIONS: The existence of "allowable maximum EI" and "required minimum PA" that is significantly associated with "not being obese" is implied, suggesting the need for lifestyle education for Japanese patients with type 2 diabetes.

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  • Impact of Prior Coronary Artery Disease (CAD)/Cerebrovascular Disease (CVD) and Diabetes Mellitus (DM) on Incident CAD/CVD in Japanese Reviewed

    Hirohito Sone

    Diabetes   68 ( Supplement 1 )   450 - P   2019.6

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    DOI: 10.2337/DB19-450-P

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  • Enhanced Response in Serum Ketone Level in Men Compared with Women by Administration of SGLT2 Inhibitor Reviewed

    Akihiro Yoshida, Yasuhiro Matsubayashi, Toshiaki Nojima, Hideki Suganami, Kohei Kaku, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-1219-P

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  • Pulse Pressure is a Stronger Predictor Than Systolic Blood Pressure for Severe Eye Diseases in Diabetes Mellitus. Reviewed International journal

    Masahiko Yamamoto, Kazuya Fujihara, Masahiro Ishizawa, Taeko Osawa, Masanori Kaneko, Hajime Ishiguro, Yasuhiro Matsubayashi, Hiroyasu Seida, Nauta Yamanaka, Shiro Tanaka, Satoru Kodama, Hiruma Hasebe, Hirohito Sone

    Journal of the American Heart Association   8 ( 8 )   e010627   2019.4

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    Background Evidence of the role of systolic blood pressure ( SBP ) in development of severe diabetic retinopathy is not strong, although the adverse effect of low diastolic blood pressure has been a partial explanation. We assessed the predictive ability of incident severe diabetic retinopathy between pulse pressure ( PP ) which considers both SBP and diastolic blood pressure, compared with SBP . Methods and Results Eligible patients (12 242, 83% men) aged 19 to 72 years from a nationwide claims database were analyzed for a median observational 4.8-year period. Severe diabetic retinopathy was defined as vision-threatening treatment-required diabetic eye diseases. Multivariate Cox regression analysis revealed that hazard ratios (95% CI ) of treatment-required diabetic eye diseases for 1 increment of standard deviation and the top tertile compared with the bottom tertile were 1.39 (1.21-1.60) and 1.72 (1.17-2.51), respectively, for PP and 1.22 (1.05-1.41) and 1.43 (0.97-2.11), respectively, for SBP adjusted for age, sex, body mass index, hemoglobin A1c, fasting plasma glucose, lipids, and smoking status. In a model with SBP and PP simultaneously as covariates, the hazard ratios of only PP (hazard ratios [95% CI ], 1.57 [1.26-1.96]) but not SBP (0.85 [0.68-1.07]) were statistically significant. Delong test revealed a significant difference in the area under the receiver operating characteristic curve between PP and SBP (area under the receiver operating characteristic curve [95% CI ], 0.58 [0.54-0.63] versus 0.54 [0.50-0.59]; P=0.03). The strongest predictor remained as hemoglobin A1c (area under the receiver operating characteristic curve [95% CI ], 0.80 [0.77-0.84]). Conclusions After excluding the significant impact of glycemic control, PP in comparison with SBP is a better predictor of severe diabetic retinopathy, suggesting a role of diastolic blood pressure and arterial stiffness in pathology.

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  • Physical Fitness Tests and Type 2 Diabetes Among Japanese: A Longitudinal Study From the Niigata Wellness Study. Reviewed

    Haruki Momma, Susumu S Sawada, Kiminori Kato, Yuko Gando, Ryoko Kawakami, Motohiko Miyachi, Cong Huang, Ryoichi Nagatomi, Minoru Tashiro, Masahiro Ishizawa, Satoru Kodama, Midori Iwanaga, Kazuya Fujihara, Hirohito Sone

    Journal of epidemiology   29 ( 4 )   139 - 146   2019.4

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    BACKGROUND: Simple physical fitness test can be a useful potential predictor of type 2 diabetes (T2DM). We examined the association between performances on simple physical fitness tests and the incidence of T2DM. METHODS: This longitudinal study was conducted in 21,802 nondiabetic Japanese (6,649 women) aged 20 to 92 years, who underwent all physical fitness tests at baseline (April 2001 to March 2002). From April 2001 to March 2008, physical fitness tests, including grip strength, vertical jump, single-leg balance with eyes closed, forward bending, whole-body reaction time, and supine legs-up, were performed every year. Participants had physical fitness tests at least two times during the period. T2DM was also annually determined based on fasting blood glucose, glycated hemoglobin, and self-reported diabetes during the period. Discrete-time logit models were used to examine the influence of the serial level of each physical fitness test on the incidence of T2DM. RESULTS: During the entire study period, 972 participants developed diabetes. Lower relative grip strength (grip strength/body weight) and single-leg balance performance were associated with a higher incidence of T2DM. For relative grip strength, as compared with the fourth quartile group, the odds ratios for other groups ranged from 1.16 to 1.56 (P for trend < 0.001). For single-leg balance, the odds ratios ranged from 1.03 to 1.49 (P for trend < 0.001). CONCLUSION: The performance of a simple single-leg balance test as well as that of a grip strength test were negatively associated with the risk of T2DM among Japanese.

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  • Safety and effective salvage regimen comprising a novel combination of brentuximab vedotin, L-asparaginase, and dexamethasone for refractory anaplastic large cell lymphoma, anaplastic lymphoma kinase negative. Reviewed International journal

    Keisuke Kawamoto, Takaharu Suzuki, Takuya Kasami, Maiko Kiryu, Hirohito Sone, Hiroaki Miyoshi, Koichi Ohshima, Jun Takizawa

    Hematological oncology   37 ( 2 )   212 - 214   2019.4

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  • 糖尿病の有無別にみた血糖・血圧・脂質・喫煙の各管理目標達成状況が冠動脈疾患発症に及ぼす影響 Reviewed

    原田 万祐子, 藤原 和哉, 大澤 妙子, 石澤 正博, 山本 正彦, 金子 正儀, 松林 泰弘, 清田 浩康, 山田 貴穂, 小川 渉, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 285   2019.4

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  • 糖尿病の有無別にみた高血圧が透析導入に及ぼす影響の検討 Reviewed

    大澤 妙子, 藤原 和哉, 山本 正彦, 原田 万祐子, 北澤 勝, 金子 正儀, 石黒 創, 石澤 正博, 松林 泰弘, 清田 浩康, 山中 菜詩, 山田 貴穂, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 219   2019.4

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  • 糖尿病(DM)・冠動脈疾患(CAD)・脳血管疾患(CVD)の既往及び組み合わせがその後のリスクへ及ぼす影響の検討 Reviewed

    藤原 和哉, 松林 泰弘, 原田 万祐子, 大澤 妙子, 金子 正儀, 山本 正彦, 山田 高穂, 清田 浩康, 加藤 公則, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 254   2019.4

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  • 医療ビッグデータを用いた糖尿病患者の下肢切断に関するリスク因子の検討 Reviewed

    金子 正儀, 藤原 和哉, 原田 万祐子, 山本 正彦, 松林 泰弘, 北澤 勝, 石井 大, 清田 浩康, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 195   2019.4

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  • 2型糖尿病患者における食事エネルギー密度と食事パターンとの関連 Reviewed

    武田 安永, 藤原 和哉, 治田 麻理子, 森川 咲子, 堀川 千嘉, 石井 大, 根立 梨奈, 加藤 光敏, 横山 宏樹, 栗原 義夫, 宮澤 一裕, 岩崎 晧一, 川井 紘一, 朝長 修, 屋宜 宣治, 前川 聡, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 116   2019.4

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  • 耐糖能状態と心血管疾患既往の有無別に見たその後の心血管疾患発症リスク Reviewed

    北澤 勝, 藤原 和哉, 原田 万祐子, 大澤 妙子, 山本 正彦, 矢口 雄大, 金子 正儀, 松林 泰弘, 山田 貴穂, 清田 浩康, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 190   2019.4

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  • Higher pulse pressure predicts initiation of dialysis in Japanese patients with diabetes. Reviewed International journal

    Taeko Osawa, Kazuya Fujihara, Mayuko Harada, Masahiko Yamamoto, Masahiro Ishizawa, Hiroshi Suzuki, Hajime Ishiguro, Yasuhiro Matsubayashi, Hiroyasu Seida, Nauta Yamanaka, Shiro Tanaka, Hitoshi Shimano, Satoru Kodama, Hirohito Sone

    Diabetes/metabolism research and reviews   35 ( 3 )   e3120   2019.3

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    AIMS: To determine incidence and predictors of starting dialysis in patients with diabetes emphasizing blood pressure variables. METHODS: A nationwide database with claim data on 18 935 people (15 789 men and 3146 women) with diabetes mellitus aged 19 to 72 years in Japan was used to elucidate predictors for starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modelling, interactions between glycaemic and blood pressure values were determined. RESULTS: During a median follow-up of 5.3 years, incidence of dialysis was 0.81 per 1000 person-years. Multivariate analysis of a model involving systolic and diastolic blood pressure (SBP and DBP) simultaneously as covariates showed that hazard ratios (HRs) for starting dialysis for each 1-SD elevation in SBP and DBP were 2.05 (95% confidence interval 1.58-2.64) and 0.66 (0.50-0.88), respectively, implying that pulse pressure (PP) was a promising predictor. For confirmation, a model involving SBP and PP simultaneously as covariates demonstrated that HRs for each 1-SD elevation in SBP and PP were 1.09 (0.81-1.48) and 1.54 (1.14-2.08), respectively, with PP the more potent predictor. Compared with HbA1c <8% and PP <60 mmHg, the HR for those with HbA1c ≥8% and PP ≥60 mmHg was 6.32 (3.42-11.7). CONCLUSIONS: In our historical cohort analysis, SBP and PP were independent predictors for starting dialysis. PP was the more potent, suggesting the contribution of increased arterial stiffness to the incidence of dialysis. Future studies are needed to conclude the independent influence of PP and HbA1c on dialysis considering other risk factors.

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  • Gemcitabine, Dexamethasone, and Cisplatin Regimen as an Effective Salvage Therapy for High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements. Reviewed

    Masaki Mitobe, Keisuke Kawamoto, Takaharu Suzuki, Maiko Kiryu, Suguru Tamura, Ayako Nanba, Tatsuya Suwabe, Tomoyuki Tanaka, Kyoko Fuse, Yasuhiko Shibasaki, Masayoshi Masuko, Hiroaki Miyoshi, Koichi Ohshima, Hirohito Sone, Jun Takizawa

    Internal medicine (Tokyo, Japan)   58 ( 4 )   575 - 580   2019.2

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    A 61-year-old woman exhibited right inguinal lymphadenopathy and right lower limb edema approximately 1 month prior to hospitalization. She was diagnosed with high grade B-cell lymphoma, and a lymph node biopsy and fluorescence in situ hybridization indicated MYC, BCL2, and BCL6 rearrangements (triple-hit lymphoma). She had progressive disease that was CD20-negative after two courses of rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine (R-CODOX-M/IVAC) therapy. Subsequent etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (EPOCH) therapy was not effective. However, after two cycles of gemcitabine, dexamethasone, and cisplatin (GDP) therapy, she achieved a complete response and was able to undergo autologous peripheral blood stem cell transplantation. GDP therapy may be effective as salvage therapy for chemotherapy-resistant triple-hit lymphoma.

    DOI: 10.2169/internalmedicine.1686-18

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  • Meat intake and incidence of cardiovascular disease in Japanese patients with type 2 diabetes: analysis of the Japan Diabetes Complications Study (JDCS). Reviewed International journal

    Chika Horikawa, Chiemi Kamada, Shiro Tanaka, Sachiko Tanaka, Atsushi Araki, Hideki Ito, Satoshi Matsunaga, Kazuya Fujihara, Yukio Yoshimura, Yasuo Ohashi, Yasuo Akanuma, Hirohito Sone

    European journal of nutrition   58 ( 1 )   281 - 290   2019.2

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    PURPOSE: Excessive meat intake has been researched as a major cause of cardiovascular disease (CVD) among healthy adults, but data on this topic in Asian patients with diabetes are sparse. The quantity and variety of available meats vary widely between Asian and Western countries. As part of a nationwide cohort study we investigated the relationship between meat intake and incidence of CVD in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c ≥ 6.5%. METHODS: Analyzed were 1353 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 8-year risk of a CVD event, including coronary heart disease (CHD) and stroke. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. RESULTS: Mean meat intake in quartiles ranged from 9.9 to 97.7 g/day. After adjusting for confounders, HRs of CHD in the 2nd, 3rd, and 4th quartiles for meat intake compared with the 1st quartile were 2.84 (95% confidence interval 1.29-6.24, p = 0.01), 3.02 (1.36-6.70, p < 0.01), and 2.99 (1.35-6.65, p = 0.01), respectively. In two groups according to meat intake, patients consuming ≥ 20 g/day of meat had a 2.94-fold higher risk of CHD than those consuming < 20 g/day (p < 0.01). There was no significant association of stroke with meat intake. CONCLUSIONS: An elevated incidence of CHD in Japanese patients with type 2 diabetes was associated with high meat intake.

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  • Baseline Lactate Level Is a Useful Predictor for Weight Loss after Long-Term SGLT2 Inhibitor Treatment

    Hirohito Sone

    Diabetes   2019

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    DOI: 10.2337/DB19-1205-P

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  • Associations of Blood Pressure (BP) with Incidence of Coronary Artery Disease (CAD)/Cerebrovascular Disease (CVD) According to Glucose Tolerance Status (GTS)

    Hirohito Sone

    Diabetes   2019

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    DOI: 10.2337/DB19-446-P

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  • Impact of Prior Cerebrovascular Disease (CVD) and Glucose Tolerance Status on Incident CVD in Japanese

    Hirohito Sone

    Diabetes   2019

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    DOI: 10.2337/DB19-1478-P

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  • Weight Status and Cardiometabolic Risk Factors among Adolescents in Japan

    Hirohito Sone

    Diabetes   2019

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    DOI: 10.2337/DB19-1335-P

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  • Predictors and Their Impact on Coronary Artery Disease (CAD) According to Glucose Tolerance Status (GTS) and Prior CAD: Historical Cohort Study in Japan

    Hirohito Sone

    Diabetes   2019

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    DOI: 10.2337/DB19-448-P

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  • Poor Adherence to Medication and HbA1c Level Predict Risk of Amputation in Patients with Diabetes Mellitus-Historical Cohort Study Using a Nationwide Claims Database

    Hirohito Sone

    Diabetes   2019

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    DOI: 10.2337/DB19-634-P

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  • Depletion of Pre-Transplant Skeletal Muscle Is a Significant Poor Prognostic Factor in Allogeneic Hematopoietic Cell Transplantation

    Hirohito Sone

    Blood   2019

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    DOI: 10.1182/BLOOD-2019-124733

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  • Adipose Tissue Insulin Resistance Predicts Ketosis via an SGLT2 Inhibitor

    Hirohito Sone

    Diabetes   2019

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    DOI: 10.2337/DB19-1215-P

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  • Serum Amylase (AMY) Level and Its Chronological Change as a Predictor of Incident Type 2 Diabetes Mellitus (T2DM)

    Hirohito Sone

    Diabetes   2019

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    DOI: 10.2337/DB19-1514-P

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  • Anaplastic large cell lymphoma, with 1,25(OH) 2 D 3 -mediated hypercalcemia: A case report. Reviewed

    Masaki Mitobe, Keisuke Kawamoto, Takaharu Suzuki, Maiko Kiryu, Ayako Nanba, Tatsuya Suwabe, Tomoyuki Tanaka, Kyoko Fuse, Yasuhiko Shibasaki, Masayoshi Masuko, Hiroaki Miyoshi, Koichi Ohshima, Hirohito Sone, Jun Takizawa

    Journal of clinical and experimental hematopathology : JCEH   59 ( 1 )   22 - 28   2019

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    Hypercalcemia due to malignant tumors including malignant lymphomas is relatively common. Among cancer patients with hypercalcemia, humoral hypercalcemia of malignancy is the most common and accounts for about 80% of all cases with hypercalcemia. 1,25-dihydroxyvitamin D
    3
    (1,25(OH)
    2
    D
    3
    )-mediated hypercalcemia is relatively rare. Although malignant lymphoma has been also reported to cause 1,25(OH)
    2
    D
    3
    -mediated hypercalcemia, it is not known whether there is any association between 1,25(OH)
    2
    D
    3
    -mediated hypercalcemia and any specific histological type of malignant lymphoma. We herein report a case of an anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK) -negative with 1,25(OH)
    2
    D
    3
    -mediated hypercalcemia, which has never been previously reported. An 80-year-old Japanese man was admitted to our department due to acute exacerbation of hypercalcemia. He was diagnosed with ALCL, ALK-negative. Serum 1,25(OH)
    2
    D
    3
    level was high and seemed to be associated with the lymphoma because the serum calcium and 1,25(OH)
    2
    D
    3
    levels improved in response to chemotherapy. Histological findings showed that many CD68 positive macrophages were observed in the microenvironment of tumor cells. Lymphoma cells or tumor microenvironmental cells may produce 1,25(OH)
    2
    D
    3
    because several previous reports showed the source of 1,25(OH)
    2
    D
    3
    can be either lymphoma or tumor microenvironmental cells. Moreover, because 1,25(OH)
    2
    D
    3
    -mediated hypercalcemia has been reported regardless of the specific histological type of lymphoma, tumor microenvironmental cells may be involved in this condition. However, we could not identify the source of 1,25(OH)
    2
    D
    3
    in this case. The association between 1,25(OH)
    2
    D
    3
    production and prognosis in malignant lymphomas is yet unknown; further studies are needed to elucidate the clinical characteristics of malignant lymphoma with 1,25(OH)
    2
    D
    3
    -mediated hypercalcemia.

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  • Physical Fitness Tests and Type 2 Diabetes Among Japanese: A Longitudinal Study From the Niigata Wellness Study. Reviewed

    Momma H, Sawada SS, Kato K, Gando Y, Kawakami R, Miyachi M, Huang C, Nagatomi R, Tashiro M, Ishizawa M, Kodama S, Iwanaga M, Fujihara K, Sone H

    J Epidemiol   29 ( 4 )   139 - 146   2019

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  • Glutamic Acid Decarboxylase Autoantibody-negative Slowly Progressive Type 1 Diabetes Mellitus: A Case Report and Literature Review. Reviewed

    Michi Kobayashi, Nobumasa Ohara, Yohei Ikeda, Ouki Nagano, Toshinori Takada, Makoto Kodama, Hirohito Sone

    Internal medicine (Tokyo, Japan)   57 ( 24 )   3581 - 3587   2018.12

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    A 59-year-old non-obese Japanese woman developed diabetes mellitus with a negative glutamic acid decarboxylase autoantibody (GADA) test result. Her hyperglycemia was initially well controlled by oral hypoglycemic agents; however, despite continued treatment the hyperglycemia gradually worsened. As she had endogenous insulin deficiency and tested positive for insulin autoantibody (IAA), insulin therapy was initiated. Few studies have investigated GADA-negative patients with slowly progressive type 1 diabetes mellitus (SPT1D). Our IAA-positive SPT1D patient progressed from the clinical onset of diabetes mellitus to starting insulin therapy relatively quickly (1.5 years), similarly to other previously reported non-obese patients with GADA-positive SPT1D.

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  • Cladribine treatment for Erdheim-Chester disease involving the central nervous system and concomitant polycythemia vera: A case report. Reviewed

    Suguru Tamura, Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Takayuki Katagiri, Takuya Kasami, Hiroki Nemoto, Shukuko Miyakoshi, Hironori Kobayashi, Yasuhiko Shibasaki, Masayoshi Masuko, Kengo Takeuchi, Koichi Ohshima, Hirohito Sone, Jun Takizawa

    Journal of clinical and experimental hematopathology : JCEH   58 ( 4 )   161 - 165   2018.12

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    Erdheim-Chester disease (ECD), a rare form of non-Langerhans cell histiocytosis, is characterized by the infiltration of foamy CD68+ and CD1a- histiocytes into multiple organ systems. Central nervous system (CNS) involvement has recently been reported to be a poor prognostic factor when treating ECD with interferon alpha. We report the case of a 66-year-old Japanese patient with ECD involving the CNS who harbored the BRAF V600E mutation and also concomitantly developed polycythemia vera with the JAK2 V617F mutation. We confirmed 2-chlorodeoxyadenosine (cladribine) therapy to be effective for the patient in this case.

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  • 当科で経験した下垂体茎断裂症候群の1例 Reviewed

    佐藤 隆明, 金子 正儀, 福武 嶺一, 安楽 匠, 種村 聡, 今西 明, 矢口 雄大, 山本 正彦, 鈴木 達郎, 石黒 創, 松林 泰弘, 山田 貴穂, 岩永 みどり, 藤原 和哉, 曽根 博仁

    新潟医学会雑誌   132 ( 11-12 )   399 - 399   2018.12

  • Relationship between intake of fruit separately from vegetables and triglycerides - A meta-analysis. Reviewed International journal

    Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Dai Ishii, Mariko Hatta, Yasunaga Takeda, Masaru Kitazawa, Yasuhiro Matsubayashi, Hitoshi Shimano, Kiminori Kato, Shiro Tanaka, Hirohito Sone

    Clinical nutrition ESPEN   27   53 - 58   2018.10

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    BACKGROUND & AIMS: High intake of fruit and vegetables is recommended for cardiovascular health. However, there have been persistent beliefs that fruits having high concentrations of fructose elevate the level of triglycerides (TG) in blood unlike vegetables. This meta-analysis aims to clarify the relationship between fruit intake and TG or hypertriglyceridemia. METHODS: Electronic literature searches were conducted for observational studies that investigated the relationship between fruit intake and hypertriglyceridemia or intervention studies that investigated the effect of increasing fruit intake on TG. Each effect size was pooled with an inverse-variance method. RESULTS: Five cross-sectional studies and only 2 intervention studies were eligible. The pooled odds ratio (OR) (95% confidence interval (CI)) of the 5 cross-sectional studies for the highest vs. the lowest fruit intake category was 0.79 (0.72-0.87). In these studies, the pooled OR for the highest vs. the lowest vegetable intake category was not significant (OR = 0.92; 95% CI, (0.82-1.03)). A linear dose-response association was observed between increases in fruit intake and ORs for hypertriglyceridemia; the OR (95% CI) for an incrementally increased intake of fruit by 1 serving/day was 0.91 (0.84-0.98). CONCLUSION: This meta-analysis suggests that high intake of fruit but not vegetables is inversely associated with hypertriglyceridemia. More trials are needed to clarify whether increasing fruit intake would reduce the level of TG and/or incident hypertriglyceridemia.

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  • Network meta‐analysis of the relative efficacy of bariatric surgeries for diabetes remission Reviewed

    Kodama S, Fujihara K, Horikawa C, Harada M, Ishiguro H, Kaneko M, Furukawa K, Matsubayashi Y, Matsunaga S, Shimano H, Tanaka S, Kato K, Sone H

    Obesity reviews   19 ( 12 )   1621 - 1629   2018.9

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  • 糖尿病重症視力障害発症とHbA1cの関連性についての検討 Reviewed

    山本 正彦, 藤原 和哉, 五十嵐 理沙, 石澤 正博, 松林 泰弘, 松永 佐澄志, 伊藤 知恵, 錦野 理絵, 山中 菜詩, 児玉 暁, 曽根 博仁

    日本糖尿病眼学会誌   22   134 - 134   2018.9

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  • Refinement of the Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation. Reviewed

    Yasuhiko Shibasaki, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Kyoko Fuse, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Miwako Narita, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

    International journal of hematology   108 ( 3 )   282 - 289   2018.9

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    The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) is a widely used tool for pre-transplant risk assessment. Allogeneic hematopoietic cell transplantation (HCT) is performed on patients with diverse backgrounds, highlighting the need for other predictors to complement the HCT-CI and support bedside decision-making. There is a strong body of evidence supporting the use of pre-transplant serum ferritin (SF) in risk assessments of allogeneic HCT. We additionally found that the Glasgow Prognostic Score (GPS), which assesses inflammatory biomarkers and predicts survival of patients with solid organ malignancies, is a useful predictive marker for overall survival (OS) and non-relapse mortality (NRM) in allogeneic HCT, independent of HCT-CI and SF. In this study, we refined the GPS by adding pre-transplant SF to improve its prognostic ability and enable better stratification; we call this revised index the HCT-specific revised Glasgow Prognostic Score (HCT-GPS). We observed that the HCT-GPS more accurately predicted NRM and early-term OS than the GPS. Moreover, the HCT-GPS provides an independent prognostic factor adjusted for the HCT-CI and disease status, and stratifies patients into four risk groups by OS and NRM. Thus, the HCT-GPS is a useful index for predicting early-term complications after allogeneic HCT in patients with hematopoietic diseases.

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  • ステロイド糖尿病を合併し歯性感染から上顎の骨髄炎を発症した2型糖尿病の1例 Reviewed

    棚橋 怜生, 山本 正彦, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 岩永 みどり, 藤原 和哉, 羽入 修, 曽根 博仁

    糖尿病   61 ( 9 )   644 - 644   2018.9

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  • 糖尿病重症視力障害発症とHbA1cの関連性についての検討

    山本 正彦, 藤原 和哉, 五十嵐 理沙, 石澤 正博, 松林 泰弘, 松永 佐澄志, 伊藤 知恵, 錦野 理絵, 山中 菜詩, 児玉 暁, 曽根 博仁

    日本糖尿病眼学会誌   22   134 - 134   2018.9

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  • Expression of programmed death ligand 1 is associated with poor prognosis in myeloid sarcoma patients. Reviewed International journal

    Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Junichi Kiyasu, Shintaro Yokoyama, Yuya Sasaki, Hirohito Sone, Masao Seto, Jun Takizawa, Koichi Ohshima

    Hematological oncology   36 ( 3 )   591 - 599   2018.8

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    Myeloid sarcoma (MS) is a rare condition and is an extramedullary tumour of immature myeloid cells. It is now known that the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway suppresses the host antitumor responses and that these products are expressed on both tumour cells and tumour-infiltrating cells in various malignancies. However, little is known about the significance of PD-1/PD-L1 expression on tumour cells and tumour microenvironmental cells in MS. To investigate the clinicopathological significance of PD-1/PD-L1 expression in MS, we analyzed 98 patients by immunohistochemistry. Of these, 10.2% of cases had neoplastic tumour cells positive for PD-L1 (nPD-L1+ ). However, the rate of nPD-L1+ was <5% (range: 0.27 to 2.97%). On the other hand, PD-L1 expression on 1 or more of stromal cells in the tumour microenvironment (miPD-L1+ ) was observed in 37.8% of cases. Because all nPD-L1+ cases expressed PD-1 on less than 5% of tumour cells, we compared the miPD-L1+ and miPD-L1- groups. There was a correlation between miPD-L1+ status and the number of PD-1-expressing tumour -infiltrating lymphocytes (PD-1+ TILs; P = .0229). miPD-L1+ was found to be associated with poorer overall survival and progression-free survival (P = .00392, P = .00261, respectively). Multivariate analysis also confirmed miPD-L1+ to be an independent poor prognostic factor. In conclusion, our study indicated that the immunotherapy blocking the PD-1/PD-L1 pathway may improve the clinical outcome of MS.

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  • Heterogeneity of intrahepatic iron deposition in transfusion-dependent iron overload patients with hematological malignancies. Reviewed International journal

    Hironori Kobayashi, Norihiko Yoshimura, Shun Uemura, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Kyoko Fuse, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    Leukemia research   70   41 - 44   2018.7

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    DOI: 10.1016/j.leukres.2018.05.005

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  • Transgenic Mice Overexpressing SREBP-1a in Male ob/ob Mice Exhibit Lipodystrophy and Exacerbate Insulin Resistance. Reviewed International journal

    Hiroshi Ohno, Takashi Matsuzaka, Nie Tang, Rahul Sharma, Kaori Motomura, Takuya Shimura, Aoi Satoh, Song-Iee Han, Yoshinori Takeuchi, Yuichi Aita, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Motohiro Sekiya, Yoshimi Nakagawa, Hirohito Sone, Naoya Yahagi, Nobuhiro Yamada, Yoshikazu Higami, Hitoshi Shimano

    Endocrinology   159 ( 6 )   2308 - 2323   2018.6

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    Sterol regulatory element-binding protein (SREBP)-1a is a key transcription factor that activates the expression of genes involved in the synthesis of fatty acids, triglycerides (TGs), and cholesterol. Transgenic mice that overexpress the nuclear form of SREBP-1a under the control of the phosphoenolpyruvate carboxykinase promoter (Tg-1a) were previously shown to display a lipodystrophic phenotype characterized by enlarged and fatty livers, diminished peripheral white adipose tissue (WAT), and insulin resistance. In the current study, we crossed these Tg-1a mice with genetically obese (ob/ob) mice (Tg-1a;ob/ob) and examined change in fat distribution between liver and adipose tissues in severe obesity and mechanism underlying the lipodystrophic phenotype in mice with Tg-1a. Tg-1a;ob/ob mice developed more severe steatohepatitis but had reduced WAT mass and body weight compared with ob/ob mice. The reduction of WAT mass in Tg-1a and Tg-1a;ob/ob mice was accompanied by enhanced lipogenesis and lipid uptake in the liver, reduced plasma lipid levels, impaired adipocyte differentiation, reduced food intake, enhanced energy expenditure, and extended macrophage infiltration and fibrosis in WAT. Despite the improved glucose tolerance, Tg-1a;ob/ob mice showed severe peripheral insulin resistance. Adenoviral hepatic expression of SREBP-1a mimicked these phenotypes. The "fat steal"-like lipodystrophy phenotype of the Tg-1a;ob/ob model demonstrates that hepatic SREBP-1a activation has a strong impact on the partition of TG accumulation, resulting in adipose-tissue remodeling by inflammation and fibrosis and insulin resistance.

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  • Relationships among cardiorespiratory fitness, muscular fitness, and cardiometabolic risk factors in Japanese adolescents: Niigata screening for and preventing the development of non-communicable disease study-Agano (NICE EVIDENCE Study-Agano) 2. Reviewed International journal

    Sakiko Yoshizawa Morikawa, Kazuya Fujihara, Mariko Hatta, Taeko Osawa, Masahiro Ishizawa, Masahiko Yamamoto, Kazuo Furukawa, Hajime Ishiguro, Satoshi Matsunaga, Yohei Ogawa, Hitoshi Shimano, Hirohito Sone

    Pediatric diabetes   19 ( 4 )   593 - 602   2018.6

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    OBJECTIVE: To examine the independent and combined associations of cardiorespiratory fitness (CRF) and muscular fitness (MF) with cardiometabolic risk factors in Japanese adolescents. METHODS: A cross-sectional study including 993 Japanese adolescents (aged 13-14 years) was undertaken. Height, body mass, blood pressure, lipid profile (non-fasting), and HbA1c were measured. The physical fitness (PF) test included measurements of CRF (20 m multistage shuttle run test), upper limb strength (hand grip strength), lower limb strength (standing long jump), and muscular endurance (sit-ups). The clustered cardiometabolic risk (CCMR) was estimated by summing standardized Z-scores of body mass index (BMI), mean arterial pressure (MAP), non-high-density lipoprotein cholesterol (non-HDL-C), and HbA1c. RESULTS: Linear regression analysis showed that all PF factors except for muscular endurance were inversely correlated with CCMR (P < .001). Among metabolic risk components, HbA1c was unrelated to PF, while non-HDL-C was inversely associated with CRF (B = -2.40; P < .001), upper limb strength (B = -1.77; P < .05), and lower limb strength (B = -1.53; P < .05) after adjustment for lifestyle factors. Logistic regression showed that the probability of having high CCMR (≥1SD) was synergistically higher in those with the lowest tertiles of both CRF and upper limb strength (P for interaction = .001); however, a substantially lower likelihood of having high CCMR was observed among individuals with the lowest tertile of upper limb strength but moderate CRF. CONCLUSIONS: Lower CRF and MF were significantly and synergistically associated with an unhealthier metabolic risk profile.

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  • A distinct subtype of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorder: adult patients with chronic active Epstein-Barr virus infection-like features. Reviewed International journal

    Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Yasuji Kozai, Koji Kato, Masaharu Miyahara, Toshiaki Yujiri, Ilseung Choi, Katsumichi Fujimaki, Tsuyoshi Muta, Masaaki Kume, Sayaka Moriguchi, Shinobu Tamura, Takeharu Kato, Hiroyuki Tagawa, Junya Makiyama, Yuji Kanisawa, Yuya Sasaki, Daisuke Kurita, Kyohei Yamada, Joji Shimono, Hirohito Sone, Jun Takizawa, Masao Seto, Hiroshi Kimura, Koichi Ohshima

    Haematologica   103 ( 6 )   1018 - 1028   2018.6

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    The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.

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  • 耐糖能及び肥満の有無別にみた代謝異常が冠動脈疾患発症に及ぼす影響の検討 Reviewed

    藤原 和哉, 松林 泰弘, 山本 正彦, 金子 正儀, 松永 佐澄志, 山田 貴穂, 清田 浩康, 山中 菜詩, 児玉 暁, 曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   50回   336 - 336   2018.6

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  • 眼科処置を要する重症糖尿病性眼疾患の発生リスクに対する腎症の影響についての検討 Reviewed

    山本 正彦, 藤原 和哉, 大澤 妙子, 原田 万祐子, 石黒 創, 石澤 正博, 岩永 みどり, 松永 佐澄志, 松林 泰弘, 清田 浩康, 山中 菜詩, 山田 貴穂, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 161   2018.4

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  • 日本人2型糖尿病患者における、ビタミンB6摂取量と糖尿病網膜症発症との関係 JDCSによる報告 Reviewed

    堀川 千嘉, 相田 麗, 田中 司朗, 鎌田 智恵実, 田中 佐智子, 吉村 幸雄, 川崎 良, 山下 英俊, 大橋 靖雄, 井藤 英喜, 赤沼 安夫, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 141   2018.4

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  • 2型糖尿病患者における食事エネルギー密度と肥満との関連 JDDMにおける検討 Reviewed

    武田 安永, 藤原 和哉, 治田 麻理子, 森川 咲子, 堀川 千嘉, 石井 大, 加藤 光敏, 横山 宏樹, 栗原 義夫, 宮澤 一裕, 岩崎 晧一, 川井 紘一, 朝長 修, 屋宜 宣治, 前川 聡, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 265   2018.4

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  • 肥満境界型糖尿病患者に対する血糖自己測定と栄養指導媒体を用いた栄養教育の併用効果について Reviewed

    長谷川 美代, 堀川 千嘉, 田代 稔, 鈴木 沙織, 藤原 和哉, 北澤 勝, 加藤 公則, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 267   2018.4

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  • 指先穿刺による血糖およびHbA1c迅速測定をもちいた糖尿病啓発の取り組み Reviewed

    山田 貴穂, 石井 大, 武田 安永, 橋本 浩平, 三ツ間 友里恵, 張 かおり, 原田 万祐子, 白石 友信, 吉岡 大志, 山本 正彦, 大澤 妙子, 石黒 創, 金子 正儀, 鈴木 浩史, 松林 泰弘, 松永 佐澄志, 藤原 和哉, 岩永 みどり, 鈴木 亜希子, 羽入 修, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 377   2018.4

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  • 糖尿病患者における脈圧が透析導入に及ぼす影響の検討 Reviewed

    大澤 妙子, 藤原 和哉, 山本 正彦, 原田 万由子, 石澤 正博, 清田 浩康, 山中 菜詩, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 160   2018.4

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  • 診断に難渋した再発性重症低血糖の原因特定に薬物血中濃度測定が有用であった一例 Reviewed

    三ツ間 友里恵, 山本 正彦, 橋本 浩平, 金子 正儀, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 岩永 みどり, 藤原 和哉, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 181   2018.4

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  • 糖尿病治療薬別にみたHbA1cと冠動脈疾患(CAD)発症リスクとの関連 Reviewed

    原田 万祐子, 藤原 和哉, 大澤 妙子, 石澤 正博, 山本 正彦, 金子 正儀, 松林 泰弘, 松永 佐澄志, 山中 菜詩, 清田 浩康, 山田 貴穂, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 258   2018.4

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  • 耐糖能及び肥満の有無に関わらず代謝異常は冠動脈疾患発症リスクを増大させる Reviewed

    藤原 和哉, 松林 泰弘, 山本 正彦, 松永 佐澄志, 清田 浩康, 山中 菜詩, 児玉 暁, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 260   2018.4

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  • Cardiovascular Disease in Japanese Patients with Type 2 Diabetes Mellitus. Reviewed

    Kazuya Fujihara, Hirohito Sone

    Annals of vascular diseases   11 ( 1 )   2 - 14   2018.3

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    Individuals with diabetes have a two- to four-fold increased risk of coronary artery disease (CAD) and higher mortality rates than those without diabetes. Because not only microvascular but also macrovascular disease in patients with diabetes are known to predispose patients to a lower quality of life as well as lead to higher mortality rates, identifying and managing risk factors of CAD is of clinical relevance in diabetes care. A number of antihyperglycemic drugs are currently approved for the treatment of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), with several new drugs having been developed during the last decade. Diabetes-related complications have been substantially reduced worldwide. However, in view of the current situation in which both the prevalence of obesity and glucose abnormality have increased worldwide, including Japan, diet and exercise remain the crucial means of treatment for patients with diabetes. Furthermore, predicting the development of CAD is essential. This review summarizes data from recent studies on cardiovascular disease in patients with T2DM, focusing on clinical trials and big data, including studies involving Japanese individuals.

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  • Predictors of the response of HbA1c and body weight after SGLT2 inhibition. Reviewed International journal

    T Abe, Y Matsubayashi, A Yoshida, H Suganami, T Nojima, T Osawa, M Ishizawa, M Yamamoto, K Fujihara, S Tanaka, K Kaku, H Sone

    Diabetes & metabolism   44 ( 2 )   172 - 174   2018.3

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    DOI: 10.1016/j.diabet.2017.10.003

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  • MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia. Reviewed

    Takashi Kozakai, Masahiko Takahashi, Masaya Higuchi, Toshifumi Hara, Kousuke Saito, Yuetsu Tanaka, Masayoshi Masuko, Jun Takizawa, Hirohito Sone, Masahiro Fujii

    International journal of hematology   107 ( 3 )   337 - 344   2018.3

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    Membrane-associated guanylate kinase with inverted orientation protein 1 (MAGI-1) is a cytoplasmic scaffold protein that interacts with various signaling molecules; it negatively controls the cell growth of various types of cells and positively controls cell-cell interaction. In T cells, MAGI-1 has been shown to inhibit Akt activity through its interaction with PTEN and MEK1. In this study we found that MAGI-1 expression is decreased in multiple (9 out of 15) human T-cell leukemia cell lines, including adult T-cell leukemia (ATL), T-cell acute lymphoblastic leukemia and chronic T-cell lymphocytic leukemia. The overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced cellular growth. While the overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced the Akt and MEK activities, the knockdown of MAGI-1 in a MAGI-1-high ATL cell line augmented the Akt and MEK activities. Collectively, the findings of the present study suggest that the decreased expression of MAGI-1 in human T cells contributes to the development of several types of T-cell leukemia, partly through the stimulation of the Akt and MEK pathways.

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  • Role of fatty liver in the association between obesity and reduced hepatic insulin clearance. Reviewed International journal

    Y Matsubayashi, A Yoshida, H Suganami, H Ishiguro, M Yamamoto, K Fujihara, S Kodama, S Tanaka, K Kaku, H Sone

    Diabetes & metabolism   44 ( 2 )   135 - 142   2018.3

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    AIM: Hepatic insulin clearance (HIC) is important in regulating plasma insulin levels. Diminished HIC causes inappropriate hyperinsulinaemia, and both obesity and fatty liver (FL), which are known to decrease HIC, can be found either together in the same patient or on their own. The mechanism by which obesity reduces HIC is presumed to be mediated by FL. However, few reports have examined the role of FL in the relationship between obesity and HIC in type 2 diabetes (T2D) patients. Therefore, our study investigated the association of HIC with clinical factors, including insulin sensitivity indices, focusing on the presence or absence of FL and obesity in T2D patients. METHOD: Baseline data from 419 patients with T2D (279 men, 140 women; mean age: 57.6 years; body mass index: 25.5kg/m2) controlled by diet and exercise were analyzed. HIC was calculated from the ratio of fasting c-peptide to fasting insulin levels (HICCIR). Correlation analyses between HICCIR and clinical variables were performed using Pearson's product-moment correlation coefficients and single regression analysis in all participants and in those with obesity and FL either alone or in combination. RESULTS: HICCIR was significantly correlated with whole-body insulin sensitivity indices and influenced by FL, but only in the FL group was obesity independently influenced HIC level. HICCIR decreased in those with both FL and obesity compared with those with only one such complication. CONCLUSION: HICCIR may be used to evaluate whole-body insulin sensitivity in T2D. Also, compared with obesity, the influence of FL strongly contributed to a reduced HIC. TRIAL REGISTRATION NUMBER: These trials were registered by the Japan Pharmaceutical Information Centre clinical trials information (JapicCTI) as 101349 and 101351.

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  • Frequent expression of CD30 in extranodal NK/T-cell lymphoma: Potential therapeutic target for anti-CD30 antibody-based therapy. Reviewed International journal

    Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Yuya Sasaki, Kyohei Yamada, Eriko Yanagida, Reiji Muto, Maiko Kiryu, Hirohito Sone, Masao Seto, Koichi Ohshima, Jun Takizawa

    Hematological oncology   36 ( 1 )   166 - 173   2018.2

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    Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is a subtype of non-Hodgkin lymphoma with a poor prognosis. Although first-line treatments for patients with localized ENKTL have been established, there is no gold standard treatment for patients with advanced ENKTL and refractory and/or relapsed disease. Anti-CD30 antibody-based therapy, including brentuximab vedotin (BV), has been shown to target malignant lymphomas with CD30 expression. In particular, this therapeutic agent has recently been suggested to be effective for Hodgkin lymphoma and mature T-cell lymphoma. However, the efficacy of BV toward ENKTL has not yet been established. Therefore, we investigated the expression of CD30 in a large cohort to evaluate BV as a potential treatment for ENKTL. In this study, 97 Japanese patients with newly diagnosed ENKTL between January 2007 and December 2015 were enrolled. Flow cytometry and immunohistochemistry were performed for the evaluation of CD30 expression. If the cut-off value of CD30 expression is 1% or more, there were 55 positive cases (56.5%). According to the localization of lesion, the frequency of CD30 expression was significantly higher in the non-nasal type than in the nasal type (P = .0394). No differences were observed in almost all clinical characteristics between CD30-positive cases and CD30-negative cases. In addition, the expression of CD30 was not a prognostic factor for either overall survival or progression-free survival. In conclusion, frequent expression of CD30 in ENKTL suggests anti-CD30 antibody-based therapy may be an effective treatment.

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  • Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis. Reviewed

    Satoru Kodama, Kazuya Fujihara, Hajime Ishiguro, Chika Horikawa, Nobumasa Ohara, Yoko Yachi, Shiro Tanaka, Hitoshi Shimano, Kiminori Kato, Osamu Hanyu, Hirohito Sone

    Journal of epidemiology   28 ( 1 )   3 - 18   2018.1

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    Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13-1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08-1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

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  • Impact of Prior Coronary Artery Disease (CAD) and Glucose Tolerance Status (GTS) on Incident CAD in Japanese Men

    Hirohito Sone

    Diabetes   2018

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    DOI: 10.2337/DB18-1488-P

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  • Impact of Carbohydrate Intake on Obesity in Japanese Patients with Type 2 Diabetes-An Analysis of the JDCP Registry

    Hirohito Sone

    Diabetes   2018

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    DOI: 10.2337/DB18-787-P

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  • Commercially available elisa kit detects factor viii inhibitory antibodies earlier than bethesda assay, in severe hemophilia a patient with joint pain

    Hirohito Sone

    International Journal of Laboratory Hematology   2018

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  • Association between Serum Amylase Level and Incidence of Type 2 Diabetes

    Hirohito Sone

    Diabetes   2018

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    DOI: 10.2337/DB18-2368-PUB

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  • Influence of SGLT2 Inhibitor on Resting Heart Rate (RHR) and Factors Related to Its Changes

    Hirohito Sone

    Diabetes   2018

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    DOI: 10.2337/DB18-1154-P

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  • 当科で経験した下垂体茎断裂症候群の1例 Reviewed

    佐藤隆明, 金子正儀, 福武嶺一, 安楽匠, 種村聡, 今西明, 矢口雄大, 山本正彦, 鈴木達郎, 石黒創, 松林泰弘, 山田貴穂, 岩永みどり, 藤原和哉, 曽根博仁

    新潟医学会雑誌   132 ( 11/12 )   399 - 399   2018

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  • Reduced Postprandial Hepatic Insulin Clearance via the DPP-4 Inhibitor Anagliptin Contributed to Improvement in Hyperglycemia in Patients with Type 2 Diabetes Mellitus

    Hirohito Sone

    Diabetes   2018

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    DOI: 10.2337/DB18-1176-P

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  • Impact of body mass index and metabolic phenotypes on coronary artery disease according to glucose tolerance status. Reviewed International journal

    K Fujihara, Y Matsubayashi, M Yamamoto, T Osawa, M Ishizawa, M Kaneko, S Matsunaga, K Kato, H Seida, N Yamanaka, S Kodama, H Sone

    Diabetes & metabolism   43 ( 6 )   543 - 546   2017.12

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    OBJECTIVE: This study aimed to examine the impact of obesity, as defined by body mass index (BMI), and a metabolically unhealthy phenotype on the development of coronary artery disease (CAD) according to glucose tolerance status. METHODS: This population-based retrospective cohort study included 123,746 Japanese men aged 18-72years (normal glucose tolerance: 72,047; prediabetes: 39,633; diabetes: 12,066). Obesity was defined as a BMI≥25kg/m2. Metabolically unhealthy individuals were defined as those with one or more of the following conditions: hypertension, hypertriglyceridaemia and/or low HDL cholesterol. A Cox proportional hazards regression model identified variables related to CAD incidence. RESULTS: The prevalences of obese subjects with normal glucose tolerance, prediabetes and diabetes were 21%, 34% and 53%, whereas those for metabolically unhealthy people were 43%, 60% and 79%, respectively. Multivariate analysis showed that a metabolically unhealthy phenotype increases hazard ratios (HRs) for CAD compared with a metabolically healthy phenotype, regardless of glucose tolerance status (normal glucose tolerance: 1.98, 95% CI: 1.32-2.95; prediabetes: 2.91, 95% CI: 1.85-4.55; diabetes: 1.90, 95% CI: 1.18-3.06). HRs for CAD among metabolically unhealthy non-obese diabetes patients and obese diabetes patients with a metabolically unhealthy status were 6.14 (95% CI: 3.94-9.56) and 7.86 (95% CI: 5.21-11.9), respectively, compared with non-obese subjects with normal glucose tolerance and without a metabolically unhealthy status. CONCLUSION: A metabolically unhealthy state can associate with CAD independently of obesity across all glucose tolerance stages. Clinicians may need to consider those with at least one or more conditions indicating a metabolically unhealthy state as being at high risk for CAD regardless of glucose tolerance status.

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  • The Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation. Reviewed International journal

    Yasuhiko Shibasaki, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Hironori Kobayashi, Kyoko Fuse, Takashi Ushiki, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Miwako Narita, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

    Clinical transplantation   31 ( 11 )   2017.11

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    Evaluation methods, such as scoring systems for predicting complications in advance, are necessary for determining the adaptation of allogeneic hematopoietic cell transplantation (HCT) and selecting appropriate conditioning regimens. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), which is based on functions of main organs, is a useful tool for pre-transplant risk assessments and has been widely applied in determining treatment strategies for patients with hematological diseases. However, as allogeneic HCT is performed on patients with diverse backgrounds, another factor, which reinforces the HCT-CI, is required to evaluate pre-transplant risk assessments. The Glasgow Prognostic Score (GPS), which assesses the combined C-reactive protein and albumin, was reported to predict survival of patients with solid-organ malignancies independently of receiving chemo/radiotherapy and stages of cancer. In this study, we applied the GPS for pre-transplant risk assessments for allogeneic HCT. The GPS successfully stratified the patients into three risk groups of overall survival (OS) and non-relapse mortality (NRM). Moreover, the GPS could predict outcomes independently of the HCT-CI for OS and NRM in multivariate analysis. The GPS is considered to be a useful tool and reinforces the HCT-CI for determining adaptation of allogeneic HCT for patients with hematopoietic neoplasms.

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  • Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies. Reviewed International journal

    Tomoyuki Tanaka, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Shiro Tara, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Sha Si, Ichiro Manabe, Masashi Sanada, Manabu Nakayama, Masayoshi Masuko, Hirohito Sone, Haruhiko Koseki, Atsushi Iwama

    The Journal of experimental medicine   214 ( 10 )   2901 - 2913   2017.10

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    Recurrent inactivating mutations have been identified in various hematological malignancies in the X-linked BCOR gene encoding BCL6 corepressor (BCOR); however, its tumor suppressor function remains largely uncharacterized. We generated mice missing Bcor exon 4, expressing a variant BCOR lacking the BCL6-binding domain. Although the deletion of exon 4 in male mice (BcorΔE4/y ) compromised the repopulating capacity of hematopoietic stem cells, BcorΔE4/y thymocytes had augmented proliferative capacity in culture and showed a strong propensity to induce acute T-cell lymphoblastic leukemia (T-ALL), mostly in a Notch-dependent manner. Myc, one of the critical NOTCH1 targets in T-ALL, was highly up-regulated in BcorΔE4/y T-ALL cells. Chromatin immunoprecipitation/DNA sequencing analysis revealed that BCOR was recruited to the Myc promoter and restrained its activation in thymocytes. BCOR also targeted other NOTCH1 targets and potentially antagonized their transcriptional activation. Bcl6-deficient thymocytes behaved in a manner similar to BcorΔE4/y thymocytes. Our results provide the first evidence of a tumor suppressor role for BCOR in the pathogenesis of T lymphocyte malignancies.

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  • Severe hypoglycaemia is a major predictor of incident diabetic retinopathy in Japanese patients with type 2 diabetes Reviewed

    S. Tanaka, R. Kawasaki, S. Tanaka-Mizuno, S. Iimuro, S. Matsunaga, T. Moriya, S. Ishibashi, S. Katayama, Y. Ohashi, Y. Akanuma, H. Sone, H. Yamashita

    DIABETES & METABOLISM   43 ( 5 )   424 - 429   2017.10

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    Aim. - Hypoglycaemia is a common complication in diabetes patients. However, its relationship with retinopathy has not been well documented in patients with type 2 diabetes (T2D). This study aimed to investigate the associations between hypoglycaemia and the incidence and progression of diabetic retinopathy (DR).
    Methods. - In this longitudinal cohort study, which was part of the Japan Diabetes Complications Study (JDCS), adult patients with T2D were recruited at 59 diabetes clinics across Japan. Their history of hypoglycaemia was assessed by standardized self-reported questionnaires. Severe hypoglycaemia was defined as having at least one episode with coma requiring an outpatients visit or hospitalization. Adjusted hazard ratios (HRs) for incidence and progression of DR over 8 years of follow-up were determined.
    Results. - Of 1221 patients without DR, 127 (10.4%) had experienced non-severe hypoglycaemia within the previous year, whereas 10 (0.8%) reported severe hypoglycaemia episodes. During the 8-year follow-up involving 8492 person-years, 329 patients developed DR. In 410 patients with prevalent DR, the adjusted HRs for incident DR were 4.35 (95% CI: 1.98-9.56; P &lt; 0.01) and, for progression of DR, 2.29 (95% CI: 0.45-11.78; P = 0.32) with severe hypoglycaemia.
    Conclusion. - Having a history of severe hypoglycaemia was one of the strongest predictors of incident DR in patients with T2D, with a fourfold increased risk. Identifying patients with greater risks of DR based on their history of hypoglycaemia may help to personalize risk evaluation in patients with diabetes. (C) 2017 Elsevier Masson SAS. All rights reserved.

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  • Comparative evaluation of torasemide and spironolactone on adverse cardiac remodeling in a rat model of dilated cardiomyopathy. Reviewed International journal

    Somasundaram Arumugam, Remya Sreedhar, Vengadeshprabhu Karuppagounder, Meilei Harima, Masahiko Nakamura, Hiroshi Suzuki, Hirohito Sone, Kenichi Watanabe

    Cardiovascular therapeutics   35 ( 5 )   2017.10

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    BACKGROUND: Chronic heart failure (CHF) involves fluid retention and volume overload, leading to impaired cardiac function. In these conditions, diuretic agents are most commonly used to treat edema and thereby reducing the volume load on the failing heart. There are several other beneficial effects of diuretics apart from their action on urinary excretion. METHODS: To identify the effects of diuretic agents on adverse cardiac remodeling in CHF, this study was carried out, where we have compared the effects of torasemide and spironolactone in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin-mediated experimental autoimmune myocarditis. RESULTS: Cardiac protein expression levels of inflammation, endoplasmic reticulum stress, and fibrosis markers were upregulated in the hearts of CHF rats, while treatment with either torasemide or spironolactone has downregulated their expression. The effect produced by spironolactone on cardiac fibrosis markers was comparably lesser than torasemide. Further, immunohistochemical analysis and histopathological studies have provided evidence to confirm the beneficial effects of these drugs on adverse cardiac remodeling in rats with CHF. CONCLUSION: Torasemide treatment has benefits against adverse cardiac remodeling in CHF rats, which was better than the protection offered by spironolactone.

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  • Comprehensive risk management for the prevention of cerebro-cardiovascular diseases in Japan Reviewed

    Tamio Teramoto, Masayuki Yokode, Hiroyasu Iso, Akihiko Kitamura, Hiroki Shiomi, Tsuyoshi Kimura, Masayasu Matsumoto, Mami Iida, Jun Sasaki, Shigeru Inoue, Ryouichi Nagatomi, Tetsuo Shoji, Hidenori Arai, Hiromi Rakugi, Hirohito Sone, Shizuya Yamashita, Shigeru Mizyzaki

    CLINICAL AND EXPERIMENTAL NEPHROLOGY   21 ( 5 )   743 - 754   2017.10

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  • Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression. Reviewed International journal

    Mohamed A E Ali, Kyoko Fuse, Yuko Tadokoro, Takayuki Hoshii, Masaya Ueno, Masahiko Kobayashi, Naho Nomura, Ha Thi Vu, Hui Peng, Ahmed M Hegazy, Masayoshi Masuko, Hirohito Sone, Fumio Arai, Atsushi Tajima, Atsushi Hirao

    Scientific reports   7 ( 1 )   11442 - 11442   2017.9

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    Hematopoietic stem cells (HSCs) in a steady state can be efficiently purified by selecting for a combination of several cell surface markers; however, such markers do not consistently reflect HSC activity. In this study, we successfully enriched HSCs with a unique stemness-monitoring system using a transgenic mouse in which green florescence protein (GFP) is driven by the promoter/enhancer region of the nucleostemin (NS) gene. We found that the phenotypically defined long-term (LT)-HSC population exhibited the highest level of NS-GFP intensity, whereas NS-GFP intensity was strongly downregulated during differentiation in vitro and in vivo. Within the LT-HSC population, NS-GFPhigh cells exhibited significantly higher repopulating capacity than NS-GFPlow cells. Gene expression analysis revealed that nine genes, including Vwf and Cdkn1c (p57), are highly expressed in NS-GFPhigh cells and may represent a signature of HSCs, i.e., a stemness signature. When LT-HSCs suffered from remarkable stress, such as transplantation or irradiation, NS-GFP intensity was downregulated. Finally, we found that high levels of NS-GFP identified HSC-like cells even among CD34+ cells, which have been considered progenitor cells without long-term reconstitution ability. Thus, high NS-GFP expression represents stem cell characteristics in hematopoietic cells, making this system useful for identifying previously uncharacterized HSCs.

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  • Successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome: A case report and literature review. Reviewed International journal

    Takayuki Katagiri, Takashi Ushiki, Masayoshi Masuko, Tomoyuki Tanaka, Shukuko Miyakoshi, Kyoko Fuse, Yasuhiko Shibasaki, Jun Takizawa, Sadao Aoki, Hirohito Sone

    Medicine   96 ( 36 )   e7975   2017.9

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    RATIONALE: Myeloid sarcoma (MS) and leukemia cutis (LC) are extramedullary tumors comprising myeloid blasts. They can occur de novo or concurrently with hematological disorders, usually acute myeloid leukemia (AML). AML chemotherapy is generally the initial therapy for MS and LC, and hematopoietic stem cell transplantation (HSCT) can be considered as additional therapy. However, treatment for older patients who are unable to continue intensive chemotherapy is not currently standardized. PATIENT CONCERNS: A 71-year-old Japanese woman was diagnosed with multiple MSs associated with myelodysplastic syndrome (MDS), using bone marrow aspiration and lymph node biopsy. DIAGNOSES: Additionally, LC was diagnosed by skin biopsy. Extramedullary MS and LC lesions were formed by massive infiltration of myeloblastic cells. INTERVENTIONS: Twenty courses of 5-azacytidine (5-Aza) were administrated as maintenance therapy after induction therapy with daunorubicin and cytarabine. OUTCOMES: Myeloblasts decreased in the bone marrow and the LC disappeared after induction therapy. The MSs completely disappeared, except for the palatine tonsil lesion, after 5-Aza maintenance therapy. 5-Aza treatment provided long-term partial response for more than 21 months. LESSONS: 5-Aza was well tolerated and may be a good option for the treatment of MS and LC associated with MDS, especially in older patients who cannot receive HSCT.

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  • 移植前予後予測モデルとしての同種造血細胞移植特異的Glasgow Prognostic Score(HCT specific Glasgow Prognostic Score as a new predictive tool for pre-transplant risk assessments)

    Shibasaki Yasuhiko, Suwabe Tatsuya, Katagiri Takayuki, Tanaka Tomoyuki, Kobayashi Hironori, Fuse Kyoko, Ushiki Takashi, Narita Miwako, Sone Hirohito, Masuko Masayoshi

    臨床血液   58 ( 9 )   1547 - 1547   2017.9

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  • Association between all-cause mortality and severity of depressive symptoms in patients with type 2 diabetes: Analysis from the Japan Diabetes Complications Study (JDCS). Reviewed International journal

    Satoshi Matsunaga, Shiro Tanaka, Kazuya Fujihara, Chika Horikawa, Satoshi Iimuro, Masafumi Kitaoka, Asako Sato, Jiro Nakamura, Masakazu Haneda, Hitoshi Shimano, Yasuo Akanuma, Yasuo Ohashi, Hirohito Sone

    Journal of psychosomatic research   99   34 - 39   2017.8

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    OBJECTIVE: The aims of this study are to confirm whether the excess mortality caused by depressive symptoms is independent of severe hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and to evaluate the association between all-cause mortality and degrees of severity of depressive symptoms in Japanese patients with T2DM. METHODS: A total of 1160 Japanese patients with T2DM were eligible for this analysis. Participants were followed prospectively for 3years and their depressive states were evaluated at baseline by the Center for Epidemiologic Studies Depression Scale (CES-D). Cox proportional hazards model was used to evaluate the relative risk of all-cause mortality and was adjusted by possible confounding factors, including severe hypoglycemia, all of which are known as risk factors for both depression and mortality. RESULTS: After adjustment for severe hypoglycemia, each 5-point increase in the CES-D score was significantly associated with excess all-cause mortality (hazard ratio 1.69 [95% CI 1.26-2.17]). The spline curve of HRs for mortality according to total CES-D scores showed that mortality risk was slightly increased at lower scores but was sharply elevated at higher scores. CONCLUSION: A high score on the CES-D at baseline was significantly associated with all-cause mortality in patients with T2DM after adjusting for confounders including severe hypoglycemia. However, only a small effect on mortality risk was found at relatively lower levels of depressive symptoms in this population. Further research is needed to confirm this relationship between the severity of depressive symptoms and mortality in patients with T2DM.

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  • Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding beta-Cell Mass and Increasing Insulin Secretory Capacity Reviewed International journal

    Hui Zhao, Takashi Matsuzaka, Yuta Nakano, Kaori Motomura, Nie Tang, Tomotaka Yokoo, Yuka Okajima, Song-iee Han, Yoshinori Takeuchi, Yuichi Aita, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Hirohito Sone, Nobuhiro Yamada, Hitoshi Shimano

    DIABETES   66 ( 7 )   1833 - 1846   2017.7

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    Dysfunctional fatty acid (FA) metabolism plays an important role in the pathogenesis of beta-cell dysfunction and loss of beta-cell mass in type 2 diabetes (T2D). Elovl6 is a microsomal enzyme that is responsible for converting C16 saturated and monounsaturated FAs into C18 species. We previously showed that Elovl6 played a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further define its role in T2D development, we assessed the effects of Elovl6 deletion in leptin receptor-deficient C57BL/KsJ db/db mice, a model of T2D. The db/db; Elovl6(-/-) mice had a markedly increased beta-cell mass with increased proliferation and decreased apoptosis, an adaptive increase in insulin, and improved glycemic control. db/db islets were characterized by a prominent elevation of oleate (C18: 1n-9), cell stress, and inflammation, which was completely suppressed by Elovl6 deletion. As a mechanistic ex vivo experiment, isolated islets from Elovl6(-/-) mice exhibited reduced susceptibility to palmitate-induced inflammation, endoplasmic reticulum stress, and beta-cell apoptosis. In contrast, oleate-treated islets resulted in impaired glucose-stimulated insulin secretion with suppressed related genes irrespective of the Elovl6 gene. Taken together, Elovl6 is a fundamental factor linking dysregulated lipid metabolism to beta-cell dysfunction, islet inflammation, and beta-cell apoptosis in T2D, highlighting oleate as the potential culprit of beta-cell lipotoxicity.

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  • Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding β-Cell Mass and Increasing Insulin Secretory Capacity

    Zhao, Hui, Matsuzaka, Takashi, Nakano, Yuta, Motomura, Kaori, Tang, Nie, Yokoo, Tomotaka, Okajima, Yuka, Han, Song-Iee, Takeuchi, Yoshinori, Aita, Yuichi, Iwasaki, Hitoshi, Yatoh, Shigeru, Suzuki, Hiroaki, Sekiya, Motohiro, Yahagi, Naoya, Nakagawa, Yoshimi, Sone, Hirohito, Yamada, Nobuhiro, Shimano, Hitoshi

    Diabetes   66 ( 7 )   1833 - 1846   2017.7

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  • Impact of Obesity and Metabolic Phenotypes on Coronary Artery Disease (CAD) According to Glucose Tolerance Status Reviewed

    Kazuya Fujihara, Satoru Kodama, Masahiko Yamamoto, Satoshi Matsunaga, Yasuhiro Matsubayashi, Masahiro Ishizawa, Mieko Koishi, Chie Ito, Nauta Yamanaka, Kiminori Kato, Hirohito Sone

    DIABETES   66   A406 - A406   2017.6

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  • Advanced Glycation End Products Induce Brain-Derived Neurotrophic Factor Release from Human Platelets through the Src Family Kinases Activation Reviewed

    Kazuo Furukawa, Ichiro Fuse, Yuriko Iwakura, Hidekazu Sotoyama, Osamu Hanyu, Hiroyuki Nawa, Nobuyuki Takei, Hirohito Sone

    DIABETES   66   A123 - A123   2017.6

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  • Associations between Hypertension and End-Stage Renal Disease (ESRD) in People With and Without Diabetes Reviewed

    Atsushi Furuya, Kazuya Fujihara, Masahiro Ishizawa, Masahiko Yamamoto, Yasuhiro Matsubayashi, Satoshi Matsunaga, Chie Ito, Mieko Koishi, Nauta Yamanaka, Kiminori Kato, Satoru Kodama, Hirohito Sone

    DIABETES   66   A138 - A138   2017.6

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  • Impact of glucose tolerance status on the development of coronary artery disease among working-age men. Reviewed

    Fujihara K, Igarashi R, Yamamoto M, Ishizawa M, Matsubayasi Y, Matsunaga S, Kato K, Ito C, Koishi M, Yamanaka N, Kodama S, Sone H

    DIABETES & METABOLISM   43 ( 3 )   261 - 264   2017.6

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    Aims. To examine the impact of glucose tolerance status on the development of coronary artery disease (CAD) in working-age men in Japan.
    Methods. This population-based retrospective cohort study included 111,621 men aged 31-60 years [63,558 with normal glucose tolerance (NGT); 37,126 with prediabetes; 10,937 with diabetes]. The Cox proportional-hazards regression model was used to identify variables related to the incidence of CAD.
    Results. Multivariate analysis showed that, compared with NGT, diabetes increased the risk of CAD by 17.3 times (95% CI: 6.36-47.0) at ages 31-40 years, by 2.74 times (95% CI: 1.85-4.05) at ages 41-50 years and by 2.47 times (95% CI: 1.69-3.59) at ages 51-60 years. The HRs for CAD in men with diabetes aged 31-40 equaled that of men with NGT aged 51-60 [18.2 (7.15-46.4) and 19.4 (8.28-45.4), respectively].
    Conclusion. The impact of diabetes on CAD was markedly greater in men aged 31-40 years compared with those aged 41-60 years. (C) 2016 Elsevier Masson SAS. All rights reserved.

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  • Clinicopathological features of cryptococcal lymphadenitis and a review of literature. Reviewed

    Kawamoto K, Miyoshi H, Suzuki T, Muto R, Yamada K, Yanagida E, Koshino M, Sasaki Y, Takizawa J, Sone H, Sugita Y, Seto M, Ohshima K

    Journal of clinical and experimental hematopathology : JCEH   57 ( 1 )   26 - 30   2017.6

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    Cryptococcosis is an invasive fungal infection in immunocompromised patients. The clinicopathological characteristics of cryptococcal lymphadenitis are not well known. We analyzed three cases of cryptococcal lymphadenitis and compared their characteristics with those in previous reports. Two patients were human immunodeficiency virus (HIV) carriers, and one patient was a human T-cell leukemia virus type-1 (HTLV-1) carrier. The age of the HTLV-1 carrier with cryptococcosis was much higher than that of the HIV-1 carriers. CD4-positive cell counts in peripheral blood were 5.8/μL (Case 1) and 79.9/μL (Case 2) in the HIV carriers and 3285/μL in the HTLV-1 carrier (Case 3). According to flow cytometric analysis of the lymph nodes of Cases 1, 2, and 3, 50.0%, 87.1%, and 85.9%, respectively, of the T-cells were CD3; 9.8%, 16.3%, and 75.8%, respectively, were CD4; and 35.5%, 77.3%, and 10.2%, respectively, were CD8. Cryptococcus neoformans was detected in tissue culture in all patients. Although gelatinous lesions and numerous fungal cocci were observed in the two HIV patients, the granuloma formation was small. Gelatinous formation and granuloma formation were observed in the HTLV-1 carrier. Necrosis was observed in all cases. In previous reports, granuloma formation, epithelioid cells, and necrotic lesions were observed in most cases. Most of the patients were also immunosuppressed. However, no HTLV-1 carrier was detected. In conclusion, lymphadenopathy in a HTLV-1 carrier may suggest the presence of cryptococcal lymphadenitis. The frequency of cryptococcosis in HTVL-1 carriers may increase with increase in the long-term survival rate of HTLV-1 carriers.

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  • Potential protective effect of lactation against incidence of type 2 diabetes mellitus in women with previous gestational diabetes mellitus: A systematic review and meta-analysis. Reviewed International journal

    Tanase-Nakao K, Arata N, Kawasaki M, Yasuhi I, Sone H, Mori R, Ota E

    Diabetes/metabolism research and reviews   33 ( 4 )   2017.5

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    Lactation may protect women with previous gestational diabetes mellitus (GDM) from developing type 2 diabetes mellitus, but the results of existing studies are inconsistent, ranging from null to beneficial. We aimed to conduct a systematic review to gather available evidence. Databases MEDLINE, CINAHL, PubMed, and EMBASE were searched on December 15, 2015, without restriction of language or publication year. A manual search was also conducted. We included observational studies (cross-sectional, case-control, and cohort study) with information on lactation and type 2 diabetes mellitus incidence among women with previous GDM. We excluded case studies without control data. Data synthesis was conducted by random-effect meta-analysis. Fourteen reports of 9 studies were included. Overall risk of bias using RoBANS ranged from low to unclear. Longer lactation for more than 4 to 12 weeks postpartum had risk reduction of type 2 diabetes mellitus compared with shorter lactation (OR 0.77, 95% CI 0.01-55.86; OR 0.56, 95% CI 0.35-0.89; OR 0.22, 95% CI 0.13-0.36; type 2 diabetes mellitus evaluation time < 2 y, 2-5 y, and >5 y, respectively). Exclusive lactation for more than 6 to 9 weeks postpartum also had lower risk of type 2 diabetes mellitus compared with exclusive formula (OR 0.42, 95% CI 0.22-0.81). The findings support the evidence that longer and exclusive lactation may be beneficial for type 2 diabetes mellitus prevention in women with previous GDM. However, the evidence relies only on observational studies. Therefore, further studies are required to address the true causal effect.

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  • Comparison of clinicopathological characteristics between T-cell prolymphocytic leukemia and peripheral T-cell lymphoma, not otherwise specified. Reviewed International journal

    Kawamoto K, Miyoshi H, Yanagida E, Yoshida N, Kiyasu J, Kozai Y, Morikita T, Kato T, Suzushima H, Tamura S, Muta T, Kato K, Eto T, Seki R, Nagafuji K, Sone H, Takizawa J, Seto M, Ohshima K

    European journal of haematology   98 ( 5 )   459 - 466   2017.5

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    OBJECTIVES: T-cell prolymphocytic leukemia (T-PLL) is a very rare, aggressive T-cell neoplasm. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T-PLL and PTCL-NOS. METHODS: We analyzed 15 T-PLL and 91 PTCL-NOS patients and also compared clinical features between T-PLL and PTCL-NOS with leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared. RESULTS: T-PLL cells were smaller in size than those of PTCL-NOS with leukemic presentation (P=.0068); moreover, PTCL-NOS cells with leukemic presentation were smaller than those of PTCL-NOS without leukemic presentation (P=.0017). Immunophenotypic patterns in T-PLL and PTCL-NOS were similar. Five-year overall survival rates of T-PLL and all PTCL-NOS patients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T-PLL and PTCL-NOS with leukemic presentation had essentially equivalent characteristics. CONCLUSION: T-PLL and PTCL-NOS may share common biological and clinical characteristics in Japanese patients.

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  • Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy. Reviewed International journal

    Watanabe K, Sreedhar R, Thandavarayan RA, Karuppagounder V, Giridharan VV, Antony S, Harima M, Nakamura M, Suzuki K, Suzuki H, Sone H, Arumugam S

    BioFactors (Oxford, England)   43 ( 2 )   187 - 194   2017.3

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    Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017.

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  • Carbohydrate intake during early pregnancy is inversely associated with abnormal glucose challenge test results in Japanese pregnant women. Reviewed International journal

    Tajima R, Yachi Y, Tanaka Y, Kawasaki YA, Nishibata I, Hirose AS, Horikawa C, Kodama S, Iida K, Sone H

    Diabetes/metabolism research and reviews   33 ( 6 )   2017.3

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    BACKGROUND: In East Asian countries, which have a high prevalence of underweight individuals, there is little information about the association between dietary factors and abnormal glucose tolerance during pregnancy. We examined the association between carbohydrate intake and moderately abnormal glucose tolerance in Japanese pregnant women. METHODS: We conducted a prospective study on 325 Japanese pregnant women without a diagnosis of diabetes mellitus prior to pregnancy. Dietary carbohydrate intake (% of total energy intake) was assessed using a 3-day dietary record during weeks 8-15 of pregnancy. Glucose tolerance was assessed by the 50 g glucose challenge test (GCT) during weeks 24-28 of pregnancy. A positive GCT result was defined by a 1-hour plasma concentration ≥ 7.8 mmol/L. Odds ratios of a positive GCT were calculated for the top and middle tertile categories of carbohydrate intake using the bottom category as reference. RESULTS: Mean (standard deviation) body mass index at the first prenatal visit was 19.7 (1.9) kg/m2 , and 95 women were underweight. Seventy-four women had positive GCT results. Carbohydrate intake was negatively associated with a positive GCT result after adjusting for age, parity, body mass index at first prenatal visit, family history of diabetes mellitus, rate of gestational weight gain, energy intake, and dietary fiber intake (odds ratio for top category: 0.46 [95% CI, 0.23-0.93]). CONCLUSIONS: These findings suggest that high carbohydrate intake was negatively associated with moderately abnormal glucose tolerance in a population with a high prevalence of underweight individuals.

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  • Dietary salt intake and diabetes complications in patients with diabetes: An overview. Reviewed

    Chika Horikawa, Hirohito Sone

    Journal of general and family medicine   18 ( 1 )   16 - 20   2017.3

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    Dietary salt restriction is an essential constituent of diabetes care in preventing or slowing the development of diabetes complications, and many diabetes management guidelines include recommendations for dietary salt intake. However, descriptions of guidelines for salt intake are sometimes confined to studies of participants without diabetes or small short-term studies of patients with diabetes. However, in response to such situations, recent longitudinal studies of patients with diabetes have reported an association between dietary salt intake and diabetes complications. Thus, this review summarizes important points in the current situation regarding guidelines on salt intake and the latest findings and future issues on dietary salt intake for diabetes care focusing on (i) the current status and issues regarding the leading guidelines for dietary salt intake for diabetes care in various regions worldwide, and (ii) findings on salt intake from recent longitudinal studies of patients with diabetes whose dietary salt intake was restricted.

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  • Patients with type 2 diabetes having higher glomerular filtration rate showed rapid renal function decline followed by impaired glomerular filtration rate: Japan Diabetes Complications Study. Reviewed International journal

    Moriya T, Tanaka S, Sone H, Ishibashi S, Matsunaga S, Ohashi Y, Akanuma Y, Haneda M, Katayama S

    Journal of diabetes and its complications   31 ( 2 )   473 - 478   2017.2

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    AIMS: The Japan Diabetes Complications Study (JDCS), a nation-wide, multicenter, prospective study of patients with type 2 diabetes, reported that hemoglobin A1c (HbA1c), systolic blood pressure, and smoking were risk factors for the onset of macroalbuminuria. This study explored the risk factors for glomerular filtration rate (GFR) decline in the JDCS patients. METHODS: We examined the 1407 JDCS patients (667 women, mean age 59years, 974 normoalbuminuria, 433 microalbuminuria) whose urinary albumin-to-creatinine ratio (UACR) and estimated GFR (eGFR) were determined at baseline with an 8-year follow-up. We divided all the patients into four groups according to baseline eGFR: G1 (120≤eGFR), G2 (90≤eGFR<120), G3 (60≤eGFR<90), G4 (eGFR<60). RESULTS: The eGFRs in groups G1 and G2 decreased at follow-up compared to those at the baseline. The risk of annual eGFR decline rate≥3ml/min/1.73m2 (rapid decliners) increased as the baseline eGFR increased. Advanced age, high HbA1c, and UACR, or diabetic retinopathy at baseline were risk factors for the rapid decliners. Especially the G1 group had a significant risk for the rapid decliners. The frequency of the patients with GFR<60ml/min/1.73m2 at the follow-up amounted to 31.1% in the rapid decliners, which was higher than 12% in the non-rapid decliners. CONCLUSIONS: In normo- and microalbuminuric patients with type 2 diabetes, extra careful attention should be paid to patients with eGFR ≥120ml/min/1.73m2 to detect cases with rapidly decreased GFR under the normal range.

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  • Comparison of baseline characteristics and clinical course in Japanese patients with type 2 diabetes among whom different types of oral hypoglycemic agents were chosen by diabetes specialists as initial monotherapy (JDDM 42). Reviewed International journal

    Fujihara K, Igarashi R, Matsunaga S, Matsubayashi Y, Yamada T, Yokoyama H, Tanaka S, Shimano H, Maegawa H, Yamazaki K, Kawai K, Sone H

    Medicine   96 ( 7 )   e6122   2017.2

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    Little is known about the relationships between patient factors and the antihyperglycemic agents that have been prescribed as initial therapy by diabetes specialists for patients with type 2 diabetes. Moreover, there has been little clarification of the subsequent usage patterns and related factors that influenced the continuation or discontinuation of the drug or the addition of another drug. To provide information on these issues, we evaluated the clinical characteristics of Japanese patients with type 2 diabetes for whom different types of oral hypoglycemic agents (i.e., either sulfonylureas, biguanides, or DPP-4 inhibitors (DPP-4Is)) were chosen as initial monotherapy by diabetes specialists and evaluated subsequent usage patterns.Prescription data on 3 different antidiabetic agents from December 2009 to March 2015 from diabetes specialists' patient registries were used to identify variables at baseline related to initial prescriptions; also, the addition of another hypoglycemic drug or discontinuation of the initial therapy was evaluated 1 year after the initial prescription. Analyzed were data on 2666 patients who received initial monotherapy with either a sulfonylurea (305 patients), biguanide (951 patients), or DPP-4I (1410 patients). Patients administered sulfonylureas were older, had a lower body mass index (BMI), longer duration of diabetes, and worse glycemic control than recipients of biguanides. Use of biguanides was related to younger age, short duration of diabetes, and obesity but was negatively associated with poor glycemic control. Older age but neither obesity nor poor glycemic control was associated with DPP-4Is. In all 3 groups a high HbA1c value was related to adding another hypoglycemic agent to the initial therapy. Moreover, adding another drug to a DPP-4I was related to a younger age and higher BMI.Patients' age, duration of diabetes, obesity, and glycemic control at baseline influenced the choice of hypoglycemic agents. Selection of a biguanide differs greatly from that of a sulfonylurea or DPP-4I with regard to age and obesity.

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  • Is the Proportion of Carbohydrate Intake Associated with the Incidence of Diabetes Complications?-An Analysis of the Japan Diabetes Complications Study. Reviewed International journal

    Horikawa C, Yoshimura Y, Kamada C, Tanaka S, Tanaka S, Matsunaga S, Hanyu O, Araki A, Ito H, Tanaka A, Ohashi Y, Akanuma Y, Sone H

    Nutrients   9 ( 2 )   2017.2

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    The appropriate proportions of macronutritional intake have been controversial in medical nutritional therapy for diabetes, and evidence of the effects of carbohydrate consumption on diabetes complications in prospective settings is sparse. We investigated the relationships between proportions of carbohydrate intake as the % of total energy and diabetes complications in a nationwide cohort of Japanese patients with type 2 diabetes aged 40-70 years with hemoglobin A1c ≥6.5%. The analysis was of 1516 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to overt nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) after 8 years. Hazard ratios (HRs) for proportions of carbohydrate intake were estimated by Cox regression adjusted for confounders. High carbohydrate intake was significantly related to higher intakes of grain, fruits, and sweets/snacks and lower intakes of soybean and soy products, vegetables, seaweed, meat and processed meat, fish and processed fish, eggs, milk and dairy products, oil, and alcoholic beverages. During the eight-year follow-up, there were 81, 275, and 129 events of overt nephropathy, diabetic retinopathy, and CVD, respectively. After adjustment for confounders, HRs for complications in patients with carbohydrate intake in the second or third tertiles (51.0%-56.4% and ≥56.5%, respectively) compared with carbohydrate intake in the first tertile (<50.9%, referent) were analyzed. No significant associations were shown in the second and third tertiles relative to first tertile (overt nephropathy: 1.05 (95% Confidence Interval, 0.54-2.06) and 0.98 (0.40-2.44); diabetic retinopathy: 1.30 (0.90-1.88) and 1.30 (0.78-2.15); and CVD: 0.95 (0.55-1.63) and 1.37 (0.69-2.72)). By exploring potentially nonlinear relationships, trends for the incidence of diabetes complications according to proportions of carbohydrate intake were not clearly shown. Findings suggested that proportions of carbohydrate intake were not associated with the incidence of diabetes complications among type 2 diabetes patients in Japan.

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  • Advanced glycation end products induce brain-derived neurotrophic factor release from human platelets through the Src-family kinase activation. Reviewed International journal

    Furukawa K, Fuse I, Iwakura Y, Sotoyama H, Hanyu O, Nawa H, Sone H, Takei N

    Cardiovascular diabetology   16 ( 1 )   20 - 20   2017.2

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    BACKGROUND: Brain-derived neurotrophic factor (BDNF) exerts beneficial effects not only on diabetic neuropathies but also on cardiovascular injury. There is argument regarding the levels of serum BDNF in patients with diabetes mellitus (DM). Because BDNF in peripheral blood is rich in platelets, this may represent dysregulation of BDNF release from platelets. Here we focused on advanced glycation end products (AGEs), which are elevated in patients with DM and have adverse effects on cardiovascular functions. The aim of this study is to elucidate the role of AGEs in the regulation of BDNF release from human platelets. METHODS: Platelets collected from peripheral blood of healthy volunteers were incubated with various concentrations of AGE (glycated-BSA) at 37 °C for 5 min with or without BAPTA-AM, a cell permeable Ca2+ chelator, or PP2, a potent inhibitor of Src family kinases (SFKs). Released and cellular BDNF were measured by ELISA and calculated. Phosphorylation of Src and Syk, a downstream kinase of SFKs, in stimulated platelets was examined by Western blotting and immunoprecipitation. RESULTS: AGE induced BDNF release from human platelets in a dose-dependent manner, which was dependent on intracellular Ca2+ and SFKs. We found that AGE induced phosphorylation of Src and Syk. CONCLUSIONS: AGE induces BDNF release from human platelets through the activation of the Src-Syk-(possibly phospholipase C)-Ca2+ pathway. Considering the toxic action of AGEs and the protective roles of BDNF, it can be hypothesized that AGE-induced BDNF release is a biological defense system in the early phase of diabetes. Chronic elevation of AGEs may induce depletion or downregulation of BDNF in platelets during the progression of DM.

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  • Unstable bodyweight and incident type 2 diabetes mellitus: A meta-analysis. Reviewed

    Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H

    Journal of diabetes investigation   8 ( 4 )   501 - 509   2017.1

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    AIMS/INTRODUCTION: The present meta-analysis aimed to clarify the association of unstable bodyweight with the risk of type 2 diabetes mellitus, an association that has been controversial among longitudinal studies. MATERIALS AND METHODS: An electronic literature search using EMBASE and MEDLINE was followed up to 31 August 2016. The relative risks (RRs) of type 2 diabetes mellitus in individuals with unstable bodyweight were pooled using the inverse variance method. RESULTS: Eight studies were eligible for the meta-analysis. The median duration of measurements of weight change and follow-up years for ascertaining type 2 diabetes mellitus were 13.5 and 9.4 years, respectively. The pooled RR for the least vs most stable category was 1.33 (95% confidence interval 1.12-1.57). Between-study heterogeneity was statistically significant (P = 0.048). Whether type 2 diabetes mellitus was ascertained by blood testing explained 66.0% of the variance in the logarithm of RR (P = 0.02). In three studies in which blood testing was carried out, type 2 diabetes mellitus risk was not significant (RR 1.06, 95% confidence interval 0.91-1.25). Furthermore, publication bias that inflated type 2 diabetes mellitus risk was statistically detected by Egger's test (P = 0.09). CONCLUSIONS: Unstable bodyweight might be modestly associated with the elevated risk of type 2 diabetes mellitus; although serious biases, such as diagnostic suspicion bias and publication bias, made it difficult to assess this association.

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  • Prevalence of non-communicable diseases and number of comorbidities according to differences in household income levels in Japan: Analysis from National Health and Nutrition Survey. Reviewed

    Horikawa C, Murayama N, Ota A, Tsuruta M, Matsunaga S, Fujihara K, Hanyu O, Sone H

    Food and nutrition Sciences   7 ( 1 )   19 - 30   2017.1

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  • Successful umbilical cord blood hematopoietic stem cell transplantation in a patient with adult T-cell leukemia/lymphoma initially achieving complete remission with anti-CC chemokine receptor 4 antibody combined chemotherapy. Reviewed

    Suwabe T, Shibasaki Y, Kaihatsu A, Katagiri T, Miyakoshi S, Fuse K, Kobayashi H, Ushiki T, Moriyama M, Takizawa J, Narita M, Sone H, Masuko M

    [Rinsho ketsueki] The Japanese journal of clinical hematology   58 ( 1 )   32 - 36   2017

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    A 62-year-old man with CHOP refractory adult T-cell leukemia/lymphoma (ATLL) received anti-CC chemokine receptor 4 antibody (mogamulizumab) combined with CHOP and achieved complete remission. At 71 days after the final administration of mogamulizumab, he received umbilical cord blood transplantation (CBT) using reduced intensity conditioning. Umbilical cord blood engraftment was confirmed on day16. Grade II acute graft-versus-host disease (GVHD) was diagnosed on day60 and was controlled by administration of methylprednisolone. There was no evidence of relapse at 9 months after CBT. Ratios of regulatory T cells in CD4 positive T cells were remarkably low during all of these periods. Since mogamulizumab reduces regulatory T cells, the frequency and severity of acute GVHD were reported to be increased in patients administered mogamulizumab before allogenic stem cell transplantation. Further experiences are needed for selecting optimal donor sources, the portability period and GVHD prophylaxis for patients using mogamulizumab before allogeneic stem cell transplantation.

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  • Peripheral T-cell lymphoma, not otherwise specified: a retrospective single-center analysis. Reviewed

    Takaharu Suzuki, Keisuke Kawamoto, Suguru Tamura, Shun Uemura, Akane Kaihatsu, Hiroki Nemoto, Hironori Kobayashi, Takashi Ushiki, Kyoko Fuse, Yasuhiko Shibazaki, Masato Moriyama, Masayoshi Masuko, Miwako Narita, Hirohito Sone, Sadao Aoki, Naoya Nakamura, Koichi Oshima, Jun Takizawa

    [Rinsho ketsueki] The Japanese journal of clinical hematology   58 ( 8 )   905 - 911   2017

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    We retrospectively analyzed clinical and pathological features, treatments, and prognoses in 28 patients with newly diagnosed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in Niigata University Medical and Dental Hospital. Of them, 16 were males and 12 were females, and their median age was 62.5 (range, 26-88) years. The International Prognostic Index was high-intermediate/high in 68% of patients. Twelve patients were treated with CHOP/THP-COP and nine with third-generation chemotherapy regimens. At a median follow-up period of 30 (range: 1-164) months, the 2-year overall survival and progression-free survival rates were 61% and 44%, respectively. Further investigation of novel agents for treating PTCL-NOS is warranted.

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  • [Myelodysplastic syndrome with refractory hemorrhage due to reduced platelet aggregation activity]. Reviewed

    Tanaka T, Kozakai T, Kitajima T, Fuse K, Kobayashi H, Ushiki T, Shibazaki Y, Moriyama M, Takizawa J, Sone H, Fuse I, Masuko M

    [Rinsho ketsueki] The Japanese journal of clinical hematology   58 ( 12 )   2402 - 2405   2017

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    <p>A 75-year-old woman suffered a cat bite 10 months after myelodysplastic syndrome (MDS) diagnosis. She visited our hospital because the internal bleeding of the wound did not improve. Although the wound was treated, the bleeding did not stop. She was hospitalized for emergency medical treatment because the bleeding volume exceeded 200 m<i>l</i>. Although her platelet count was normal, the platelet function test showed a decrease in collagen and arachidonic acid aggregation. After platelet transfusion, her bleeding stopped. Patients with MDS may potentially have platelet dysfunction. In the case of bleeding without thrombocytopenia, a platelet function test should be performed and treatment intervention, such as platelet transfusion, should be considered.</p>

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  • Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles. Reviewed

    Kurokawa Y, Sone H, Win-Shwe TT, Zeng Y, Kimura H, Koyama Y, Yagi Y, Matsui Y, Yamazaki M, Hirano S

    International Journal of Nanomedicine   12   3967 - 3975   2017

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    Dendrimers have been expected as excellent nanodevices for brain medication. An amine-terminated polyamidoamine dendrimer (PD), an unmodified plain type of PD, has the obvious disadvantage of cytotoxicity, but still serves as an attractive molecule because it easily adheres to the cell surface, facilitating easy cellular uptake. Single-photon emission computed tomographic imaging of a mouse following intravenous injection of a radiolabeled PD failed to reveal any signal in the intracranial region. Furthermore, examination of the permeability of PD particles across the blood–brain barrier (BBB) in vitro using a commercially available kit revealed poor permeability of the nanoparticles, which was suppressed by an inhibitor of caveolae-mediated endocytosis, but not by an inhibitor of macropinocytosis. Physicochemical analysis of the PD revealed that cationic PDs are likely to aggregate promptly upon mixing with body fluids and that this prompt aggregation is probably driven by non-Derjaguin–Landau– Verwey–Overbeek attractive forces originating from the surrounding divalent ions. Atomic force microscopy observation of a freshly cleaved mica plate soaked in dendrimer suspension (culture media) confirmed prompt aggregation. Our study revealed poor transfer of intravenously administered cationic PDs into the intracranial nervous tissue, and the results of our analysis suggested that this was largely attributable to the reduced BBB permeability arising from the propensity of the particles to promptly aggregate upon mixing with body fluids.

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  • The SIL index is a simple and objective prognostic indicator in diffuse large B-cell lymphoma.

    Tomita N, Suzuki T, Miyashita K, Yamamoto W, Motohashi K, Tachibana T, Takasaki H, Kawasaki R, Hagihara M, Hashimoto C, Takemura S, Koharazawa H, Yamazaki E, Taguchi J, Fujimaki K, Fujita H, Sakai R, Fujisawa S, Motomura S, Takizawa J

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  • Development and evaluation of the Japanese version of the Audit of Diabetes-Dependent Quality of Life for patients with diabetes. Reviewed

    Ayumi Sugawara Hirose, Kazuya Fujihara, Flaminia Miyamasu, Shigeru Iwakabe, Misa Shimpo, Yoriko Heianza, Chika Horikawa, Yoko Yachi, Hirohito Sone

    Diabetology international   7 ( 4 )   384 - 390   2016.12

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    Objectives: Our objective was to undertake linguistic validation and cultural adaptation of the Japanese version of the Audit of Diabetes-Dependent Quality of Life (JP-ADDQoL) and to evaluate its psychometric properties when completed by Japanese patients with diabetes. Methods: We followed the standard linguistic validation procedure and subsequently evaluated the reliability (internal consistency) and construct validity (exploratory and confirmatory factor analyses) of the translated version by surveying 239 Japanese patients with diabetes. Results: We translated 19 items for the JP-ADDQoL. The internal consistency was excellent (Cronbach's alpha = 0.933). In the exploratory factor analysis, four factors were extracted, and most of the items in all four factors had high loadings. Forced one-factor analysis revealed all factor loadings other than those for sex life to be >0.40 (sex life: 0.398). Confirmatory factor analysis indicated an acceptable fit for the JP-ADDQoL. Conclusions: The JP-ADDQoL showed adequate reliability and acceptable validity. Examining not only the impact of diabetes on a specific domain of life but also its importance for each patient leads to more accurate and individualized measurement of the patient's QoL.

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  • CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα. Reviewed International journal

    Nakagawa Y, Satoh A, Tezuka H, Han SI, Takei K, Iwasaki H, Yatoh S, Yahagi N, Suzuki H, Iwasaki Y, Sone H, Matsuzaka T, Yamada N, Shimano H

    Scientific reports   6   39182 - 39182   2016.12

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    CREB3L3 is involved in fatty acid oxidation and ketogenesis in a mutual manner with PPARα. To evaluate relative contribution, a combination of knockout and transgenic mice was investigated. On a ketogenic-diet (KD) that highlights capability of hepatic ketogenesis, Creb3l3-/- mice exhibited reduction of expression of genes for fatty oxidation and ketogenesis comparable to Ppara-/- mice. Most of the genes were further suppressed in double knockout mice indicating independent contribution of hepatic CREB3L3. During fasting, dependency of ketogenesis on CREB3L3 is lesser extents than Ppara-/- mice suggesting importance of adipose PPARα for supply of FFA and hyperlipidemia in Creb3l3-/- mice. In conclusion CREB3L3 plays a crucial role in hepatic adaptation to energy starvation via two pathways: direct related gene regulation and an auto-loop activation of PPARα. Furthermore, as KD-fed Creb3l3-/- mice exhibited severe fatty liver, activating inflammation, CREB3L3 could be a therapeutic target for NAFLD.

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  • Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression. Reviewed International journal

    Kikuchi T, Orihara K, Oikawa F, Han SI, Kuba M, Okuda K, Satoh A, Osaki Y, Takeuchi Y, Aita Y, Matsuzaka T, Iwasaki H, Yatoh S, Sekiya M, Yahagi N, Suzuki H, Sone H, Nakagawa Y, Yamada N, Shimano H

    Molecular metabolism   5 ( 11 )   1092 - 1102   2016.11

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    OBJECTIVE: The transcription factor cyclic AMP-responsive element-binding protein H (CREBH, encoded by Creb3l3) is highly expressed in the liver and small intestine. Hepatic CREBH contributes to glucose and triglyceride metabolism by regulating fibroblast growth factor 21 (Fgf21) expression. However, the intestinal CREBH function remains unknown. METHODS: To investigate the influence of intestinal CREBH on cholesterol metabolism, we compared plasma, bile, fecal, and tissue cholesterol levels between wild-type (WT) mice and mice overexpressing active human CREBH mainly in the small intestine (CREBH Tg mice) under different dietary conditions. RESULTS: Plasma cholesterol, hepatic lipid, and cholesterol crystal formation in the gallbladder were lower in CREBH Tg mice fed a lithogenic diet (LD) than in LD-fed WTs, while fecal cholesterol output was higher in the former. These results suggest that intestinal CREBH overexpression suppresses cholesterol absorption, leading to reduced plasma cholesterol, limited hepatic supply, and greater excretion. The expression of Niemann-Pick C1-like 1 (Npc1l1), a rate-limiting transporter mediating intestinal cholesterol absorption, was reduced in the small intestine of CREBH Tg mice. Adenosine triphosphate-binding cassette transporter A1 (Abca1), Abcg5/8, and scavenger receptor class B, member 1 (Srb1) expression levels were also reduced in CREBH Tg mice. Promoter assays revealed that CREBH directly regulates Npc1l1 expression. Conversely, CREBH null mice exhibited higher intestinal Npc1l1 expression, elevated plasma and hepatic cholesterol, and lower fecal output. CONCLUSION: Intestinal CREBH regulates dietary cholesterol flow from the small intestine by controlling the expression of multiple intestinal transporters. We propose that intestinal CREBH could be a therapeutic target for hypercholesterolemia.

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  • Clinicopathological, Cytogenetic, and Prognostic Analysis of 131 Myeloid Sarcoma Patients. Reviewed International journal

    Kawamoto K, Miyoshi H, Yoshida N, Takizawa J, Sone H, Ohshima K

    The American journal of surgical pathology   40 ( 11 )   1473 - 1483   2016.11

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    Myeloid sarcoma (MS) is an extramedullary tumor of immature myeloid cells. We analyzed 131 patients with MS, including: (1) de novo MS; (2) MS with concomitant acute myeloid leukemia (AML); (3) MS following myelodysplastic syndrome, myeloproliferative neoplasm, or chronic myelogenous leukemia; and (4) MS as a recurrence of AML. The most common development site was the lymph node. Testicular lesions were statistically more frequent in MS as a recurrence of AML than in other types of MS (P=0.0183). MS tended to lack myeloid markers (myeloperoxidase was present in 63.2%, CD68 in 51.3%, CD13 in 48.7%, and CD33 in 48.7% of patients) and express T-cell markers such as CD3 (20.7%) and CD5 (34.2%). All T-cell marker-positive MS cases were negative for the αβ and γδ T-cell receptors on immunohistochemistry. Underlying myelodysplastic syndrome or myeloproliferative neoplasm was a poor prognostic factor (vs. de novo MS: P=0.0383; vs. MS with concomitant AML: P=0.0143). However, there was no statistical difference in prognosis between de novo MS and MS with concomitant AML (P=0.288). There were no significant differences in prognosis between the prognoses of T-cell marker-positive and T-cell marker-negative MS cases. In addition, CXCR4 expression was a poor prognostic factor in MS (P=0.0229). This study involves the largest MS cohort to date and expands the clinical and pathologic knowledge of the disease.

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  • Quantitative assessment of genetic testing for type 2 diabetes mellitus based on findings of genome-wide association studies. Reviewed International journal

    Satoru Kodama, Kazuya Fujihara, Hajime Ishiguro, Chika Horikawa, Nobumasa Ohara, Yoko Yachi, Shiro Tanaka, Hitoshi Shimano, Kiminori Kato, Osamu Hanyu, Hirohito Sone

    Annals of epidemiology   26 ( 11 )   816 - 818   2016.11

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  • Utility of nonblood-based risk assessment for predicting type 2 diabetes mellitus: A meta-analysis Reviewed International journal

    Sakiko Yoshizawa, Satoru Kodama, Kazuya Fujihara, Hajime Ishiguro, Masahiro Ishizawa, Yasuhiro Matsubayashi, Satoshi Matsunaga, Takaho Yamada, Hitoshi Shimano, Kiminori Kato, Osamu Hanyu, Hirohito Sone

    PREVENTIVE MEDICINE   91   180 - 187   2016.10

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    Objective. Nonblood-based risk assessment for type 2 diabetes mellitus (T2DM) that depends on data based on a questionnaire and anthropometry is expected to avoid unnecessary diagnostic testing and overdiagnosis due to blood testing. This meta-analysis aims to assess the predictive ability of nonblood-based risk assessment for future incident T2DM.Methods. Electronic literature search was conducted using EMBASE and MEDLINE (from January 1, 1997 to October 1, 2014). Included studies had to use at least 3 predictors for T2DM risk assessment and allow reproduction of 2 x 2 contingency table data (i.e., true positive, true negative, false positive, false negative) to be pooled with a bivariate random-effects model and hierarchical summary receiver-operating characteristic model. Considering the importance of excluding individuals with a low likelihood of T2DM from diagnostic blood testing, we especially focused on specificity and LR-.Results. Eighteen eligible studies consisting of 184,011 participants and 7038 cases were identified. The pooled estimates (95% confidence interval) were as follows: sensitivity = 0.73 (0.66-0.79), specificity = 0.66 (0.59-0.73), LR+ = 2.13 (1.81-2.50), and LR- = 0.41 (0.34-0.50).Conclusions. Nonblood-based assessment of risk of T2DM could produce acceptable results although the feasibility of such a screener needs to be determined in future studies. (C) 2016 Elsevier Inc. All rights reserved.

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  • Association of eating three meals irregularly with changes in BMI and weight among young Japanese men and women: A 2-year follow-up. Reviewed International journal

    Yoko Ibe, Happei Miyakawa, Yasuko Fuse-Nagase, Ayumi Sugawara Hirose, Reiko Hirasawa, Yoko Yachi, Kazuya Fujihara, Kazuto Kobayashi, Hitoshi Shimano, Hirohito Sone

    Physiology & behavior   163   81 - 87   2016.9

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    OBJECTIVE: Epidemiological longitudinal investigations of the association between not eating three meals regularly and changes in BMI and weight are scarce. The aim of this study was to investigate whether or not regularly eating three meals was associated with changes in BMI and weight in young Japanese men and women. METHODS: Study participants were 1241 men and 897 women aged 19.0±1.2 and 18.8±0.8years, respectively, who underwent health checkups at a university in Japan in 2001 as the baseline and subsequently in 2003. Weight and height were measured at baseline and 2years later. Whether an individual ate three meals regularly was determined by a self-report questionnaire in 2001. RESULTS: During the 2-year follow-up, the BMI gain was 0.347 for men and 0.067 for women. In the logistic regression analysis, for men, eating three meals irregularly was significantly associated with a 4% BMI gain (OR 1.60, CI 1.11-2.30), 6% BMI gain (OR 1.72, CI 1.12-2.63), 4kg weight gain (OR 2.01, CI 1.29-3.13), 6kg weight gain (OR 1.86, CI 1.02-3.37), and incidence of obesity (BMI ≧ 25)(OR 2.96, CI 1.22-7.17). For women, eating three meals irregularly was significantly associated with a 4% BMI loss (OR 1.99, CI 1.01-3.94), 6% BMI loss (OR 2.79, CI 1.29-6.03), 4kg weight loss (OR 3.85, CI 1.62-9.12), 6kg weight loss (OR 7.65, CI 2.06-28.46), and the incidence of underweight (OR 3.95, CI 1.32-11.89). CONCLUSIONS: The current results suggested that eating three meals irregularly was associated with subsequent BMI and weight gains for men and subsequent BMI and weight losses for women; both groups were around 20years of age. Self-reported eating behavior in this study might be used to screen and evaluate young Japanese men and women at high risk for changes in BMI and weight in a practical clinical setting.

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  • Impact of individual components and their combinations within a family history of hypertension on the incidence of hypertension: Toranomon hospital health management center study 22. Reviewed International journal

    Risa Igarashi, Kazuya Fujihara, Yoriko Heianza, Masahiro Ishizawa, Satoru Kodama, Kazumi Saito, Shigeko Hara, Osamu Hanyu, Ritsuko Honda, Hiroshi Tsuji, Yasuji Arase, Hirohito Sone

    Medicine   95 ( 38 )   e4564   2016.9

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    Although a family history (FH) of hypertension is a risk factor for the development of hypertension, only a few studies have investigated in detail the impact of individual components of an FH on incident hypertension. We investigated the impact of individual components and their combinations on the presence or development of hypertension considering obesity, smoking habits, physical activity, and other metabolic parameters.Studied were 12,222 Japanese individuals without hypertension (n = 9,766) and with hypertension (n = 2,456) at the baseline examination. The presence or incidence of hypertension during 5 years after a baseline examination was assessed by the presence of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or a self-reported history of clinician-diagnosed hypertension. In this prospective study, the odds ratio for incident hypertension was 1.39 (95% confidence interval [CI], 1.22, 1.59) for individuals with any FH of hypertension compared with those without such an FH. Individuals with an FH of hypertension in both parents and one or more grandparents had an odds ratio of 3.05 (95% CI 1.74, 5.36) for hypertension compared with those without an FH of hypertension. FH was associated with incident hypertension independently of other modifiable risk factors such as obesity, smoking, physical inactivity, hyperglycemia, hyperuricemia, and hypertriglyceridemia.A parental history of hypertension was an essential component within an FH for incident hypertension. FH of hypertension over two generations with both parents affected was the most important risk factor for incident hypertension. Although an FH is not a modifiable risk factor, modifying other risk factors could contribute to reducing the risk of hypertension even among individuals with a family history of hypertension.

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  • 輸血依存患者における肝臓内鉄含有量を評価するための二重エネルギーCTの重要性(Significance of dual-energy CT to evaluate liver iron content in transfusion-dependent patients)

    Kobayashi Hironori, Yoshimura Norihiko, Suwabe Tatsuya, Katagiri Takayuki, Miyakoshi Shukuko, Ushiki Takashi, Fuse Kyoko, Shibasaki Yasuhiko, Moriyama Masato, Takizawa Jun, Narita Miwako, Sone Hirohito, Masuko Masayoshi

    臨床血液   57 ( 9 )   1524 - 1524   2016.9

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  • Cluster-randomized trial to improve the quality of diabetes management: The study for the efficacy assessment of the standard diabetes manual (SEAS-DM). Reviewed

    Hiroshi Noto, Yukio Tanizawa, Toru Aizawa, Hirohito Sone, Narihito Yoshioka, Yasuo Terauchi, Nobuya Inagaki, Mitsuhiko Noda

    Journal of diabetes investigation   7 ( 4 )   539 - 43   2016.7

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    AIMS/INTRODUCTION: 'The Standard Diabetes Manual' has been developed by clinical researchers from multiple major institutions in Japan, such as the National Center for Global Health and Medicine, as a comprehensive disease management program, including collaboration between primary care physicians (PCPs) and specialist services. The present study evaluated the efficacy of the manual as a quality improvement strategy in diabetes care by PCPs. MATERIALS AND METHODS: A total of 42 PCPs in eight domestic districts of the Japan Medical Association were allocated to either the intervention group or the control group in a cluster-randomized design. The PCPs in both groups were provided with a copy of the Diabetes Treatment Guide published by the Japan Diabetes Society, and the PCPs in the intervention group additionally received a copy of the manual and a 30-min relevant seminar at the inception of the intervention. The primary end-point was the adherence to the following performances as quality indicators: evaluation of retinopathy, and urinary albumin excretion measurements and serum creatinine measurements, as recommended by the Japan Medical Association. RESULTS: A total of 416 patients were enrolled by 36 PCPs. During the 1-year follow-up period, the proportion of PCPs who adhered to recommendation-concordant measurements of urinary albumin excretion was significantly higher in the intervention group than in the control group (adherence: 17.9% vs 5.3%, P = 0.016). The other parameters were not statistically different between the two groups. CONCLUSIONS: Implementation of 'The Standard Diabetes Manual' potentially leads to an improved quality of diabetes management by PCPs.

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  • Maximum BMI and microvascular complications in a cohort of Japanese patients with type 2 diabetes: the Japan Diabetes Complications Study Reviewed

    Shiro Tanaka, Sachiko Tanaka, Satoshi Iimuro, Shun Ishibashi, Hidetoshi Yamashita, Tatsumi Moriya, Shigehiro Katayama, Yasuo Akanuma, Yasuo Ohashi, Nobuhiro Yamada, Atsushi Araki, Hideki Ito, Hirohito Sone

    JOURNAL OF DIABETES AND ITS COMPLICATIONS   30 ( 5 )   790 - 797   2016.7

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    Aims: The aim of this study was to examine the associations between possible indices of obesity based on information on weight history and the incidence of microvascular complications.
    Methods: A cohort of individuals with type 2 diabetes from 59 institutes in Japan was followed for 8 years. Patients were classified into three categories according to weight at entrance and past maximum weight: normal (BMI at baseline &lt;25 kg/m(2) and maximum BMI &lt;25 kg/m(2)), past obesity (BMI at baseline &lt;25 kg/m2 and maximum BMI &gt;= 25 kg/m(2)), and current obesity (BMI at baseline 25 kg/m(2)) groups. The outcomes were diabetic retinopathy and overt nephropathy.
    Results: BMI at maximum and baseline of the 1809 patients was 26.5 +/- 3.5 and 23.1 +/- 3.0 kg/m(2) (p &lt; 0.01), respectively (23.0 +/- 1.6 and 20.6 +/- 1.9 kg/m(2) for normal, 27.4 +/- 2.0 and 22.8 +/- 1.4 kg/m(2) for past obesity, and 30.1 +/- 2.9 and 27.0 +/- 1.8 kg/m(2) for current obesity). The hazard ratios of past and current obesity compared to normal were 1.92 (95% CI, 1.08-3.41; p = 0.03) and 221 (1.16-4.22; p = 0.02), respectively, for overt nephropathy and 138 (1.05-1.83; p = 0.02) and 1.64 (1.18-2.28; p &lt; 0.01), respectively, for diabetic retinopathy after adjustment for confounders.
    Conclusions: Past obesity as well as current obesity were associated with increased risks of microvascular complications. Further identification of high-risk populations may be possible by classifying normal weight patients by past obesity. (C) 2016 Elsevier Inc. All rights reserved.

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  • Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system. Reviewed International journal

    Yoshimi Nakagawa, Fusaka Oikawa, Seiya Mizuno, Hiroshi Ohno, Yuka Yagishita, Aoi Satoh, Yoshinori Osaki, Kenta Takei, Takuya Kikuchi, Song-Iee Han, Takashi Matsuzaka, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Naoya Yahagi, Masaaki Isaka, Hiroaki Suzuki, Hirohito Sone, Satoru Takahashi, Nobuhiro Yamada, Hitoshi Shimano

    Scientific reports   6   27857 - 27857   2016.6

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    cAMP responsive element binding protein 3-like 3 (CREB3L3), a transcription factor expressed in the liver and small intestine, governs fasting-response energy homeostasis. Tissue-specific CREB3L3 knockout mice have not been generated till date. To our knowledge, this is the first study using the one-step CRISPR/Cas9 system to generate CREB3L3 floxed mice and subsequently obtain liver- and small intestine-specific Creb3l3 knockout (LKO and IKO, respectively) mice. While LKO mice as well as global KO mice developed hypertriglyceridemia, LKO mice exhibited hypercholesterolemia in contrast to hypocholesterolemia in global KO mice. LKO mice demonstrated up-regulation of hepatic Srebf2 and its corresponding target genes. No phenotypic differences were observed between IKO and floxed mice. Severe liver injury was observed in LKO mice fed a methionine-choline deficient diet, a model for non-alcoholic steatohepatitis. These results provide new evidence regarding the hepatic CREB3L3 role in plasma triglyceride metabolism and hepatic and intestinal CREB3L3 contributions to cholesterol metabolism.

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  • MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B-cell lymphoma Reviewed

    Keisuke Kawamoto, Hiroaki Miyoshi, Noriaki Yoshida, Naoya Nakamura, Koichi Ohshima, Hirohito Sone, Jun Takizawa

    CANCER SCIENCE   107 ( 6 )   853 - 861   2016.6

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    Genomic alterations and protein expression levels have been established as prognostic factors for survival in patients with diffuse large B-cell lymphoma (DLBCL). In particular, double-hit DLBCL (DHL), which exhibits translocations in MYC and BCL2 and/or BCL6, is known to be associated with a poor prognosis. However, the clinical significance of gene alterations and protein expression levels for MYC, B-cell lymphoma (BCL)2, and BCL6 are unclear. In this study, we analyzed 61 adult patients diagnosed with DLBCL without DHL, who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, or similar regimens. There were no differences in the distribution of MYC expression rates among the different MYC gene statuses. In log-rank tests, MYC translocation was a prognostic factor for overall survival (OS; P = 0.011), whereas BCL2 and BCL6 translocation were not prognostic indicators (P = 0.999 and P = 0.925, respectively). Although the expression levels of MYC and BCL6 were not significantly associated with OS, the expression of BCL2 was a prognostic factor for OS (P = 0.027). Furthermore, copy number gains in the MYC, BCL2, and BCL6 genes did not affect OS. MYC translocation (hazard ratio, 4.769; range, 1.518-14.98; P = 0.007) and BCL2 protein expression (hazard ratio, 3.072; range, 1.002-9.413; P = 0.049) were independent prognostic factors for survival in multivariate analyses. In conclusion, MYC translocation and BCL2 expression may need to be investigated at the initial diagnosis to predict prognosis in patients with DLBCL.

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  • Body Mass Index (BMI), Waist Circumference (WC) and Waist Height Ratio (WHtR) Cutoff Values, and the Impact of Their Combinations on Future Diabetes among Japanese Individuals Reviewed

    Risa Igarashi, Kazuya Fujihara, Yoriko Heianza, Masahiro Ishizawa, Megumi Tsuruta, Mariko Hatta, Sakiko Yoshizawa, Chika Hirikawa, Satoshi Matsunaga, Osamu Hanyu, Satoru Kodama, Koji Sato, Kiminori Kato, Hirohito Sone

    DIABETES   65   A519 - A520   2016.6

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  • The Dinakara equation for adjusting DLCO for hemoglobin in the HCT-CI is superior to the Cotes equation for predicting high-risk patients in allogeneic hematopoietic stem cell transplantation Reviewed

    Yasuhiko Shibasaki, Takayuki Katagiri, Hironori Kobayashi, Takashi Ushiki, Miwako Narita, Hirohito Sone, Tatsuo Furukawa, Masayoshi Masuko

    AMERICAN JOURNAL OF HEMATOLOGY   91 ( 5 )   E296 - E297   2016.5

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  • [Features of Japanese diabetic macroangiopathy]. Reviewed

    Masanori Kaneko, Kazuo Furukawa, Hirohito Sone

    Nihon rinsho. Japanese journal of clinical medicine   74 Suppl 2   22 - 6   2016.4

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  • [The 43rd Scientific Meeting: Perspectives of Internal Medicine; Genetic predisposition and related life-style underlying metabolic disorders; 2. Genetic and Environmental Susceptibility; 3) Epidemiology and large-scale clinical data analysis in metabolic diseases]. Reviewed

    Hirohito Sone

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   105 ( 3 )   383 - 90   2016.3

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  • Comparison of lipid parameters to predict cardiovascular events in Japanese mild-to-moderate hypercholesterolemic patients with and without type 2 diabetes: Subanalysis of the MEGA study Reviewed

    Hirohito Sone, Tomoko Nakagami, Rimei Nishimura, Naoko Tajima

    DIABETES RESEARCH AND CLINICAL PRACTICE   113   14 - 22   2016.3

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    Aims: To determine whether specific lipid parameters are better predictors of cardiovascular disease (CVD) in Japanese mild-to-moderate hypercholesterolemic patients with and without diabetes.
    Methods: Mildly or moderately hypercholesterolemic patients with no history of CVD received diet therapy or diet therapy plus pravastatin. In this post-hoc subanalysis, 5-year data from 3170 patients (668 diabetes, 2502 non-diabetes) on diet therapy alone were used to compare lipid parameters as predictors of CVD. We examined the data by tertiles, using hazard ratio (HR) per one-standard deviation (SD) increment (decrease for high-density lipoprotein cholesterol, HDL-C), chi(2) value, receiver operating characteristic curve analysis, and spline analysis.
    Results: In mild-to-moderate hypercholesterolemic patients with diabetes, increased total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C and decreased HDL-C were strongly associated with increased incidence of CVD (tertile analysis). In non-diabetes, increased non-HDL-C, and LDL-C/HDL-C were significantly associated with increased incidence of CVD. A one-SD decrease in HDL-C and a one-SD increment in non-HDL-C, TC/HDL-C, and LDL-C/HDL-C were significantly associated with increased HRs for CVD in both diabetes and non-diabetes. Linear CVD risk increases were found for non-HDL-C in diabetes and for non-HDL-C and HDL-C in non-diabetes (spline analysis).
    Conclusions: In mild-to-moderate hypercholesterolemia, CVD risk prediction by stratifications of single or combination of traditional lipid parameter values illustrates various patterns. Parameters including HDL-C are better predictors of cardiovascular risk than only using TC or LDL-C alone. Non-HDL-C could be the most useful lipid parameter to assess CVD risk, considering it is easy to calculate and less affected by food intake. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

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  • Comparison of clinical characteristics in patients with type 2 diabetes among whom different antihyperglycemic agents were prescribed as monotherapy or combination therapy by diabetes specialists. Reviewed

    Kazuya Fujihara, Osamu Hanyu, Yoriko Heianza, Akiko Suzuki, Takaho Yamada, Hiroki Yokoyama, Shiro Tanaka, Hiroaki Yagyu, Hitoshi Shimano, Atsunori Kashiwagi, Katuya Yamazaki, Koichi Kawai, Hirohito Sone

    Journal of diabetes investigation   7 ( 2 )   260 - 9   2016.3

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    AIMS/INTRODUCTION: We compared clinical characteristics in patients with type 2 diabetes for whom different antihyperglycemic agents were prescribed as monotherapy or combination therapy by diabetes specialists in Japan. MATERIALS AND METHODS: Prescription data for 2005, 2008 and 2011 from diabetes specialists' patient registries identified variables related to prescription of different antihyperglycemic agents. RESULTS: A total of 33,251 prescriptions in 2005, 25,119 in 2008 and 20,631 in 2011 were analyzed. Prescribing insulin was related to younger age, long duration of diabetes and glycated hemoglobin (HbA1c) ≥8.0%, but was negatively associated with obesity. Prescribing sulfonylureas was related to older age and long duration of diabetes, but not to obesity. Use of biguanides was related to younger age, short duration of diabetes and obesity, but was negatively associated with HbA1c ≥8.0%. A short duration of diabetes and HbA1c ≥8.0% were associated with use of a DPP-4 inhibitor, but not with obesity. Prescribing GLP-1 receptor agonists was related to younger age, obesity and HbA1c ≥8.0%. Odds ratios for each antihyperglycemic combination therapy were determined based on the characteristics of each included antihyperglycemic agent. CONCLUSIONS: These results could be expected to reflect in part the consensus of diabetes specialists, and might provide guidance regarding pharmacotherapy in the clinical setting.

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  • Assessment of kidney dysfunction with cystatin C- and creatinine-based estimated glomerular filtration rate and predicting type 2 diabetes: Toranomon Hospital Health Management Center Study 21 Reviewed

    Yoriko Heianza, Shigeko Hara, Kazumi Saito, Hiroshi Tsuji, Shiro Tanaka, Satoru Kodama, Tetsuro Kobayashi, Yasuji Arase, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   113   60 - 68   2016.3

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    Objective: Whether early stages of kidney dysfunction assessed by the estimated glomerular filtration rate from cystatin C measurements (eGFRCysC) rather than from creatinine measurements (eGFRCr) would more precisely reflect the risk of developing type 2 diabetes (T2D) has not been clarified. We compared the risk of developing T2D associated with renal dysfunction indicated by eGFRCysC or eGFRCr measurements.
    Methods: Studied were 2131 Japanese individuals without diabetes. Hazard ratios (HRs) for the development of T2D over 3-5 y were calculated across categories of eGFRCysC and eGFRCr, respectively.
    Results: Reduced levels of eGFRCysC were associated with a step-wise increase in the cumulative incidence rate of T2D (p = 0.007). In comparison with the eGFRCysC &gt;85th percentile group (&gt;= 117.4 ml/min/1.73 m(2)), the lowest group, which was the eGFRCysC &lt;15th percentile group (&lt;86.2 ml/min/1.73 m(2)), had an adjusted HR of 2.30 (95% CI 1.13, 4.68) for T2D. Compared with the eGFRCr &gt;85th percentile group, the lowest eGFRCr group (&lt;15th percentile) had an HR of 1.19 (0.63, 2.24) for T2D. However, individuals with eGFRCr &lt;60 ml/min/1.73 m(2) had a significantly increased risk of T2D. Clustering of both low eGFRCysC and low eGFRCr further elevated the HR for T2D compared with the presence of either.
    Conclusions: Although eGFRCr in ranges indicating chronic kidney disease reflected an elevated risk of developing diabetes, earlier stages of kidney dysfunction indicated by reduced eGFRCysC, which could not be captured by reduced eGFRCr, would be a marker for an elevated risk of developing T2D. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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  • Meta-analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus. Reviewed International journal

    Satoru Kodama, Kazuya Fujihara, Hajime Ishiguro, Chika Horikawa, Nobumasa Ohara, Yoko Yachi, Shiro Tanaka, Hitoshi Shimano, Kiminori Kato, Osamu Hanyu, Hirohito Sone

    Diabetes/metabolism research and reviews   32 ( 2 )   178 - 86   2016.2

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    BACKGROUND: Our aim is to examine the dose-response association between cumulative genetic risk and actual risk of type 2 diabetes mellitus (T2DM) and the influence of adjustment for covariates on T2DM risk through a comprehensive meta-analysis of observational studies. METHODS: Electronic literature search using EMBASE and MEDLINE (from 2003 to 2014) was conducted for cross-sectional or longitudinal studies that presented the odds ratio (OR) for T2DM in each group with categories based on the total number of risk alleles (RAs) carried (RAtotal ) using at least two single-nucleotide polymorphisms. Spline regression model was used to determine the shape of the relationship between the difference from the referent group of each study in RAtotal (ΔRAtotal ) and the natural logarithms of ORs (log OR) for T2DM. RESULTS: Sixty-five eligible studies that included 68 267 cases among 182 603 participants were analysed. In both crude and adjusted ORs, defined by adjusting the risk for at least two confounders among age, gender and body mass index, the slope of the log OR for T2DM became less steep as the ΔRAtotal increased. In the analysis limited to 14 cross-sectional and four longitudinal studies presenting both crude and adjusted ORs, regression curves of both ORs in relation to ΔRAtotal were almost identical. CONCLUSION: Using only single-nucleotide polymorphisms for T2DM screening was of limited value. However, when genotypic T2DM risk was considered independently from risk in relation to covariates, it was suggested that genetic profiles might have a supplementary role related to conventional T2DM risk factors in identifying individuals at high risk of T2DM. Copyright © 2015 John Wiley & Sons, Ltd.

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  • Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells.

    Katsura M, Cyou-Nakamine H, Zen Q, Zen Y, Nansai H, Amagasa S, Kanki Y, Inoue T, Kaneki K, Taguchi A, Kobayashi M, Kaji T, Kodama T, Miyagawa K, Wada Y, Akimitsu N, Sone H

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  • In Search of the Ideal Resistance Training Program to Improve Glycemic Control and its Indication for Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis Reviewed

    Hajime Ishiguro, Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Ayumi Sugawara Hirose, Reiko Hirasawa, Yoko Yachi, Nobumasa Ohara, Hitoshi Shimano, Osamu Hanyu, Hirohito Sone

    SPORTS MEDICINE   46 ( 1 )   67 - 77   2016.1

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    Background Resistance training (RT) is effective for glycemic control in type 2 diabetes mellitus (T2DM) patients. However, the characteristics of an RT program that will maximize its effect and those of patients that will especially benefit from RT are unknown.
    Objective The objectives of this systematic review were to identify via a comprehensive meta-analysis the characteristics of an RT program for patients with T2DM that might increase the patients' improvement in glycemic control and the characteristics of patients that will benefit from RT. Data Sources Electronic-based literature searches of MEDLINE and EMBASE entries from 1 January 1966 to 25 August 2014 were conducted to identify clinical trials examining the effect of RT on glycemic control among patients with T2DM. Study keywords were text words and thesaurus terms related to RT and T2DM.
    Study Selection Studies were included if they (1) were clinical trials consisting of two groups with and without RT exercise intervention; (2) had an intervention period of at least 5 weeks; (3) clarified that all patients had T2DM; and (4) reported or made it possible to estimate the effect size [i.e., change in glycosylated hemoglobin (HbA1c) in the RT group minus that in the control group] and its corresponding standard error.
    Study Appraisal and Synthesis Methods The effect size in each study was pooled with a random-effects model. Analyses were stratified by several key characteristics of the patients and RT exercise programs; meta-regression analysis was then used to detect a difference in the effect size among strata within each factor. Linear regression analyses were added by entering each of the following profiles: patients' baseline characteristics [mean baseline age, body mass index (BMI), and HbA1c levels] and exercise characteristics (total sets per week, total sets per bout of exercise, frequency, and intensity).
    Results There were 23 eligible studies comprising 954 patients with T2DM. The pooled effect size (95 % confidence interval) was -0.34 % (-0.53 to -0.16). A program with multiple sets (&gt;= 21 vs. &lt;21) per one RT bout was associated with a large effect size (P = 0.03); however, the linear correlation between the number of sets and effect size was not significant (P = 0.56). A larger effect size was observed in studies with participants with diabetes of a relatively short duration (&lt;6 vs. &gt;= 6 years; P = 0.04) or a high baseline HbA(1c) [&gt;= 7.5 % (58 mmol/mol) vs. &lt;7.5 %; P = 0.01] while a smaller effect size was observed in studies with a particularly high mean baseline BMI value (&gt;= 32 vs. &lt;32 kg/m(2); P = 0.03). Linear regression analyses predicted that each increment of 1 % in the baseline HbA(1c) would enlarge the effect size by 0.036 %, while each increment of 1 kg/m(2) in the baseline BMI decreased it by 0.070 % in the range between 22.3 and 38.8 kg/m(2).
    Conclusion In terms of glycemic control, RT could be recommended in the early stage of T2DM, especially for patients with relatively poor glycemic control. More benefit would be elicited in less obese patients within a limited range of the BMI. A substantial amount of exercise might be required to stimulate post-exercise glucose uptake, although the dose-dependency was not specifically clarified.

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  • The SIL index is a simple and objective prognostic indicator in diffuse large B-cell lymphoma

    Hirohito Sone

    Leukemia & Lymphoma   2016

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  • Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice. Reviewed International journal

    Noriko Suzuki-Kemuriyama, Takashi Matsuzaka, Motoko Kuba, Hiroshi Ohno, Song-Iee Han, Yoshinori Takeuchi, Masaaki Isaka, Kazuto Kobayashi, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Katsuhiro Miyajima, Dai Nakae, Naoya Yahagi, Yoshimi Nakagawa, Hirohito Sone, Nobuhiro Yamada, Hitoshi Shimano

    PloS one   11 ( 6 )   e0157580   2016

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    Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, can progress to steatohepatitis (NASH) and advanced liver damage, such as that from liver cirrhosis and cancer. Recent studies have shown the benefits of consuming n-3 polyunsaturated fatty acids (PUFAs) for the treatment of NAFLD. In the present study, we investigated and compared the effects of the major n-3 PUFAs-eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6)-in preventing atherogenic high-fat (AHF) diet-induced NAFLD. Mice were fed the AHF diet supplemented with or without EPA or DHA for four weeks. Both EPA and DHA reduced the pathological features of AHF diet-induced NASH pathologies such as hepatic lobular inflammation and elevated serum transaminase activity. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on AHF diet-induced hepatic inflammation and ROS generation, but no difference in fibrosis. Both EPA and DHA could be effective for treatment of NAFLD and NASH. Meanwhile, the two major n-3 polyunsaturated fatty acids might differ in a relative contribution to pathological intermediate steps towards liver fibrosis.

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  • Fulminant Type 1 Diabetes Mellitus Associated with Coxsackie Virus Type A2 Infection: A Case Report and Literature Review Reviewed

    Nobumasa Ohara, Masanori Kaneko, Takeaki Nishibori, Kazuhiro Sato, Tatsuo Furukawa, Tadashi Koike, Hirohito Sone, Kenzo Kaneko, Kyuzi Kamoi

    INTERNAL MEDICINE   55 ( 6 )   643 - 646   2016

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    A 65-year-old Japanese man presented to our hospital in June 2013 with a 6-day history of fever and fatigue, a 24-h history of thirst, and polyuria. His temperature was 37.8 degrees C and he was alert. However, laboratory tests revealed severe hyperglycemia, undetectable C-peptide levels, and diabetic ketoacidosis. Serum antibody testing confirmed a Coxsackie virus A2 infection. A variety of viral infections are reported to be involved in the development of fulminant type 1 diabetes mellitus (FT1D). Our patient is the first reported case of FT1D associated with Coxsackie virus A2 infection and supports the etiological role of common viral infections in FT1D.

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  • Fibromyalgia in a Patient with Cushing's Disease Accompanied by Central Hypothyroidism Reviewed

    Nobumasa Ohara, Shinichi Katada, Takaho Yamada, Naomi Mezaki, Hiroshi Suzuki, Akiko Suzuki, Osamu Hanyu, Yuichiro Yoneoka, Izumi Kawachi, Takayoshi Shimohata, Akiyoshi Kakita, Masatoyo Nishizawa, Hirohito Sone

    INTERNAL MEDICINE   55 ( 21 )   3185 - 3190   2016

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    A 39-year-old woman with a 3-year history of a rounded face developed widespread myalgia. Detailed examinations revealed no disorders that could explain the pain other than concomitant Cushing's disease and central hypothyroidism. Both the hypercortisolemia and hypothyroidism completely resolved after the patient underwent surgery to treat Cushing's disease, but she continued to experience unresolved myalgia and met the diagnostic criteria for fibromyalgia. Few studies have so far investigated patients with fibromyalgia associated with Cushing's syndrome. In our case, the hypothyroidism caused by Cushing's disease probably played an important role in triggering and exacerbating fibromyalgia. This highlights the need to examine the endocrine function in patients with muscle pain.

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  • Rapid Normalization of High Glutamic Acid Decarboxylase Autoantibody Titers and Preserved Endogenous Insulin Secretion in a Patient with Diabetes Mellitus: A Case Report and Literature Review Reviewed

    Nobumasa Ohara, Masanori Kaneko, Tatsuo Furukawa, Tadashi Koike, Hirohito Sone, Shoichiro Tanaka, Kenzo Kaneko, Kyuzi Kamoi

    INTERNAL MEDICINE   55 ( 5 )   485 - 489   2016

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    A 59-year-old Japanese woman developed diabetes mellitus without ketoacidosis in the presence of glutamic acid decarboxylase autoantibody (GADA) (24.7 U/mL). After the amelioration of her hyperglycemia, the patient had a relatively preserved serum C-peptide level. Her endogenous insulin secretion capacity remained almost unchanged during 5 years of insulin therapy. The patient's GADA titers normalized within 15 months. The islet-related autoantibodies, including GADA, are believed to be produced following the autoimmune destruction of pancreatic beta cells and are predictive markers of type 1 diabetes mellitus. Therefore, the transient appearance of GADA in our patient may have reflected pancreatic autoimmune processes that terminated without progression to insulin deficiency.

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  • A case of hypoglycemia attributable to atypical antipsychotic drugs Reviewed

    Hajime Ishiguro, Osamu Hanyu, Satoshi Houya, Kazuaki Morohashi, Ganji Kuroiwa, Osamu Kuwabara, Tsukasa Nakamaru, Katsuya Fuse, Kouji Sato, Hirohito Sone

    Diabetology International   6 ( 4 )   341 - 346   2015.12

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    We report a 55-year-old Japanese man who presented with symptomatic hypoglycemia attributable to atypical antipsychotic drugs (APD). He had been taking olanzapine, quetiapine, and paliperidone. One morning, his consciousness level dropped without inducement and his blood glucose was low. His symptoms improved after intravenous glucose infusion. These episodes reoccurred a few times, but ceased after APD were stopped. Physical examination did not find any organic disease that might cause hypoglycemia. Hyperglycemia, dyslipidemia, and body weight gain are well-documented side-effects of APD, but hypoglycemia is rare. There are a variety of hypotheses on how APD cause hypoglycemia: (1) Weight gain and dyslipidemia caused by APD might increase insulin resistance, meaning that excess insulin is secreted, causing hypoglycemia. (2) The quantity of basal insulin secreted by pancreatic beta cells might be enhanced by APD, which might cause hypoglycemia. (3) APD might work as an antagonist of muscarinic receptors such that insulin secretion might continue even after the glucose level has returned to normal, which might cause hypoglycemia. However, the mechanism is not fully understood and more research is needed.

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  • Fatal tracheal aspergillosis during rituximab combined chemotherapy for diffuse large B-cell lymphoma that developed after lung transplantation Reviewed

    K. Kawamoto, Y. Shibasaki, S. Sato, H. Nemoto, J. Takizawa, M. Narita, M. Tsuchida, H. Sone, M. Masuko

    Transplant Infectious Disease   17 ( 6 )   872 - 875   2015.12

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    Invasive tracheal aspergillosis (ITA) is an infection that is unique to patients who have undergone lung transplantation (LT). Although the activity of this disease often appears on imaging, we encountered a case of ITA that became exacerbated, despite few computed tomography (CT) findings, during rituximab combined chemotherapy for diffuse large B-cell lymphoma. ITA developed during immunosuppressive therapy after LT. Because CT findings may show false-negative results, bronchoscopy is recommended for such cases.

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  • Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr(-/-) mouse model Reviewed

    Motoko Kuba, Takashi Matsuzaka, Rie Matsumori, Ryo Saito, Naoko Kaga, Hikari Taka, Kei Ikehata, Naduki Okada, Takuya Kikuchi, Hiroshi Ohno, Song-Iee Han, Yoshinori Takeuchi, Kazuto Kobayashi, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Hirohito Sone, Naoya Yahagi, Yoji Arakawa, Tsutomu Fujimura, Yoshimi Nakagawa, Nobuhiro Yamada, Hitoshi Shimano

    SCIENTIFIC REPORTS   5   17604   2015.12

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    Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can develop into liver cirrhosis and cancer. Elongation of very long chain fatty acids (ELOVL) family member 6 (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition. Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH. In the present study, we further investigated the role of Elovl6 in the progression of lithogenic diet (LD)-induced steatohepatitis. We showed that the absence of Elovl6 suppresses hepatic lipid accumulation, plasma total cholesterol and total bile acid (BA) levels in LDL receptor-deficient (Ldlr(-/-)) mice challenged with a LD. The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder. These findings suggest that Elovl6-mediated changes in hepatic FA composition, especially oleic acid (C18:1n-9), control handling of hepatic cholesterol and BA, which protects against hepatotoxicity and steatohepatitis, but promotes gallstone formation in LD-fed Ldlr(-/-) mice.

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  • [Clinical and pathophysiological features of Japanese patients with type 2 diabetes mellitus and their risk factors for diabetic complication]. Reviewed

    Sone H

    Nihon rinsho. Japanese journal of clinical medicine   73 ( 12 )   1979 - 1987   2015.12

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  • Clinical Significance of MYC, BCL2 and BCL6 Rearrangement and Protein Expression in GCB and Non-GCB Type Diffuse Large B-Cell Lymphoma Invited Reviewed

    Keisuke Kawamoto, Jun Takizawa, Hiroaki Miyoshi, Noriaki Yoshida, Yasuhiko Shibasaki, Masayoshi Masuko, Hirohito Sone, Naoya Nakamura, Koichi Ohshima

    BLOOD   126 ( 23 )   2015.12

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  • Risk factors associated with abnormal cognition in Japanese outpatients with diabetes, hypertension or dyslipidemia Reviewed

    Hiroki Yokoyama, Mayumi Ogawa, Jun Honjo, Shinichiro Okizaki, Daishiro Yamada, Ryushi Shudo, Hitoshi Shimizu, Hirohito Sone, Masakazu Haneda

    DIABETOLOGY INTERNATIONAL   6 ( 4 )   268 - 274   2015.12

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    Aims According to the recent increase in life expectancy in patients with diabetes, the incidence of dementia with diabetes is increasing drastically in Japan. However, the number of studies on the prevalence of abnormal cognition and the associated risk factors in a large number of outpatients with diabetes in a primary care setting is very limited.Methods The Mini-Mental State Examination (MMSE) test was performed in 1,449 outpatients aged >= 50 years with diabetes, hypertension or dyslipidemia (126 without and 1,323 with diabetes). Prevalence of abnormal cognition defined as an MMSE score <24 and the associated risk factors were explored.Results Prevalence of abnormal cognition was 5.8 % in total, and was 8.3 % in outpatients aged >= 65 years with diabetes. Logistic regression analysis after adjustment for age, sex, BMI and smoking indicated that abnormal cognition was associated with lower serum albumin and higher uric acid levels in all subjects. In subjects with diabetes, in addition to the associations with serum albumin and uric acid levels, lower renal function, retinopathy, use of insulin and a-glucosidase inhibitor, and non-use of pioglitazone and metformin were significantly associated with abnormal cognition independent of the effect of duration of diabetes, hypertension, dyslipidemia, and history of coronary heart disease and stroke.Conclusions Because of the higher prevalence of abnormal cognition in aged outpatients with diabetes found in primary care practice and significant associations with serum albumin, uric acid, renal function, retinopathy and antidiabetic drugs, there is a need for early diagnosis and strategies against dementia.

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  • Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy Reviewed

    Yoshinori Osaki, Yoshimi Nakagawa, Shoko Miyahara, Hitoshi Iwasaki, Akiko Ishii, Takashi Matsuzaka, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Naoya Yahagi, Hiroaki Suzuki, Hirohito Sone, Ken Ohashi, Shun Ishibashi, Nobuhiro Yamada, Hitoshi Shimano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   466 ( 3 )   536 - 540   2015.10

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    HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. (C) 2015 Elsevier Inc. All rights reserved.

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  • Prevalence of resistant hypertension and associated factors in Japanese subjects with type 2 diabetes

    H. Yokoyama, S. Araki, S. Watanabe, J. Honjo, S. Okizaki, D. Yamada, R. Shudo, H. Shimizu, H. Sone, M. Haneda

    DIABETES RESEARCH AND CLINICAL PRACTICE   110 ( 1 )   18 - 25   2015.10

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    Objective: The prevalence of treatment resistant hypertension (RH) depends on methods used for blood pressure (BP) measurements, goals of BP, and therapeutic efforts in terms of medication and adherence. We focused on diabetic subjects and explored the prevalence of RH in primary care practice.
    Methods: In 1737 subjects with type 2 diabetes who continued regular visits, office BP was evaluated by multiple measurements over one year. RH was defined as using more than four antihypertensive drugs or failure to achieve the goal with three antihypertensive drugs from different classes. The RH prevalence was investigated with BP goals &lt;130/80 and 140/90 mmHg.
    Results: The percentage of subjects who achieved BP goals &lt;130/80 and 140/90 were 70.5% and 93.8% with adherence to medication &gt;= 95%, and the corresponding prevalence rates of RH in treated subjects were 28.4% and 21.8%, respectively. Factors independently associated with RH were age (odds ratio 1.02 [95% CI 1.01-1.04]), body mass index (1.10 [1.06-1.13]), variability in systolic BP (1.06 [1.02-1.09]), triglycerides (2.86 [1.34-6.11]), macroalbuminuria (3.33 [2.03-5.48]), estimated glomerular filtration rate (0.98 [0.97-0.99]), retinopathy (1.91 [1.39-2.61]), and family history of hypertension (1.85 [1.23-2.21]). Worsening albuminuria and glomerular filtration rate enhanced the prevalence of RH in a graded manner.
    Conclusion: Careful estimation of office BP values over one year with a high achievement of BP goals and adequate adherence revealed that the prevalence of RH in type 2 diabetes is high. RH was characterized by accumulation of cardiovascular genetic and environmental risks. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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  • Impact of population aging on trends in diabetes prevalence: A meta-regression analysis of 160,000 Japanese adults Reviewed

    Hadrien Charvat, Atsushi Goto, Maki Goto, Machiko Inoue, Yoriko Heianza, Yasuji Arase, Hirohito Sone, Tomoko Nakagami, Xin Song, Qing Qiao, Jaakko Tuomilehto, Shoichiro Tsugane, Mitsuhiko Noda, Manami Inoue

    JOURNAL OF DIABETES INVESTIGATION   6 ( 5 )   533 - 542   2015.9

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    Aims/IntroductionTo provide age- and sex-specific trends, age-standardized trends, and projections of diabetes prevalence through the year 2030 in the Japanese adult population.
    Materials and MethodsIn the present meta-regression analysis, we included 161,087 adults from six studies and nine national health surveys carried out between 1988 and 2011 in Japan. We assessed the prevalence of diabetes using a recorded history of diabetes or, for the population of individuals without known diabetes, either a glycated hemoglobin level of 6.5% (48mmol/mol) or the 1999 World Health Organization criteria (i.e., a fasting plasma glucose level of 126mg/dL and/or 2-h glucose level of 200mg/dL in the 75-g oral glucose tolerance test).
    ResultsFor both sexes, prevalence appeared to remain unchanged over the years in all age categories except for men aged 70years or older, in whom a significant increase in prevalence with time was observed. Age-standardized diabetes prevalence estimates based on the Japanese population of the corresponding year showed marked increasing trends: diabetes prevalence was 6.1% among women (95% confidence interval [CI] 5.5-6.7), 9.9% (95% CI 9.2-10.6) among men, and 7.9% (95% CI 7.5-8.4) among the total population in 2010, and was expected to rise by 2030 to 6.7% (95% CI 5.2-9.2), 13.1% (95% CI 10.9-16.7) and 9.8% (95% CI 8.5-12.0), respectively. In contrast, the age-standardized diabetes prevalence using a fixed population appeared to remain unchanged.
    ConclusionsThis large-scale meta-regression analysis shows that a substantial increase in diabetes prevalence is expected in Japan during the next few decades, mainly as a result of the aging of the adult population.

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  • Pioglitazone treatment and cardiovascular event and death in subjects with type 2 diabetes without established cardiovascular disease (JDDM 36)

    H. Yokoyama, S. Araki, K. Kawai, K. Hirao, M. Oishi, K. Sugimoto, H. Sone, H. Maegawa, A. Kashiwagi

    DIABETES RESEARCH AND CLINICAL PRACTICE   109 ( 3 )   485 - 492   2015.9

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    Aims: The protective association of pioglitazone with cardiovascular events and death was investigated over 6-years in large-scale type 2 diabetic subjects without established cardiovascular disease in a primary care setting.
    Methods: A six-year observational cohort study including 2864 subjects with type 2 diabetes without established cardiovascular disease was performed. The primary endpoint was a composite of first occurrence of cardiovascular disease or death. The effect of pioglitazone use at a baseline year with a Cox proportional hazard model and the time-dependent use in each one-year examination interval with a pooled logistic regression model were analyzed.
    Results: Baseline use of pioglitazone (n = 493) did not show a statistically protective effect on the primary endpoint (n = 175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43-1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33-0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone. Among a total of 898 subjects who took pioglitazone during the period, 43% experienced a discontinuation at least once; however, serious adverse effects were rare.
    Conclusions: This observational study indicated a protective association of pioglitazone with cardiovascular disease and death in type 2 diabetic subjects without established vascular disease, particularly those with nephropathy. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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  • レシピエントに対する移植前評価としてのHCT-CI/年齢スコアの臨床的意義(The clinical relevance of HCT-CI/age score as pre-transplant assessment for recipients)

    Katagiri Takayuki, Shibasaki Yasuhiko, Suwabe Tatsuya, Miyakoshi Shukuko, Fuse Kyoko, Kobayashi Hironori, Ushiki Takashi, Moriyama Masato, Takizawa Jun, Narita Miwako, Sone Hirohito, Masuko Masayoshi

    臨床血液   56 ( 9 )   1665 - 1665   2015.9

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  • HSCT後のγ/δT細胞低値およびTreg細胞高値はいずれも再発の独立リスク因子である(Both low γ/δ T cells and high Treg cells after HSCT is an independent risk factor for relapse)

    Shibasaki Yasuhiko, Miyakoshi Syukuko, Suwabe Tatsuya, Katagiri Takayuki, Fuse Kyoko, Kobayashi Hironori, Ushiki Takashi, Moriyama Masato, Takizawa Jun, Narita Miwako, Sone Hirohito, Furukawa Tatsuo, Masuko Masayoshi

    臨床血液   56 ( 9 )   1666 - 1666   2015.9

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  • Possible Involvement of Lung Cells Harboring an Abnormal Karyotype in the Pathogenesis of Pulmonary Alveolar Proteinosis Associated with Myelodysplastic Syndrome Reviewed

    Hirohito Sone

    Annals of the American Thoracic Society   12 ( 8 )   1251 - 1253   2015.8

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  • The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.

    Engström W, Darbre P, Eriksson S, Gulliver L, Hultman T, Karamouzis MV, Klaunig JE, Mehta R, Moorwood K, Sanderson T, Sone H, Vadgama P, Wagemaker G, Ward A, Singh N, Al-Mulla F, Al-Temaimi R, Amedei A, Colacci AM, Bisson WH

    2015.6

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    DOI: 10.1093/carcin/bgv030

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  • Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

    Goodson WH, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, Lasfar A, Carnero A, Azqueta A, Amedei A, Charles AK, Collins AR, Ward A, Salzberg AC, Colacci A, Olsen AK, Berg A, Barclay BJ, Zhou BP, Hu Z

    2015.6

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  • The association of level of reduction of Wilms' tumor gene 1 mRNA transcript in bone marrow and outcome in acute myeloid leukemia patients Reviewed

    Yasuhiko Shibasaki, Yoshinobu Seki, Tomoyuki Tanaka, Syukuko Miyakoshi, Kyoko Fuse, Takashi Kozakai, Hironori Kobayashi, Takashi Ushiki, Takashi Abe, Toshio Yano, Masato Moriyama, Takashi Kuroha, Noriatsu Isahai, Jun Takizawa, Miwako Narita, Satoru Koyama, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

    LEUKEMIA RESEARCH   39 ( 6 )   667 - 671   2015.6

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    We focused on the level of reduction of Wilms' tumor gene 1 (WT1) mRNA in bone marrow as minimal residual disease during chemotherapies in adult acute myeloid leukemia (AML) patients. Forty-eight patients were enrolled in this study. Log levels of reduction of WT1 mRNA transcript after induction therapy compared with those at diagnosis were associated with disease-free survival (DFS) (P = 0.0066) and overall survival (OS) (P = 0.0074) in patients who achieved complete remission. Also log levels of reduction of WT1 mRNA transcript after final consolidation therapy compared with those at diagnosis were associated with DFS (P = 0.015) and OS (P = 0.012). By multivariate analysis, log levels of reduction of WT1 mRNA transcript after induction therapy and after final consolidation therapy compared with those at diagnosis were extracted as risk factors for outcome. Our results suggest that early and deep reduction of tumor burden may be important for the outcome of AML patients. In addition, it may be useful for the decision to proceed with allogeneic SCT as post-remission therapy. (C) 2015 Elsevier Ltd. All rights reserved.

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  • Risk of the development of Type 2 diabetes in relation to overall obesity, abdominal obesity and the clustering of metabolic abnormalities in Japanese individuals: does metabolically healthy overweight really exist? The Niigata Wellness Study Reviewed

    Y. Heianza, K. Kato, S. Kodama, N. Ohara, A. Suzuki, S. Tanaka, O. Hanyu, K. Sato, H. Sone

    DIABETIC MEDICINE   32 ( 5 )   665 - 672   2015.5

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    AimsWe investigated the risk of developing diabetes across various metabolic phenotypes by considering the presence of overall adiposity or abdominal adiposity and the number of metabolic abnormalities and aimed to clarify whether a healthy overweight' phenotype, that is, overweight with no metabolic abnormalities, was protective of the development of diabetes.
    MethodsWe studied 29564 Japanese individuals without diabetes. The 5-year incidence of diabetes was assessed according to a combination of either overweight (BMI25.0kg/m(2)) or abdominal obesity (waist circumference 90cm in men and 80cm in women) and the number of metabolic factors present (hypertension, elevated triglyceride concentration, low HDL cholesterol concentration and impaired fasting glucose).
    ResultsA total of 1188 individuals developed diabetes. Compared with normal weight individuals with none of the four metabolic abnormalities, in overweight individuals with none of the four abnormalities there was an odds ratio (OR) of 2.32 [95% confidence interval (CI) 1.50, 3.59] for diabetes; having any one metabolic abnormality increased the risk of developing diabetes among normal weight individuals [OR 3.23 (2.55, 4.10)] and overweight individuals [OR 5.00 (3.77, 6.63)]. Among overweight individuals, the presence of impaired fasting glucose alone substantially elevated the risk of diabetes by 8.98-fold (5.52, 14.6) in comparison with the absence of the four metabolic factors.
    ConclusionsBeing healthy overweight' was associated with a higher OR of developing future diabetes among Japanese individuals than normal weight individuals with no metabolic abnormalities, and being overweight with one or more abnormalities had a further elevated OR compared with healthy overweight' people.
    What's new
    Japanese men and women who were healthy overweight', that is, overweight with none of the four metabolic abnormalities, were at risk of developing diabetes in comparison with those who were metabolically healthy and of normal weight. Each additional metabolic abnormality (hypertension, elevated triglycerides, low HDL cholesterol and impaired fasting glucose) increased the risk of developing Type2 diabetes in all four groups of people: overweight, abdominal adiposity, normal weight and normal abdominal adiposity.

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  • Correlation between SNP genotypes and periodontitis in Japanese type II diabetic patients: a preliminary study Reviewed

    Teerasak Damrongrungruang, Hiroshi Ogawa, Sayaka Hori-Matsumoto, Kumiko Minagawa, Osamu Hanyu, Hirohito Sone, Hideo Miyazaki

    ODONTOLOGY   103 ( 2 )   233 - 240   2015.5

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    The present study aims to investigate the correlation between SNP genotype patterns and periodontitis severity in Japanese type II diabetic patients. A cross-sectional study in 43 Japanese diabetic patients with periodontitis was performed. Blood samples were drawn for single nucleotide polymorphism (SNP) analyses and periodontal index (probing pocket depth and clinical attachment level) was subsequently recorded. Twelve functional genes with SNPs that had been shown to be associated with diabetes and/or inflammation were genotyped using a nuclease-mediated SNP-specific ligation method. Subjects with two or more sites with clinical attachment level a parts per thousand yen6 mm and who additionally had one or more sites with pocket depth a parts per thousand yen5 mm were classified as having severe periodontitis. Proportions of risk genotypes/non-risk genotypes between severe and non-severe periodontitis were subsequently compared. A high frequency (21/43 participants, 49 %) of adiponectin gene polymorphism (ADIPOQ 45T &gt; G) homozygous risk genotype (TT genotype) was observed in the participants. The frequency of TGF-beta 1 SNP (29C &gt; T) risk genotype (TT genotype) in severe periodontitis (34 %, n = 11) was significantly higher than in non-severe periodontitis (0 %, n = 0) (p = 0.04). Our study suggests that TGF-beta 1 SNPs (29C &gt; T) may be used as one of the risk indicators for severe periodontitis in Japanese diabetic patients.

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  • Trajectory of body mass index before the development of type 2 diabetes in Japanese men: Toranomon Hospital Health Management Center Study 15 Reviewed

    Yoriko Heianza, Yasuji Arase, Satoru Kodama, Hiroshi Tsuji, Shiro Tanaka, Kazumi Saito, Shigeko Hara, Hirohito Sone

    Journal of Diabetes Investigation   6 ( 3 )   289 - 294   2015.5

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    Aims/IntroductionWe aimed to investigate the long-term trajectory of general adiposity assessed by the body mass index (BMI) before the onset of type2 diabetes in Japanese individuals.
    Materials and MethodsWe retrospectively examined data on 1,553 Japanese men without diabetes. Mean BMI and incident cases of diabetes (diabetes indicated by fasting glucose concentrations 7.0mmol/L, a self-reported history of clinician-diagnosed diabetes, or glycated hemoglobin 6.5% (48mmol/mol) were assessed on an annual basis over a 10-year period after the baseline examination.
    ResultsMean (standard deviation) BMI at the time of diagnosis was 24.4kg/m(2) (3.1kg/m(2)) among cases of diabetes (n=191). An increasingly high BMI was associated with the early stage of the disease development, such as an 8- to 10-year prediagnosis period; individuals who developed diabetes experienced a prolonged and stable elevated BMI of 24.4kg/m(2) over the 8years before the diagnosis of diabetes. The mean BMI among the non-cases of diabetes did not exceed 23.2kg/m(2) throughout the period.
    ConclusionsThese results suggested that Japanese men who eventually developed diabetes during the 10-year observation period were not characterized as obese, but had stable high-normal BMIs before the onset of diabetes. Previous evidence showed that values for glycemic markers rapidly increased before the development of diabetes; however, the present study showed a slight gain in BMI in the earlier stage of the natural history of diabetes followed by a prolonged period of overweight.

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  • Fasting glucose and HbA1c levels as risk factors for the development of hypertension in Japanese individuals: Toranomon hospital health management center study 16 (TOPICS 16) Reviewed

    Y. Heianza, Y. Arase, S. Kodama, S. D. Hsieh, H. Tsuji, K. Saito, S. Hara, H. Sone

    Journal of Human Hypertension   29 ( 4 )   254 - 259   2015.4

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    We investigated the effect of elevated concentrations of fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c) on the risk of development of hypertension among apparently healthy Japanese. Studied were 9584 individuals without known diabetes and hypertension. During a 5-year follow-up period, 1098 individuals developed hypertension. Elevated concentrations of FPG, rather than of HbA1c, were significantly predictive of future hypertension. Compared with the lowest quartile category of FPG (&lt
    4.9 mmol l-1), the second (4.9-&lt
    5.2 mmol l-1), third (5.2-&lt
    5.6 mmol l-1) and highest (≥ 5.6 mmol l-1) quartile categories had age-, sex- and body mass index-adjusted odds ratios (95% confidence interval) of 1.35 (1.10, 1.66), 1.39 (1.13, 1.71) and 1.85 (1.51, 2.28) for hypertension, respectively. In the highest quartile of FPG, the multivariate-adjusted OR was 1.37 (1.10, 1.70) compared with the lowest quartile. Results of these adjusted models showed no significant association across quartile categories of HbA1c concentrations and an increased risk of developing hypertension. The joint effect of hyperglycemia and overweight, older age or prehypertension resulted in further elevated ORs for hypertension than the absence of such an association. Higher FPG levels rather than HbA1c were strongly predictive of future hypertension among Japanese. Hyperglycemia along with older age, overweight and prehypertension contributed to identifying individuals at increased risk of developing hypertension.

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  • Simple self-reported behavioral or psychological characteristics as risk factors for future type 2 diabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 14 Reviewed

    Yoriko Heianza, Yasuji Arase, Satoru Kodama, Hiroshi Tsuji, Kazuya Fujihara, Kazumi Saito, Shigeko Hara, Hirohito Sone

    JOURNAL OF DIABETES INVESTIGATION   6 ( 2 )   236 - 241   2015.3

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    Aims/IntroductionDepression, anger, sleep disorders and cognitive impairment are regarded as presenting a high risk for diabetes. We investigated whether responses to single statements on a self-report questionnaire on the presence of each of these four factors were associated with the development of type 2 diabetes.
    Materials and MethodsWe investigated 3,211 Japanese individuals without diabetes. Cumulative incidence rate and hazard ratios (HRs) for future type 2 diabetes over 7-13years were evaluated according to the presence of lack of perseverance, anger, memory loss or sleep disorders.
    ResultsResults of Cox regression analysis showed that lack of perseverance (age- and sex-adjusted HR 1.41, 95% confidence interval 1.07-1.84), anger, (HR 1.51, 95% confidence interval 1.07-2.12) or memory loss (HR 1.47, 95% confidence interval 1.14-1.90) was predictive of the development of diabetes. Even after adjustment for metabolic factors including glycemic measurements, anger was significantly associated with an increased risk of future diabetes. Individuals with both anger and memory loss had a 1.94-fold (95% confidence interval 1.19-3.15) increased risk of type2 diabetes than those without those two symptoms.
    ConclusionsResponses to a simple self-report questionnaire as to whether individuals were aware of anger or memory loss were associated with the development of type2 diabetes independent of traditional risk factors for diabetes in this cohort of Japanese individuals.

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  • Potential impact of joint association of alanine aminotransferase and gamma-glutamyltransferase on insulin resistance in Japan: The Toranomon Hospital Health Management Center Study 19 (TOPICS 19) Reviewed

    Yasuji Arase, Yoriko Heianza, Shigeko Hara, Yuki Ohmoto-Sekine, Kazuhisa Amakawa, Hiroshi Tsuji, Kyoko Ogawa, Kazumi Saito, Satoru Kodama, Kenji Ikeda, Hiromitsu Kumada, Tetsuro Kobayashi, Hirohito Sone

    HEPATOLOGY RESEARCH   45 ( 3 )   247 - 258   2015.3

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    AimTo investigate the potential impact of joint association of alanine aminotransferase (ALT) and -glutamyltransferase (GGT) on insulin resistance and -cell dysfunction in healthy Japanese individuals with a normal range of liver enzymes.
    MethodsThis study included 1010 individuals (545 men and 465 women) aged 20-89 years who underwent an oral glucose tolerance test for health screening. Participants were divided into four groups on the basis of median values for ALT and GGT: (i) both ALT and GGT low (both-low); (ii) ALT high and GGT low (ALT-high); (iii) ALT low and GGT high (GGT-high); and (iv) both ALT and GGT high (both-high). Logistic regression analysis was used to investigate the relationship between liver enzyme and insulin dynamics, such as Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) and insulinogenic index (IGI). The insulin resistance was defined when HOMA-IR was 2.5 or more. IGI of less than 0.4 was considered to be decreased early-phase insulin secretion.
    ResultsMean values of HOMA-IR in men was 1.5 in the both-low group, 1.8 in ALT-high, 1.8 in GGT-high and 2.8 in both-high. The mean HOMA-IR in women was 1.3 in the both-low group, 1.3 in ALT-high, 1.6 in GGT-high and 2.0 in both-high. HOMA-IR in the both-high group was significantly higher than that in the both-low group regardless of the difference of sex. Multivariate analysis showed that insulin resistance occurred when the patient had high liver enzymes.
    ConclusionCombining the two liver function markers would be effective for identifying individuals with insulin resistance.

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  • The Combination of Elevated Triglycerides and Abnormal Fasting Glucose Increases Risk of Cerebral Infarction in Patients With Mild to Moderate Hypercholesterolemia: A Post Hoc Analysis of the MEGA Study Reviewed

    Tomoko Nakagami, Rimei Nishimura, Hirohito Sone, Naoko Tajima

    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS   20 ( 2 )   169 - 173   2015.3

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    Background: While triglycerides (TGs) and diabetes increase the risk of cardiovascular disease (CVD), their combined effects have not been quantified. We explored the combined effect of elevated TGs and glucose on CVD in a post hoc analysis of the large-scale Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study. Material and Methods: In the MEGA Study, 8214 patients with mild to moderate hypercholesterolemia were randomly allocated to the diet alone group or diet plus pravastatin group and followed for 5 years. Of those, 7832 patients included in the intention-to-treat analysis were stratified into 4 groups: abnormal fasting glucose (AFG) plus high TGs, high TGs alone, AFG alone, and normal fasting glucose plus normal TGs (reference). Cox proportional hazard models were used to compare the incidence of and mortality from CVD in the 4 groups.
    Results: Incidence of CVD and coronary heart disease was significantly higher in the groups with AFG alone (hazard ratio [HR], 2.02 and 3.38; P &lt; .01, respectively) and AFG plus high TGs (HR, 2.87 and 3.87; P &lt; .01, respectively) than the reference group. A similar relation was found in models adjusting for high-density lipoprotein cholesterol (HDL-C). Although the incidence of cerebral infarction was significantly higher only in the group with AFG plus high TGs (HR, 2.16; P = .01), it was marginally significantly higher than the reference group after adjustment for HDL-C (HR, 1.86; P = .06). Diet plus pravastatin treatment reduced the risk of cerebral infarction by 66% in the group with AFG plus high TGs (P = .03).
    Conclusions: Our findings contribute to the formulation of the hypothesis that patients with hypercholesterolemia having AFG plus high TGs have an increased risk of cerebral infarction. These are compatible with the result from the main study that patients with hypercholesterolemia randomized to diet plus pravastatin had a reduced risk of cerebral infarction.

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  • Reply to: Relationship between leptin and blood pressure in patients with multiple system atrophy Reviewed

    Tetsutaro Ozawa, Hirohito Sone, Masatoyo Nishizawa

    Journal of the Neurological Sciences   348 ( 1-2 )   285   2015.1

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  • Cardioprotective Food Function as Underpinning Strategy for Disease Prevention Dietary Antioxidants in Diabetic Cardiac Complications

    Hirohito Sone

    Clinical Aspects of Functional Foods and Nutraceuticals   2015

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  • DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis.

    Kubo N, Toh H, Shirane K, Shirakawa T, Kobayashi H, Sato T, Sone H, Sato Y, Tomizawa S, Tsurusaki Y, Shibata H, Saitsu H, Suzuki Y, Matsumoto N, Suyama M, Kono T, Ohbo K, Sasaki H

    2015

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  • Circulating Malondialdehyde-Modified LDL-Related Variables and Coronary Artery Stenosis in Asymptomatic Patients with Type 2 Diabetes Reviewed

    Kazuya Fujihara, Hiroaki Suzuki, Akira Sato, Satoru Kodama, Yoriko Heianza, Kazumi Saito, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Naoya Yahagi, Hiroaki Yagyu, Hirohito Sone, Hitoshi Shimano

    JOURNAL OF DIABETES RESEARCH   2015   507245   2015

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    Aims. To elucidate the levels of malondialdehyde-modified LDL (MDA-LDL)-related variables for predicting coronary artery stenosis (CAS) by coronary CT angiography (CCTA) in asymptomatic patients with type 2 diabetes (T2DM). Methods. Enrolled were 36 Japanese patients with T2DM who underwent CCTA and in whom MDA-LDL levels were measured. Definition of CAS was luminal narrowing of &gt;= 50%. Trends through tertiles of each MDA-LDL-related variable were analyzed with a general linear model. The ability of each MDA-LDL-related variable to predict CAS was compared to areas under the curve (AUCs) in receiver operating characteristic curve (ROC) analysis. Results. Seventeen patients had CAS. Each MDA-IDL-related variable was an independent predictor of CAS (P = 0.039 for MDALDL, P = 0.013 for MDA-LDL/LDL-C, P = 0.047 for MDA-LDL/HDL-C, and P = 0.013 for (MDA-LDULDL-C)/HDL-C). AUCs of MDA-LDL, MDA-LDL/LDL-C, MDA-LDL/HDL-C, and (MDA-LDULDLC)/HDL-C were 0.675 (95% CI 0.496-0.854), 0.765 (0.602-0.927), 0.752 (0.592-0.913), and 0.799 (0.643-0.955), respectively, for predicting CAS. Trends throughout the tertiles showed significant associations between N4DA-LDL/LDL-C, N4DA-LDL/41DL-C, or (MDALDL/LDL-C)/41DL-C and CAS (P 0.003 for MDA-LDL/LDL-C, P=0.042 for MDA-LDULIDL-C, and P 0.001 for (MDA-LDULDL-C)/HDL-C). Conclusions. Data suggest that measurements of MDA-LDL/LDL-C, MDA-LDL/HDLC, and (MakLDULDL-C)/HDL-C are useful for predicting CAS.

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  • Type 1 Diabetes Mellitus and Isolated Adrenocorticotropin Deficiency Manifested by Parkinsonism: A Case Report and Literature Review Reviewed

    Nobumasa Ohara, Naoyuki Kojima, Takashi Sato, Tomoo Ikarashi, Hirohito Sone, Yutaka Oki, Kyuzi Kamoi, Masao Hara, Hideo Sasaki

    INTERNAL MEDICINE   54 ( 20 )   2629 - 2635   2015

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    A 67-year-old woman developed isolated adrenocorticotropin deficiency (IAD), which manifested as lethargy, a 20-kg body weight loss, hypoglycemia, and parkinsonism, and began corticosteroid replacement. Her symptoms resolved rapidly, and her weight returned to normal within six months. However, she then developed slowly progressive type 1 diabetes mellitus (T1D) with co-existing Hashimoto thyroiditis, and commenced insulin therapy. To our knowledge, this is the first reported case of parkinsonism associated with IAD. In addition, because diabetes mellitus, including T1D, could be latent in patients with untreated IAD, careful assessment of glucose metabolism is needed after commencing corticosteroid replacement until weight regain is achieved.

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  • Late Onset Post-Transfusion Hepatitis E Developing during Chemotherapy for Acute Promyelocytic Leukemia Reviewed

    Kyoko Fuse, Yuichi Matsuyama, Masato Moriyama, Shukuko Miyakoshi, Yasuhiko Shibasaki, Jun Takizawa, Tatsuo Furukawa, Ichiro Fuse, Hiro Matsumura, Shigeharu Uchida, Yoshifumi Takahashi, Kenya Kamimura, Hiroyuki Abe, Takeshi Suda, Yutaka Aoyagi, Hirohito Sone, Masayoshi Masuko

    INTERNAL MEDICINE   54 ( 6 )   657 - 661   2015

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    We herein report the case of a leukemia patient who developed hepatitis E seven months after undergoing a transfusion with contaminated blood products. The latency period in this case was significantly longer than that of typical hepatitis E. Recently, chronic infection with hepatitis E virus (HEV) genotype 3 has been reported in immunocompromised patients. There is a possibility that our patient was unable to eliminate the virus due to immunosuppression following chemotherapy and the administration of steroids. The prevalence of HEV in healthy Japanese individuals is relatively high and constitutes a critical source of infection via transfusion. Hepatitis E is an important post-transfusion infection, and immunocompromised patients may exhibit a long latency period before developing the disease.

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  • The factors that affect exercise therapy for patients with type 2 diabetes in Japan: a nationwide survey Reviewed

    S. Arakawa, T. Watanabe, H. Sone, Y. Tamura, M. Kobayashi, R. Kawamori, Y. Atsumi, Y. Oshida, S. Tanaka, S. Suzuki, S. Makita, I. Ohsawa, Yuzo Sato

    Diabetology International   6 ( 1 )   19 - 25   2015

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    Purpose: This study was performed to investigate important factors of exercise therapies for diabetes patients in Japan. Methods: Subjects were 5,100 patients with type 2 diabetes mellitus. Data from 3,685 patients (88.2 % effective answer rate) who answered the question whether they are performing exercise therapy or not by the questionnaire were analyzed. We used multiple logistic regression analysis to assess the factors associated with exercise therapy in diabetes patients. Results: Exercise and non-exercise therapy groups had 1,926 and 1,759 patients, respectively. The HbA1c level of the exercise therapy group was significantly lower than that in the non-exercise therapy group. The multivariate odds ratios (ORs) of possible factors affecting the exercise therapy group adjusted for age, gender, BMI and living area were as follows: frequency of exercise therapy guidance [OR = 1.89, 95 % confidence interval = 1.40–2.56
    reference group (ref.): no exercise therapy guidance], detailed exercise prescription such as type (1.32, 1.08–1.61), frequency (1.60, 1.24–2.06) and duration (1.63, 1.32–2.01
    ref.: no exercise prescription), patients who enjoy physical exercise (4.85, 2.97–7.93
    ref.: patients who dislike physical exercise) and high level of physical activity (2.31, 1.77–3.03
    ref.: low level of physical activity). Conclusion: The results of the current study showed that, concerning exercise therapy education, it is important to maintain the motivation of the patients to participate in exercise therapies, to increase the frequency of guidance, and to provide more detailed exercise prescription such as frequency and duration.

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  • Imaging of Body Iron Stores in Transfusion-Dependent Patients By Liver Dual-Energy CT Reviewed

    Hironori Kobayashi, Norihiko Yoshimura, Takashi Ushiki, Yasuhiko Shibasaki, Masato Moriyama, Jun Takizawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    BLOOD   124 ( 21 )   2014.12

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  • The circulating level of leptin and blood pressure in patients with multiple system atrophy Reviewed

    Tetsutaro Ozawa, Jun Tokunaga, Musashi Arakawa, Atsushi Ishikawa, Ryoko Takeuchi, Akio Yokoseki, Hirohito Sone, Masatoyo Nishizawa

    JOURNAL OF THE NEUROLOGICAL SCIENCES   347 ( 1-2 )   349 - 351   2014.12

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    Patients with multiple system atrophy (MSA) frequently exhibit orthostatic hypotension (OH). Leptin, an adipose-derived hormone, contributes to the sympathetic control of blood pressure (BP), and loss of leptin may cause OH. We aimed to clarify the relationship between leptin and OH in MSA. Serum leptin levels were measured in 36 patients with MSA, 25 patients with other atypical parkinsonian disorders (APDs), including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome, and 26 control subjects. Blood samples were obtained after fasting for 12 h. In MSA patients, baseline BP was measured in the recumbent position after a 3-min rest, and orthostatic changes in BP were evaluated after 0-3 min of standing. Serum leptin levels did not differ significantly between MSA patients (5.9 +/- 0.8 ng/ml), other APD patients (5.2 +/- 0.8 ng/ml), and controls (6.1 +/- 1.3 ng/ml; P = 0.8). In MSA patients, serum leptin levels correlated significantly with body mass index ( P = 0.01), but not baseline BPs (systolic BP, P = 0.20; diastolic BP, P = 0.44) or orthostatic drop in BP (systolic BP, P = 0.13; diastolic BP, P = 0.58). Our observations indicated that the circulating level of leptin was preserved, and OH occurred independent of the leptin level in MSA patients. (C) 2014 Elsevier B.V. All rights reserved.

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  • High cholesterol intake is associated with elevated risk of type 2 diabetes mellitus - A meta-analysis(1-4) Reviewed

    Ryoko Tajima, Satoru Kodama, Miho Hirata, Chika Horikawa, Kazuya Fujihara, Yoko Yachi, Sakiko Yoshizawa, Kaoruko Tada Iida, Hirohito Sone

    CLINICAL NUTRITION   33 ( 6 )   946 - 950   2014.12

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    Background & aims: Some foods rich in cholesterol are associated with high risk of type 2 diabetes (T2D). To confirm the association between dietary cholesterol intake and T2D risk, we performed a meta-analysis of observational studies.
    Methods: We searched for longitudinal studies that provided data on the relative risk (RR) for T2D in relation to the cholesterol intake level using MEDLINE (from 1950 for July 10, 2013) and EMBASE (from 1974 to July 10, 2013). The RR for the highest vs. lowest cholesterol intake category or for an increment of 100 mg/day in cholesterol consumption was pooled with an inverse-variance method.
    Results: Five studies met the inclusion criteria. Compared with the lowest category, the highest category had a significantly higher association with T2D risk (RR [95% confidence interval (CI)], 1.25 [1.16-1.36]). The pooled RR for a 100-mg/day increment was also significant (RR [95% CI], 1.11 [1.06-1.15]).
    Conclusion: Current meta-analysis suggested that high intake of cholesterol was positively associated with future T2D risk. (C) 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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  • Efficacy of HMG-CoA reductase inhibitors in the prevention of cerebrovascular attack in 1016 patients older than 75 years among 4014 type 2 diabetic individuals Reviewed

    Toshio Hayashi, Kiyoshi Kubota, Seinosuke Kawashima, Hirohito Sone, Hiroshi Watanabe, Takashi Ohrui, Koutaro Yokote, Minoru Takemoto, Atsushi Araki, Mitsuhiko Noda, Hiroshi Noto, Ichiro Sakuma, Masao Yoshizumi, Koichiro Ina, Hideki Nomura

    INTERNATIONAL JOURNAL OF CARDIOLOGY   177 ( 3 )   860 - 866   2014.12

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    Background/objectives: HMG-CoA reductase inhibitors (statins) reduce ischemic heart disease (IHD) in middle-aged diabetic individuals, and LDL-cholesterol (LDL-C) is a risk factor. However, their preventive effects on cerebrovascular attack (CVA) have not been identified in elderly, especially in elderly &gt;= 75 years (late elderly), who account for approximately 30% of diabetic individuals in Japan. Randomized controlled studies of statins for late elderly are difficult to carry out, because many co-morbidities in elderly disrupt randomized controlled conditions.
    Methods: We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) with 5.5 years of follow-up since 2004. A total of 4014 type 2 diabetic patients without previous IHD or CVA (n = 1936 women; age = 67.4 +/- 9.5 years; = 75 years: n = 1016) were enrolled, while 405 patients were registered as sub-cohort patients. We recorded detailed information on medications and laboratory data after every change in medication in patients of sub-cohort and suffered from IHD or CVA. We subdivided statin-users into prevalent, new and non-users.
    Results: A total of 104 CVAs occurred during 5.5-years. Plasma HDL-C level was inversely correlated with CVA in patients &gt;= 65 years. In case-control study, among patients who were not prescribed statins, CVA increased in age-dependent manner. CVA incidence was lower in prevalent and new statin-users than in non-users (hazard ratio [HR]: 0.46, 0.523), especially in late elderly (HR: 0.51, 0.21). Statins reduced CVAs mainly due to a direct effect and partially due to the effects of HDL-C and glucose metabolism. No significant differences were observed between statins.
    Conclusion: Statins prevented CVA in middle-aged, elderly and late elderly diabetic patients via a direct effect. This study is the first to demonstrate the usefulness of observational studies for statistically analyzing agents' effects on late elderly. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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  • Impact on short-term glycaemic control of initiating diabetes care versus leaving diabetes untreated among individuals with newly screening-detected diabetes in Japan Reviewed

    Yoriko Heianza, Akiko Suzuki, Kazuya Fujihara, Shiro Tanaka, Satoru Kodama, Osamu Hanyu, Hirohito Sone

    JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH   68 ( 12 )   1189 - 1195   2014.12

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    Background The impact of early initiation of diabetes care soon after the identification of hyperglycaemia rather than leaving diabetes untreated on changes in glycaemic control has not been fully clarified. We aimed to quantify the effect of initiating and continuing diabetes care compared with not starting management of diabetes on short-term changes in glycaemic control among the Japanese with newly screening-detected diabetes.
    Methods We retrospectively reviewed data from a nationwide claims database to assess histories of physician-diagnosed diabetes or hyperglycaemia, as well as the use of antidiabetic agents, blood testing for hyperglycaemia or dietary advice among individuals without a history of diabetes care. Changes in glycated haemoglobin (HbA1c) concentrations were evaluated using baseline data and data from a health examination during the following year.
    Results Among 1393 individuals with newly screening-detected diabetes, 62% (n=864) did not initiate diabetes management during the follow-up period; 49.2% (n=425) of the untreated group had poor glycaemic control (HbA1c =7%) at the baseline examination. Only 38% (n=529) began diabetes management in medical settings. Individuals who remained untreated had a 1.87 (95% CI 1.38 to 2.52) or 1.63 (1.10 to 2.41) times higher risk of absolute increases in HbA1c &gt;= 0.5% or &gt;= 1%, respectively, compared with the treated patients, a difference that was significant. Making more frequent clinic visits especially after the first visit was dose-dependently associated with improved HbA1c levels compared with no diabetes management.
    Conclusions In comparison with a lack of management of diabetes, immediately initiating and continuing diabetes care after identification of hyperglycaemia in a screening setting would contribute to clinically meaningful, improved glycaemic control in the Japanese.

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  • Body Mass Index and Mortality Among Japanese Patients With Type 2 Diabetes: Pooled Analysis of the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial Reviewed

    Shiro Tanaka, Sachiko Tanaka, Satoshi Iimuro, Yasuo Akanuma, Yasuo Ohashi, Nobuhiro Yamada, Atsushi Araki, Hideki Ito, Hirohito Sone

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   99 ( 12 )   E2692 - E2696   2014.12

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    Context: Previous studies on the association between body mass index (BMI) and mortality in diabetes do not necessarily provide a comprehensive view in terms of the global population because of the exclusion of individuals with a BMI less than 18.5 kg/m(2).
    Objective: The objective of the study was to examine the association between BMI and mortality.
    Design, Setting, and Participants: We analyzed pooled data from 2 cohorts of 2620 Japanese patients with type 2 diabetes followed up for 6.3 years. Patients with a history of cardiovascular disease or cancer were excluded.
    Main Outcome Measure: The end point was all-cause mortality. Hazard ratios were estimated by Cox regression adjusted for age, smoking, leisure-time physical activity, and other confounders.
    Results: An analysis using BMI categories of 14.4-18.5 (5.2%), 18.5-22.4 (37.3%), 22.5-24.9 (31.0%), and 25.0-37.5 kg/m(2) (26.6%) revealed no significant trend in mortality among patients with a BMI of 18.5 kg/m(2) or greater (trend P = .69). In contrast, the hazard ratio of patients with a BMI less than 18.5 kg/m(2) vs 22.5-24.9 kg/m(2) was 2.58 (95% confidence interval 1.38-4.84; P = .01). Exclusion of deaths in the first 4 years of follow-up decreased the hazard ratio only slightly.
    Conclusions: The lowest mortality rate was observed among patients with a BMI of 18.5-24.9 kg/m2, and obesity hadnobenefits regarding mortality. Further research is needed in lean patients, especially among aging populations in East Asia.

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  • Hepatic CREB3L3 Controls Whole-Body Energy Homeostasis and Improves Obesity and Diabetes Reviewed

    Yoshimi Nakagawa, Aoi Satoh, Sachiko Yabe, Mika Furusawa, Naoko Tokushige, Hitomi Tezuka, Motoki Mikami, Wakiko Iwata, Akiko Shingyouchi, Takashi Matsuzaka, Shiori Kiwata, Yuri Fujimoto, Hidehisa Shimizu, Hirosuke Danno, Takashi Yamamoto, Kiyoaki Ishii, Tadayoshi Karasawa, Yoshinori Takeuchi, Hitoshi Iwasaki, Masako Shimada, Yasushi Kawakami, Osamu Urayama, Hirohito Sone, Kazuhiro Takekoshi, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Naoya Yahagi, Hiroaki Suzuki, Nobuhiro Yamada, Hitoshi Shimano

    ENDOCRINOLOGY   155 ( 12 )   4706 - 4719   2014.12

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    Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism. Here, we show that CREB3L3 confers a wide spectrum of metabolic responses to starvation in vivo. Adenoviral and transgenic overexpression of nuclear CREB3L3 induced systemic lipolysis, hepatic ketogenesis, and insulin sensitivity with increased energy expenditure, leading to marked reduction in body weight, plasma lipid levels, and glucose levels. CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor(PPAR) alpha promoter in an autoloop fashion and is crucial for the ligand transactivation of PPAR alpha by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1 alpha. CREB3L3 directly and indirectly controls fibroblast growth factor 21 expression and its plasma level, which contributes at least partially to the catabolic effects of CREB3L3 on systemic energy homeostasis in the entire body. Therefore, CREB3L3 is a therapeutic target for obesity and diabetes.

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  • Log Reduction Levels of WT1 mRNA Expression in BM after Chemotherapies Are Predictive Markers of Good Prognosis in AML Patients Achieved CR after Induction Therapy Reviewed

    Yasuhiko Shibasaki, Yoshinobu Seki, Tomoyuki Tanaka, Syukuko Miyakoshi, Kyoko Fuse, Takashi Kozakai, Hironori Kobayashi, Takashi Ushiki, Takashi Abe, Toshio Yano, Masato Moriyama, Takashi Kuroha, Noriatsu Isahai, Jun Takizawa, Miwako Narita, Satoru Koyama, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

    BLOOD   124 ( 21 )   2014.12

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  • Role of sleep duration as a risk factor for Type 2 diabetes among adults of different ages in Japan: the Niigata Wellness Study Reviewed

    Y. Heianza, K. Kato, K. Fujihara, S. Tanaka, S. Kodama, O. Hanyu, K. Sato, H. Sone

    DIABETIC MEDICINE   31 ( 11 )   1363 - 1367   2014.11

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    AimTo compare the role of short sleep duration as a risk factor for diabetes among adults of different ages.
    MethodsThe study enrolled 38987 Japanese individuals without diabetes, and the 8-year risk of developing diabetes attributable to different sleep durations (&lt;5.5h, 5.5 to &lt;6.5h, 6.5 to &lt;7.0h, 7.0-7.5h, &gt;7.5-8.0h, or &gt;8.0h) was assessed among individuals aged 45, 46-59 or 60years.
    ResultsDuring the 8-year follow-up period, 2085 individuals developed diabetes. Overall, individuals with a short sleep duration of &lt;5.5h or 5.5 to &lt;6.5h had, respectively, a 1.53-fold (95% CI 1.19, 1.97) or 1.25-fold (95% CI 1.10, 1.42) increased risk of diabetes as compared with those who had 7.0-7.5h of sleep. A sleep duration of &lt;5.5h or 5.5 to &lt;6.5h was predictive of the development of diabetes among individuals aged 45years, but not among those aged 60years. With increasing age, the effect of short sleep duration on the risk of diabetes was attenuated.
    ConclusionsShort sleep duration was predictive of diabetes among young or middle-aged Japanese adults but not among elderly individuals after age was considered. Managing habitual short sleep and the possible reasons for having such short sleep duration could be particularly important for young or middle-aged adults in the development of future diabetes.

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  • Stability and Changes in Metabolically Healthy Overweight or Obesity and Risk of Future Diabetes: Niigata Wellness Study Reviewed

    Yoriko Heianza, Kiminori Kato, Satoru Kodama, Akiko Suzuki, Shiro Tanaka, Osamu Hanyu, Koji Sato, Hirohito Sone

    OBESITY   22 ( 11 )   2420 - 2425   2014.11

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    ObjectiveStability and changes in obesity and metabolic health status from a baseline period and longitudinally investigated their impact on predicting future diabetes were assessed.
    MethodsStudied were 27,478 Japanese individuals without diabetes. Metabolically healthy (MH) was indicated by having 1 among impaired fasting glucose, hypertension, hypertriglyceridemia and low HDL cholesterol concentration. Metabolically abnormal (MA) was indicated by having 2 of those metabolic abnormalities. A cut-off value of BMI 25.0 defined overweight or obesity (O) or normal weight (NW). Hazard ratio (HR) for diabetes for a 6-year period was investigated after changes in phenotypes were assessed during the previous 2 years.
    ResultsCompared with maintaining MH-NW, transitioning to MH-O from MH-NW resulted in a multivariate-adjusted HR of 1.96 (95% CI: 1.18, 3.25) for diabetes. With a stable MH-O the HR for diabetes was 2.59 (2.00, 3.34) while change from MH-O to MH-NW resulted in an HR of 1.30 (0.61, 2.76). Transitioning to MA-O from MH-O was associated with an HR of 7.09 (5.41, 9.30). With a stable MA-O the risk of diabetes was substantially elevated with an HR of 12.5 (10.5, 14.9).
    ConclusionsExamining the transitory nature of apparently benign or unhealthy obese phenotypes was effective for differentiating high-risk individuals for future diabetes.

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  • High risk of failing eradication of Helicobacter pylori in patients with diabetes: A meta-analysis Reviewed

    Chika Horikawa, Saroru Kodama, Kazuya Fujihara, Reiko Hirasawa, Yoko Yachi, Akiko Suzuki, Osamu Hanyu, Hitoshi Shimano, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   106 ( 1 )   81 - 87   2014.10

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    Aims: Eradication of Helicobacter pylori (HP) is an effective approach to improve intestinal symptoms and prevent gastric cancer. However, there has been concern that the presence of diabetes reduces the effectiveness of antibiotics. We performed this meta-analysis to investigate the effect of diabetes on the risk of failing eradication in patients with diabetes.
    Methods: An electronic literature search was conducted using Biosis, MEDLINE, Embase, PASCAL, and SciSearch through November 30, 2012. Selected studies had to provide data on the number of individuals who received treatment for HP infection and on the failure of HP eradication in groups with and without diabetes. Two authors independently extracted relevant data.
    Results: Data were obtained from 8 eligible studies (693 total participants including 273 participants with diabetes). Overall, the pooled risk ratio (RR) of failing HP eradication for diabetic patients compared with non-diabetic participants was 2.19 [95% CI, 1.65-2.90] (P &lt; 0.001). Excluding the 2 studies that used a non-standard protocol for HP eradication, individuals with diabetes had a higher risk of failure of eradication compared to those without diabetes (RR = 2.31 [95% CI, 1.72-3.11]).
    Conclusions: Current meta-analysis confirmed the higher risk of HP eradication failure in individuals with diabetes compared with those without diabetes, suggesting the necessity of prolonging treatment or developing a new regimen for HP eradication in patients with diabetes. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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  • Dietary Sodium Intake and Incidence of Diabetes Complications in Japanese Patients with Type 2 Diabetes: Analysis of the Japan Diabetes Complications Study (JDCS) Reviewed

    Chika Horikawa, Yukio Yoshimura, Chiemi Kamada, Shiro Tanaka, Sachiko Tanaka, Osamu Hanyu, Atsushi Araki, Hideki Ito, Akira Tanaka, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   99 ( 10 )   3635 - 3643   2014.10

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    Context: Many guidelines recommend that patients with type 2 diabetes should reduce their dietary sodium intake. However, the relationship between dietary sodium intake and incidence of diabetic complications in patients with type 2 diabetes has not been explored.
    Objective: Our objective was to investigate the relationship between dietary sodium intake and incidence of diabetes complications.
    Participants: The study was of a nationwide cohort of patients with type 2 diabetes aged 40 to 70 years with hemoglobin A1c (HbA1c) &gt;= 6.5%.
    Main Outcome Measures: After excluding nonresponders to a dietary survey, 1588 patients were analyzed. Baseline dietary intake was assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to cardiovascular disease (CVD), overt nephropathy, diabetic retinopathy, and all-cause mortality.
    Results: Mean daily dietary sodium intake in quartiles ranged from 2.8 to 5.9 g. After adjustment for confounders, hazard ratios for CVD in patients in the second, third, and fourth quartiles of sodium intake compared with the first quartile were 1.70 (95% confidence interval, 0.98-2.94), 1.47 (0.82-2.62), and 2.07 (1.21-3.90), respectively (trend P &lt; .01). In addition, among patients who had HbA1c &gt;= 9.0%, the hazard ratio for CVD in patients in the top vs bottom quartile of sodium in take was dramatically elevated compared with patients with HbA1c &lt;9.0% (1.16 [0.56-2.39] and 9.91 [2.66-36.87], interaction P &lt; .01). Overt nephropathy, diabetic retinopathy, and all-cause mortality were not significantly associated with sodium intake.
    Conclusions: Findings suggested that high dietary sodium intake is associated with elevated incidence of CVD in patients with type 2 diabetes and that there is a synergistic effect between HbA1c values and dietary sodium intake for the development of CVD.

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  • Importance of high-density lipoprotein cholesterol levels in elderly diabetic individuals with type IIb dyslipidemia: A 2-year survey of cardiovascular events Reviewed

    Koichiro Ina, Toshio Hayashi, Atsushi Araki, Seinosuke Kawashima, Hirohito Sone, Hiroshi Watanabe, Takashi Ohrui, Koutaro Yokote, Minoru Takemoto, Kiyoshi Kubota, Mitsuhiko Noda, Hiroshi Noto, Qun-Fang Ding, Jie Zhang, Ze-Yun Yu, Byung-Koo Yoon, Hideki Nomura, Masafumi Kuzuya

    GERIATRICS & GERONTOLOGY INTERNATIONAL   14 ( 4 )   806 - 810   2014.10

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    AimThe risk factors for ischemic heart disease (IHD) or cerebrovascular accident (CVA) in elderly diabetic individuals with type IIb dyslipidemia are not fully known. Therefore, we investigated the relationship between lipid levels and IHD and CVA in diabetic individuals with type IIb dyslipidemia.
    MethodThe Japan Cholesterol and Diabetes Mellitus Study is a prospective cohort study of 4014 type 2 diabetic patients (1936 women; age 67.49.5 years). The primary end-points were the onset of IHD or CVA. Lipid and glucose levels, and other factors were investigated in relation to the occurrence of IHD or CVA. A total of 462 participants were included in the group of patients with type IIb dyslipidemia.
    ResultsThe 462 diabetic participants with type IIb dyslipidemia were divided into those who were aged &lt;65 years, 65-74 years and &gt;75 years (n=168, 190 and 104, respectively). High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol/HDL-C were significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged &lt;65 years, and HDL-C and diastolic blood pressure was significantly associated with cardiovascular events in patients aged 65-74 years. Non-HDL-C was not significantly associated with the risk of cardiovascular events. Multiple regression analysis showed that lower HDL-C was significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged &lt;65 years and 65-74 years.
    ConclusionsLower HDL-C was an important risk factor for cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged &lt;75 years. Geriatr Gerontol Int 2014; 14: 806-810.

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  • A possible link between BDNF and mTOR in control of food intake Reviewed

    Nobuyuki Takei, Kazuo Furukawa, Osamu Hanyu, Hirohito Sone, Hiroyuki Nawa

    FRONTIERS IN PSYCHOLOGY   5   1093   2014.9

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    Food intake is intricately regulated by glucose, amino acids, hormones, neuropeptides, and trophic factors through a neural circuit in the hypothalamus. Brain-derived neurotrophic factor (BDNF), the most prominent neurotrophic factor in the brain, regulates differentiation, maturation, and synaptic plasticity throughout life. Among its many roles, BDNF exerts an anorexigenic function in the brain. However, the intracellular signaling induced by BDNF to control food intake is not fully understood. One candidate for the molecule involved in transducing the anorexigenic activity of BDNF is the mammalian target of rapamycin (mTOR). mTOR senses extracellular amino acids, glucose, growth factors, and neurotransmitters, and regulates anabolic reactions response to these signals. Activated mTOR increases protein and lipid synthesis and inhibits protein degradation. In the hypothalamus, mTOR activation is thought to reduce food intake. Here we summarize recent findings regarding BDNF- and mTOR-mediated feeding control, and propose a link between these molecules in eating behavior.

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  • Second trimester postload glucose level as an important predictor of low birth weight infants: Tanaka Women's Clinic Study Reviewed

    Yoko Yachi, Yasuhiro Tanaka, Izumi Nishibata, Sakiko Yoshizawa, Kazuya Fujihara, Satoru Kodama, Akiko Suzuki, Osamu Hanyu, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   105 ( 3 )   E16 - E19   2014.9

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    Although it is well known that the maternal prepregnancy BMI is a strong contributor to fetal growth, our results showed that a low postload glucose level, although within normal range, independent of maternal BMI was strongly associated with an increased risk of low birth weight births among Japanese mothers. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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  • Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice Reviewed

    Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Mayumi Nomoto, Hirohito Sone, Kenji Suzuki, Kenichi Watanabe

    NEUROSCIENCE LETTERS   579   134 - 139   2014.9

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    BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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  • Activation of the Leukemia Plasmacytoid Dendritic Cell Line PMDC05 by Toho-1, a Novel IDO Inhibitor Reviewed

    Akie Yamahira, Miwako Narita, Minami Iwabuchi, Takayoshi Uchiyama, Shunpei Iwaya, Rie Ohiwa, Yoshinori Nishizawa, Takafumi Suzuki, Yusaku Yokoyama, Shigeo Hashimoto, Jun Takizawa, Hirohito Sone, Masuhiro Takahashi

    ANTICANCER RESEARCH   34 ( 8 )   4021 - 4028   2014.8

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    Background/Aim: Indoleamine-2,3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan metabolism and plays an immunosuppressive role. Antigen-presenting cells, when activated, increase the expression of IDO, which results in the suppression of subsequent immune reaction. A novel IDO inhibitor, Toho-1, was explored for its applicability to immunotherapy. Materials and Methods: We investigated the effects of Toho-1 on antigen presentation and antigen-specific cytotoxic T-lymphocyte-inducing ability of leukemia plasmacytoid dendritic cell line PMDC05, which was established in our laboratory. Results: While antigen presentation-associated molecules in PMDC05 cells were increased by stimulation with lipopolysaccharide and interferon-gamma, IDO mRNA and protein expression were also enhanced. Such treatment of PMDC05 cells in combination with Toho-1 enhanced the antigen-presenting and CTL-inducing ability of PMDC05 cells. Conclusion: These findings suggest the ability of Toho-1 to potentiate antigen-presenting cells and its applicability in immunotherapy of cancer.

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  • Metabolically Healthy Obesity, Presence or Absence of Fatty Liver, and Risk of Type 2 Diabetes in Japanese Individuals: Toranomon Hospital Health Management Center Study 20 (TOPICS 20) Reviewed

    Yoriko Heianza, Yasuji Arase, Hiroshi Tsuji, Kazuya Fujihara, Kazumi Saito, Shiun Dong Hsieh, Shiro Tanaka, Satoru Kodama, Shigeko Hara, Hirohito Sone

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   99 ( 8 )   2952 - 2960   2014.8

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    Objective: We investigated whether the metabolically healthy obese (MHO) phenotype was associated with an increased risk of the development of diabetes. If so, we aimed to determine what factors could explain this finding.
    Design, Setting, and Participants: Studied were 8090 Japanese individuals without diabetes. Metabolic health status was assessed by common clinical markers: blood pressure, triglycerides, high-density lipoprotein-cholesterol, and fasting glucose concentrations. The cutoff value for obesity or normal weight (NW) was a body mass index of 25.0 kg/m(2).
    Results: The 5-year incidence rate of diabetes was 1.2% (n = 58 of 4749) in metabolically healthy NW (MHNW) individuals, 2.8% (n = 20 of 719) in MHO individuals, 6.0% (n = 102 of 1709) in metabolically abnormalNWindividuals, and 10.3%(n = 94 of 913) in metabolically abnormal obese individuals. Although MHO individuals had no or one metabolic factor, 47.8% had ultrasonographic fatty liver (FL). The MHO group had a significantly increased risk of diabetes compared with the MHNW group [multivariate adjusted odds ratio (OR) 2.23 (95% confidence interval [CI] 1.33, 3.75)], but this risk was attenuated after adjustment for FL. Compared with the MHNW/non-FL group, the risk of diabetes in the MHO/non-FL group was not significantly elevated [OR 1.01 (95% CI 0.35, 2.88)]. However, the MHO/FL and MHNW/FL groups had similarly elevated risks of diabetes [OR 4.09 (95% CI 2.20, 7.60) and 3.16 (1.78, 5.62), respectively].
    Conclusions: Almost half of the MHO participants had FL, which partially explained the increased risk of diabetes among the obese phenotypes. The presence of FL should be evaluated to assess whether an individual was actually in a metabolically benign state for the prediction of diabetes.

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  • Cohort Profile: The Japan Diabetes Complications Study: a long-term follow-up of a randomised lifestyle intervention study of type 2 diabetes Reviewed

    Shiro Tanaka, Sachiko Tanaka, Satoshi Iimuro, Hidetoshi Yamashita, Shigehiro Katayama, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

    INTERNATIONAL JOURNAL OF EPIDEMIOLOGY   43 ( 4 )   1054 - 1062   2014.8

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    The Japan Diabetes Complications Study, a randomised lifestyle intervention study of type 2 diabetes conducted at 59 institutes throughout Japan that enrolled 2033 eligible patients from January 1995 to March 1996, was directed at: (i) determining the incidence and progression rates of complications of diabetes; (ii) exploring clinical risk factors for complications of diabetes; and (iii) determining the association between lifestyle factors, including diet and physical activity, and complications of diabetes, in addition to comparing, in a randomised manner, the effects on type 2 diabetes of an extensive lifestyle intervention and conventional treatment. The protocol for the study originally specified four study populations according to primary outcomes, consisting of: (1) a macroangiopathy group (N = 1771); (ii) a nephropathy group (N = 1607); (iii) a retinopathy-incident group (N = 1221); and (iv) a retinopathy-progression group (N = 410). The primary outcomes were: (i) development of retinopathy; (ii) progression of retinopathy; (iii) development of overt nephropathy; and (iv) occurrence of macroangiopathic events including proven coronary heart disease and stroke. The study was originally planned to follow patients for 8 years, and an extended follow-up is ongoing. Information about primary outcomes, laboratory tests, and other clinical variables for each patient was collected at a central data centre through an annual report from each investigator. Additionally, extensive lifestyle surveys were conducted at baseline and 5 years after the beginning of the study intervention in both the intervention and conventional treatment groups. A description of the occurrence of complications of diabetes and of all-cause mortality, provided in this paper, demonstrated a clear gender-based difference in cardiovascular disease and all-cause mortality. The data set of the study is not freely available, but collaborative ideas are welcome. Potential collaborators should discuss ideas informally with the principal investigator by e-mail.

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  • Role of Body Mass Index History in Predicting Risk of the Development of Hypertension in Japanese Individuals Toranomon Hospital Health Management Center Study 18 (TOPICS 18) Reviewed

    Yoriko Heianza, Satoru Kodama, Yasuji Arase, Shiun Dong Hsieh, Sakiko Yoshizawa, Hiroshi Tsuji, Kazumi Saito, Shiro Tanaka, Shigeko Hara, Hirohito Sone

    HYPERTENSION   64 ( 2 )   247 - +   2014.8

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    It has not been clarified whether overall adiposity in early adulthood or at the lifetime maximum weight would confer a residual risk of hypertension after considering the risk associated with current adiposity. Studied were 6121 Japanese without hypertension. The risk of developing hypertension 4 years after a baseline examination was investigated using the body mass index in the early 20s, at the lifetime maximum, or at the baseline examination. An elevated body mass index at baseline or at the maximum rather than in the early 20s was strongly associated with future hypertension. Compared with individuals with low body mass index both at baseline and in the early 20s, those with an elevated body mass index at the baseline alone had an odds ratio of 1.89 (95% confidence interval, 1.58-2.27) and those with an elevated body mass index both at baseline and in the early 20s had the highest odds ratio of 2.26 (1.76-2.89). Individuals with an elevated body mass index both at baseline and at the maximum had a 2.26-fold (1.87-2.72) increased risk of hypertension compared with those without the 2 factors. An elevated body mass index at the baseline examination weakened the favorable influence of a low body mass index in early adulthood on developing hypertension. Adding information on body mass index in early adulthood or at the maximum in addition to that at the baseline examination contributed to differentiating the risk of hypertension among Japanese, particularly among those with an elevated overall adiposity at present.

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  • [Successful treatment with bortezomib in a patient with systemic primary AL amyloidosis manifesting severe gastrointestinal bleeding]. Reviewed

    Ida T, Hayashi K, Ida T, Hirano S, Nakamura F, Sone H, Fujiwara M

    [Rinsho ketsueki] The Japanese journal of clinical hematology   55 ( 7 )   808 - 814   2014.7

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    We present a systemic primary AL amyloidosis patient with severe gastrointestinal bleeding for whom treatment with bortezomib and dexamethasone was very effective. An 83-year-old woman was admitted to our hospital suffering from multiple gastric ulcers with bleeding. She had monoclonal protein (IgG, λ) in her serum. Systemic primary AL amyloidosis was diagnosed. She was also suspected of having amyloid deposition in cardiac muscle, as well as her bladder and intestinal mucosa. However, we were unable to carry out other invasive examinations due to her bleeding tendency. She was treated with bortezomib and dexamethasone. Her bleeding tendency gradually diminished. After one year, the bleeding tendency had completely resolved. However, she still had amyloid deposition in her gastric mucosa and skin.

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  • Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion Reviewed

    Nie Tang, Takashi Matsuzaka, Marii Suzuki, Yuta Nakano, Hui Zao, Tomotaka Yokoo, Noriko Suzuki-Kemuriyama, Motoko Kuba, Yuka Okajima, Yoshinori Takeuchi, Kazuto Kobayashi, Hitoshi Iwasaki, Shigeru Yatoh, Akimitsu Takahashi, Hiroaki Suzuki, Hirohito Sone, Masako Shimada, Yoshimi Nakagawa, Naoya Yahagi, Nobuhiro Yamada, Hitoshi Shimano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   450 ( 1 )   318 - 323   2014.7

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    ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids and is related to the development of obesity-induced insulin resistance via the modification of the fatty acid composition. In this study, we investigated the role of systemic Elovl6 in the pancreatic islet and beta-cell function. Elovl6 is expressed in both islets and beta-cell lines. In mice fed with chow, islets of the Elovl6(-/-) mice displayed normal architecture and beta-cell mass compared with those of the wild-type mice. However, when fed a high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin resistance observed in normal mice was attenuated and glucose-stimulated insulin secretion (GSIS) increased in the islets of Elovl6(-/-) mice compared with those of the wild-type mice. Enhanced GSIS in the HFHS Elovl6-/- islets was associated with an increased ATP/ADP ratio and the suppression of ATF-3 expression. Our findings suggest that Elovl6 could be involved in insulin secretory capacity per beta-cell and diabetes. (C) 2014 Elsevier Inc. All rights reserved.

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  • Food groups and weight gain in Japanese men.

    Ibe Y, Takahashi Y, Sone H

    2014.6

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  • Commentary on the United Kingdom Prospective Diabetes Study outcomes model 2: Need for long-term follow up and quality of life data in Asian patients Reviewed

    Shiro Tanaka, Sachiko Tanaka, Hirohito Sone

    JOURNAL OF DIABETES INVESTIGATION   5 ( 3 )   281 - 283   2014.5

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    DOI: 10.1111/jdi.12207

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  • Meta-Analysis of the Quantitative Relation Between Pulse Pressure and Mean Arterial Pressure and Cardiovascular Risk in Patients With Diabetes Mellitus Reviewed

    Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Sakiko Yoshizawa, Yoko Yachi, Shiro Tanaka, Nobumasa Ohara, Satoshi Matsunaga, Takaho Yamada, Osamu Hanyu, Hirohito Sone

    AMERICAN JOURNAL OF CARDIOLOGY   113 ( 6 )   1058 - 1065   2014.3

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    Results of epidemiologic studies that investigated the significance of pulse pressure (PP) and mean arterial pressure (MAP) in terms of risk of cardiovascular disease (CVD) in patients with diabetes mellitus are inconsistent. We performed a quantitative meta-analysis to estimate CVD risk in relation to PP or MAP. Electronic literature search was conducted for prospective studies providing data on CVD risk for an increment in baseline MAP or PP in patients with diabetes mellitus. The pooled CVD risk for a 10-mm Hg increase in each blood pressure (BP) index was estimated with a random-effects model. There were 17 eligible studies consisting of 52,647 patients and 5,112 CVD cases. The pooled relative risk (95% confidence interval) of CVD for an increment of 10 mm Hg was 1.10 (1.04 to 1.16) for PP and 1.09 (0.98 to 1.21) for MAP. Significant between-study heterogeneity was observed (I-2 [p value]; 76.5% [p &lt; 0.001] for PP, 67.8% [p = 0.005] for MAP). In studies concurrently investigating CVD risk for the 4 indexes (i.e., PP, MAP, systolic BP, and diastolic BP), the pooled relative risk (95% confidence interval) was 1.17 (1.09 to 1.26) for PP, 1.11 (1.06 to 1.15) for MAP, 1.14 (1.06 to 1.22) for systolic BP, and 1.06 (0.94 to 1.19) for diastolic BP. In conclusion, the current meta-analysis suggested that PP was the strongest indicator among the 4 commonly used BP indexes. However, the large heterogeneity urged cautious interpretation of the study results. (c) 2014 Elsevier Inc. All rights reserved.

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  • Quantitative relationship between body weight gain in adulthood and incident type 2 diabetes: a meta-analysis Reviewed

    S. Kodama, C. Horikawa, K. Fujihara, S. Yoshizawa, Y. Yachi, S. Tanaka, N. Ohara, S. Matsunaga, T. Yamada, O. Hanyu, H. Sone

    OBESITY REVIEWS   15 ( 3 )   202 - 214   2014.3

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    This meta-analysis quantified the risk of type 2 diabetes mellitus (T2DM) preceded by body weight (BW) gain in the general population. Systematic literature searches retrieved 15 eligible studies. The BW gain was divided into early weight-gain, which was defined as BW gain from early adulthood (18-24 years of age) to cohort entry (&gt;= 25 years of age), and late weight-gain, which was defined as BW gain from cohort entry. The pooled relative risk (RR; 95% confidence interval [CI]) of T2DM for an increment of BW gain standardized into a 5-kg m(-2) increment in the body mass index (BMI) was 3.07 (2.49-2.79) for early weight-gain and 2.12 (1.74-2.58) for late weight-gain. When limiting analysis to studies that concurrently examined T2DM risk for current BMI (defined in both groups as BMI at cohort entry), a larger magnitude of T2DM risk was revealed for early weight-gain compared with current BMI (RR [95% CI], 3.38 [2.20-5.18] vs. 2.39 [1.58-3.62]), while there was little difference between late weight-gain (RR [95% CI], 2.21 [1.91-2.56]) and current BMI (RR [95% CI], 2.47 [1.97-3.30]). The meta-analysis suggested that BW gain was a quantifiable predictor of T2DM, as well as current obesity in adults. Particularly, BW gain in early rather than middle-to-late adulthood played an important role in developing T2DM.

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  • Dietary intake in Japanese patients with type 2 diabetes: Analysis from Japan Diabetes Complications Study Reviewed

    Chika Horikawa, Yukio Yoshimura, Chiemi Kamada, Shiro Tanaka, Sachiko Tanaka, Akane Takahashi, Osamu Hanyu, Atsushi Araki, Hideki Ito, Akira Tanaka, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

    JOURNAL OF DIABETES INVESTIGATION   5 ( 2 )   176 - 187   2014.3

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    Aims/IntroductionThough there are many differences in dietary habits and in the metabolic basis between Western and Asian people, the actual dietary intake in Asian patients with diabetes has not been investigated in a nationwide setting, unlike in Western countries. We aimed to clarify dietary intake among Japanese individuals with type 2 diabetes, and identify differences in dietary intake between Japanese and Western diabetic patients.
    Materials and MethodsNutritional and food intakes were surveyed and analyzed in 1,516 patients with type 2 diabetes aged 40-70years from outpatient clinics in 59 university and general hospitals using the food frequency questionnaire based on food groups (FFQg).
    ResultsMean energy intake for all participants was 1737412kcal/day, and mean proportions of total protein, fat, and carbohydrate comprising total energy intake were 15.7, 27.6 and 53.6%, respectively. They consumed a low-fat energy-restricted diet' compared with Western diabetic patients, and the proportion of fat consumption was within the suggested range that has been traditionally recommended in Western countries. As a protein source, consumption of fish (100g) and soybean products (71g) was larger than that of meat (50g) and eggs (29g). These results imply that dietary content and food patterns among Japanese patients with type 2 diabetes are quite close to those reported as suitable for prevention of obesity, type 2 diabetes, cardiovascular disease, and total mortality in Europe and America.
    ConclusionsA large difference was shown between dietary intake by Japanese and Western patients. These differences are important to establish ethnic-specific medical nutrition therapy for diabetes.

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  • Efficacy of Habitual Exercise for Improving Lipid Profiles Depends on the PPRA gamma Genotype in Japanese Males Reviewed

    Yasuko Sone, Reiko Hirasawa, Ikuyo Ichi, Tomoko Isbikawa, Satoru Kodama, Hirohito Sone, Shigenobu Egawa, Kazuo Kawahara, Yuzuru Otsuka, Yoko Fujiwara

    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY   60 ( 1 )   66 - 70   2014.2

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    Peroxisome proliferator-activated receptor gamma (PPAR gamma) responds to thiazolidinedione derivatives, which are ligands of PPAR gamma, and affects insulin resistance. Recently, a PPAR gamma study reported that in high-fat-diet-induced obesity, the phosphorylation of PPAR gamma prevented the transcription of specific PPAR gamma targets that have anti-obesity effects. We previously reported that genetic variants of the fatty acid desaturase were associated with plasma lipid profiles and could contribute to dyslipidemia in Japanese males. The aim of this study was to investigate the anti-obesity effects of PPAR gamma variants on lipid profiles. One hundred and thirty-eight (138) Japanese males participated in the study. Their serum lipid markers and the fatty acid composition of their red blood cell (RBC) membranes were determined. The stearoyl-CoA desaturase 1 (SCD1) indices were represented as the fatty acid product : precursor ratios. The participants were genotyped for the single-nucleotide polymorphism rs2938392 in the PPAR gamma gene. The participants' fitness habits were also surveyed by questionnaire. The effects of habitual exercise on the measured lipid parameters were compared in each genotype group. No association between the genotypes in the PPAR gamma gene and the biochemical data was found. However, the serum triglyceride levels and the SCD1 indices in RBC membranes were significantly higher in the participants who carried the major rs2938392 allele (A/A) and did not habitually exercise than in those who did exercise. These findings indicate that the risk for detrimental lipid profiles in the absence of habitual exercise depends on the PPAR gamma genotype in Japanese males.

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  • Hypertension increases urinary excretion of immunoglobulin G, ceruloplasmin and transferrin in normoalbuminuric patients with type 2 diabetes mellitus Reviewed

    Nobumasa Ohara, Osamu Hanyu, Satoshi Hirayama, Osamu Nakagawa, Yoshifusa Aizawa, Seiki Ito, Hirohito Sone

    JOURNAL OF HYPERTENSION   32 ( 2 )   432 - 438   2014.2

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    Objective:Increased urinary excretion of certain plasma proteins, such as immunoglobulin G (IgG), ceruloplasmin and transferrin, with different molecular radii of 55 angstrom or less and different isoelectric points have been reported to precede development of microalbuminuria in patients who have diabetes mellitus with hypertension. We examined how hypertension affects these urinary proteins in a diabetic state.Methods:Excretion of IgG, ceruloplasmin, transferrin, albumin, 2-macroglobulin with a large molecular radius of 88 angstrom and N-acetylglucosaminidase in first-morning urine samples were measured in normoalbuminuric patients (urinary albumin-to-creatinine ratio&lt;15mg/g) with hypertension and nondiabetes mellitus (group hypertension, n=32), type 2 diabetes mellitus and normotension (group diabetes mellitus, n=52) and type 2 diabetes mellitus and hypertension (group Both, n=45), and in age-matched controls (n=72).Results:Urinary IgG, ceruloplasmin, transferrin, albumin and N-acetylglucosaminidase and estimated glomerular filtration rate (eGFR) were significantly elevated in groups diabetes mellitus and Both compared with controls. Furthermore, urinary IgG, ceruloplasmin and transferrin in group Both were significantly higher than those in group diabetes mellitus. These exhibited a positive and relatively strong association with eGFR compared with controls. No significant difference in urinary albumin or N-acetylglucosaminidase was found between the two diabetic groups. In contrast, group hypertension had elevated urinary transferrin without any changes in the other compounds. Urinary 2-macroglobulin did not differ among the four groups.Conclusion:These findings suggest that normoalbuminuric diabetic patients without hypertension have both glomerular hemodynamic changes such as increased intraglomerular hydraulic pressure and altered proximal tubules, and that hypertension increases intraglomerular hydraulic pressure. Increased urinary IgG, ceruloplasmin and transferrin may reflect an increase in intraglomerular hydraulic pressure.

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  • Reversible brain atrophy and cognitive impairment in an adolescent Japanese patient with primary adrenal Cushing's syndrome. Reviewed International journal

    Nobumasa Ohara, Hiroshi Suzuki, Akiko Suzuki, Masanori Kaneko, Masahiro Ishizawa, Kazuo Furukawa, Takahiro Abe, Yasuhiro Matsubayashi, Takaho Yamada, Osamu Hanyu, Takayoshi Shimohata, Hirohito Sone

    Neuropsychiatric disease and treatment   10   1763 - 7   2014

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    Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

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  • Early Diagnosis of Hepatic Intravascular Lymphoma: A Case Report and Literature Review Reviewed

    Hiroyuki Abe, Kenya Kamimura, Maiko Mamizu, Yasuhiko Shibazaki, Takanobu Ishiguro, Shin-ichi Katada, Yu-ki Nishiyama, Yoshifumi Takahashi, Yu-ya Hatano, Ken-ichi Mizuno, Yukari Watanabe, Aiko Nagashima, Jun Takizawa, Manabu Takeuchi, Hirokazu Kawai, Minoru Nomoto, Hirohito Sone, Masatoyo Nishizawa, Yutaka Aoyagi

    INTERNAL MEDICINE   53 ( 6 )   587 - 593   2014

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    Hepatic intravascular large B-cell lymphoma (IVL) is a rare disease entity that involves invasion into various organs. Due to the aggressive behavior and poor prognosis of the disease and the difficulty in making an early diagnosis, some cases are diagnosed at autopsy. Early suspicion and the use of imaging studies and liver biopsies are key for diagnosing IVL; however, no reports have described the results of imaging studies due to the limited number of cases. We herein report the results of imaging studies of hepatic IVL, including the findings PET-CT, dynamic-CT, EOB-MRI and CEUS. These results may help physicians to make an early diagnosis and improve the prognosis.

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  • Comparison of the Framingham Risk Score, UK Prospective Diabetes Study (UKPDS) Risk Engine, Japanese Atherosclerosis Longitudinal Study-Existing Cohorts Combine (JALS-ECC) and Maximum Carotid Intima-Media Thickness for Predicting Coronary Artery Stenosis in Patients with Asymptomatic Type 2 Diabetes Reviewed

    Kazuya Fujihara, Hiroaki Suzuki, Akira Sato, Tomoko Ishizu, Satoru Kodama, Yoriko Heianza, Kazumi Saito, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Naoya Yahagi, Hirohito Sone, Hitoshi Shimano

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   21 ( 8 )   799 - 815   2014

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    Aims: To compare the efficacy of Framingham Risk Score (FRS), UK Prospective Diabetes Study (UKPDS) risk engine, a risk score based on the Japanese Atherosclerosis Longitudinal Study-Existing Cohorts Combine (JALS-ECC), the maximum intima-media thickness (max-IMT) determined on coronary computed tomography angiography (CCTA) and their combination in asymptomatic patients with type 2 diabetes.
    Methods: A total of 116 Japanese patients with type 2 diabetes underwent CCTA. The risk of coronary heart disease was calculated according to the FRS, UKPDS and JALS-ECC. We evaluated the reclassification of coronary artery stenosis (CAS) based on the risk score categories after adding each IMT related variable.
    Results: Sixty-eight patients had CAS. The areas under the curves (AUCs) in the receiver operating characteristic curve analyses of FRS, UKPDS and JALS-ECC were 0.763 (95% confidence interval [CI]: 0.674-0.853), 0.785 (95% CI: 0.703-0.868) and 0.767 (95% CI: 0.681-0.853), respectively. The AUCs for FRS, UKPDS and JALS-ECC combined with the max-IMT were 0.788 (95% CI: 0.705-0.872), 0.800 (95% CI: 0.720-0.879) and 0.786 (95% CI: 0.703-0.869), respectively. Combining the max-IMT with the risk scores improved the identification of subjects with stenotic lesions, in particular, those in the first, second and third tertiles of the FRS, first and second tertiles of the UKPDS and first and second tertiles of the JALS-ECC (P=0.054, P=0.056, P=0.015, P=0.082, P=0.060, P=0.007, and P=0.080, respectively). The net reclassification improvement increased following the addition of a max-IMT of &gt;= 1.9 mm (32.4% in FRS, 19.9% in UKPDS and 51.7% in JALS-ECC).
    Conclusions: These data suggest that combining a risk score with the max-IMT improves the prediction of CAS in comparison with the risk score alone.

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  • Relationship between a Low Ankle Brachial Index and All-Cause Death and Cardiovascular Events in Subjects with and without Diabetes Reviewed

    Hiroki Yokoyama, Hirohito Sone, Jun Honjo, Shinichiro Okizaki, Daishiro Yamada, Ryushi Shudo, Hitoshi Shimizu, Tatsumi Moriya, Masakazu Haneda

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   21 ( 6 )   574 - 581   2014

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    Aims: The association between a low ankle brachial index (ABI) and mortality and vascular morbidity in Japanese individuals with diabetes and the independence of this association from other risk factors have not yet been examined in the primary care setting among a large number of patients.Methods: An observational prospective cohort study was performed among 3,004 Japanese individuals (2,598 patients with diabetes) to examine all-cause death and cardiovascular disease (CVD) in relation to low ABI (< 0.9) values and other risk factors.Results: Low ABI values were found in 127 subjects (4.2%) and was associated with smoking, diabetes, hypertension, pulse pressure, glycosylated hemoglobin A(1C), lipid profiles, glomerular filtration rate, uric acid and prevalent CVD at baseline. Over 13,242 person-years, 93 deaths and 117 cases of CVD occurred. In a multivariate Cox regression analysis, the hazard ratio for low-normal ABI values was 3.97 (95% CI, 2.29 to 6.88) for all-cause death and 2.86 (95% CI, 1.83-4.49) for fatal and non-fatal CVD and all-cause death. Similar hazard ratios were found when the subjects were confined to those with diabetes. All risk analyses indicated that age, a low ABI, diabetes, a history of CVD and smoking remained significantly and independently predictive of CVD and all-cause death.Conclusions: A low ABI exhibits significant cross-sectional associations with conventional risk factors and further more with the glomerular filtration rate, uric acid level and presence of prevalent CVD at baseline, and a low ABI independently predicts subsequent death and cardiovascular events. These findings support the concept that a low ABI is an integrated marker of an excess risk of death and cardiovascular events, independent of conventional risk factors.

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  • Weight Loss Maintenance for 2 Years after a 6-Month Randomised Controlled Trial Comparing Education-Only and Group-Based Support in Japanese Adults Reviewed

    Yoshio Nakata, Masafumi Okada, Koichi Hashimoto, Yoshinori Harada, Hirohito Sone, Kiyoji Tanaka

    OBESITY FACTS   7 ( 6 )   376 - 387   2014

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    Objective: Our previous study, a 6-month randomised controlled trial, demonstrated that a group based support promoted weight loss as compared to an education only intervention. The purpose of this study was to examine weight loss maintenance for 2 years. Methods: Originally, 188 overweight Japanese adults, aged 40-65 years, were randomly assigned to 3 groups: control, education only or group based support. After the 6-month intervention, 125 participants in the education-only and the group-based support groups were followed up for 2 years. The primary outcome was the amount of weight lost. The participants were retrospectively grouped into quartiles of percent weight loss for secondary analyses. Results: At the end of follow-up, the amount of weight lost in the education only and the group based support groups was the same (3.3 kg). Secondary analyses using data of those who completed the study (n = 100) revealed that the participants in the highest quartile of percent weight loss significantly increased their step counts and moderate-to-vigorous physical activity compared with the lowest quartile. No significant differences were observed in the energy intake among the four groups. Conclusion: The effects of group based support disappear within 2 years. Increasing physical activity may be a crucial factor for successful maintenance of weight loss. (C) 2014 S. Karger GmbH, Freiburg

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  • Manifestations of Fulminant CD8 T-cell Post-transplant Lymphoproliferative Disorder Following the Administration of Rituximab for Lymphadenopathy with a High Level of Epstein-Barr Virus (EBV) Replication after Allogeneic Hematopoietic Stem Cell Transplantation Reviewed

    Tomoyuki Tanaka, Jun Takizawa, Shukuko Miyakoshi, Takashi Kozakai, Kyoko Fuse, Yasuhiko Shibasaki, Masato Moriyama, Koichi Ohshima, Ken Toba, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

    INTERNAL MEDICINE   53 ( 18 )   2115 - 2119   2014

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    We herein report the case of a 22-year-old woman with severe aplastic anemia who underwent allogeneic hematopoietic stem cell transplantation (HSCT). After HSCT, the Epstein-Barr virus (EBV)-DNA load in the peripheral blood gradually increased, and the patient presented with a fever and lymphadenopathy on day 56 post-HSCT. Although we administered rituximab, her clinical condition worsened. After rituximab treatment, CD8 T-cells emerged and became dominant in the peripheral blood, some of which were positive on an EBV-specific tetramer analysis. However, an open biopsy of the lymphadenopathy lesions revealed the CD8 T-cells to be infected with EBV, exhibiting proliferation with oligoclonality. The patient ultimately died of multiple organ failure on day 99 post-HSCT.

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  • Association of Helicobacter pylori Infection with Glycemic Control in Patients with Diabetes: A Meta-Analysis Reviewed

    Chika Horikawa, Satoru Kodama, Kazuya Fujihara, Yoko Yachi, Shiro Tanaka, Akiko Suzuki, Osamu Hanyu, Hitoshi Shimano, Hirohito Sone

    JOURNAL OF DIABETES RESEARCH   2014   250620   2014

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    Objective. To assess the association between Helicobacter pylori (HP) infection and glycemic control in patients with diabetes through a meta-analytic approach. Research Design and Methods. Electronic literature searches were conducted for cross-sectional studies that examined the hemoglobin A1c (A1C) level by whether patients with diabetes were or were not carriers of HP. Mean differences in A1C between groups with and without HP infection were pooled with a random-effects model. Results. Thirteen eligible studies were included in this meta-analysis. Overall, the HP carriers did not have significantly higher A1C levels compared with HP noncarriers (mean difference (95% CI), 0.19% (-0.18 to 0.46), P = 0.16). When the analysis was limited to studies targeting patients with type 1 diabetes, there was also no significant difference in A1C (0.69% (-0.31 to 1.68), P = 0.18). Conclusions. There was insufficient evidence that HP infection worsened glycemic control in patients with diabetes.

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  • Comparison of different aspects of BMI history to identify undiagnosed diabetes in Japanese men and women: Toranomon hospital health management center study 12 (TOPICS 12) Reviewed

    S. Yoshizawa, Y. Heianza, Y. Arase, K. Saito, S. D. Hsieh, H. Tsuji, O. Hanyu, A. Suzuki, S. Tanaka, S. Kodama, H. Shimano, S. Hara, H. Sone

    Diabetic Medicine   31 ( 11 )   1378 - 1386   2014

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    Aims: To examine current BMI and various aspects of BMI history as pre-screening tools for undiagnosed diabetes in Japanese individuals. Methods: This cross-sectional study included 16 226 men and 7026 women aged 30-75 years without a self-reported history of clinician-diagnosed diabetes. We estimated the probability of having undiagnosed diabetes (fasting glucose ≥ 7.0 mmol/l and/or HbA&lt
    inf&gt
    1c&lt
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    ≥ 48 mmol/mol (≥ 6.5%) for the following variables: current BMI, BMI in the early 20s (BMI&lt
    inf&gt
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    ), lifetime maximum BMI (BMI&lt
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    max&lt
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    ), change between BMI in the early 20s and current BMI (ΔBMI&lt
    inf&gt
    20y-cur&lt
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    ), change between BMI in the early 20s and maximum BMI (ΔBMI&lt
    inf&gt
    20y-max&lt
    /inf&gt
    ), and change between lifetime maximum and current BMI (ΔBMI&lt
    inf&gt
    max-cur&lt
    /inf&gt
    ). Results: The prevalence of undiagnosed diabetes was 3.3% (771/23252) among participants. BMI&lt
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    max&lt
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    , ΔBMI&lt
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    20y-max&lt
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    and current BMI (1-sd increments) were more strongly associated with diabetes than the other factors (multivariate odds ratio 1.58 [95% CI 1.47-1.70] in men and 1.65 [95% CI 1.43-1.90] in women for BMI&lt
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    multivariate odds ratio 1.47 [95% CI 1.37-1.58] in men and 1.61 [95% CI 1.41-1.84] in women for ΔBMI&lt
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    20y-max&lt
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    multivariate odds ratio 1.47 [95% CI 1.36-1.58] in men and 1.63 [95% CI 1.40-1.89] in women for current BMI). The probability of having diabetes was markedly higher in those with both the highest tertile of BMI&lt
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    and greatest ΔBMI&lt
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    however, a substantially lower likelihood of diabetes was observed among individuals with the lowest and middle tertiles of current BMI (&lt
    24.62 kg/m&lt
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    in men and &lt
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    2&lt
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    in women). Conclusions: Lifetime maximum BMI and BMI changes from early adulthood were strongly associated with undiagnosed diabetes. Adding BMI history to people's current BMI would improve the identification of individuals with a markedly higher probability of having undiagnosed diabetes.

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  • Utility of the Triglyceride Level for Predicting Incident Diabetes Mellitus According to the Fasting Status and Body Mass Index Category: The Ibaraki Prefectural Health Study Reviewed

    Kazuya Fujihara, Ayumi Sugawara, Yoriko Heianza, Toshimi Sairenchi, Fujiko Irie, Hiroyasu Iso, Mikio Doi, Hitoshi Shimano, Hiroshi Watanabe, Hirohito Sone, Hitoshi Ota

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   21 ( 11 )   1152 - 1169   2014

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    Aim: The levels of lipids, especially triglycerides (TG), and obesity are associated with diabetes mellitus (DM). Although typically measured in fasting individuals, non-fasting lipid measurements play an important role in predicting future DM. This study compared the predictive efficacy of lipid variables according to the fasting status and body mass index (BMI) category.
    Methods: Data were collected for 39,196 nondiabetic men and 87,980 nondiabetic women 40-79 years of age who underwent health checkups in Ibaraki-Prefecture, Japan in 1993 and were followed through 2007. The hazard ratios (HRs) for DM in relation to sex, the fasting status and BMI were estimated using a Cox proportional hazards model.
    Results: A total of 8,867 participants, 4,012 men and 4,855 women, developed DM during a mean follow-up of 5.5 years. TG was found to be an independent predictor of incident DM in both fasting and non-fasting men and non-fasting women. The multivariable-adjusted HR for DM according to the TG quartile (Q) 4 vs. Q1 was 1.18 (95% confidence interval (CI): 1.05, 1.34) in the non-fasting men with a normal BMI (18.5-24.9). This trend was also observed in the non-fasting women with a normal BMI. That is, the multivariable-adjusted HRs for DM for TG Q2, Q3 and Q4 compared with Q1 were 1.07 (95% CI: 0.94, 1.23), 1.17 (95% CI: 1.03, 1.34) and 1.48 (95% CI: 1.30, 1.69), respectively.
    Conclusions: The fasting and non-fasting TG levels in men and non-fasting TG levels in women are predictive of future DM among those with a normal BMI. Clinicians must pay attention to those individuals at high risk for DM.

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  • Primary fibroblast cultures and karyotype analysis for the olive ridley sea turtle (Lepidochelys olivacea).

    Fukuda T, Katayama M, Kinoshita K, Kasugai T, Okamoto H, Kobayashi K, Kurita M, Soichi M, Donai K, Uchida T, Onuma M, Sone H, Isogai E, Inoue-Murayama M

    2014

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  • Food groups and weight gain in Japanese men

    Hirohito Sone

    Clinical Obesity   2014

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    DOI: 10.1111/COB.12056

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  • Quality and accuracy of Internet information concerning a healthy diet Reviewed

    Reiko Hirasawa, Yoko Yachi, Sakiko Yoshizawa, Chika Horikawa, Yoriko Heianza, Ayumi Sugawara, Yasuko Sone, Kazuo Kondo, Hitoshi Shimano, Kazumi Saito, Satoru Kodama, Hirohito Sone

    INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION   64 ( 8 )   1007 - 1013   2013.12

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    The Internet is used by many consumers interested in healthy living. The aim of the present study was to explore the variations among Internet information concerning a healthy diet and to evaluate the potential for misleading information. To conduct a descriptive analysis, the search term "healthy diet'' was entered into three search engines and the first 100 results were examined. Of the evaluated 48 websites, 5, 26 and 11, respectively, gave references, date when information was updated and cautioned users. For assessment of accuracy, six dietary guidelines were used as references and the website was scored according to the number of recommended dietary features that matched the guidelines. Websites that specified their objectives scored significantly higher when matched with each guideline than the websites that did not state four guidelines (p&lt;0.05). Internet information on a "healthy diet'' was likely to only partially follow recommendations of the guidelines.

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  • Intakes of Dietary Fiber, Vegetables, and Fruits and Incidence of Cardiovascular Disease in Japanese Patients With Type 2 Diabetes Reviewed

    Shiro Tanaka, Yukio Yoshimura, Chiemi Kamada, Sachiko Tanaka, Chika Horikawa, Ryota Okumura, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

    DIABETES CARE   36 ( 12 )   3916 - 3922   2013.12

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    OBJECTIVEFoods rich in fiber, such as vegetables and fruits, prevent cardiovascular disease (CVD) among healthy adults, but such data in patients with diabetes are sparse. We investigated this association in a cohort with type 2 diabetes aged 40-70 years whose HbA(1c) values were 6.5% in Japan Diabetes Society values.RESEARCH DESIGN AND METHODSIn this cohort study, 1,414 patients were analyzed after exclusion of patients with history of CVDs and nonresponders to a dietary survey. Primary outcomes were times to stroke and coronary heart disease (CHD). Hazard ratios (HRs) of dietary intake were estimated by Cox regression adjusted for systolic blood pressure, lipids, energy intake, and other confounders.RESULTSMean daily dietary fiber in quartiles ranged from 8.7 to 21.8 g, and mean energy intake ranged from 1,442.3 to 2,058.9 kcal. Mean daily intake of vegetables and fruits in quartiles ranged from 228.7 to 721.4 g. During the follow-up of a median of 8.1 years, 68 strokes and 96 CHDs were observed. HRs for stroke in the fourth quartile vs. the first quartile were 0.39 (95% CI 0.12-1.29, P = 0.12) for dietary fiber and 0.35 (0.13-0.96, P = 0.04) for vegetables and fruits. There were no significant associations with CHD. The HR per 1-g increase was smaller for soluble dietary fiber (0.48 [95% CI 0.30-0.79], P &lt; 0.01) than for total (0.82 [0.73-0.93], P &lt; 0.01) and insoluble (0.79 [0.68-0.93], P &lt; 0.01) dietary fiber.CONCLUSIONSIncreased dietary fiber, particularly soluble fiber, and vegetables and fruits were associated with lower incident stroke but not CHD in patients with type 2 diabetes.

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  • Effect of postmenopausal status and age at menopause on type 2 diabetes and prediabetes in Japanese individuals: Toranomon Hospital Health Management Center study 17 (TOPICS 17) Reviewed

    Yoriko Heianza, Yasuji Arase, Satoru Kodama, Shiun Dong Hsieh, Hiroshi Tsuji, Kazumi Saito, Hitoshi Shimano, Shigeko Hara, Hirohito Sone

    Diabetes Care   36 ( 12 )   4007 - 4014   2013.12

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    Objective-Findings on the effect of menopause or age at menopause on the presence of hyperglycemia are controversial, and why women after menopause have a higher probability of having hyperglycemia than men in the same age range remains unknown. Research design and methods-We reviewed data on 29,189 men, 6,308 premenopausalwomen, and 4,570 postmenopausal women in Japan. Odds ratios (ORs) for diabetes or prediabetes indicated by American Diabetes Association criteria were calculated for men and for pre- and postmenopausal women. Results-Compared with premenopausal women, women after natural menopause had an age-adjusted OR of 1.40 (95% CI 1.03-1.89) for diabetes, and women after menopause by surgical or other causes had an age-adjusted OR of 1.59 (1.07-2.37). The age-adjusted OR in men was 4.02 (3.15-5.14). Compared with premenopausal nondiabetic women, postmenopausal nondiabetic women had a significantly elevated OR of 1.33 (1.20-1.48) for prediabetes
    nondiabetic men had an OR of 1.93 (1.77-2.10) independently of age and demographic and metabolic factors. Even among women aged &lt
    50 years, postmenopausal status was significantly associated with an elevated OR (1.50 [1.18-1.91]) for dysglycemia (either diabetes or prediabetes). Postmenopausal women aged ≥50 years had a particularly elevated OR for dysglycemia, regardless of age at menopause. Conclusions-The postmenopausal state was significantly associated with the presence of dysglycemia independently of normal aging, although the increased probability in postmenopausal women did not equal that in men. Among women, menopause and older age might additively influence the elevated probability of dysglycemia. © 2013 by the American Diabetes Association.

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  • [Stroke in the elderly people with diabetes mellitus]. Reviewed

    Minagawa S, Hanyu O, Sone H

    Nihon rinsho. Japanese journal of clinical medicine   71 ( 11 )   1948 - 1953   2013.11

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  • Use of high-normal levels of haemoglobin A(1C) and fasting plasma glucose for diabetes screening and for prediction: a meta-analysis. Reviewed International journal

    Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Reiko Hirasawa, Yoko Yachi, Sakiko Yoshizawa, Shiro Tanaka, Yasuko Sone, Hitoshi Shimano, Kaoruko Tada Iida, Kazumi Saito, Hirohito Sone

    Diabetes/metabolism research and reviews   29 ( 8 )   680 - 92   2013.11

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    BACKGROUND: Using high-normal levels of haemoglobin A1C (Abnormal-A1C ) or fasting plasma glucose (FPG) (Abnormal-FPG) for diabetes screening are expected to improve the ability to detect persons with or at high risk of diabetes. We assessed the diagnostic and predictive capacity for diabetes of Abnormal-A1C and Abnormal-FPG. We compared these to the combined use of the two measures to the single use of either measurement. METHODS: We analysed 31 eligible cross-sectional or cohort studies that assessed diagnostic or predictive ability, respectively, by using lower A1C and FPG cutoff values than recommended by current diabetes criteria. Positive and negative likelihood ratios (LR+ and LR-) were calculated to assess the ability to confirm or exclude diabetes, respectively, on the basis of a bivariate random-effects model. RESULTS: With both Abnormal-A1C and Abnormal-FPG, the pooled LR+ was above 4 for diagnosing diabetes and above 3 for predicting diabetes. However, the pooled LR- for predicting diabetes was higher with Abnormal-A1C (0.48) and Abnormal-FPG (0.49) in comparison with that for diagnosing diabetes (0.27, Abnormal-A1C ; 0.28, Abnormal-FPG). In eight studies that assessed the predictive ability of the combination of A1C and FPG, using either Abnormal-A1C or Abnormal-FPG could lower LR- to 0.17 from 0.43 for only Abnormal-A1C and from 0.38 for only Abnormal-FPG. Accordingly, LR+ was also lowered to 2.37 from 3.36 for only Abnormal-A1C and from 3.84 for only-Abnormal-FPG. CONCLUSION: The use of the two blood glucose tests had insufficient capacity to identify subjects at high risk for diabetes but had considerable capacity to identify undiagnosed diabetes.

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  • Efficacy and safety in sitagliptin therapy for diabetes complicated by non-alcoholic fatty liver disease Reviewed

    Yasuji Arase, Yusuke Kawamura, Yuya Seko, Mariko Kobayashi, Fumitaka Suzuki, Yoshiyuki Suzuki, Norio Akuta, Masahiro Kobayashi, Hitomi Sezaki, Satoshi Saito, Tetsuya Hosaka, Kenji Ikeda, Hiromitsu Kumada, Yuki Ohmoto-Sekine, Shiun Dong Hsieh, Kazuhisa Amakawa, Kyoko Ogawa, Naoki Matsumoto, Akiko Iwao, Hiroshi Tsuji, Shigeko Hara, Yasumichi Mori, Minoru Okubo, Hirohito Sone, Tetsuro Kobayashi

    HEPATOLOGY RESEARCH   43 ( 11 )   1163 - 1168   2013.11

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    AimThe aim of this case-control study was to assess the efficacy and safety of dipeptidyl peptidase-4 inhibitor (sitagliptin) for type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD).
    MethodsTwenty NAFLD patients with T2DM treated by sitagliptin were retrospectively enrolled as the sitagliptin group. These patients were given sitagliptin between January 2010 and July 2011. Another 20 NAFLD patients with T2DM treated only with diet and exercise for 48weeks were selected as the control group. Serum levels of fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before and 12, 24, 36 and 48weeks after the initiation of treatment.
    ResultsIn the sitagliptin group, average HbA1c levels decreased approximately 0.7% at 48weeks after the initiation of sitagliptin. Next, average FPG levels decreased approximately 15mg/dL at 48weeks after the initiation of sitagliptin. The serum levels of HbA1c and FPG in the sitagliptin group decreased with statistical significance compared to those in the control group (P&lt;0.05). All the patients could take sitagliptin of 50mg/day without reduction necessitated by sitagliptin-related side-effects. There were no significant changes of average AST and ALT levels during follow up of 48weeks in both sitagliptin and control groups.
    ConclusionOur results indicate sitagliptin is effective and safe for the treatment of T2DM complicated with NAFLD.

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  • Diabetic Cardiomyopathy and Oxidative Stress Reviewed

    Somasundaram Arumugam, Vengadeshprabhu Karuppagounder, Rajarajan A. Thandavarayan, Vigneshwaran Pitchaimani, Hirohito Sone, Kenichi Watanabe

    Diabetes: Oxidative Stress and Dietary Antioxidants   25 - 32   2013.11

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    Diabetes mellitus (DM) is the most common metabolic disorder associated with high mortality, which is mostly due to its cardiovascular complications. Diabetic cardiomyopathy (CM) is characterized by abnormal ventricular function in the absence of DM-associated risk factors such as obesity, hypertension, hypercholesterolemia, or coronary artery disease. Oxidative stress plays a pivotal role in the development of diabetic CM, in which chronic hyperglycemia plays a major role. As this develops, the endogenous antioxidant system becomes suppressed and so cannot counter-balance the increased oxidative stress. The metabolic abnormalities of DM cause mitochondrial superoxide overproduction, which further enhances the production of other reactive species, including nitric oxide, hydroxyl radical, hydrogen peroxide and peroxy nitrite, causing aggravation of the myocardial damage. In addition, free-radical-mediated platelet activation in the narrowed arteries culminates in acute myocardial infarction and stroke, indirectly affecting cardiac function. This chapter focuses on various aspects of the oxidative stress induced by reactive species during the pathogenesis of diabetic CM. © 2014 Elsevier Inc. All rights reserved.

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  • Association of living alone with the presence of undiagnosed diabetes in Japanese men: The role of modifiable risk factors for diabetes: Toranomon hospital health management center study 13 (TOPICS 13) Reviewed

    Y. Heianza, Y. Arase, S. Kodama, S. D. Hsieh, H. Tsuji, K. Saito, H. Shimano, S. Hara, H. Sone

    Diabetic Medicine   30 ( 11 )   1355 - 1359   2013.11

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    Aims: To investigate whether living alone was associated with the presence of undiagnosed diabetes and whether this association could be attenuated by modifiable lifestyle habits. Methods: This cross-sectional study included 6400 Japanese men without a history of diagnosed diabetes. Individuals with currently undiagnosed diabetes were identified through fasting glucose concentration ≥7.0 mmol/l or HbA1c concentration ≥ 48 mmol/mol (≥ 6.5%). Effect modification was examined using body mass index, hypertension, history of dyslipidaemia, drinking habits, smoking habits, physical activity, vegetable intake, emotional stress and depressed mood. Results: Men who lived alone (n = 1098) had a significantly elevated odds ratio for having undiagnosed diabetes in an age-adjusted model (odds ratio 1.45, 95% CI 1.07, 1.96
    P = 0.018). After adjustment for lifestyle factors, the association was slightly attenuated (odds ratio 1.40, 95% CI 1.02, 1.91
    P = 0.036). After further adjustment for all factors mentioned above, living alone was still marginally significantly associated with the presence of undiagnosed diabetes (odds ratio 1.38, 95% CI 1.003, 1.90
    P = 0.048). A significant association of living alone with the presence of undetected diabetes was particularly observed among men who were overweight, currently smoked and were physically inactive, or had any one of those three factors. Conclusions: The association between undiagnosed diabetes and living alone can be partially influenced by modifiable lifestyle factors. Men who lived alone, especially those who did not engage in favourable lifestyle habits, were more likely to have undiagnosed diabetes. Such individuals have a higher probability of having undetected diabetic hyperglycaemia and would need to undergo glucose tests to identify the disease. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

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  • [Cutting-edge of medicine; clinical epidemiology regarding clinical and pathophysiological features of Japanese patients with type 2 diabetes mellitus]. Reviewed

    Sone H, Akanuma Y, Yamada N

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   102 ( 10 )   2714 - 2722   2013.10

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  • TFE3 Controls Lipid Metabolism in Adipose Tissue of Male Mice by Suppressing Lipolysis and Thermogenesis Reviewed

    Yuri Fujimoto, Yoshimi Nakagawa, Aoi Satoh, Kanako Okuda, Akiko Shingyouchi, Ayano Naka, Takashi Matsuzaka, Hitoshi Iwasaki, Kazuto Kobayashi, Naoya Yahagi, Masako Shimada, Shigeru Yatoh, Hiroaki Suzuki, Satomi Yogosawa, Tetsuro Izumi, Hirohito Sone, Osamu Urayama, Nobuhiro Yamada, Hitoshi Shimano

    ENDOCRINOLOGY   154 ( 10 )   3577 - 3588   2013.10

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    Transcription factor E3 (TFE3) is a transcription factor that binds to E-box motifs and promotes energy metabolism-related genes. We previously reported that TFE3 directly binds to the insulin receptor substrate-2 promoter in the liver, resulting in increased insulin response. However, the role of TFE3 in other tissues remains unclear. In this study, we generated adipose-specific TFE3 transgenic (aP2-TFE3 Tg) mice. These mice had a higher weight of white adipose tissue (WAT) and brown adipose tissue than wild-type (WT) mice under fasting conditions. Lipase activity in the WAT in these mice was lower than that in the WT mice. Them RNA level of adipose triglyceride lipase (ATGL), the rate-limiting enzyme for adipocyte lipolysis, was significantly decreased in aP2-TFE3 Tg mice. The expression of Foxo1, which directly activates ATG Lexpression, was also suppressed in transgenic mice. Promoter analysis confirmed that TFE3 suppressed promoter activities of the ATGL gene. In contrast, G0S2 and Perilipin1, which attenuate ATGL activity, were higher in transgenic mice than in WT mice. These results indicated that the decrease in lipase activity in adipose tissues was due to a decrease in ATGL expression and suppression of ATGL activity. We also showed that thermogenesis was suppressed in aP2-TFE3 Tg mice. The decrease in lipolysis in WAT of aP2-TFE3 Tg mice inhibited the supply of fatty acids to brown adipose tissue, resulting in the inhibition of the expression of thermogenesis-related genes such as UCP1. Our data provide new evidence that TFE3 regulates lipid metabolism by controlling the gene expression related to lipolysis and thermogenesis in adipose tissue.

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  • Association Between Remission of Macroalbuminuria and Preservation of Renal Function in Patients With Type 2 Diabetes With Overt Proteinuria Reviewed

    Hiroki Yokoyama, Shin-ichi Araki, Jun Honjo, Shinichiro Okizaki, Daishiro Yamada, Ryushi Shudo, Hitoshi Shimizu, Hirohito Sone, Tatsumi Moriya, Masakazu Haneda

    DIABETES CARE   36 ( 10 )   3227 - 3233   2013.10

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    OBJECTIVEStudies on the rate of remission of macroalbuminuria in patients with type 2 diabetes mellitus (T2DM) and the effects of reduction in albuminuria on renal prognosis in a primary care setting are absolutely lacking.RESEARCH DESIGN AND METHODSA total of 211 T2DM patients with albuminuria 300 mg/g were enrolled in a prospective observational study (mean of 4.5 years). The incidence of patients with remission of macroalbuminuria at every 1-year study time point after starting intensified diabetes treatment and the factors associated with remission were evaluated. The association of reduction in albuminuria with renal events (doubling of serum creatinine and end-stage renal disease) was also investigated.RESULTSDuring the 5-year study period, remission to microalbuminuria occurred in 116 patients and the 5-year cumulative incidence was 58.3%. Notably, most cases (82.8%) obtained remission at the 1-year study time point. The remission rate increased with achieving therapeutic targets for blood pressure and blood glucose. Remission and reduction in albuminuria of 50% were associated with preservation of renal function. In particular, patients who obtained both remission and 50% reduction at the 1-year study time point exhibited a significantly reduced risk for renal events as compared with those with no remission and no reduction (adjusted hazard ratio 0.30 [95% CI 0.12-0.76]).CONCLUSIONSRemission of macroalbuminuria occurs frequently and is associated with the preservation of renal function in T2DM patients. The initial adequate diabetes treatment aimed at reducing albuminuria may lead to improved renal prognosis in the primary care setting.

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  • Diabetic Retinopathy and Microalbuminuria Can Predict Macroalbuminuria and Renal Function Decline in Japanese Type 2 Diabetic Patients: Japan Diabetes Complications Study Reviewed

    Tatsumi Moriya, Shiro Tanaka, Ryo Kawasaki, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone, Hidetoshi Yamashita, Shigehiro Katayama

    DIABETES CARE   36 ( 9 )   2803 - 2809   2013.9

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    OBJECTIVE To examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline.RESEARCH DESIGN AND METHODS We explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (&lt;150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR-)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR-)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years.RESULTS Annual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94-6.50; P = 0.07), 10.40 (4.91-22.03; P &lt; 0.01), and 11.55 (5.24-25.45; P &lt; 0.01) in NA(DR+), MA(DR-), and MA(DR+), respectively, in comparison with NA(DR-). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (-1.92 mL/min/1.73 m(2)/year) than in the other groups.CONCLUSIONS In normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists.

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  • Body Weight Change and Type 2 Diabetes Reviewed

    Satoru Kodama, Chika Horikawa, Sakiko Yoshizawa, Kazuya Fujihara, Yoko Yachi, Shiro Tanaka, Akiko Suzuki, Osamu Hanyu, Hiroaki Yagyu, Hirohito Sone

    EPIDEMIOLOGY   24 ( 5 )   778 - 779   2013.9

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  • Direct effect of dasatinib on proliferation and cytotoxicity of natural killer cells in in vitro study Reviewed

    Takayoshi Uchiyama, Naoya Sato, Miwako Narita, Akie Yamahira, Minami Iwabuchi, Tatsuo Furukawa, Hirohito Sone, Masuhiro Takahashi

    HEMATOLOGICAL ONCOLOGY   31 ( 3 )   156 - 163   2013.9

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    Lymphocytosis predominantly due to natural killer (NK) cells has been reported in nearly a half of chronic myelogenous leukemia (CML) patients who were being treated with dasatinib. Besides, dasatinib-treated patients with lymphocytosis have a better prognosis than patients without lymphocytosis. In order to elucidate the effects of dasatinib on the proliferation of lymphocyte subset, dasatinib was added to the culture of peripheral blood mononuclear cells with IL-2 (lymphokine-activated killer culture) or a low dose of IL-2 with zoledronate ( T-cell culture). In both culture conditions, NK cells were increased in both percentage and absolute number in the culture with dasatinib compared with control culture without dasatinib. The increase of NK cells was dose dependent of dasatinib in the range of 2-25nM. NK cell cytotoxicity of cultured cells with dasatinib was demonstrated to be superior to control cells without dasatinib in cytotoxicity assay using EGFP-transfected K562 cells as target cells. The present study suggested that lymphocytosis in dasatinib-treated CML patients is at least partly associated with a direct effect of dasatinib to stimulate the proliferation of NK cells. Favourable prognosis in patients with dasatinib-induced lymphocytosis might be associated with the effects of dasatinib to potentiate NK cytotoxicity in vivo. Copyright (c) 2012 John Wiley & Sons, Ltd.

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  • Molecular understanding of curcumin in diabetic nephropathy Reviewed

    Vivian Soetikno, Kenji Suzuki, Punniyakoti T. Veeraveedu, Somasundaram Arumugam, Arun P. Lakshmanan, Hirohito Sone, Kenichi Watanabe

    Drug Discovery Today   18 ( 15-16 )   756 - 763   2013.8

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    Diabetic nephropathy is characterized by a plethora of signaling abnormalities. Recent trials have suggested that intensive glucose-lowering treatment leads to hypoglycemic events, which can be dangerous. Curcumin is the active ingredient of turmeric, which has been widely used in many countries for centuries to treat numerous diseases. The preventive and therapeutic properties of curcumin are associated with its antioxidant and anti-inflammatory properties. Here, we highlight the renoprotective role of curcumin in diabetes mellitus (DM) with an emphasis on the molecular basis of this effect. We also briefly discuss the numerous approaches that have been undertaken to improve the pharmacokinetics of curcumin. © 2013 Elsevier Ltd. All rights reserved.

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  • Genetic Variants of the Fatty Acid Desaturase Gene Cluster Are Associated with Plasma LDL Cholesterol Levels in Japanese Males Reviewed

    Yasuko Sone, Toshimi Kido, Tomomi Ainuki, Mariko Sonoda, Ikuyo Ichi, Satoru Kodama, Hirohito Sone, Kazuo Kondo, Yutaka Morita, Shigenobu Egawa, Kazuo Kawahara, Yuzuru Otsuka, Yoko Fujiwara

    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY   59 ( 4 )   325 - 335   2013.8

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    Fatty acid (FA) compositions in tissues are related to metabolic disorders, and consequently the appropriate management of underlying FA compositions in tissues is considered to be important. However, the relationship among the serum lipid profiles, the FA composition of the red blood cell (RBC) membranes and genetic variations in the fatty acid desaturase (FADS) genes in Japanese men is unclear. In this study, the subjects recruited were 137 Japanese men, 40 to 60 y old, who had a regular health checkup. Their serum lipid profile and the relative FA composition of the RBC membranes were measured. They were genotyped for the single nucleotide polymorphisms (SNPs) rs174553, rs174546, rs99780 and rs174583 in FADS gene. Multiple regression analysis was conducted to detect the relationship among hyperlipidemia, the FA composition of the RBC and the FADS genotypes. As a result, the homozygous genotype for the minor alleles in rs174553, rs174546, rs99780 were found to be associated with lower low-density lipoprotein cholesterol (LDL-C) levels and a lower LDL-C/total-cholesterol ratio. The homozygous genotype for the minor alleles reduced the risk of high LDL-C level (R-2=0.50, beta=-0.20, p=0.009), whereas, the arachidonic acid (AA) levels in the carriers of the homozygous genotype for the minor alleles tended to be lower compared with the carriers of the major alleles. However, no significant differences were observed in any FA level among the three genotypes for four SNPs. These results indicate that the appropriate management of serum LDL-C levels depending on genetic predisposition in FADS genotypes should be encouraged.

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  • Importance of high-density lipoprotein cholesterol control during pravastatin treatment in hypercholesterolemic Japanese with type 2 diabetes mellitus: A post hoc analysis of MEGA study Reviewed

    Rimei Nishimura, Hirohito Sone, Tomoko Nakagami, Naoko Tajima

    DIABETES RESEARCH AND CLINICAL PRACTICE   100 ( 2 )   E31 - E33   2013.5

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    To investigate the role of HDL-C in cardiovascular risk reduction, we evaluated using data from a diabetic population in a large clinical trial with pravastatin. A significant risk reduction in CVD was found only in diabetic patients who had both a reduction in LDL-C and an increase in HDL-C. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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  • Predicting Macro- and Microvascular Complications in Type 2 Diabetes Reviewed

    Shiro Tanaka, Sachiko Tanaka, Satoshi Iimuro, Hidetoshi Yamashita, Shigehiro Katayama, Yasuo Akanuma, Nobuhiro Yamada, Atsushi Araki, Hideki Ito, Hirohito Sone, Yasuo Ohashi

    DIABETES CARE   36 ( 5 )   1193 - 1199   2013.5

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    OBJECTIVE-To develop and validate a risk engine that calculates the risks of macro- and microvascular complications in type 2 diabetes.
    RESEARCH DESIGN AND METHODS-We analyzed pooled data from two clinical trials on 1,748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7.2 years. End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy. We fit a multistate Cox regression model to derive an algorithm for prediction. The predictive accuracy of the calculated 5-year risks was cross-validated.
    RESULTS-Sex, age, HbA(1c), years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro- and microvascular complications and were incorporated into the risk engine. The observed-to-predicted (O/P) ratios for each event were between 0.93 and 1.08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events. In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0.30 for CHD and 0.72 for stroke). C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0.725, 0.696, and 0.767) but moderate for stroke and progression of retinopathy (0.636 and 0.614). By combining macro- and microvascular risks, the classification of low- and high-risk patients was improved by a net reclassification improvement of 5.7% (P = 0.02).
    CONCLUSIONS-The risk engine accurately predicts macro- and microvascular complications and would provide helpful information in risk classification and health economic simulations.

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  • Leisure-time physical activity is a significant predictor of stroke and total mortality in Japanese patients with type 2 diabetes: Analysis from the Japan Diabetes Complications Study (JDCS) Reviewed

    H. Sone, S. Tanaka, S. Tanaka, S. Suzuki, H. Seino, O. Hanyu, A. Sato, T. Toyonaga, K. Okita, S. Ishibashi, S. Kodama, Y. Akanuma, N. Yamada

    Diabetologia   56 ( 5 )   1021 - 1030   2013.5

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    Aims/hypothesis: Our aim was to clarify the association between leisure-time physical activity (LTPA) and cardiovascular events and total mortality in a nationwide cohort of Japanese diabetic patients. Methods: Eligible patients (1,702) with type 2 diabetes (mean age, 58.5 years
    47% women) from 59 institutes were followed for a median of 8.05 years. A comprehensive lifestyle survey including LTPA and occupation was performed using standardised questionnaires. Outcome was occurrence of coronary heart disease (CHD), stroke and total mortality. The adjusted HR and 95% CI were calculated by Cox regression analysis. Results: A significant reduction in HR in patients in the top (≥15.4 metabolic equivalents [MET] h/week) vs the bottom tertile (≤3.7 MET h/week) of LTPA, adjusted by age, sex and diabetes duration, was observed in stroke (HR 0.55, 95% CI 0.32, 0.94) and total mortality (HR 0.49, 95% CI 0.26, 0.91) but not in CHD (HR 0.77, 95% CI 0.48, 1.25). The HR for stroke became borderline significant or nonsignificant after adjustment for lifestyle or clinical variables including diet or serum lipids. The significantly reduced total mortality by LTPA was independent of these variables and seemed not to be, at least mainly, attributed to reduced cardiovascular disease. Conclusions/interpretation: In Japanese persons with type 2 diabetes, LTPA of 15.4 MET h/week or more was associated with a significantly lower risk of stroke partly through ameliorating combinations of cardiovascular risk factors. It was also associated with significantly reduced total mortality but independently of cardiovascular risk factors or events. These findings, implying differences from Western diabetic populations, should be considered in the clinical management of East Asians with diabetes. © 2013 Springer-Verlag Berlin Heidelberg.

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  • Two authors reply Reviewed

    Satoru Kodama, Hirohito Sone

    American Journal of Epidemiology   177 ( 8 )   863   2013.4

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  • [Effect of smoking on diabetes mellitus and dyslipidemia (effect of smoking on glucose and lipid metabolism)]. Reviewed

    Saito K, Sone H

    Nihon rinsho. Japanese journal of clinical medicine   71 ( 3 )   443 - 448   2013.3

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  • Comparison of Education-Only versus Group-Based Intervention in Promoting Weight Loss: A Randomised Controlled Trial (vol 4, pg 222, 2011)

    Nakata, Yoshio, Okada, Masafumi, Hashimoto, Koichi, Harada, Yoshinori, Sone, Hirohito, Tanaka, Kiyoji

    OBESITY FACTS   6 ( 1 )   89 - 90   2013.3

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  • Development of a Screening Score for Undiagnosed Diabetes and Its Application in Estimating Absolute Risk of Future Type 2 Diabetes in Japan: Toranomon Hospital Health Management Center Study 10 (TOPICS 10) Reviewed

    Yoriko Heianza, Yasuji Arase, Kazumi Saito, Shiun Dong Hsieh, Hiroshi Tsuji, Satoru Kodama, Shiro Tanaka, Yasuo Ohashi, Hitoshi Shimano, Nobuhiro Yamada, Shigeko Hara, Hirohito Sone

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   98 ( 3 )   1051 - 1060   2013.3

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    Objective: The objective of the study was to develop a screening score for undiagnosed diabetes by eliciting information on noninvasive clinical markers and to assess its effectiveness for identifying the presence of diabetes and predicting future diabetes.
    Design, Setting, and Participants: A screening score was cross-sectionally developed for 33 335 Japanese individuals aged 18-88 years without known diabetes who underwent a health examination. We validated its utility and compared it with existing screening tools in an independent population (n = 7477). After initial assessment of the instrument, 7332 nondiabetic individuals were followed up for a mean 4.0 years.
    Results: Prevalence of undiagnosed diabetes (fasting plasma glucose &gt;= 7.0 mmol/L or glycated hemoglobin &gt;= 6.5%) was 2.9% (n = 965). Diabetes score included age, sex, family history of diabetes, current smoking habit, body mass index, and hypertension with an area under the receiver-operating characteristics curve of 0.771. Screening with 8 or more points yielded a sensitivity of 72.7% and a specificity of 68.1%. In the validation cohort, the area under the receiver-operating characteristics curve was 0.806. The developed score with 8 or more points had better positive predictive value (9.6%) and positive likelihood ratio (2.52) compared with existing tools (positive predictive value, from 6.9% to 9.4%; positive likelihood ratio, from 1.77 to 2.46) in which each tool's highest combination of sensitivity and specificity was observed. The 4-year cumulative risk of developing diabetes gradually escalated in association with higher screening scores at the initial examination.
    Conclusions: Our algorism could serve as a self-assessment tool for undiagnosed diabetic patients needing timely medical care and as a prognostic tool for individuals without present diabetes who must be closely followed up to prevent future diabetes. (J Clin Endocrinol Metab 98: 1051-1060, 2013)

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  • Fruit Intake and Incident Diabetic Retinopathy with Type 2 Diabetes Reviewed

    Shiro Tanaka, Yukio Yoshimura, Ryo Kawasaki, Chiemi Kamada, Sachiko Tanaka, Chika Horikawa, Yasuo Ohashi, Atsushi Araki, Hideki Ito, Yasuo Akanuma, Nobuhiro Yamada, Hidetoshi Yamashita, Hirohito Sone

    EPIDEMIOLOGY   24 ( 2 )   204 - 211   2013.3

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    Background: Antioxidants and dietary fiber are postulated to have preventive effects on diabetic retinopathy, but evidence is lacking. We investigated this association in a cohort with type 2 diabetes 40-70 years of age with hemoglobin (Hb)A(1C) 6.5%, originally part of the Japan Diabetes Complications Study.
    Methods: After excluding people who did not respond to a dietary survey and patients with diabetic retinopathy or a major ocular disease at baseline, we analyzed 978 patients. Baseline dietary intake was assessed by a food frequency questionnaire based on food groups and 24-hour dietary records. Primary outcome was incident diabetic retinopathy determined using international severity scales.
    Results: Mean fruit intake in quartiles ranged from 23 to 253 g/day, with increasing trends across quartiles of fruit intake for vitamin C, vitamin E, carotene, retinol equivalent, dietary fiber, potassium, and sodium. Mean energy intake ranged from 1644 to 1863 kcal/day, and fat intake was approximately 25%. HbA(1C), body mass index, triglycerides, and systolic blood pressure were well controlled. During the 8-year follow-up, the numbers of incident cases of diabetic retinopathy from the first through the fourth quartiles of fruit intake were 83, 74, 69, and 59. Multivariate-adjusted hazard ratios for the second, third, and fourth quartiles of fruit intake compared with the first quartile were 0.66 (95% confidence interval = 0.46-0.92), 0.59 (0.41-0.85), and 0.48 (0.32-0.71) (test for trend, P &lt; 0.01). There was no substantial effect modification by age, sex, HbA(1C), diabetes duration, overweight, smoking, and hypertension. Risk for diabetic retinopathy declined with increased intake of fruits and vegetables, vitamin C, and carotene.
    Conclusion: Increased fruit intake in ranges commonly consumed was associated with reduced incident diabetic retinopathy among patients adhering to a low-fat energy-restricted diet. (Epidemiology 2013;24: 204-211)

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  • Role of alcohol drinking pattern in type 2 diabetes in Japanese men: the Toranomon Hospital Health Management Center Study 11 (TOPICS 11) Reviewed

    Yoriko Heianza, Yasuji Arase, Kazumi Saito, Hiroshi Tsuji, Kazuya Fujihara, Shiun Dong Hsieh, Satoru Kodama, Hitoshi Shimano, Nobuhiro Yamada, Shigeko Hara, Hirohito Sone

    AMERICAN JOURNAL OF CLINICAL NUTRITION   97 ( 3 )   561 - 568   2013.3

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    Background: Findings of past studies on the effect of drinking patterns on diabetes risk have been inconsistent.
    Objective: We aimed to investigate the role of drinking frequency and usual quantity consumed in the development of type 2 diabetes.
    Design: Enrolled were 1650 Japanese men without diabetes (diabetes: fasting plasma glucose &gt;= 7.0 mmol/L, glycated hemoglobin &gt;= 6.5%, or self-reported clinician-diagnosed diabetes). Average alcohol consumption and 12 combinations of frequency and usual quantity per drinking occasion were assessed at the baseline examination. The absolute risk and HR for the development of diabetes were calculated.
    Results: During a mean follow-up period of 10.2 y, 216 individuals developed diabetes. Lifetime abstainers (n = 153) had a relatively low incidence of diabetes (9.1/1000 person-years), similar to moderate consumers (99-160 g ethanol/wk; 9.0/1000 person-years). Increasingly higher quantities of alcohol usually consumed per occasion increased the risk of diabetes regardless of drinking frequency. The lowest incidence rate of diabetes (8.5/1000 person-years) was associated with the consumption of &lt;1 drink (&lt;23 g ethanol) per occasion over &gt;= 6 times/wk. Binge drinking (&gt;= 3 drinks per occasion) significantly increased the risk of future diabetes regardless of frequency (HR: 1.79; 95% CI: 1.17, 2.74) compared with &lt;1 drink per occasion.
    Conclusions: Among current drinkers, a drinking pattern of &lt;1 drink per occasion regularly over 6 times within a week was associated with the lowest risk of developing diabetes. Usual quantity per drinking occasion was a more important determinant than was weekly drinking frequency in the association between alcohol consumption and risk of diabetes in Japanese men. Am J Clin Nutr 2013;97:561-8.

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  • Risk of Cardiovascular Diseases Is Increased Even with Mild Diabetic Retinopathy The Japan Diabetes Complications Study Reviewed

    Ryo Kawasaki, Shiro Tanaka, Sachiko Tanaka, Sachi Abe, Hirohito Sone, Koutaro Yokote, Shun Ishibashi, Shigehiro Katayama, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hidetoshi Yamashita

    OPHTHALMOLOGY   120 ( 3 )   574 - 582   2013.3

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    Objective: Diabetic retinopathy (DR) is linked to cardiovascular risk in diabetic patients. This study examined whether mild-stage DR is associated with risk of coronary heart disease (CHD) and stroke in type 2 diabetic patients of the Japan Diabetes Complications Study (JDCS).
    Design: Prospective cohort study.
    Participants: In the JDCS, there were 2033 Japanese persons with type 2 diabetes free of cardiovascular diseases at baseline.
    Methods: Diabetic retinopathy was ascertained from clinical and photographic grading (70%) following the international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Incident CHD and stroke were followed up prospectively annually up to 8 years.
    Main Outcome Measures: Eight-year incidence of CHD and stroke compared between persons with or without DR.
    Results: After adjusting for traditional cardiovascular risk factors, persons with mild to moderate nonproliferative DR had a higher risk of CHD (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.17-2.97) and stroke (HR, 2.69; 95% CI, 1.03-4.86). Presence of retinal hemorrhages or microaneurysms was associated with risk of CHD (HR, 1.63; 95% CI, 1.04-2.56) but was not associated with stroke (P = 0.06). Presence of cotton-wool spots was associated with risk of incident stroke (HR, 2.39; 95% CI, 1.35-4.24) but was not associated with CHD (P = 0.66). When information about DR was added in the prediction models for CHD and stroke based on traditional cardiovascular risk factors, the area under the receiver operating curve improved from 0.682 to 0.692 and 0.640 to 0.677, and 9% and 13% of persons were reclassified correctly for CHD and stroke, respectively.
    Conclusions: Type 2 diabetic patients with even a mild stage of DR, such as dot hemorrhages, are already at higher risk of CHD and stroke independent of traditional risk factors.
    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;120:574-582 (C) 2013 by the American Academy of Ophthalmology.

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  • The hyperglycemia stimulated myocardial endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the transgenic-non-obese type 2 diabetic rats: A differential role of unfolded protein response (UPR) signaling proteins Reviewed

    Arun Prasath Lakshmanan, Meilei Harima, Kenji Suzuki, Vivian Soetikno, Masaki Nagata, Takashi Nakamura, Toshihiro Takahashi, Hirohito Sone, Hiroshi Kawachi, Kenichi Watanabe

    INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY   45 ( 2 )   438 - 447   2013.2

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    It has been well demonstrated that excessive blood glucose level could be detrimental to the myocardial function through the variety of mechanisms, of which endoplasmic reticulum stress (ERS) could play an unprecedented role through the activation of unfolded protein response (UPR). Recently, reports are coming out with the evidences that UPR signaling proteins are regulated differentially depend on the experimental conditions and cell types. In addition, ERS has been proposed to be closely associated with the regulation of lipogenesis. Therefore, in this study we tried to find out the expressions of myocardial UPR signaling proteins as well as proteins involved in lipid and glucose metabolism in non-obese type 2 diabetic mellitus (DM) condition using Spontaneous Diabetic Toni (SDT) rat. We have found the significant up-regulation of oxidative, nitrosative and ERS marker proteins in the myocardium of the SDT rats, in comparison to its normal (Sprague-Dawley - SD) rats. In addition, the sub-arm-of UPR signaling proteins, such as p-PERK, p-eIF2 alpha, ATF6, CHOP/GADD153, TRAF2, apoptotic signaling proteins, such as BAD, cytochrome C, cleaved caspase-7 and -12, were significantly up-regulated in the SDT rats, in comparison to the SD rats. Interestingly, there were no significant changes in the phosphorylation of IRE-1 alpha, and XBP-1 protein expression. In addition, the proteins involved in lipid and glucose metabolisms, such as PPAR alpha, PPAR gamma, CPT1, PGC-1 alpha except GLUT4, and the proteins involved in insulin signaling, such as p-Akt and p-PI3K were shown significant attenuation in its expressions in the SDT rats, when compared with the SD rats. Taken together, it is suggested that the activation of PERK and ATF6 pathway are the major determinant rather than the IRE-1 alpha-XBP1 pathway for the ERS-mediated metabolic dysfunction, which might eventually leads to diabetic cardiomyopathy in non-obese type 2 DM. (c) 2012 Elsevier Ltd. All rights reserved.

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  • Association Between Physical Activity and Risk of All-Cause Mortality and Cardiovascular Disease in Patients With Diabetes A meta-analysis Reviewed

    Satoru Kodama, Shiro Tanaka, Yoriko Heianza, Kazuya Fujihara, Chika Horikawa, Hitoshi Shimano, Kazumi Saito, Nobuhiro Yamada, Yasuo Ohashi, Hirohito Sone

    DIABETES CARE   36 ( 2 )   471 - 479   2013.2

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    OBJECTIVE-The association between habitual physical activity (PA) and lowered risk of all-cause mortality (ACM) and cardiovascular disease (CVD) has been suggested in patients with diabetes. This meta-analysis summarizes the risk reduction in relation to PA, focusing on clarifying dose-response associations.
    RESEARCH DESIGN AND METHODS-Electronic literature searches were conducted for cohort studies that examined relative risk (RR) of ACM or CVD in relation to PA in patients with diabetes. For the qualitative assessment, RR for the highest versus the lowest PA category in each study was pooled with a random-effects model. We added linear and spline regression analyses to assess the quantitative relationship between increases in PA and ACM and CVD risk.
    RESULTS-There were 17 eligible studies. Qualitatively, the highest PA category had a lower RR [95% CI] for ACM (0.61 [0.52-0.70]) and CVD (0.71 [0.60-0.84]) than the lowest PA category. The linear regression model indicated a high goodness of fit for the risk of ACM (adjusted R-2 = 0.44, P = 0.001) and CVD (adjusted R-2 = 0.51, P = 0.001), with the result that a 1 MET-h/day incrementally higher PA was associated with 9.5% (5.0-13.8%) and 7.9% (4.3-11.4%) reductions in ACM and CVD risk, respectively. The spline regression model was not significantly different from the linear model in goodness of fit (P = 0.14 for ACM risk; P = 0.60 for CVD risk).
    CONCLUSIONS-More PA was associated with a larger reduction in future ACM and CVD risk in patients with diabetes. Nevertheless, any amount of habitual PA was better than inactivity. Diabetes Care 36:471-479, 2013

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  • Metabolic predictors of ischemic heart disease and cerebrovascular attack in elderly diabetic individuals: Difference in risk by age Reviewed

    Toshio Hayashi, Atsushi Araki, Seinosuke Kawashima, Hirohito Sone, Hiroshi Watanabe, Takashi Ohrui, Koutaro Yokote, Minoru Takemoto, Kiyoshi Kubota, Mitsuhiko Noda, Hiroshi Noto, Koichiro Ina, Hideki Nomura

    Cardiovascular Diabetology   12 ( 1 )   10   2013.1

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    Background: High LDL-cholesterol (LDL-C) and glucose levels are risk factors for ischemic heart disease (IHD) in middle-aged diabetic individuals
    however, the risk among the elderly, especially the very elderly, is not well known. The aim of this study was to identify factors that predict IHD and cerebrovascular attack (CVA) in the elderly and to investigate their differences by age.Methods: We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) with 5.5 years of follow-up. A total of 4,014 patients with type 2 diabetes and without previous IHD or CVA (1,936 women
    age 67.4 ± 9.5 years, median 70 years
    &lt
    65 years old, n = 1,261
    65 to 74 years old, n = 1,731
    and ≥ 75 years old, n = 1,016) were recruited on a consecutive outpatient basis from 40 hospitals throughout Japan. Lipids, glucose, and other factors related to IHD or CVA risk, such as blood pressure (BP), were investigated using the multivariate Cox hazard model.Results: One hundred fifty-three cases of IHD and 104 CVAs (7.8 and 5.7/1,000 people per year, respectively) occurred over 5.5 years. Lower HDL-cholesterol (HDL-C) and female gender were correlated with IHD in patients ≥75 years old (hazard ratio (HR):0.629, P &lt
    0.01 and 1.132, P &lt
    0.05, respectively). In contrast, systolic BP (SBP), HbA1C, LDL-C and non-HDL-C were correlated with IHD in subjects &lt
    65 years old (P &lt
    0.05), and the LDL-C/HDL-C ratio was correlated with IHD in all subjects. HDL-C was correlated with CVA in patients ≥75 years old (HR: 0.536, P &lt
    0.01). Kaplan-Meier estimator curves showed that IHD occurred more frequently in patients &lt
    65 years old in the highest quartile of the LDL-C/HDL-C ratio. In patients ≥75 years old, IHD and CVA were both the most frequent among those with the lowest HDL-C levels.Conclusions: IHD and CVA in late elderly diabetic patients were predicted by HDL-C. LDL-C, HbA1C, SBP and non-HDL-C are risk factors for IHD in the non-elderly. The LDL-C/HDL-C ratio may represent the effects of both LDL-C and HDL-C. These age-dependent differences in risk are important for developing individualized strategies to prevent atherosclerotic disease.Trial registration: UMIN-CTR, UMIN00000516. © 2013 Hayashi et al
    licensee BioMed Central Ltd.

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  • Diabetes and Risk of Hearing Impairment in Adults: A Meta-Analysis Reviewed

    Chika Horikawa, Satoru Kodama, Shiro Tanaka, Kazuya Fujihara, Reiko Hirasawa, Yoko Yachi, Hitoshi Shimano, Nobuhiro Yamada, Kazumi Saito, Hirohito Sone

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   98 ( 1 )   51 - 58   2013.1

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    Context: Recently, several studies have investigated the relationship between diabetes and hearing impairment, but results were inconsistent.
    Objective: Our objective was to compare the prevalence of hearing impairment between diabetic and nondiabetic adults. Data Sources : We performed a systematic literature search using MEDLINE (1950 to May 30, 2011) and EMBASE (1974 to May 30, 2011).
    Study Selection: Cross-sectional studies were included if data on numbers of hearing-impaired and non-hearing-impaired cases with diabetes were presented. Hearing impairment was limited to that assessed by pure-tone audiometry that included at least 2 kHz of frequency range and was defined as progressive, chronic, sensorineural, or without specified cause.
    Data Extraction: Two authors independently extracted relevant data. Odd ratios (ORs) of hearing impairment related to diabetes calculated in each study were pooled with the random-effects model.
    Data Synthesis: Data were obtained from 13 eligible studies (20,194 participants and 7,377 cases). Overall pooled OR (95% confidence interval) of hearing impairment for diabetic participants compared with nondiabetic participants was 2.15 (1.72-2.68). OR was higher in younger participants (mean age, &lt;= 60 yr) than in those over 60 yr among which the OR remained significant (2.61 and 1.58, P = 0.008). The strength of the association between diabetes and prevalence of hearing impairment was not significantly influenced by whether participants were matched for age and gender (P = 0.68) or whether participants chronically exposed to noisy environments were excluded (P = 0.19).
    Conclusions: Current meta-analysis suggests that the higher prevalence of hearing impairment in diabetic patients compared with nondiabetic patients was consistent regardless of age. (J Clin Endocrinol Metab 98: 51-58, 2013)

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  • Nutrition education in Japanese medical schools: A follow-up survey Reviewed

    Hideo Orimo, Takahiro Ueno, Hiroshi Yoshida, Hirohito Sone, Akira Tanaka, Hiroshige Itakura

    Asia Pacific Journal of Clinical Nutrition   22 ( 1 )   144 - 149   2013.1

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    A questionnaire survey was used to determine the status of nutrition education in Japanese medical schools in 2009. A similar survey was conducted in 2004, at which time nutritional education was determined to be inadequate in Japanese medical schools. The current questionnaire was sent to the directors of Centers for Medical Education of 80 medical schools, who represented all medical schools in Japan. Sixty-seven medical schools (83.8%) responded, of which 25 schools (37.3%) offered dedicated nutrition courses and 36 schools (53.7%) did not offer dedicated nutrition courses but offered something related to nutrition in other courses
    six schools (9.0%) did not offer any nutrition education. Overall, 61 schools (91.0%) offered at least some nutritional topics in their undergraduate education. Nevertheless, only 11 schools (16.4%) seem to dedicate more than 5 hours to substantial nutrition education as judged by their syllabi. Although the mean length of the course was 11 hours, substantial nutrition education accounted for only 4.2 hours. Of the 25 medical schools that offered dedicated nutrition courses, seven schools offered the nutrition course as a stand-alone course and 18 schools offered it as an integrated course. In conclusion, the status of nutrition education in Japan has improved slightly but is still inadequate.

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  • TFE3 inhibits myoblast differentiation in C2C12 cells via down-regulating gene expression of myogenin Reviewed

    Ayano Naka, Kaoruko Tada Iida, Yoshimi Nakagawa, Hitoshi Iwasaki, Yoshinori Takeuchi, Aoi Satoh, Takashi Matsuzaka, Kiyo-aki Ishii, Kazuto Kobayashi, Shigeru Yatoh, Masako Shimada, Naoya Yahagi, Hiroaki Suzuki, Hirohito Sone, Nobuhiro Yamada, Hitoshi Shimano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   430 ( 2 )   664 - 669   2013.1

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    Transcription factor E3 (TFE3) belongs to a basic-helix-loop-helix family, and is involved in the biology of osteoclasts, melanocytes and their malignancies. We previously reported the metabolic effects of TFE3 on insulin in the liver and skeletal muscles in animal models. In the present study, we explored a novel role for TFE3 in a skeletal muscle cell line. When TFE3 was overexpressed in C2C12 myoblasts by adenovirus before induction of differentiation, myogenic differentiation of C2C12 cells was significantly inhibited. Adenovirus-mediated TFE3 overexpression also suppressed the gene expression of muscle regulatory factors (MRFs), such as MyoD and myogenin, during C2C12 differentiation. In contrast, knockdown of TFE3 using adenovirus encoding short-hairpin RNAi specific for TFE3 dramatically promoted myoblast differentiation associated with significantly increased expression of MRFs. Consistent with these findings, promoter analyses via luciferase reporter assay and electrophoretic mobility shift assay suggestid that TFE3 negatively regulated myogenin promoter activity by direct binding to an E-box, E2, in the myogenin promoter. These findings indicated that TFE3 has a regulatory role in myoblast differentiation, and that transcriptional suppression of myogenin expression may be part of the mechanism of action. (C) 2012 Elsevier Inc. All rights reserved.

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  • Low BMI at age 20years predicts gestational diabetes independent of BMI in early pregnancy in Japan: Tanaka Women's Clinic Study Reviewed

    Y. Yachi, Y. Tanaka, I. Nishibata, A. Sugawara, S. Kodama, K. Saito, H. Sone

    Diabetic Medicine   30 ( 1 )   70 - 73   2013.1

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    Aims Maternal obesity and weight gain since early adulthood are known predictors of gestational diabetes in Western countries. However, their impact has not been evaluated well in Asia, where mean BMI levels are generally lower than in Western countries. We therefore examined the associations of BMI at age 20years and BMI change since age 20years with the risk of gestational diabetes in Japanese pregnant women. Methods Six hundred and twenty-four consecutive pregnant women without recognized diabetes before pregnancy, whose initial obstetric clinic visit was before 13weeks' gestation, were prospectively observed. Weight at age 20years was self-reported. Baseline height and weight measurements were obtained at the initial obstetric visit. Multivariate logistic regression analysis estimated the risk of incident gestational diabetes for BMI change since 20years and BMI at age 20years. Results Twenty-eight women developed incident gestational diabetes. By multivariate logistic regression analysis that adjusted for maternal age, parity and baseline BMI, we observed a statistically significant inverse association between BMI at age 20years and incidence of gestational diabetes (odds ratio 0.68, 95% CI 0.51-0.92). Similarly, when we assessed the association of BMI change since age 20years, adjusted for maternal age and parity, BMI change was associated with an increased risk of gestational diabetes (odds ratio 1.26, 95%CI 1.03-1.53). When we focused on the threshold of risk of gestational diabetes, women with BMI at 20years of less than 18kg/m2 had a 6.30-fold (2.26-17.59) greater risk than women with both BMI at age 20years of 18kg/m2 or more and BMI change since age 20years of less than 1.85. Conclusions Both low BMI at age 20years and BMI change since age 20years were significantly associated with increased risk of incident gestational diabetes. © 2012 Diabetes UK.

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  • The Relationship between Diabetic Neuropathy and Sleep Apnea Syndrome: A Meta-Analysis. Reviewed International journal

    Kazuya Fujihara, Satoru Kodama, Chika Horikawa, Sakiko Yoshizawa, Ayumi Sugawara, Reiko Hirasawa, Hitoshi Shimano, Yoko Yachi, Akiko Suzuki, Osamu Hanyu, Hirohito Sone

    Sleep disorders   2013   150371 - 150371   2013

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    Aims. High prevalence of sleep apnea syndrome (SAS) has been reported in patients with diabetes. However, whether diabetic neuropathy (DN) contributes to this high prevalence is controversial. Our aim of this study is to compare the prevalence of SAS between patients with and without DN. Methods. Systematic literature searches were conducted for cross-sectional studies that reported the number of patients with DN and SAS using MEDLINE (from 1966 to Nov 5, 2012) and EMBASE (from 1974 to Nov 5, 2012). Odds ratios (ORs) of SAS related to DN were pooled with the Mantel-Haenszel method. Results. Data were obtained from 5 eligible studies (including 6 data sets, 880 participants, and 429 cases). Overall, the pooled OR of SAS in patients with DN compared with that in non-DN patients was significant (OR (95% CI), -1.95 (1.03-3.70)). The pooled OR of SAS was 1.90 (0.97-3.71) in patients with type 2 diabetes. Excluding data on patients with type 1 diabetes, a higher OR was observed in younger patients (mean age <60 years) than in those ≥60 years among whom the OR remained significant (3.82; 95% CI, 2.24-6.51 and 1.17; 95% CI, 0.81-1.68). Conclusions. Current meta-analysis suggested the association of some elements of neuropathy with SAS in type 2 diabetes. Further investigations are needed to clarify whether the association is also true for patients with type 1 diabetes.

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  • Carotid artery plaque and LDL-to-HDL cholesterol ratio predict atherosclerotic status in coronary arteries in asymptomatic patients with type 2 diabetes mellitus Reviewed

    Kazuya Fujihara, Hiroaki Suzuki, Akira Sato, Satoru Kodama, Yoriko Heianza, Kazumi Saito, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Nobuhiro Yamada, Hirohito Sone, Hitoshi Shimano

    Journal of Atherosclerosis and Thrombosis   20 ( 5 )   452 - 464   2013

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    Aims: To investigate the clinical predictors of coronary atherosclerosis and to assess the utility of maximum-IMT for predicting coronary atherosclerosis in asymptomatic type 2 diabetic patients. Methods: One hundred one Japanese patients with type 2 diabetes underwent computed tomography coronary angiography. Definitions of coronary artery stenosis and vulnerable coronary plaque were luminal narrowing of ≥50% and any coronary plaque with positive vessel remodeling and low attenuation, respectively. Carotid intima-media thickness (IMT) was assessed using B-mode ultrasound. Results: Of the 101 patients, 40 had coronary artery stenosis without vulnerable coronary plaque, 7 had vulnerable coronary plaque without coronary artery stenosis, and 23 had coronary artery stenosis with vulnerable coronary plaque. Male sex (p= 0.031), duration of diabetes (p= 0.024), systolic blood pressure (SBP) (p=0.039), and the LDL/HDL ratio (LDL/HDL) (p=0.013) were independent predictors of coronary artery stenosis and the LDL/HDL (p=0.042) independently predicted vulnerable coronary plaque by logistic regression analyses. Areas under the curves in receiver operating characteristic curve analysis of the maximum-IMT, LDL/HDL, and these two parameters combined were 0.711 (95% CI 0.601-0.820), 0.618 (0.508-0.728), and 0.732 (0.632-0.831), respectively, for predicting coronary artery stenosis and 0.655 (0.537-0.773), 0.629 (0.504-0.754), and 0.710 (0.601- 0.818), respectively, for predicting vulnerable coronary plaque. Conclusions: Male sex, duration of diabetes, elevated SBP, and LDL/HDL were independent predictors of coronary artery stenosis. LDL/HDL was an independent predictor of vulnerable coronary plaque. Maximum-IMT predicted both coronary stenosis and vulnerable coronary plaque. Adding LDL/HDL improved the prediction of coronary artery stenosis and vulnerable coronary plaque.

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  • Various Components of Blood Pressure as Stroke Risk in Japanese Patients With Type 2 Diabetes: Analysis from the Japan Diabetes Complications Study (JDCS)

    Hirohito Sone

    Diabetes   2013

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  • Combined Risk of Alcohol Intake and Smoking for Development of Type 2 Diabetes in the General Population in Japan: The Ibaraki Prefectural Health Study

    Hirohito Sone

    Diabetes   2013

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  • Effects of Recommendation Notices for Clinic Visits by Nationwide Health Screening System in Japan

    Hirohito Sone

    Diabetes   2013

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  • Elovl6 Promotes Nonalcoholic Steatohepatitis Reviewed

    Takashi Matsuzaka, Ayaka Atsumi, Rie Matsumori, Tang Nie, Haruna Shinozaki, Noriko Suzuki-Kemuriyama, Motoko Kuba, Yoshimi Nakagawa, Kiyoaki Ishii, Masako Shimada, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Kazuhiro Takekoshi, Hirohito Sone, Naoya Yahagi, Hiroaki Suzuki, Soichiro Murata, Makoto Nakamuta, Nobuhiro Yamada, Hitoshi Shimano

    HEPATOLOGY   56 ( 6 )   2199 - 2208   2012.12

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    Nonalcoholic steatohepatitis (NASH) is associated with obesity and type 2 diabetes, and an increased risk for liver cirrhosis and cancer. ELOVL family member 6, elongation of very long chain fatty acids (Elovl6), is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have shown previously that Elovl6 is a major target for sterol regulatory element binding proteins in the liver and that it plays a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further investigate the role of Elovl6 in the development of NASH and its underlying mechanism, we used three independent mouse models with loss or gain of function of Elovl6, and human liver samples isolated from patients with NASH. Our results demonstrate that (1) Elovl6 is a critical modulator for atherogenic high-fat diet-induced inflammation, oxidative stress, and fibrosis in the liver; (2) Elovl6 expression is positively correlated with severity of hepatosteatosis and liver injury in NASH patients; and (3) deletion of Elovl6 reduces palmitate-induced activation of the NLR family pyrin domain-containing 3 inflammasome; this could be at least one of the underlying mechanisms by which Elovl6 modulates the progress of NASH. Conclusion: Hepatic long-chain fatty acid composition is a novel determinant in NASH development, and Elovl6 could be a potential therapeutic target for the prevention and treatment of NASH. (HEPATOLOGY 2012;56:2199-2208)

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  • Development of a new scoring system for predicting the 5 year incidence of type 2 diabetes in Japan: the Toranomon Hospital Health Management Center Study 6 (TOPICS 6) Reviewed

    Y. Heianza, Y. Arase, S. D. Hsieh, K. Saito, H. Tsuji, S. Kodama, S. Tanaka, Y. Ohashi, H. Shimano, N. Yamada, S. Hara, H. Sone

    Diabetologia   55 ( 12 )   3213 - 3223   2012.12

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    Aims/hypothesis The aims of this study were to assess the clinical significance of introducing HbA1c into a risk score for diabetes and to develop a scoring system to predict the 5 year incidence of diabetes in Japanese individuals. Methods The study included 7,654 non-diabetic individuals aged 40-75 years. Incident diabetes was defined as fasting plasma glucose (FPG) ≤7.0 mmol/l, HbA1c ≤6.5% (48 mmol/mol) or self-reported clinician-diagnosed diabetes. We constructed a risk score using non-laboratory assessments (NLA) and evaluated improvements in risk prediction by adding elevated FPG, elevated HbA1c or both to NLA. Results The discriminative ability of the NLA score (age, sex, family history of diabetes, current smoking and BMI) was 0.708. The difference in discrimination between the NLA + FPG and NLA + HbA1c scores was non-significant (0.836 vs 0.837
    p=0.898). A risk score including family history of diabetes, smoking, obesity and both FPG and HbA1c had the highest discrimination (0.887, 95% CI 0.871, 0.903). At an optimal cut-off point, sensitivity and specificity were high at 83.7% and 79.0%, respectively. After initial screening using NLA scores, subsequent information on either FPG or HbA1c resulted in a net reclassification improvement of 42.7% or 52.3%, respectively (p&lt
    0.0001). When both were available, net reclassification improvement and integrated discrimination improvement were further improved at 56.7% (95% CI 47.3%, 66.1%) and 10.9% (9.7%, 12.1%), respectively. Conclusions/interpretation Information on HbA1c or FPG levels after initial screening by NLA can precisely refine diabetes risk reclassification. © Springer-Verlag 2012.

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  • Enhancement of antigen presenting ability in the leukemic plasmacytoid dendritic cell line (PMDC05) by lentiviral vector-mediated transduction of CD80 gene Reviewed

    Akie Yamahira, Miwako Narita, Kayoko Ishii, R. M. Chamila Jayathilake, Minami Iwabuchi, Naoya Satoh, Takayoshi Uchiyama, Tomoyo Taniguchi, Shigeo Hashimoto, Noriyuki Kasahara, Emmanuelle Faure, Brooke Bogan, Jun Takizawa, Hirohito Sone, Masuhiro Takahashi

    LEUKEMIA RESEARCH   36 ( 12 )   1541 - 1546   2012.12

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    PMDC05, a leukemic plasmacytoid dendritic cell (pDC) line which was established in our laboratory, showed a capacity of generating antigen-specific cytotoxic T lymphocytes (CTLs). In order to enhance an antigen presenting ability of PMDC05, PMDC05 was transduced with CD80 gene by lentiviral vector, which was named as PMDC11. PMDC11 displayed a strong antigen presenting ability even without any stimulation, and by culturing with stimulators such as calcium ionophore PMDC11 gained a more potent antigen presenting ability. Our data suggested PMDC11 could be applied as antigen presenting cells more efficiently in adoptive cellular immunotherapy for tumors and severe infections in comparison with PMDC05. (C) 2012 Elsevier Ltd. All rights reserved.

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  • Cholesterol sulfate induces expression of the skin barrier protein filaggrin in normal human epidermal keratinocytes through induction of ROR alpha Reviewed

    Osamu Hanyu, Hanako Nakae, Takashi Miida, Yuko Higashi, Hirotoshi Fuda, Motohiro Endo, Atsushi Kohjitani, Hirohito Sone, Charles A. Strott

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   428 ( 1 )   99 - 104   2012.11

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    Cholesterol sulfate is abundant in the human epidermis and is a putative natural ligand for retinoic acid receptor-related orphan receptor alpha (ROR alpha). Although direct binding of cholesterol sulfate is expected to activate ROR alpha, cholesterol sulfate can also induce ROR alpha expression and increase ROR alpha target gene expression. The purpose of this study was to determine whether cholesterol sulfate induces profilaggrin expression, a precursor of the barrier protein filaggrin in the epidermis, through activation of ROR alpha by directly binding to ROR alpha, or through increased ROR alpha expression. Immunohistochemical and polymerase chain reaction (PCR) analyses showed that ROR alpha was expressed in normal human epidermal keratinocytes (NHEKs) and that its expression increased during keratinocyte differentiation in parallel with that of profilaggrin and cholesterol sulfotransferase, which catalyzes the synthesis of cholesterol sulfate. Exogenous cholesterol sulfate significantly increased both ROR alpha and profilaggrin expression in NHEKs, whereas no effect on profilaggrin expression was observed in cells in which ROR alpha was knocked down with small interfering RNA (siRNA). Additionally, a luciferase reporter gene assay revealed that exogenous ROR alpha dose-dependently increased the activity of the profilaggrin gene promoter even in the absence of cholesterol sulfate, and that this response involves activator protein-1. In conclusion, the results of this study indicate that cholesterol sulfate induces filaggrin expression through increased ROR alpha expression. Further studies are required to fully elucidate the mechanisms involved. (C) 2012 Elsevier Inc. All rights reserved.

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  • Self-reported rate of eating is significantly associated with body mass index in Japanese patients with type 2 diabetes. Japan Diabetes Clinical Data Management Study Group (JDDM26) Reviewed

    Aki Saito, Koichi Kawai, Morifumi Yanagisawa, Hiroki Yokoyama, Nobuichi Kuribayashi, Hidekatsu Sugimoto, Mariko Oishi, Takako Wada, Koichi Iwasaki, Azuma Kanatsuka, Noriharu Yagi, Fuminobu Okuguchi, Kazuhiro Miyazawa, Keiko Arai, Kazumi Saito, Hirohito Sone

    APPETITE   59 ( 2 )   252 - 255   2012.10

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    We examined whether the rate of eating was associated with the body mass index and glycemic control status in Japanese patients with type 2 diabetes (50% women, mean +/- SD age 59.4 +/- 7.5 years). Rapid eating was significantly associated with body mass index (p = 0.047). The body mass index of those who reported eating quickly was 0.8 kg/m(2) higher than in individuals who reported eating at medium speed even after adjustment for known confounders. No significant association was observed between the rate of eating and HbA(1c). Our findings suggest an association between self-reported rapid eating and an elevated body mass index in patients with type 2 diabetes. (C) 2012 Elsevier Ltd. All rights reserved.

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  • Development of Coronary Heart Disease and Cerebral Stroke in Japanese Elderly Patients with Nonalcoholic Fatty Liver Diseases

    OGAWA Kyoko, OHMONTO SEKINE Yuki, HARA Shigeko, OKUDA Chikao, AMAKAWA Kazuhisa, ARIMOTO Satao, KATO Hisahito, HSIEH Shiun Dong, TANABE Maho, OGATA Chie, ISHIHARA Makiko, TSUJI Hiroshi, SAITO Kazumi, KODAMA Satoru, SONE Hirohito, ARASE Yasuji

    Official Journal of the Japanese Society of Human Dry Dock   27 ( 3 )   561 - 567   2012.9

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    <b>Objective: </b>Metabolic syndrome enhances coronary heart disease and cerebral stroke. However, few longitudinal studies have been conducted on the incidence of coronary heart disease and cerebral stroke in Japanese patients with non-alcoholic fatty liver disease (NAFLD) and the risk factors for its development. <br><b>Methods: </b>A total of 1,798 NAFLD patients with an age of ≥60 years were enrolled. The primary event was the first onset of coronary heart disease or cerebral stroke. Independent factors associated with the incidence rate of such events were analyzed by the Kaplan-Meyer method and the Cox proportional hazard model. The mean observation period was 7.5 years.<br><b>Results: </b>The number of cases of coronary heart disease or cerebral stroke that developed was 137. The 10th year cumulative development rate was 11.7% in the NAFLD patients. Cox proportional hazards analysis revealed the following: 1) Coronary heart disease occurred with statistical significance when patients had poor control of blood pressure, smoking, low high density lipoprotein level, and high glucose level. 2) Ischemic stroke occurred with statistical significance when patients had poor control of blood pressure, an age of ≥70 years, and high glucose level. 3) Hemorrhagic stroke occurred with statistical significance when patients had poor control of blood pressure, age ≥70 years, low albumin level of <3.9 g/dL and high aspartate aminotransferase to platelet ratio index. <br><b>Conclusion: </b>Our study indicates that the risk factors for the development of vascular disease are different for coronary heart disease, ischemic stroke and hemorrhagic stroke in Japanese elderly patients with NAFLD.

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  • Screening for pre-diabetes to predict future diabetes using various cut-off points for HbA1c and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4)

    Y. Heianza, Y. Arase, K. Fujihara, H. Tsuji, K. Saito, S. D. Hsieh, S. Kodama, H. Shimano, N. Yamada, S. Hara, H. Sone

    DIABETIC MEDICINE   29 ( 9 )   E279 - E285   2012.9

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    Diabet. Med. 29, e279-e285 (2012) Abstract Aim To evaluate various screening criteria for pre-diabetes to identify which combination of impaired fasting glucose and elevated HbA1c values performs most effectively in predicting future diabetes in a large cohort of Japanese individuals. Methods The study included 4670 men and 1571 women without diabetes (diabetes: fasting plasma glucose = 7.0 mmol/l, HbA1c= 48 mmol/mol (= 6.5%), or self-reported clinician-diagnosed diabetes). Pre-diabetes was diagnosed by a combination of impaired fasting glucose (fasting plasma glucose 5.66.9 mmol/l or 6.16.9 mmol/l) and elevated HbA1c [3946 mmol/mol (5.76.4%) or 4246 mmol/mol (6.06.4%)]. Results During a 5-year follow-up, 338 incident cases of diabetes occurred. The combination of HbA1c 3946 mmol/mol (5.76.4%) and fasting plasma glucose 5.66.9 mmol/l yielded the highest sensitivity (86%) and generated a large population-attributable per cent risk (78%) for predicting development of diabetes. Among individuals classified as having pre-diabetes by any of the four combined criteria, 20.532.0% reverted to the normoglycaemic state as having neither elevated HbA1c nor impaired fasting glucose at the last follow-up examination. At 5.6 years after the baseline examination, however, pre-diabetic individuals who fulfilled both HbA1c 4246 mmol/mol (6.06.4%) and fasting plasma glucose 6.16.9 mmol/l had a 100% cumulative risk of developing diabetes. Conclusions The combination of HbA1c 3946 mmol/mol (5.76.4%) and fasting plasma glucose 5.66.9 mmol/l would have the best performance in reducing the likelihood of missing future cases of diabetes. Identifying pre-diabetic individuals who strictly fulfil HbA1c 4246 mmol/mol (6.06.4%) and fasting plasma glucose 6.16.9 mmol/l would predict definite progression to diabetes.

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  • Low Lung Function and Risk of Type 2 Diabetes in Japanese Men: The Toranomon Hospital Health Management Center Study 9 (TOPICS 9) Reviewed

    Yoriko Heianza, Yasuji Arase, Hiroshi Tsuji, Kazumi Saito, Kazuhisa Amakawa, Shiun Dong Hsieh, Satoru Kodama, Hitoshi Shimano, Nobuhiro Yamada, Shigeko Hara, Hirohito Sone

    MAYO CLINIC PROCEEDINGS   87 ( 9 )   853 - 861   2012.9

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    Objective: To evaluate the effect of elevated fasting plasma glucose (FPG) and hemoglobin A(1c) (HbA(1c)) concentrations on lung dysfunction and to prospectively investigate whether reduced lung function would be independently predictive of diabetes.
    Participants and Methods: From January 6, 1997, through December 22, 2008, we observed 5346 men with no history of diabetes or lung dysfunction. Hazard ratios (HRs) for incident diabetes (FPG &gt;= 126 mg/dL, HbA(1c)&gt;= 6.5%, or self-reported clinician-diagnosed diabetes) were estimated for spirometry indices as continuous and categorical variables.
    Results: Elevated HbA(1c) concentrations within the normal range were significantly and more strongly associated with reduced forced vital capacity and forced expiratory volume in the first second after expiration (FEV1) than were FPG concentrations. During a 4.0-year follow-up, diabetes developed in 214 individuals. A 10-point decrease in percentage of FEV1 predicted value was associated with an increased HR of 1.21 (95% confidence interval [CI], 1.09-1.34; P=.001) for diabetes after adjustment for demographic factors and body mass index. This association remained significant even after adjustment for metabolic factors, smoking status, and FPG or HbA(1c) concentrations but was attenuated substantially after adjustment for baseline HbA(1c) values (HR, 1.13; 95% CI, 1.01-1.26; P=.03). Lower quartile (Q) categories of percentage of FEV1 predicted value were associated with increased risk of diabetes independently of known predictors including HbA(1c) (HR, 1.73; 95% CI, 1.14-2.62 for Q1; and HR, 1.76; 95% CI, 1.15-2.69 for Q2).
    Conclusion: Reduced lung function was significantly related to chronic glycemic exposure within a normal range. Relatively low pulmonary function was an independent risk factor for diabetes in apparently healthy Japanese men. (C) 2012 Mayo Foundation for Medical Education and Research square Mayo Clin Proc. 2012:87(9);853-861

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  • HbA(1c) variability and the development of microalbuminuria in type 2 diabetes: Tsukuba Kawai Diabetes Registry 2 Reviewed

    A. Sugawara, K. Kawai, S. Motohashi, K. Saito, S. Kodama, Y. Yachi, R. Hirasawa, H. Shimano, K. Yamazaki, H. Sone

    DIABETOLOGIA   55 ( 8 )   2128 - 2131   2012.8

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    The aim of this study was to examine the association between HbA(1c) variability and the development of microalbuminuria as defined by an albumin/creatinine ratio a parts per thousand yen3.4 mg/mmol (a parts per thousand yen30 mg/g) in at least two of three consecutive urine samples in Japanese patients with type 2 diabetes.
    HbA(1c) level was measured in 812 serially registered normoalbuminuric adults aged 21-79 years with type 2 diabetes. After registration, a 1-year period to establish baseline values for mean HbA(1c) and HbA(1c) variability (measured as the intrapersonal SD of serially collected HbA(1c)) was decided upon. The association between HbA(1c) variability and the development of microalbuminuria was determined by Cox regression analysis after adjustment for other risk factors for microalbuminuria.
    Microalbuminuria occurred in 193 patients during the observation period of (mean +/- SD) 4.3 +/- 2.7 years. Even after adjustment for mean HbA(1c), HbA(1c) variability was a significant predictor of microalbuminuria independently of the mean HbA(1c); the HR for every 1% (95% CI) increase in mean HbA(1c) was 1.22 (1.06, 1.40) (p = 0.005), and that for HbA(1c) variability was 1.35 (1.05, 1.72) (p = 0.019). The effects of these two variables were quite similar when 1 SD was used; the HR for every 1 SD increase (95% CI) in HbA(1c) was 1.23 (1.07, 1.43) (p = 0.005), and that for HbA(1c) variability was 1.20 (1.03, 1.39) (p = 0.019).
    HbA(1c) variability affects the development of microalbuminuria independently of mean HbA(1c) in type 2 diabetes. Further studies should be performed to evaluate the influence of HbA(1c) variability on other complications and in individuals of other ethnicities with type 2 diabetes.

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  • [Characteristics of diabetic macroangiopathy in Japan and East Asia]. Reviewed

    Sone H

    Nihon rinsho. Japanese journal of clinical medicine   70 Suppl 5   305 - 312   2012.7

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  • Present situation of exercise therapy for patients with diabetes mellitus in Japan: A nationwide survey Reviewed

    Y. Sato, K. Kondo, T. Watanabe, H. Sone, M. Kobayashi, R. Kawamori, Y. Tamura, Y. Atsumi, Y. Oshida, S. Tanaka, S. Suzuki, S. Makita, I. Ohsawa, S. Imamura

    Diabetology International   3 ( 2 )   86 - 91   2012.6

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    Purpose: This study was performed to investigate the actual situation and problems of exercise therapy in Japan. Methods: A self-recording questionnaire was prepared and sent to 1,200 randomly selected diabetologists and non-specialist physicians of the Japan Medical Association. Responses were obtained from 403 physicians (34% response rate). Two subgroups of the physicians were extracted according to the rate of exercise guidance provided to patients at their initial visit to the clinic: more than 70% [high-rate of exercise guidance (HG) group, N = 212] and less than 50% [low-rate of exercise guidance (LG) group, N = 131]. Results: The rate of exercise guidance was significantly lower (p &lt
    0. 001) than that of dietary guidance. About 65 and 53% of physicians in both groups responded that their "lack of time" and the "absence of an additional consultation fee," respectively, were the main problems they faced for implementing exercise guidance to patients. Compared with the HG group, a higher number of physicians in the LG group responded that there were no specialized physical exercise educators in their clinics (p &lt
    0. 001). As to the reasons why patients do not perform exercise, 70% of physicians responded that patients "had no time to exercise" and "were not eager to perform exercise."Conclusions: The current survey revealed that, in Japan, the proportion of exercise guidance is low because physicians have no time, they receive no additional consultation fee, and specialized physical exercise educators are lacking. Although an improvement in these factors may lead to higher rates of exercise guidance, we consider that the preparation of specific exercise guidelines for type 2 diabetes patients is essential to effectively implement this therapy in clinical practice. © 2012 The Japan Diabetes Society.

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  • [New vision of secondary and tertiary prevention in diabetic complication]. Reviewed

    Fujihara K, Sone H

    Nihon rinsho. Japanese journal of clinical medicine   70 Suppl 3   561 - 569   2012.5

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  • Quantification of BCR-ABL mRNA in Plasma/Serum of Patients with Chronic Myelogenous Leukemia Reviewed

    Miwako Narita, Anri Saito, Aya Kojima, Minami Iwabuchi, Naoya Satoh, Takayoshi Uchiyama, Akie Yamahira, Tatsuo Furukawa, Hirohito Sone, Masuhiro Takahashi

    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES   9 ( 10 )   901 - 908   2012

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    Quantification of tumor-associated mRNA extracted from blood cells/tissues containing tumor cells is used for evaluation of treatment efficacy or residual tumor cell burden in tumors including leukemia. However, this method using tumor cell-containing blood/tissue is difficult to evaluate the whole tumor cell burden in the body. In order to establish an efficient method to evaluate the whole tumor cell burden in the body, we tried to quantify tumor-associated mRNA existing in plasma/serum instead of leukemia cell-containing blood cells in patients with chronic myelogenous leukemia (CML) and compared the levels of BCR-ABL mRNA between plasma/serum and peripheral blood cells. mRNA of BCR-ABL, WT1 or GAPDH (control molecule) was detected by real-time RT-PCR using RNA extracted from plasma/serum of almost all the patients with CML. Copy numbers of BCR-ABL mRNA were significantly correlated between plasma/serum and peripheral blood cells. However, levels of BCR-ABL mRNA extracted from serum were low compared with those extracted with peripheral blood cells. The present findings suggest that although real-time RT-PCR of mRNA existing in plasma/serum could be used for evaluating the whole tumor cell burden in the body, it's required to establish an efficient method to quantify plasma/serum mRNA by nature without degrading during the procedure.

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  • Impact of psychological stress caused by the Great East Japan Earthquake on glycemic control in patients with diabetes Reviewed

    K. Fujihara, A. Saito, Y. Heianza, H. Gibo, H. Suzuki, H. Shimano, K. Saito, S. Kodama, N. Yamada, H. Sone

    Experimental and Clinical Endocrinology and Diabetes   120 ( 9 )   560 - 563   2012

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    We examined the relationship between psychological stress and the worsening of glycemic control in diabetic patients at the time of the Great East Japan Earthquake. HbA1c levels in diabetic patients before and after the disaster were evaluated with the General Health Questionnaire (GHQ) and other questions including those on changes in diet, exercise, psychological stress and drug intake in 320 consecutive diabetic patients who had been followed in a diabetes clinic. Logistic regression analysis revealed that the total GHQ scores (odds ratio [OR] 1.03 [95% confidence interval 1.01-1.06]
    p&lt
    0.01) and interruption of drug intake (OR 4.48 [1.57-12.7]
    p=0.01) were independently associated with worsening of glycemic control defined as an increase in the HbA1c level equal to or greater than 0.5%. Among the scores on the GHQ, those for somatic symptoms (OR 1.18 [1.01-1.38]
    p=0.03) and sleep disturbances or anxiety (OR 1.26 [1.08-1.46]
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    0.01) were independently associated with glycemic control. These results suggest that psychological stress during a disaster has independent effects on worsening of glycemic control. © Georg Thieme Verlag KG Stuttgart · New York.

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  • Diagnosis and Management of Type I and Type V Hyperlipoproteinemia Reviewed

    Takanari Gotoda, Koji Shirai, Takao Ohta, Junji Kobayashi, Shinji Yokoyama, Shinichi Oikawa, Hideaki Bujo, Shun Ishibashi, Hidenori Arai, Shizuya Yamashita, Mariko Harada-Shiba, Masaaki Eto, Toshio Hayashi, Hirohito Sone, Hiroaki Suzuki, Nobuhiro Yamada

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   19 ( 1 )   1 - 12   2012

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    Both type I and type V hyperlipoproteinemia are characterized by severe hypertriglyceridemia due to an increase in chylomicrons. Type I hyperlipoproteinemia is caused by a decisive abnormality of the lipoprotein lipase (LPL)- apolipoprotein C-II system, whereas the cause of type V hyperlipoproteinemia is more complicated and more closely related to acquired environmental factors. Since the relationship of hypertriglyceridemia with atherosclerosis is not as clear as that of hypercholesterolemia, and since type I and V hyperlipoproteinemia are relatively rare, few guidelines for their diagnosis and treatment have been established; however, type I and V hyperlipoproteinemia are clinically important as underlying disorders of acute pancreatitis, and appropriate management is necessary to prevent or treat such complications. Against such a background, here we propose guidelines primarily concerning the diagnosis and management of type I and V hyperlipoproteinemia in Japanese.

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  • Idiopathic Macrocytosis in Smokers

    Takahashi Masuhiro, Yamahira Akie, Uchiyama Takayoshi, Iwabuchi Minami, Sato Naoya, Takizawa Jun, Sone Hirohito, Narita Miwako

    Official Journal of the Japanese Society of Human Dry Dock   27 ( 4 )   689 - 696   2012

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    <b>Objective:</b> Smoking has been reported to be one of the risk factors of myelodysplastic syndrome (MDS). In order to clarify the process of progression to MDS in a certain group of smokers, it is important to identify the initial hematological abnormalities associated with the early stage of MDS in smokers. <br><b>Methods:</b> Relationships of hematological parameters such as WBC count, RBC count, Hb, Ht, MCH and MCV with level of smoking were investigated by univariate and multivariate analyses in 234 male workers at a single workplace after obtaining informed consent.<br><b>Results:</b> Univariate analysis demonstrated that correlations of smoking-related factors (number of cigarettes per day, duration of smoking [years] and smoking index [defined as number of cigarettes per day x duration of smoking]) with WBC count, Ht, MCH and MCV were significantly positive. Multivariate analysis using age, smoking-related factors, alcohol intake and BMI as explanatory valuables showed that age, alcohol intake and BMI were not confounding variables for smoking-related factors and revealed a remarkable significant positive correlation between each smoking-related factor and MCV.<br><b>Conclusion:</b> Smoking-associated macrocytosis, which was demonstrated in the present study, was not due to deficiency of vitamin B<sub>12</sub> or folic acid because of no pancytopenia observed but was considered to be a qualitative abnormality of erythrocytes. Taken together with the findings of previous studies concerning smoking-associated functional abnormalities of erythrocytes and leukocytes and the high incidence of MDS in smokers, our results indicate that idiopathic macrocytosis in smokers could be an initial sign of progression to MDS, in which macrocytosis and multi-lineage abnormalities are characteristic findings.

    DOI: 10.11320/ningendock.27.689

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  • Determining Optimal Combined Thresholds of HbA1c and Fasting Plasma Glucose as Predictors of Type 2 Diabetes: The Toranomon Hospital Health Management Center Study

    Hirohito Sone

    Diabetes   2012

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    DOI: 10.2337/DB12-1329-1552

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  • Low Lung Function and Risk of Type 2 Diabetes in Japanese Men: The Toranomon Hospital Health Management Center Study

    Hirohito Sone

    Diabetes   2012

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  • Erratum: Accumulation of cardiovascular risks in Japanese women with abnormal glucose and mild to moderate hypercholesterolemia (International Journal of Cardiology (2011) 152,2 (254-256)) Reviewed

    Tomoko Nakagami, Rimei Nishimura, Hirohito Sone, Naoko Tajima

    International Journal of Cardiology   153 ( 2 )   238   2011.12

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    DOI: 10.1016/j.ijcard.2011.10.005

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  • siRNA-mediated knockdown of aryl hydrocarbon receptor nuclear translocator 2 affects hypoxia-inducible factor-1 regulatory signaling and metabolism in human breast cancer cells.

    Qin XY, Wei F, Yoshinaga J, Yonemoto J, Tanokura M, Sone H

    2011.10

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  • Xenoestrogens down-regulate aryl-hydrocarbon receptor nuclear translocator 2 mRNA expression in human breast cancer cells via an estrogen receptor alpha-dependent mechanism.

    Qin XY, Zaha H, Nagano R, Yoshinaga J, Yonemoto J, Sone H

    2011.10

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    DOI: 10.1016/j.toxlet.2011.07.007

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  • Accumulation of cardiovascular risks in Japanese women with abnormal glucose and mild to moderate hypercholesterolemia Reviewed

    Tomoko Nakagami, Rimei Nishimura, Hirohito Sone, Naoko Tajima

    INTERNATIONAL JOURNAL OF CARDIOLOGY   152 ( 2 )   254 - 256   2011.10

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    DOI: 10.1016/j.ijcard.2011.07.091

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  • Ghrelin attenuates cAMP-PKA signaling to evoke insulinostatic cascade in islet β-cells.

    Dezaki K, Damdindorj B, Sone H, Dyachok O, Tengholm A, Gylfe E, Kurashina T, Yoshida M, Kakei M, Yada T

    2011.9

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    DOI: 10.2337/db11-0368

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  • Factors associated with inappropriate weight loss attempts by early adolescent girls in Japan Reviewed

    A. Sugawara, M. Sato, K. Totsuka, K. Saito, S. Kodama, A. Fukushi, Y. Yamanashi, E. Matsushima, Y. Fujiwara, E. Suzuki, K. Kondo, S. Yamamoto, H. Sone

    Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity   16 ( 3 )   e157 - e163   2011.9

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    Attempting to lose weight by normal or underweight adolescent girls is a serious issue in many countries. It has been reported that the mode of attempted weight loss does not differ between normal weight and overweight girls. These inappropriate weight loss attempts (IWLA) by normal or underweight adolescent girls is associated with various health issues, but factors associated with IWLA have only been marginally elucidated. In this study, we applied a single multivariate regression analysis to clarify independent factors for IWLA. Study subjects were 134 pairs of early adolescent girls (aged 12-15) and their mothers. In addition to IWLA, many factors including height, weight, body image, perceived weight status, depressive symptoms, media influence and self-esteem were surveyed in both mothers and daughters and subjected to multivariate analysis. Approximately half of girls surveyed had IWLA, even though all were of normal weight and 62.9% knew that they were of normal weight. IWLA were independently associated with depressive symptoms (OR (95% CI); 2.80 (1.21-6.50), p=0.016) independent of actual or perceived weight status. Factors significantly associated with IWLA by the girls were percentage deviation of weight from standard weight (%DW) and media influence on the girls themselves, and media influence on and self-esteem of their mothers. IWLA, which were frequently observed among early adolescent girls even among those of normal weight, were closely related to depressive status. IWLA were significantly associated with not only factors related to the girls (1.09 (1.04-1.14), p=0.001), but also with maternal psychological factors (1.06 (1.00-1.13), p=0.035) conveyed by the media. Future prospective or interventional studies are required to clarify whether these factors could be targeted in an effort to prevent IWLA. (Eating Weight Disord. 16: e157-e163, 2011). (C) 2011, Editrice Kurtis

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  • AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats.

    Kohno D, Sone H, Tanaka S, Kurita H, Gantulga D, Yada T

    2011.7

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  • Weight History as a Screening Tool for Identifying Undiagnosed Diabetes and Pre-Diabetes in Japanese Men: The Toranomon Hospital Health Management Center Study (TOPICS) Reviewed

    Sakiko Yoshizawa, Yoriko Heianza, Kazuya Fujiwara, Shigeko Hara, Kazumi Saito, Hiroshi Tsuji, Satoru Kodama, Yasuji Arase, Nobuhiro Yamada, Kinori Kosaka, Hirohito Sone

    DIABETES   60   A235 - A235   2011.7

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  • Weight History as a Screening Tool for Identifying Undiagnosed Diabetes and Pre-Diabetes in Japanese Men: The Toranomon Hospital Health Management Center Study (TOPICS) Reviewed

    Sakiko Yoshizawa, Yoriko Heianza, Kazuya Fujiwara, Shigeko Hara, Kazumi Saito, Hiroshi Tsuji, Satoru Kodama, Yasuji Arase, Nobuhiro Yamada, Kinori Kosaka, Hirohito Sone

    DIABETES   60   A235 - A235   2011.7

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  • Nifedipine, a calcium-channel blocker, attenuated glucose intolerance and white adipose tissue dysfunction in type 2 diabetic KK-A(y) mice.

    Iwai M, Kanno H, Inaba S, Senba I, Sone H, Nakaoka H, Horiuchi M

    2011.2

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    DOI: 10.1038/ajh.2010.198

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  • Nanometer resolution stress measurement of the Si gate using illumination-collection-type scanning near-field Raman spectroscopy with a completely metal-inside-coated pyramidal probe.

    Hosaka S, Aramomi Y, Sone H, Yin Y, Sato E, Tochigi K

    2011.1

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    DOI: 10.1088/0957-4484/22/2/025206

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  • [Diabetes mellitus and metabolic syndrome in epidemiological studies]. Reviewed

    Sone H

    Nihon rinsho. Japanese journal of clinical medicine   69 Suppl 1   93 - 100   2011.1

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  • Evaluation of Clinical Predictors of Vulnerable Coronary Plaque Detected by CT Angiography in Asymptomatic Patients with Type 2 Diabetes (T2DM)

    Hirohito Sone

    Diabetes   2011

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  • HbA1c Variability and Risk of Development of Microalbuminuria in Japanese Patients with Type 2 Diabetes: A Pilot Study, Tsukuba Kawai Diabetes Registry 3

    Hirohito Sone

    Diabetes   2011

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  • Self-Reported Rate of Eating Is Associated with BMI but Not with Glycemic Control Status in Japanese Patients with Type 2 Diabetes

    Hirohito Sone

    Diabetes   2011

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  • [Prevention and management of atherosclerotic complications of diabetes]. Reviewed

    Sone H

    Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics   48 ( 3 )   253 - 256   2011

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    DOI: 10.3143/geriatrics.48.253

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  • Flow-Mediated Dilation is Associated with Microalbuminuria Independent of Cardiovascular Risk Factors in Type 2 Diabetes - Interrelations with Arterial Thickness and Stiffness Reviewed

    Hiroki Yokoyama, Hirohito Sone, Kazumi Saito, Daishiro Yamada, Jun Honjo, Masakazu Haneda

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   18 ( 9 )   744 - 752   2011

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    Aims: To investigate whether endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is associated with urinary albumin excretion (UAE) and is interrelated with carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) in type 2 diabetes.Methods: We measured FMD, IMT and PWV in 158 subjects with type 2 diabetes (normo- 49, micro- 64, macroalbuminuria 45), explored the determinants of FMD, and analyzed the relationship of FMD with traditional cardiovascular risk factors according to IMT and PWV levels.Results: Microalbuminuria was significantly associated with lower FMD, higher IMT and higher PWV compared to normoalbuminuria (p<0.001 for all). FMD was significantly correlated with IMT and PWV, and also with traditional risk factors, UAE, glomerular filtration rate, diabetic retinopathy, and neuropathy. Multivariate regression analysis revealed that UAE remained a significant determinant of FMD independent of traditional risk factors, metabolic control, and renal function. The relationship of FMD with IMT and PWV was less pronounced in subjects with increased IMT and PWV.Conclusions: In individuals with type 2 diabetes, FMD is impaired in subjects with microalbuminuria and is associated with IMT and PWV only when these values are not increased, i.e., at an early stage of atherosclerosis.

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  • [Epidemiology of diabetic microangiopathy in Japan--comparison with Western countries]. Reviewed

    Sone H

    Nihon rinsho. Japanese journal of clinical medicine   68 Suppl 9   13 - 20   2010.11

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  • Comparison between Fasting and Post-Load Glucose Values as a Continuous Risk Factor for Cardiovascular Disease: A Meta-Analysis Reviewed

    Satoru Kodama, Chika Horikawa, Yui Anasako, Kazumi Saito, Reiko Hirasawa, Yoko Ibe, Yoko Yachi, Miho Asumi, Hitoshi Shimano, Nobuhiro Yamada, Hirohito Sone

    DIABETES   59 ( Suppl )   A298 - A298   2010.6

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  • [Japan Diabetes Complications Study (JDCS)]. Reviewed

    Sone H, Yamada N

    Nihon rinsho. Japanese journal of clinical medicine   70 Suppl 3   281 - 289   2010.5

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  • Body image: International comparisons: From the symposium held at the 15th international congress of dietetics Reviewed

    Ayumi Sugawara, Jun Yanagishita, Ayami Sano, Yueching Wong, Duc Son N.T Le, Jeanne B. Martin, Shigeru Yamamoto, Hirohito Sone

    Nutrition Today   45 ( 3 )   113 - 117   2010.5

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    To be thin is the desire of many young women because of idealized body images in the media as well as cultural factors. This review summarizes the content of the symposium, "International Comparison of Body Image," which was part of the 15th International Congress of Dietetics held in Yokohama, Japan, on September 8 to 11, 2008. Body image is a term that refers to one's perception of his/her own physical appearance and how that body appears to others. A negative body image usually has unfavorable consequences, such as the development of an eating disorder. The desire for thinness is widespread, even in non-Western countries. For example, young Japanese women have an even stronger desire to be thin than their American or Vietnamese counterparts. Abnormal eating behaviors are common among adolescents in both Western and non-Western countries. Therefore, we should monitor inappropriate weight loss attempts, especially by adolescents in all countries. Copyright © 2010 Lippincott Williams &amp
    Wilkins.

    DOI: 10.1097/NT.0b013e3181dec6bb

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  • Absorption and effectiveness of orally administered low molecular weight collagen hydrolysate in rats.

    Watanabe-Kamiyama M, Shimizu M, Kamiyama S, Taguchi Y, Sone H, Morimatsu F, Shirakawa H, Furukawa Y, Komai M

    2010.1

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    DOI: 10.1021/jf9031487

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  • Oxygenomics in environmental stress

    Hirohito Sone

    Redox Report   2010

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    DOI: 10.1179/174329210X12650506623843

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  • Low HDL Cholesterol Is Associated With the Risk of Stroke in Elderly Diabetic Individuals Changes in the risk for atherosclerotic diseases at various ages Reviewed

    Tosmo Hayashi, Seinosuke Kawashima, Hideki Itoh, Nobuhiro Yamada, Hirohito Sone, Hiroshi Watanabe, Yoshiyuki Hattori, Takashi Ohrui, Koutaro Yokote, Hideki Nomura, Hiroyuki Umegaki, Akihisa Iguchi

    DIABETES CARE   32 ( 7 )   1221 - 1223   2009.7

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    OBJECTIVE - To clarify the relationship between lipid levels and ischemic heart disease (IHD) and cerebrovascular disease (CVD) in diabetic individuals.
    RESEARCH DESIGN AND METHODS - The Japan Cholesterol and Diabetes Mellitus Study is a prospective cohort study of 4,014 type 2 diabetic patients (1,936 women; mean +/- SD age 67.4 +/- 9.5 years). Lipid and glucose levels and other factors were investigated in relation to occurrence of IHD or CVD.
    RESULTS - IHD and CVD occurred in 1.59 and 1.43% of participants, respectively, over a 2-year period. The relation of lower HDL or higher LDL cholesterol to occurrence of IHD in subjects &lt;65 years old was significant. Lower HDL cholesterol was also significantly related to CVD in subjects :65 years old and especially in those &gt;75 years old (n = 1,016 odds ratio 0.511 [95% CI 0.239-0.918]; P &lt; 0.05). Stepwise multiple regression analysis with onset of CVD as a dependent variable showed the same result.
    CONCLUSIONS - Lower HDL cholesterol is an important risk factor for not only IHD but also CVD, especially in diabetic elderly individuals.

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  • [Progress in clinical care of cardiovascular diseases complicated with diabetes mellitus]. Reviewed

    Sone H, Yamada N

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   98 ( 4 )   794 - 801   2009.4

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    DOI: 10.2169/naika.98.794

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  • 1) Current Status of Diabetic Vascular Complication in Japan. from the View Point of the Results of Japan Diabetes Complication Study (JDCS)

    Sone Hirohito, Akanuma Yasuo, Yamada Nobuhiro

    Nihon Naika Gakkai Kaishi   98   84a - 84a   2009

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    DOI: 10.2169/naika.98.84a

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  • Effect of low-intensity exercise training on glucose and lipid metabolism and cardiorespiratory fitness in the elderly Reviewed

    Kodama Satoru, Miao Shu, Kazumi Saito, Haruka Murakami, Tomohiro Okura, Kiyoji Tanaka, Shinya Kuno, Ryuichi Ajisaka, Nobuhiro Yamada, Hirohito Sone

    JOURNAL OF AGING AND PHYSICAL ACTIVITY   16 ( Suppl. S )   S111 - S112   2008.7

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  • Effect of different dietary carbohydrate/fat ratios on glucose metabolism in type 2 diabetic patients: A meta-analysis Reviewed

    Satoru Kodama, Kazumi Saito, Yoko Yachi, Yoko Ibe, Mihoko Asumi, Miho Maki, Emiko Suzuki, Hitoshi Shimano, Nobuhiro Yamada, Hirohito Sone

    DIABETES   57   A470 - A470   2008.6

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  • Factors affecting remission of microalbuminuria in patients with type 2 diabetes: the Tsukuba Kawai Diabetes Registry (TKDR)2 Reviewed

    Kazumi Saito, Koichi Kawaii, Satoru Kodama, Shiro Tanaka, Keni Ro Sakamaki, Ayumi Sugawara, Mut-Sumi Sato, Yasuko Sone, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yama, Hirohito Sone

    DIABETES   57   A211 - A211   2008.6

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  • Importance of lipid levels in elderly diabetic individuals - Baseline characteristics and 1-year - Survey of cardiovascular events Reviewed

    Toshio Hayashi, Seinosuke Kawashima, Hideki Itoh, Nobuhiro Yamada, Hirohito Sone, Hiroshi Watanabe, Yoshiyuki Hattori, Takashi Ohrui, Masashi Yoshizumi, Koutaro Yokote, Kiyoshi Kubota, Hideki Nomura, Hiroyuki Umegaki, Akihisa Iguchi

    CIRCULATION JOURNAL   72 ( 2 )   218 - 225   2008.2

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    Background The respective incidences of ischemic heart and cerebrovascular disease (IHD, CVD) are high in diabetic individuals. Complications of dyslipidemia increase the risk, but direct evidence is limited, so a cohort prospective study (Japan-CDM) was conducted.
    Methods and Results The study group comprised 4,014 subjects with type 2 diabetes (1,936 women, 2,078 men; mean age 67.4 +/- 9.5 years) who were divided into dyslipidemic patients (79.1%) with or without medication (medicated, 50.9%; not medicated, 28.2%) and normo-lipidemic patients (20.9%). The incidence of IHD, CVD, arteriosclerosis obliterans (ASO), congestive heart failure (CHF) and death was assessed. IHD and CVD occurred in 0.82 and 0.67%, respectively, during the first year following registration. CHF, ASO and sudden death occurred in 0.27%, 0.12% and 0.12%, respectively. There was a significant statistical difference in the relation of elevated levels of high-density lipoprotein-cholesterol to lower rates of IHD and CVD. IHD and CVD in males were dependent on the level of low-density lipoprotein-cholesterol (LDL-C): 0.45%, 1.56%, 1.78%, 1.91% and 2.34% were observed in less than 2.11, 2.11 - 2.62, 2.63 - 3.15, 3.16 - 3.67, and more than 3.68 mol/L of LDL-C. In the lowest LDL-C group, death other than from vascular diseases was increased. Age, sex (male) and complicated hypertension increased the risk of events. Patients who were prescribed anti hyperlipidemic agents suffered less events than patients who were not being treated, which suggests direct effects of therapy.
    Conclusion Strict lipid control may be effective for reducing the incidence of vascular events in Japanese diabetic individuals.

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  • [Intervention study for elevating high density lipoprotein cholesterol level]. Reviewed

    Kodama S, Sone H

    Nihon rinsho. Japanese journal of clinical medicine   65 Suppl 7   264 - 269   2007.7

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  • Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver Reviewed

    Takashi Yamamoto, Hitoshi Shimano, Noriyuki Inoue, Yoshimi Nakagawa, Takashi Matsuzaka, Akimitsu Takahashi, Naoya Yahagi, Hirohito Sone, Hiroaki Suzuki, Hideo Toyoshima, Nobuhiro Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   282 ( 16 )   11687 - 11695   2007.4

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    Sterol regulatory element-binding protein ( SREBP)-1c is a transcription factor that controls synthesis of fatty acids and triglycerides in the liver and is highly regulated by nutrition and hormones. In the current studies we show that protein kinase A ( PKA), a mediator of glucagon/cAMP, a fasting signaling, suppresses SREBP-1c by modulating the activity of liver X receptor alpha( LXR alpha), a dominant activator of SREBP-1c expression. Activation of PKA repressed LXR-induced SREBP-1c expression both in rat primary hepatocytes and mouse livers. Promoter analyses revealed that the LXR alpha-binding site in the SREBP-1c promoter is responsible for PKA inhibitory effect on SREBP-1c transcription. In vitro and in vivo PKA directly phosphorylated LXR alpha, and the two consensus PKA target sites ( 195, 196 serines and 290, 291 serines) in its ligand binding/heterodimerization domain were crucial for the inhibition of LXR signaling. PKA phosphorylation of LXR alpha caused impaired DNA binding activity by preventing LXR alpha/RXR dimerization and decreased its transcription activity by inhibiting recruitment of coactivator SCR-1 and enhancing recruitment of corepressor NcoR1. These results indicate that LXR alpha is regulated not only by oxysterol derivatives but also by PKA-mediated phosphorylation, which suggests that nutritional regulation of SREBP-1c and lipogenesis could be regulated at least partially through modulation of LXR.

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  • Effect of exercise training on serum high-sensitivity C-reactive protein concentration in healthy middle-aged and elderly subjects

    Ryuichi Ajisaka, Takumi Tanabe, Takeshi Otsuki, Haruka Murakami, Seiji Maeda, Kiyoji Tanaka, Hirohito Sone, Shinya Kuno

    JAPANESE JOURNAL OF PHYSICAL FITNESS AND SPORTS MEDICINE   56 ( 1 )   179 - 189   2007.2

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    High-sensitivity C-reactive protein (CRP) is a novel risk factor for coronary artery disease. It is well known that body weight loss is effective in reducing serum CRP concentration : however, the effect of exercise training on serum CRP concentration has not been fully elucidated. The purpose of this study was to examine the effect of a 24-week exercise training program on serum CRP concentration in 169 healthy middle-aged and elderly subjects (65.9 +/- 6.4 years) Each subject Underwent baseline testing (peak oxygen Uptake, daily physical activity, body weight, and serum CRP levels), and repeated these tests on completion of the training program. The subjects were classified into 2 groups based on initial CRP levels : normal &lt; 1.0 mg/L, n=139, and high &gt;= 1.0 mg/L, n = 30. On completion of the program, both daily physical activity and peak oxygen uptake increased significantly (+33.9 +/- 72.4%, p &lt; 0.0001, +5.4 +/- 14.7%, p= 0.014, respectively). However, body weight did not change significantly. In addition, CRP levels of the entire group did not change significantly. However, CRP levels significantly decreased among the high baseline CRP group (from 1.82 +/- 0.81 mg/L to 0.98 +/- 0.59 mg/L, p &lt; 0.0001). it was concluded that serum CRP levels are reduced without body weight loss in response to exercise training in healthy middle-aged and elderly subjects with high initial CRP levels.

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  • [Metabolic syndrome in Japanese patient with diabetes analysis from JDCS]. Reviewed

    Sone H, Akanuma Y, Yamada N

    Nihon rinsho. Japanese journal of clinical medicine   64 Suppl 9   74 - 83   2006.12

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  • [Long-term intervention studies of diabetic macroangiopathy in Japan and western countries]. Reviewed

    Sone H, Yamada N

    Nihon rinsho. Japanese journal of clinical medicine   64 ( 11 )   2021 - 2030   2006.11

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  • Aldo-keto reductase 1 family B7 is the gene induced in response to oxidative stress in the livers of Long-Evans Cinnamon rats.

    Jia G, Takahashi R, Zhang Z, Tsuji Y, Sone H

    2006.10

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  • Distribution of retinylester-storing stellate cells in the arrowtooth halibut, Atheresthes evermanni.

    Yoshikawa K, Imai K, Seki T, Higashi-Kuwata N, Kojima N, Yuuda M, Koyasu K, Sone H, Sato M, Senoo H, Irie T

    2006.10

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  • Leptin resistance conferred by a combination of single nucleotide polymorphism and the adoption of a Western lifestyle in urban areas of Thailand.

    Yanagisawa Y, Iwamoto S, Kawabata T, Nakamura Y, Charupoonphol P, Supannatas S, Sone H, Kaneko Y, Watanabe S, Komatsu F, Sakuma M, Miyagi S, Hasegawa K, Kagawa Y

    2006

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  • Leptin resistance conferred by a combination of single nucleotide polymorphism and the adoption of a western lifestyle in urban areas of Thailand

    Hirohito Sone

    The Journal of Nutrition, Health & Aging   2006

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  • Exercise Training for Ameliorating Cardiovascular Risk Factors-focusing on Exercise Intensity and Amount

    Kodama Satoru, Miao Shu, Yamada Nobuhiro, Sone Hirohito

    Int. J. Sport Health Sci.   4   325 - 338   2006

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    Exercise training suppresses cardiovascular risk factors by improving lipid/glucose metabolism, insulin resistance and hypertension. There is an optimum amount and intensity of exercise that will suppress each risk factor, although limited information is currently available on this area. For instance, the level of high-density lipoprotein cholesterol seems to be dependent more on the amount than on the intensity of exercise training; the situation with exercise-induced suppression of triglyceride levels is less clear. It is notable that the ability of mild intensity or a low amount of exercise to suppress or prevent cardiovascular risk factors is largely unknown. This knowledge is essential for prescribing safe and effective exercise training to elderly people. At the same time, very few studies on the associations between cardiovascular risk factors in response to exercise can be found. For example, improvement in lipid metabolism or insulin resistance seems to be related to the weight loss seen during exercise training but weight-independent effects could also be observed. The optimal intensity and amount of exercise training for each cardiovascular risk factor and the relationships between the effects of exercise training on each risk factor need to be clarified in the near future in order to establish guidelines that can be applied to the majority of elderly people at risk of cardiovascular diseases.

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  • Sterol regulatory element-binding proteins activate insulin gene promoter directly and indirectly through synergy with BETA2/E47 Reviewed

    M Amemiya-Kudo, J Oka, T Ide, T Matsuzaka, H Sone, T Yoshikawa, N Yahagi, S Ishibashi, J Osuga, N Yamada, T Murase, H Shimano

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 41 )   34577 - 34589   2005.10

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    Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47. Here we have demonstrated that the insulin promoter is a novel target for SREBPs established as lipid-synthetic transcription factors. Promoter analyses of rat insulin I gene in non-beta cells revealed that nuclear SREBP-1c activates the insulin promoter through three novel SREBP-binding sites (SREs), two of which overlap with E-boxes, binding sites for BETA2/ E47. SREBP-1c activation of the insulin promoter was markedly enhanced by co-expression of BETA2/ E47. This synergistic activation by SREBP-1c/ BETA2/ E47 was not mediated through SREs but through the E-boxes on which BETA2/ E47 physically interacts with SREBP-1c, suggesting a novel function of SREBP as a co-activator. These two cis-DNA regions, E1 and E2, with an appropriate distance separating them, were mandatory for the synergism, which implicates formation of SREBP-1c center dot BETA2 center dot E47 complex in a DNA looping structure for efficient recruitment of CREB- binding protein/ p300. However, in the presence of PDX1, the synergistic action of SREBP-1c with BETA2/E47 was canceled. SREBP-1c-mediated activation of the insulin promoter and expression became overt in beta cell lines and isolated islets when endogenous PDX-1 expression was low. This cryptic SREBP-1c action might play a compensatory role in insulin expression in diabetes with beta cell lipotoxicity.

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  • Effects of aerobic training on visceral fat and glucose metabolism in older adults

    Y Hayashi, K Tanaka, H Sone, S Kuno

    JAPANESE JOURNAL OF PHYSICAL FITNESS AND SPORTS MEDICINE   54 ( 4 )   305 - 313   2005.8

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    Excess accumulation of visceral fat is reported to promote insulin resistance. However, it is not known whether or not insulin resistance improves without reducing visceral fat. Recent studies have reported, however, that exercise can improve insulin resistance. The aim of this study was to examine the effects of low-intensity exercise training on insulin resistance and visceral fat. Participants were 26 older adults, aged 63.9 +/- 3.9 years, who were divided into two groups based on visceral fat area (VFA, cm(2)) measured by X-ray computed tomography. Eight men (153.4 +/- 49.4 cm(2)) and 5 women (151.9 +/- 45.5 cm(2)) were classified as having a VFA of 100 cm(2) or more (VFO group), and 6 men and 6 women as having less than 100 cm(2) (C group). After a 14-week exercise training program, VFA in women of the VFO group was significantly reduced (126.3 +/- 40.0 cm(2)); though it did not reach 100 cm(2). However, homeostasis model assessment (HOMA-IR), an index of insulin resistance, significantly improved from 4.6 +/- 1.9 to 2.2 +/- 1.1 among women in the VFO group. These data suggest that improvements in insulin resistance for women with relatively high VFA are weakly associated with exercise-induced reductions in VFA. Based on these results, the activation of skeletal muscle with physical activity has the possibility of being independently associated with an improvement in insulin resistance without a significant decrease of VFA.

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  • Transgenic mice overexpressing SREBP-1a under the control of the PEPCK promoter exhibit insulin resistance, but not diabetes. International journal

    Akimitsu Takahashi, Hitoshi Shimano, Yoshimi Nakagawa, Takashi Yamamoto, Kaori Motomura, Takashi Matsuzaka, Hirohito Sone, Hiroaki Suzuki, Hideo Toyoshima, Nobuhiro Yamada

    Biochimica et biophysica acta   1740 ( 3 )   427 - 33   2005.6

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    Sterol regulatory element-binding protein-1 (SREBP-1) is a transcription factor which regulates genes involved in the synthesis of fatty acids and triglycerides. The overexpression of nuclear SREBP-1a in transgenic mice under the control of the PEPCK promoter (TgSREBP-1a) caused a massively enlarged fatty liver and disappearance of peripheral white adipose tissue. In the current study, we estimated the impact of this lipid transcription factor on plasma glucose/insulin metabolism in vivo. TgSREBP-1a exhibited mild peripheral insulin resistance as evidenced by hyperinsulinemia both at fasting and after intravenous glucose loading, and retarded glucose reduction after insulin injection due to decreased plasma leptin levels. Intriguingly, hyperinsulinemia in TgSREBP-1a mice was markedly exacerbated in a fed state and sustained after intravenous glucose loading, and paradoxically decreased after the portal injection of glucose. TgSREBP-1a mice consistently showed very small plasma glucose increases after portal glucose loading because of a large capacity for hepatic glucose uptake. These data suggested that hepatic insulin resistance emerges postprandially. In addition, pancreatic islets from TgSREBP-1a were enlarged. These data demonstrate that SREBP-1a activation in the liver has a strong impact on plasma insulin levels, implicating the potential role of SREBPs in hepatic insulin metabolism relating to insulin resistance.

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  • [Prevalence and incidence of diabetic microangiopathy in Japan]. Reviewed

    Sone H, Yamada N, Yamashita H, Katayama S, Akanuma Y

    Nihon rinsho. Japanese journal of clinical medicine   63 Suppl 6   18 - 22   2005.6

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  • [Recent trends in diabetic complications in Japan]. Reviewed

    Sone H, Saito Y, Yoshimura Y, Ishibashi S, Ito H, Yamashita H, Yamazaki Y, Katayama S, Ohashi Y, Akanuma Y, Yamada N

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   93 ( 11 )   2427 - 2434   2004.11

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  • 効果的な内臓脂肪の減量方法

    田中喜代次, 中田由夫, 大蔵倫博, 曽根博仁

    文部科学省科学技術振興調整費報告書「地域の中高齢者における 生活機能増進法の具体策~体力年齢の若返り法とその地位システム~」   56-57   2004.8

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  • 内蔵脂肪に関する最新情報

    田中喜代次, 中田由夫, 大蔵倫博, 曽根博仁

    文部科学省科学技術振興調整費報告書「地域の中高齢者における生活機能増進法の具体策~体力年齢の若返り法とその地位システム~」   18-19   2004.8

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  • Type 2 diabetes prevalence in Asian subjects: Response to McNeely and Boyko Reviewed

    Hirohito Sone, Sachiko Mizuno, Yasushi Ohashi, Nobuhiro Yamada

    DIABETES CARE   27 ( 5 )   1252 - 1252   2004.5

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    DOI: 10.2337/diacare.27.5.1251

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  • [Vascular dysfunction in metabolic syndrome: 2) Risk for coronary artery disease]. Reviewed

    Sone H, Yamada N

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   93 ( 4 )   670 - 676   2004.4

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  • Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice Reviewed

    T Matsuzaka, H Shimano, N Yahagi, M Amemiya-Kudo, H Okazaki, Y Tamura, Y Iizuka, K Ohashi, S Tomita, M Sekiya, A Hasty, Y Nakagawa, H Sone, H Toyoshima, S Ishibashi, J Osuga, N Yamada

    DIABETES   53 ( 3 )   560 - 569   2004.3

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    Insulin and glucose together have been previously shown to regulate hepatic sterol regulatory element-binding protein (SREBP)-1c expression. We sought to explore the nutritional regulation of lipogenesis through SREBP-1c induction in a setting where effects of sugars versus insulin could be distinguished. To do so, mice were insulin depleted by streptozotocin (STZ) administration and subjected to a fasting-refeeding protocol with glucose, fructose, or sucrose. Unexpectedly, the insulin-depleted mice exhibited a marked induction of SREBP-1c on all sugars, and this increase in SREBP-1c was even more dramatic than in the non-STZ-administered controls. The time course of changes in SREBP-1 induction varied depending on the type of sugars in both control and STZ-administered mice. Glucose refeeding gave a peak of SREBP-1c induction, whereas fructose refeeding caused slow and gradual increments, and sucrose refeeding fell between these two responses. Expression of various lipogenic enzymes were also gradually increased over time, irrespective of the types of sugars, with greater intensities in STZ-administered than in nontreated mice. In contrast, induction of hepatic glucokinase and suppression of phoshoenolpyruvate carboxykinase were insulin dependent in an early refed state. These data clearly demonstrate that nutritional regulation of SREBP-1c and lipogenic genes may be completely independent of insulin as long as sufficient carbohydrates are available.

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  • 内臓脂肪に関する最新情報「地域の中高齢者における.生活機能増進法の具体策 ~体力年齢の若返り法とその地位システム~」

    田中喜代次, 中田由夫, 大藏倫博, 曽根博仁

    文部科学省科学技術振興調整費報告書   18-19   2004.1

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  • Using a customized DNA microarray for expression profiling of the estrogen-responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals

    Hirohito Sone

    Environmental Health Perspectives   2004

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    DOI: 10.1289/EHP.6753

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  • Gene interaction network suggests dioxin induces a significant linkage between aryl hydrocarbon receptor and retinoic acid receptor beta

    Hirohito Sone

    Environmental Health Perspectives   2004

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    DOI: 10.1289/TXG.7020

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  • Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling Reviewed

    T Yoshikawa, T Ide, H Shimano, N Yahagi, M Amemiya-Kudo, T Matsuzaka, S Yatoh, T Kitamine, H Okazaki, Y Tamura, M Sekiya, A Takahashi, AH Hasty, R Sato, H Sone, JI Osuga, S Ishibashi, N Yamada

    MOLECULAR ENDOCRINOLOGY   17 ( 7 )   1240 - 1254   2003.7

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    Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors that form obligate heterodimers with retinoid X receptors (RXRs). These nuclear receptors play crucial roles in the regulation of fatty acid metabolism: LXRs activate expression of sterol regulatory element-binding protein 1c (SREBP-1c), a dominant lipogenic gene regulator, whereas PPARalpha promotes fatty acid beta-oxidation genes. In the current study, effects of PPARs on the LXR-SREBP-1c pathway were investigated. Luciferase assays in human embryonic kidney 293 cells showed that overexpression of PPARalpha and gamma dose-dependently inhibited SREBP-1c promoter activity induced by LXR. Deletion and mutation studies demonstrated that the two LXR response elements (LXREs) in the SREBP-1c promoter region are responsible for this inhibitory effect of PPARs. Gel shift assays indicated that PPARs reduce binding of LXR/RXR to LXRE. PPARalpha-selective agonist enhanced these inhibitory effects. Supplementation with RXR attenuated these inhibitions by PPARs in luciferase and gel shift assays, implicating receptor interaction among LXR, PPAR, and RXR as a plausible mechanism. Competition of PPARalpha ligand with LXR ligand was observed in LXR/RXR binding to LXRE in gel shift assay, in LXR/RXR formation in nuclear extracts by coimmunoprecipitation, and in gene expression of SREBP-1c by Northern blot analysis of rat primary hepatocytes and mouse liver RNA. These data suggest that PPARalpha activation can suppress LXR-SREBP-1c pathway through reduction of LXR/RXR formation, proposing a novel transcription factor cross-talk between LXR and PPARalpha in hepatic lipid homeostasis.

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  • Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. II. LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling Reviewed

    T Ide, H Shimano, T Yoshikawa, N Yahagi, M Amemiya-Kudo, T Matsuzaka, M Nakakuki, S Yatoh, Y Iizuka, S Tomita, K Ohashi, A Takahashi, H Sone, T Gotoda, JI Osuga, S Ishibashi, N Yamada

    MOLECULAR ENDOCRINOLOGY   17 ( 7 )   1255 - 1267   2003.7

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    Fatty acid metabolism is transcriptionally regulated by two reciprocal systems: peroxisome proliferator-activated receptor (PPAR)alpha controls fatty acid degradation, whereas sterol regulatory element-binding protein-1c activated by liver X receptor (LXR) regulates fatty acid synthesis. To explore potential interactions between LXR and PPAR, the effect of LXR activation on PPARalpha signaling was investigated. In luciferase reporter gene assays, overexpression of LXRalpha or beta suppressed PPARalpha-induced peroxisome proliferator response element-luciferase activity in a dose-dependent manner. LXR agonists, T0901317 and 22(R)hydroxycholesterol, dose dependently enhanced the suppressive effects of LXRs. Gel shift assays demonstrated that LXR reduced binding of PPARalpha/retinoid X receptor (RXR) alpha to peroxisome proliferator response element. Addition of increasing amounts of RXRalpha restored these inhibitory effects in both luciferase and gel shift assays, suggesting the presence of RXRalpha competition. In vitro protein binding assays demonstrated that activation of LXR by an LXR agonist promoted formation of LXR/RXRalpha and, more importantly, LXR/PPARalpha heterodimers, leading to a reduction of PPARalpha/RXRalpha formation. Supportively, in vivo administration of the LXR ligand to mice and rat primary hepatocytes substantially decreased hepatic mRNA levels of PPARalpha-targeted genes in both basal and PPARalpha agonist-induced conditions. The amount of nuclear PPARalpha/RXR heterodimers in the mouse livers was induced by treatment with PPARalpha ligand, and was suppressed by superimposed LXR ligand. Taken together with data from the accompanying paper (Yoshikawa, T., T. Ide, H. Shimano, N. Yahagi, M. Amemiya-Kudo, T. Matsuzaka, S. Yatoh, T. Kitamine, H. Okazaki, Y. Tamura, M. Sekiya, A. Takahashi, A. H. Hasty, R. Sato, H. Sone, J. Osuga, S. Ishibashi, and N. Yamada, Endocrinology 144: 1240-1254) describing PPARalpha suppression of the LXR-sterol regulatory element-binding protein-1c pathway, we propose the presence of an intricate network of nutritional transcription factors with mutual interactions, resulting in efficient reciprocal regulation of lipid degradation and lipogenesis.

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  • Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion.

    Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Yamamoto TT

    2003.1

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  • DNA-adduct formation in lungs, nasal mucosa, and livers of rats exposed to urban roadside air in Kawasaki City, Japan

    Hirohito Sone

    Environmental Research   2003

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    DOI: 10.1016/S0013-9351(03)00063-X

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  • The need to integrate diabetes education and treatment - Reply

    Hirohito Sone

    Hormone and Metabolic Research   2003

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    DOI: 10.1055/S-2003-41313

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  • Polymorphism, heteroplasmy, mitochondrial fusion and diabetes

    Hirohito Sone

    Bioscience Reports   2003

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    DOI: 10.1023/B:BIRE.0000019189.35983.B9

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  • [Large-scale randomized intervention trial on diabetes in Japan]. Reviewed

    Sone H, Yamada N

    Nihon rinsho. Japanese journal of clinical medicine   60 Suppl 10   44 - 50   2002.10

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  • Genetic and physiological analysis of branched-chain alcohols and isoamyl acetate production in Saccharomyces cerevisiae.

    Yoshimoto H, Fukushige T, Yonezawa T, Sone H

    2002.8

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    DOI: 10.1007/s00253-002-1041-5

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  • [Recent studies on hyperlipidemia]. Reviewed

    Sone H, Yamada N

    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   91 ( 4 )   1202 - 1207   2002.4

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  • Acetyl-coenzyme A Synthetase is a New Lipogenic Enzyme Controlled by Sterol Regulatory Element-binding Protein-1. Reviewed

    Sone, H, Shimano, H, Sakakura, Y, Inoue, N, Amemiya-Kudo, M, Takahashi, A, Yokoo, T, Osawa, M, Iwama, A, Yamada, N

    Am J Physiol Endocrinol Metab   282   E222-230   2002.1

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  • Dual regulation of mouse Delta(5)- and Delta(6)-desaturase gene expression by SREBP-1 and PPAR alpha Reviewed

    T Matsuzaka, H Shimano, N Yahagi, M Amemiya-Kudo, T Yoshikawa, AH Hasty, Y Tamura, J Osuga, H Okazaki, Y Iizuka, A Takahashi, H Sone, T Gotoda, S Ishibashi, N Yamada

    JOURNAL OF LIPID RESEARCH   43 ( 1 )   107 - 114   2002.1

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    In the process of seeking sterol regulatory element-binding protein 1a (SREBP-1a) target genes, we identified and cloned a cDNA clone encoding mouse Delta(5)-desaturase (D5D). The hepatic expression of D5D as well as Delta(6)-desaturase (D6D) was highly activated in transgenic mice overexpressing nuclear SREBP-1a, -1c, and -2. Disruption of the SREBP-1 gene significantly reduced the expression of both desaturases in the livers of SREBP-1-deficient mice refed after fasting. The hepatic expression of both desaturases was downregulated by dietary PUFA, which were reported to suppress SREBP-1c gene expression. Sustained expression of hepatic nuclear SREBP-1c protein in the transgenic mice abolished the PUFA suppression of both desaturases. Although these data suggested that SREBP-1c regulates D5D and D6D expression, there was no difference in either the D5D or D6D mRNA level between fasted and refed normal mouse livers, indicating a mechanism for fasting induction of both desaturases. Administration of fibrate, a pharmacological ligand for peroxisome proliferator activating receptor alpha (PPARalpha), caused a significant increase in expression of both desaturases. The data suggested that D5D and D6D expression is dually regulated by SREBP-1c and PPARalpha, two reciprocal transcription factors for fatty acid metabolism, and could be involved in lipogenic gene regulation by producing PUFA.

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  • Genetic and physiological analysis of branched-chain alcohols and isoamyl acetate production in Saccharomyces cerevisiae

    Hirohito Sone

    Applied Microbiology and Biotechnology   2002

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    DOI: 10.1007/S00253-002-1041-5

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  • Modal Birefringence dependent supercontinuum due to cross-phase modulation in a dispersion-flattened/decreasing fiber

    Hirohito Sone

    Optical Review   2002

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  • Influences of polyunsaturated fatty acids and insulin on NO production and ET-1 production in human vascular endothelial cells

    Hirohito Sone

    Diabetes   2001

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  • Kinematic approach to gait analysis in patients with rheumatoid arthritis involving the knee joint Reviewed

    Michihiro Sakauchi, Katsuhiko Narushima, Hirohito Sone, Yutaka Kamimaki, Yuichiro Yamazaki, Shinjiro Kato, Takashi Takita, Norihiro Suzuki, Kimio Moro

    Arthritis Care and Research   45 ( 1 )   35 - 41   2001

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    Objective. To analyze abnormal gait patterns in patients with rheumatoid arthritis involving the knee joint. Methods. In 2 patient groups with rheumatoid arthritis, changes in relevant angular parameters in the sagittal plane were analyzed by an electromagnetic tracking instrument. One group consisted of patients with knee joint involvement and severe inflammation without progressive destruction
    the other group had knee joint involvement with progressive destruction and low disease activity. Knee angle was measured as the projected angle in the sagittal plane formed by 3 sensors (hip-knee-ankle)
    the changing mean angle, angular velocity, and angular acceleration were displayed. Furthermore, the angle formed by the vector element's endpoints for each sensor's displacement (designated α angle) was measured continuously. Results. Compared with age-matched controls, patients with severe inflammatory knee joint involvement showed limitation of a angle change in the stance phase, and patients with knee joint destruction had shortened swing phase duration and decreased α angle change in the swing phase. A sharpened α angular velocity change curve was observed in the latter. Characteristic differences between groups with inflammation and destruction were more clearly evident from the a angle than from the knee angle itself. Conclusion. We observed gait differences between rheumatoid arthritis patients with active inflammatory arthritic knee joint involvement without progressive destruction and those with joint destruction and minimal inflammation. Features of gait disturbance in rheumatoid arthritis were not simple, even with a single major site. Therefore, techniques such as biokinetic gait analysis can provide practical information about functional joint integrity in this patient population that could aid in therapeutic decision making. © 2001 by the American College of Rheumatology.

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  • Effects of life style modification on patients with type 2 diabetes: The Japan Diabetes Complications Study (JDCStudy)

    Hirohito Sone

    Diabetes   2000

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  • Increased mutant frequency and altered mutation spectrum of the lacI transgene in Wilson disease rats with hepatitis

    Hirohito Sone

    Cancer Research   2000

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  • Vascular endothelial GLUT1 overexpression activates multiple signal transduction pathways

    Hirohito Sone

    Diabetes   1999

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  • Glucose-mediated regulation of glucose transport and GLUT1 expression in different retinal cells in culture

    Hirohito Sone

    Diabetes   1999

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  • Vascular endothelial growth factor levels in the aqueous and serum in diabetic retinopathy with or without neovascular glaucoma Reviewed

    Tadahiko Kozawa, Hirohito Sone, Yukichi Okuda, Yasushi Kawakami, Yasuo Sekine, Masayuki Imai, Sachiko Hommura, Makoto Inatomi, Shigeo Yaguchi, Katsuhiko Matsuo, Toshiaki Segawa, Hideo Suzuki, Kamejiro Yamashita

    Journal of Japanese Ophthalmological Society   102 ( 11 )   731 - 738   1998.11

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    We determined the levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in the aqueous and serum in non-insulin dependent diabetic patients with proliferative retinopathy (n=12) and neovascular glaucoma (n=11). The aqueous levels of PEGF/VPF were significantly higher in both groups than in 10 diabetics without such complications. The levels were very high in patients with neovascular glaucoma, suggesting that VEGF/VPF is involved in the pathogenesis and progression of diabetic neovascular glaucoma. The serum levels were not significantly related to the presence or the stage of retinopathy. The findings suggest the possibility of treatment of neovascular glaucoma using anti-VRGF/VFP preparations.

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  • Evaluation of alpha(1)-adrenoceptor antagonist and antioxidant therapy on diabetes-induced changes in retinal NAD(P)-redox status: Evidence against "pseudohypoxia?"

    Hirohito Sone

    Diabetes   1998

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  • Vascular endothelial growth factor (VEGF) enhances glucose transport in retinal endothelial cells through upregulation of GLUT1 glucose transporter

    Hirohito Sone

    Diabetes   1998

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  • Change in the expression of vascular endothelial growth factor (VEGF) by swimming

    Hirohito Sone

    Diabetes   1998

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  • Non-invasive ultrasonic analysis of femoral artery wall in patients with NIDDM: Evaluation of early arteriosclerotic lesions and relationship between diabetic neuropathy

    Hirohito Sone

    Diabetes   1997

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  • Effects of pancreatic hormones and vasoactivators on vascular endothelial growth factor production of human vascular smooth muscle cells

    Hirohito Sone

    Diabetes   1997

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  • Modulation of vascular endothelial growth factor (VEGF) in animal models of diabetic retinopathy: Future implications

    Hirohito Sone

    Diabetes   1997

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  • Acute glucose deprivation and progesterone induce vascular endothelial growth factor on retinal pigment epithelial cells

    Hirohito Sone

    Diabetes   1996

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  • Non-invasive evaluation of lower limb circulation in non-insulin dependent diabetic patients

    Hirohito Sone

    Diabetes   1996

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  • Radioiodinated metaiodo-benzylguanidine scintigraphy for pheochromocytoma Reviewed

    Hirohito Sone, Yukichi Okuda, Yasushi Nakamura, Nobuyoshi Ishikawa, Takashi Yamaoka, Yasushi Kawakami, Masato Odawara, Teruhiko Matsushima, Koichi Kawai, Kamejiro Yamashita

    Hormone Research in Paediatrics   46 ( 3 )   138 - 142   1996

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    Radioiodinated metaiodobenzylguanidine (MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. We describe herein the first case of a definite adrenocortical adenoma that demonstrated false-positive uptake on MIBG scintigraphy. In addition, we reviewed all 13 reported cases showing false-positive uptake, and suggest that careful evaluation is needed before diagnosing a ‘silent’ or ‘asymptomatic’ pheochromocytoma. © 1996 S. Karger AG, Basel.

    DOI: 10.1159/000185010

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  • Study of vegf/vpf levels in diabetic proliferative retinopathy and nephropathy

    Hirohito Sone

    Diabetes   1995

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  • Transient nephrogenic diabetes insipidus accompanied by possible psychogenic polydipsia Reviewed

    Hirohito Sone, Koichi Kawai, Masaaki Nishi, Shuya Shimakura, Chieko Bannai, Yasushi Kawakami, Masato Odawara, Teruhiko Matsushima, Yukichi Okuda, Kamejiro Yamashita

    Hormone Research in Paediatrics   44 ( 4 )   193 - 196   1995

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    A 50-year-old Japanese man had been suffering from polydipsia and polyuria for 2 months without any other specific symptoms. His daily urinary output reached 5 liters. On admission, no abnormalities of the kidneys, heart, thyroid, adrenals, pituitary or hypothalamus were detected by laboratory tests and MRI of the head. Pure psychogenic polydipsia was ruled out because his urine volume did not decrease sufficiently with 18 h of water deprivation and the subsequent injection of aqueous vasopressin. Plasma arginine vasopressin (AVP) levels against plasma osmolality remained within the normal range during the test. These results indicated that diabetes insipidus in this case was caused by renal insensitivity to AVP. The symptoms disappeared spontaneously, and marked improvement was observed in a second water deprivation test 1 month later, although the maximum urine concentration was still subnormal. The combination of both latent insufficiency of AVP secretion and impairment of the renal countercurrent system induced by psychogenic polydipsia was speculated as a possible mechanism for the transient nephrogenic diabetes insipidus in this case. © 1995 S. Karger AG, Basel.

    DOI: 10.1159/000184624

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  • Effect of tzp-4238 on bone-mineral content and strength of osteoporotic rats

    Hirohito Sone

    Calcified Tissue International   1994

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▶ display all

Books

  • 糖尿病薬物療法指導力アップ講座 : 症例でわかる 明日のケアに活かせる : 看護師、薬剤師、管理栄養士…糖尿病スタッフの力で患者を支える

    朝倉, 俊成, 曽根, 博仁

    メディカ出版  2019.9  ( ISBN:9784840468954

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    Total pages:205p   Language:Japanese

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  • すべての診療科で役立つ栄養学と食事・栄養療法

    曽根, 博仁

    羊土社  2019.1  ( ISBN:9784758108980

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    Total pages:245p   Language:Japanese

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  • 「臨床栄養」別冊 栄養指導・管理のためのスキルアップシリーズ vol.8 糖尿病の最新食事療法のなぜに答える 実践編

    本田 佳子, 佐野 喜子, 曽根 博仁, 大橋 健( Role: Joint editor)

    医歯薬出版  2018.4 

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    Total pages:152  

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  • 「臨床栄養」別冊 栄養指導・管理のためのスキルアップシリーズ vol.7 糖尿病の最新食事療法のなぜに答える 基礎編

    安孫子 亜津子, 荒木 厚, 石澤 正博, 岩永 みどり, 植木 浩二郎, 江口 有一郎, 絵本 正憲, 金澤 昭雄, 金子 正儀, 川村 智行, 北田 宗弘, 古家 大祐, 鈴木 裕美, 津田 謹輔, 西川 直子, 西村 理明, 羽田 勝計, 星出 聡, 細川 雅也, 松下 真弥, 三島 修一, 村山 賢一郎, 森 克仁, 森 保道, 安田 大二郎, 谷内 洋子, 八幡 和明, 山下 滋雄, 本田 佳子, 佐野 喜子, 曽根 博仁, 大橋 健( Role: Joint editor)

    医歯薬出版  2017.10 

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    Total pages:152  

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  • 糖尿病の最新食事療法のなぜに答える

    本田, 佳子, 佐野, 喜子, 曽根, 博仁, 大橋, 健

    医歯薬出版  2017  ( ISBN:9784263708514

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    Total pages:2冊   Language:Japanese

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  • 臨床栄養学 疾患別編 改訂第2版 (栄養科学イラストレイテッド)

    本田 佳子, 土江 節子, 曽根 博仁( Role: Joint editor)

    羊土社  2016.3  ( ISBN:4758108838

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    Total pages:312  

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  • 臨床栄養学 基礎編 改訂第2版 (栄養科学イラストレイテッド)

    本田 佳子, 土江 節子, 曽根 博仁( Role: Joint editor)

    羊土社  2016.3  ( ISBN:475810882X

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    Total pages:184  

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  • 臨床栄養学

    本田, 佳子, 土江, 節子, 曽根, 博仁

    羊土社  2016.3  ( ISBN:9784758108829

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    Total pages:2冊   Language:Japanese

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  • 月刊糖尿病 Vol.6No.8(2014年 特集:境界型糖尿病の診断と治療管理

    曽根博仁( Role: Sole author)

    医学出版  2014.8  ( ISBN:4287820630

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    Total pages:96  

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  • スポーツ医学【内科】

    赤間, 高雄, 浅川, 伸, 伊東, 和雄, 内田, 直, 坂本, 静男, 児玉, 暁(医学), 清水, 和弘, 曽根, 博仁, 夏井, 裕明, 難波, 聡, 渡部, 厚一

    化学同人  2014.3  ( ISBN:9784759817058

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    Total pages:xi, 217p   Language:Japanese

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  • 臨床栄養学ノート : 基礎編&疾患別編

    本田, 佳子, 土江, 節子, 曽根, 博仁

    羊土社  2012.5  ( ISBN:9784758108874

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    Total pages:285p   Language:Japanese

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  • 臨床栄養学ノート 基礎編&疾患別編 (栄養科学イラストレイテッド)

    本田佳子, 土江節子, 曽根博仁( Role: Joint editor)

    羊土社  2012.4  ( ISBN:4758108870

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    Total pages:288  

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  • 栄養科学イラストレイテッド臨床栄養学 疾患別編

    本田佳子, 土江節子, 曽根博仁( Role: Joint editor)

    羊土社  2012.2  ( ISBN:4758108722

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    Total pages:270  

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  • 臨床栄養学

    本田, 佳子, 土江, 節子, 曽根, 博仁

    羊土社  2012.2  ( ISBN:9784758108713

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    Total pages:2冊   Language:Japanese

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  • 12 生活習慣病と食生活Ⅲ 動脈硬化とその他の生活習慣病

    改訂 食と健康(NHK出版)  2012 

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  • 日本人の生活習慣と生活習慣病

    生活習慣病学会ニュースレター  2012 

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  • 糖尿病とがん

    Medical View Point 33(2)  2012 

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  • 厳格な血糖コントロールは糖尿病腎症(CKD)の発症・進展を抑制できるか?

    臨床透析28(2)  2012 

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  • 脳・心・腎関連を見逃さない Ⅱ脳・心・腎関連各論 脂質異常症と脳・心・腎関連

    糖尿病診療マスター10(4)  2012 

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  • 曽根博仁,片山茂裕,山下英俊,赤沼安夫,山田信博

    日本臨床70(増刊号3)  2012 

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  • 糖尿病の予防・管理・治療 糖尿病における二次・三次予防の新しい考え方

    日本臨床 70(増刊号3)  2012 

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  • 曽根博仁,田中司朗,片山茂裕,山下英俊,山田信博

    he Lipid 23(2)  2012 

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  • 糖尿病患者における脂質異常の重要性-JDCSから明らかになったこと‐

    Medical View Point 6  2012 

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  • 11 生活習慣病と食生活Ⅱ 糖尿病

    改訂 食と健康(NHK出版)  2012 

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  • 10 生活習慣病と食生活Ⅰ 肥満とやせ・メタボリックシンドローム

    改訂 食と健康(NHK出版)  2012 

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  • 糖化蛋白

    救急・集中治療別冊「急性期患者の糖代謝とSCCM/ASPEN栄養管理ガイドライン」  2012 

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  • 6糖尿病の治療 血糖コントロールと合併症抑制のエビデンス-総論

    Visual糖尿病臨床のすべて 糖尿病予防と治療のエビデンス(中山書店)  2012 

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  • 12米国糖尿病学会(ADA)の基準 HbA1c(国際標準値)5.7~6.4%と空腹時血糖値異常による“前糖尿病”診断とその後の 2 型糖尿病発症リスク

    糖尿病学2012(診断と治療社)  2012 

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  • 内分泌代謝 生涯教育のためのセルフトレーニング問題と解説(第2集)

    日本内科学会専門医部会編(日本内科学会)  2012 

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  • 我が国の臨床疫学研究 JDCSの成果:何を診るか?

    Heart View 15  2011 

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  • 飲酒と心房細動リスクの関連

    肥満と糖尿病 10  2011 

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  • 血清カリウム低値と2型糖尿病発症リスク

    肥満と糖尿病10  2011 

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  • 日本人2型糖尿病患者における大血管合併症の疫学

    糖尿病54  2011 

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  • わが国の糖尿病大血管症の現状

    Pharma Medica 29  2011 

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  • 疫学的研究から見た糖尿病とメタボリックシンドロームとの関係

    日本臨床 69増刊号1(日本臨床社)  2011 

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  • 糖尿病奨励に対するLDLコレステロール(C)管理基準値:現行のガイドライン(120/100mg/dl)でよいか?

    内分泌・糖尿病・代謝内科32  2011 

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  • 運動療法の評価方法

    糖尿病運動療法指導マニュアル(南江堂)  2011 

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  • 患者ごとの運動指針 b特別な状に応じた運動指導

    糖尿病運動療法指導マニュアル(南江堂)  2011 

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  • 患者ごとの運動指針 a.患者における具体的な運動指導の実際

    糖尿病運動療法指導マニュアル(南江堂)  2011 

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  • 糖尿病と脳卒中 疫学の面から予防法を探る

    糖尿病合併症 25  2011 

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  • 生活習慣病に対する食育指導-特に日本人女性のやせ過ぎを中心に-

    成人病と生活習慣病 41  2011 

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  • 動脈硬化の予防と治療-糖尿病

    日老医誌 48  2011 

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  • 若年女性の減量行動とその関連因子

    肥満と糖尿病 63  2011 

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  • 妊娠中の耐糖能異常と周産期予後-妊娠中の耐糖能異常スクリーニング-

    肥満と糖尿病 10  2011 

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  • 糖尿病大血管合併症の現状と課題

    日本糖尿病眼学会誌15  2011 

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  • 糖尿病-エーワンシー(HbA1c)で早期発見コントロール-

    東京都糖尿病協会会報 6  2011 

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  • 日本人女性のBMIとやせの現状

    茨城県母性衛生学会誌  2011 

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  • 我が国の糖尿病患者における心血管病の発症とそのリスクをみる-欧米人との比較を含めて

    Vascular Medicine 7  2011 

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  • 動脈硬化症と脂質異常症の理解のために 糖尿病が果たす役割

    Medicina 48  2011 

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  • 脂質異常症-高LDLコレステロール血症

    今日の治療指針2011(医学書院)  2011 

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  • 運動療法の実施状況

    糖尿病運動療法指導マニュアル(南江堂)  2011 

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  • 糖尿病と動脈硬化-疫学的知見

    動脈硬化予防10(4)  2011 

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  • 動脈硬化と運動・身体活動-予防・改善のための取り組み- 疫学研究 運動と動脈硬化の疫学

    臨床スポーツ医学28  2011 

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  • 日本人糖尿病患者の実態-JDCS

    診断と治療 99  2011 

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  • Webを使用した減量指導効果のエビデンス

    肥満と糖尿病10  2011 

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  • 米国糖尿病学会の新しいPre-diabetes(前糖尿病状態)診断基準におけるHbA1c(国際基準値)5.7~6.4%と空腹時血糖値異常による糖尿病発症の予測

    肥満と糖尿病 10  2011 

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  • 糖尿病・耐糖能異常

    循環器内科 70  2011 

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  • 特集:糖尿病網膜症-診断と治療の将来展望‐糖尿病網膜症への内科的アプローチ

    PRACTICE 28  2011 

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  • わが国におけるメタボリックシンドロームのエビデンスと診断基準

    栄養医学雑誌 69  2011 

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  • コホート研究からの最新知見:JDCS (Japan Diabetes Complications Study)

    医学のあゆみ 238  2011 

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  • 特集 プライマリーケアにおける動脈硬化のリスクファクターの包括的管理 日本人の動脈硬化リスクファクターをどのように包括管理するか

    動脈硬化予防 10  2011 

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  • メタボリックシンドローム

    今日の治療指針 私はこう治療している(医学書院)  2011 

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  • TOPICS 日本人の糖尿病は変化しているのか

    スマートな糖尿病診断と治療の進め方(中山書店)  2011 

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  • 合併症治療における禁煙指導の意味

    ヴィジュアル糖尿病臨床のすべて「糖尿病合併症 鑑別ポイントとベスト管理法」(中山書店)  2011 

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  • 糖尿病診療に必要な知識1 2型糖尿病の血管合併症-JDCSの成果

    糖尿病学の進歩2011 第45集(診断と治療社)  2011 

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  • 介入研究から得られた肥満症診療のEBM 生活習慣介入による肥満の一次予防

    日本臨床 68増刊号2  2010 

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  • 特集:αグルコシダーゼ阻害薬 企画にあたって

    糖尿病の最新治療 2  2010 

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  • 糖尿病の治療薬-最近の動向(その1)

    茨城県糖尿病協会会報かいらく 179  2010 

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  • 日本人の肥満の特徴

    漢方と最新治療 19  2010 

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  • 動脈硬化を克服する―現状と将来展望―

    糖尿病診療マスター8  2010 

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  • αグルコシダーゼ阻害薬の特徴と種類、食後血糖のエビデンス

    糖尿病の最新治療 2  2010 

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  • 文献紹介 食品の値段は食生活や健康に関連する:20年間のCARDIA Studyから

    栄養学雑誌 68  2010 

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  • 特集 糖尿病合併症とその治療に関するエポックメーキングトピックスの展開 日本人糖尿病患者の合併症についての長期研究 JDCSは何を明らかにしてきたか

    糖尿病診療マスター8  2010 

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  • 生活習慣病の臨床エビデンス 脂質パラメータの特徴と最近の研究動向-心血管イベント発症予測能の比較から

    肥満と糖尿病9  2010 

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  • 特集「運動と生活習慣病のかかわりにせまる」運動と糖尿病のかかわりにせまる―糖尿病の一次予防・二次予防における身体活動・運動の意義―

    Life Style Medicine 4  2010 

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  • 特集「禁煙支援と歯周病予防」座談会

    肥満と糖尿病 9  2010 

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  • 喫煙の合併症の関係は? 糖尿病患者が喫煙するとどんな合併症になりやすいですか

    肥満と糖尿病 9  2010 

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  • 動脈硬化の抑制および心血管疾患の予防を目ざした生活習慣改善のエビデンス

    Mebio 27  2010 

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  • 文献PICK UP 尿酸値と2型糖尿病発症の関連

    SEASONAL POST 2  2010 

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  • 若年女性のやせ願望の実態とその問題点

    臨床婦人科産科 64  2010 

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  • 米国糖尿病学会報告:食事・運動療法に関する発表より

    肥満と糖尿病 9  2010 

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  • 慢性合併症の臨床4 Japan Diabetes Complications Study (JDCS)

    糖尿病学の進歩 2010(日本糖尿病学会編)  2010 

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  • 糖尿病のための運動プログラム

    中高年者の疾病予防・改善のための運動プログラム. (日本体育協会)  2010 

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  • 高血圧症に対する運動プログラム

    中高年者の疾病予防・改善のための運動プログラム. (日本体育協会)  2010 

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  • 睡眠と脂質異常症

    成人病と生活習慣病40  2010 

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  • 脂質パラメータの特徴と最近の研究動向―心血管イベント発症予測能の比較か

    肥満と糖尿病 9  2010 

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  • 日本人2型糖尿病患者における血管合併症の発症予防と進展抑制に関する研究:JDCS

    日本臨床68  2010 

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  • 禁煙はCKDにどのようなかかわりを持っているか?

    Life Style Medicine 4  2010 

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  • 生活習慣病発症リスクと最大酸素摂取量

    体育の科学 60  2010 

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  • 無症候性脳梗塞と血清コレステロール値との関係

    肥満と糖尿病 9  2010 

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  • 生活習慣病発症リスクと最大酸素摂取量

    体育の科学60  2010 

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  • 糖尿病

    今日の診断指針 第6版(医学書院)  2010 

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  • ヘモグロビンA1C

    Cardio Diabetic Frontier (メディカルレビュー社)  2010 

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  • 肥満・肥満症の成因と発症機序 行動要因 運動不足・低身体活動

    日本臨床68増刊号2  2010 

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  • 脂質異常症・セミナー 新しい指標と活用法 nonHDL-Cと脂質比(LDL-C/HDL-C, TC/HDL-C)

    Medical Practice 27  2010 

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  • 生活習慣指導介入に糖尿病合併症を防ぐ効果はあるか?

    肥満と糖尿病9  2010 

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  • 2型糖尿病発症関連因子としての尿酸値

    肥満と糖尿病9  2010 

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  • 糖尿病網膜症のリスク因子

    糖尿病 2  2010 

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  • 糖尿病治療の最前線 食事・運動療法と生活習慣の改善

    Current Therapy 28  2010 

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  • 2型糖尿病食事療法における糖・脂質比が糖・脂質代謝指標に与える影響

    糖尿病学2010 (診断と治療社)  2010 

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  • 動脈硬化を克服する-現状と将来展望-

    糖尿病診療マスター8  2010 

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  • 糖尿病診断基準の見直しを受けたこれからの糖尿病診断・治療のあり方

    よぼう医学 448  2010 

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  • Japan Diabetes Complications Study (JDCS)

    Optimal Therapy3  2010 

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  • 生活習慣病の予防、健康面からの米を中心とした日本型食生活の有用性

    日経メディカル12  2010 

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  • 糖尿病血管合併症の疫学

    脈管学50  2010 

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  • 臨床現場が求めるHbA1c基準値

    検査と技術38  2010 

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  • リリー賞受賞講演 日本人糖尿病患者の特徴と病態に関する臨床疫学的研究

    糖尿病 53  2010 

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  • 米国糖尿病学会報告:うつに関する発表より

    肥満と糖尿病9  2010 

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  • 生活習慣と脳卒中予防の関係は?

    肥満と糖尿病 9  2010 

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  • 疾患別栄養と病態 ―内分泌疾患

    医科栄養学(建昴社)  2010 

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  • 糖尿病合併症の疫学-JDCS

    糖尿病ナビゲーター改訂版 (メディカルレビュー社)  2010 

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  • 炭水化物

    医科栄養学(建昴社)  2010 

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  • エネルギー代謝

    医科栄養学(建昴社)  2010 

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  • ミネラル―ヨード

    医科栄養学(建昴社)  2010 

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  • Body Image: International comparisons - From the symposium held in the 15th International Congress of Dietetics

    Nutrition Today45  2010 

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  • Body Image: International comparisons - From the symposium held in the 15th International Congress of Dietetics

    Nutrition Today45  2010 

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  • 糖尿病性細小血管症. 糖尿病性細小血管症の本邦における疫学―欧米との比較.

    日本臨床 69増刊号 9(日本臨床社)  2010 

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  • JDCS (Japan Diabetes Complications Study) .

    日本医師会雑誌第139巻特別号 生涯教育シリーズ79 糖尿病診療2010(日本医師会)  2010 

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  • ライフスタイルの是正

    日本医師会雑誌第139巻特別号 生涯教育シリーズ79 糖尿病診療2010(日本医師会)  2010 

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  • 我が国の糖尿病患者の血管合併症の現況:JDCSからの知見

    Angiology Froniter 8  2009 

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  • 血糖値高めを運動で解決

    すこやかファミリー 602  2009 

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  • 体力と向上させると心筋梗塞などのリスクが低下する

    べんちのーと78  2009 

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  • 全死亡および冠動脈疾患リスクにおける心肺機能の意義

    肥満と糖尿病 8  2009 

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  • 糖尿病の予防・治療のための運動療法の新展開

    肥満と糖尿病 8  2009 

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  • 生活機能の維持及び身体活動増進と糖尿病予防

    臨床スポーツ医学 26  2009 

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  • 糖尿病の血管合併症のトータルケア:早期診断、そして予防へ」わが国の血管合併症の実態:JDCSより

    日本内科学会雑誌 98  2009 

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  • 糖尿病と脳血管障害の疫学 –我が国のテータを中心に-

    内分泌・糖尿病科 29  2009 

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  • 糖尿病網膜症の治療戦略:より良い視力予後を目指した治療戦略確立への道

    あたらしい眼科26  2009 

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  • 生活習慣病における運動の意義とエビデンス

    日本未病システム学会雑誌15  2009 

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  • 第42回日本痛風・核酸代謝学会総会 教育講演:動脈硬化高リスク病態としての糖尿病とメタボリックシンドローム

    痛風と核酸代謝33  2009 

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  • 糖尿病を中心とした疫学-JDCSなどわが国の研究を中心に-

    新・心臓病診療プラクティス14 心血管イベントのリスクファクターとその管理(文光堂)  2009 

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  • 大血管症

    糖尿病の栄養指導 2009 第43回糖尿病学の進歩(日本糖尿病学会編 診断と治療社)  2009 

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  • 2型糖尿病における低脂肪食

    肥満と糖尿病  2009 

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  • 糖尿病食事療法に関するエビデンス -糖尿病とアルコールに関するエビデンス-

    内分泌・糖尿病科28  2009 

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  • わが国におけるHDLとCardiovascular Riskの疫学を知る

    Vascular Medicine  2009 

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  • 糖尿病の食事療法-管理栄養士がいない場合の方法

    今日の治療指針2009年版(医学書院)  2009 

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  • 糖尿病の冠疾患とそのリスクファクターの疫学:わが国と欧米のエビデンス

    日本内科学会雑誌 98  2009 

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  • 糖尿病の発症予防と治療における運動の意義―大規模臨床研究のエビデンス―

    プラクティス 26  2009 

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  • 保険診療では糖尿病はどのようにアプローチするか?

    Vascular Medicine 5  2009 

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  • 体力(有酸素運動能力)がその後の健康と寿命に与える影響

    肥満と糖尿病 8  2009 

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  • 胎児期から成人疾患予防~胎生期栄養とメタボリックシンドローム

    肥満と糖尿病 8  2009 

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  • 日本人女性のやせすぎの現状およびやせすぎが引き起こしうる健康リスク

    肥満と糖尿病  2009 

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  • 糖尿病薬(速効性インスリン分泌促進薬)

    治療薬イラストレイテッド改訂版 (羊土社)  2009 

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  • 太りすぎるとどんながんになりやすいですか? 肥満とがん発症リスクとの関係は?

    肥満と糖尿病  2009 

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  • JDCS(Japan Diabetes Complications Study)

    生活習慣病キーワード第3巻(医事出版社)  2009 

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  • The athlete with type 2 diabetes (Ch.25)

    Principles & Practice of Primary Care Sports Medicine(西村書店)  2009 

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  • 2型糖尿病のエビデンス

    はじめての人でもわかる エビデンスを活かす糖尿病療養指導(中外医学社)  2009 

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  • 運動療法 総論―効果と限界―

    日本臨床2008増刊「身体活動・運動と生活習慣病」(日本臨床社)  2009 

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  • メタボリックシンドロームと運動の効果

    「新しい保健指導に求められる個別運動プログラム作成・実践ガイド」(杏林書院)  2009 

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  • 日本人2型糖尿病における糖尿病性腎症および大血管障害の発症について -糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDC Study)から-

    日本糖尿病合併症学会誌 23(1)  2009 

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  • 糖尿病性腎症に対する低たんぱく食:無作為化比較対照試験のメタアナリシス

    栄養学雑誌 67  2009 

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  • The athlete with type 2 diabetes (Ch.25)

    Principles & Practice of Primary Care Sports Medicine(西村書店)  2009 

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  • 食後高血糖に対する運動療法の効果は?

    肥満と糖尿病  2008 

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  • わが国における肥満の動向-メタボリックシンドロームとの関連で-

    日本臨床2008増刊「新時代の糖尿病学(2)」(日本臨床社)  2008 

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  • 血管合併症の発症・進展の阻止

    日本臨床2008増刊「新時代の糖尿病学(3)」(日本臨床社)  2008 

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  • 糖尿病患者は肥満か? 肥満患者は食べ過ぎか?

    肥満と糖尿病 7  2008 

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  • 糖尿病発症リスクとしてのメタボリックシンドローム

    EBMジャーナル9  2008 

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  • 日本人におけるメタボリックシンドロームの疫学―日本人糖尿病患者におけるメタボリックシンドローム―

    診断と治療 96  2008 

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  • 英国における2型糖尿病に対する薬物療法の介入研究から何を学びましたか?

    肥満と糖尿病 7  2008 

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  • 文献紹介「ビタミンEサプリメントの摂取はハプトグロビン2-2遺伝子型を持つ中高齢2型糖尿病患者において心血管疾患を抑制する -前向き二重盲検臨床試験-」

    栄養学雑誌66  2008 

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  • やせすぎ、太り過ぎと癌のリスク

    肥満と糖尿病7  2008 

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  • 糖尿病網膜症―病態研究と治療の最前線―

    日本糖尿病合併症学会誌 22  2008 

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  • サプリメントとしてのビタミンと心血管疾患のリスク

    肥満と糖尿病 7  2008 

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  • 糖尿病と動脈硬化 ―その管理と効果―

    The Lipid 19  2008 

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  • 日本人の糖尿病と血管合併症-JDCS研究

    成人病と生活習慣病 38  2008 

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  • 糖尿病大血管合併症と血糖コントロール

    肥満と糖尿病 7  2008 

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  • 産業医のための生活習慣病と動脈硬化、リスクとその管理-糖尿病における動脈硬化症とそのリスクファクター管理

    成人病と生活習慣病 38  2008 

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  • 糖尿病領域で見えてきたニッポン・エビデンス

    糖尿病診療マスター6  2008 

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  • 2型糖尿病患者の肥満度 ―断面調査の結果から―

    肥満と糖尿病 7  2008 

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  • 糖尿病の冠疾患とそのリスクファクターの疫学:わが国と欧米のエビデンス

    日本冠疾患学会雑誌 14  2008 

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  • 糖尿病患者においてウエスト周囲径を測定する意義は?

    肥満と糖尿病 7  2008 

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  • 有酸素運動による血清脂質改善効果

    糖尿病学2008 (診断と治療社)  2008 

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  • 日本人を対象にした糖尿病診療の前向き大規模介入研究

    日本臨床2008増刊「新時代の糖尿病学(3)」(日本臨床社)  2008 

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  • Japan Diabetes Complications Study (JDCS) 日本人2型糖尿病患者の特徴と現状

    臨床研究の新しい潮流-医学研究のパラダイム・シフト 医学のあゆみ別冊  2008 

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  • JDCS

    Diabetes Frontier 19  2008 

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  • STOP-NIDDM (The Study To Prevent Non-insulin-dependent diabetes mellitus)

    キーワードで学ぶメタボリックシンドローム(中外医学社)  2008 

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  • わが国における糖尿病合併症大規模臨床研究のエビデンス―欧米との比較―

    日本臨床2008増刊「新時代の糖尿病学」(日本臨床社)  2008 

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  • 糖尿病細小血管合併症発症の環境要因

    日本臨床2008増刊「新時代の糖尿病学」(日本臨床社)  2008 

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  • 糖尿病大血管合併症の克服をめざして 大規模臨床研究からの新しいエビデンス

    糖尿病学の進歩 第42集(日本糖尿病学会編 診断と治療社)  2008 

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  • JDCS(Japan Diabetes Complications Study)におけるメタボリックシンドローム

    キーワードで学ぶメタボリックシンドローム(中外医学社)  2008 

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  • DPP (Diabetes prevention program)

    キーワードで学ぶメタボリックシンドローム(中外医学社)  2008 

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  • 肥満とOA

    整形外科Salvus 2  2008 

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  • JDCS

    日本臨床2008増刊「大規模臨床試験」(日本臨床社)  2008 

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  • 生活習慣病のための検査-検査値をどうみるか 糖尿病に関する検査

    Life Style Medicine 1  2007 

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  • 生活習慣病を予防する運動プログラム

    糖尿病を予防するプログラム 運動器の機能向上のための介護予防実践マニュアル~科学的根拠に基づく効果的かつ安全な実践に向けて~(社会保険研究所)  2007 

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  • 総合討論 糖尿病対策を生活習慣病からアプローチ

    糖尿病UP DATE 賢島セミナー23(医歯薬出版)  2007 

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  • 高脂血症からみた糖尿病とガイドラインの効果的活用

    糖尿病UP DATE 賢島セミナー23 (医歯薬出版)  2007 

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  • 内分泌疾患の成因・病態・診断・治療の概要

    人体の構造と機能および疾病の成り立ち-疾病の成因・病態・診断・治療の概略 (医歯薬出版)  2007 

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  • 糖尿病とその合併症

    スタンダード栄養・食料シリーズ4 “疾病の成り立ち II臓器別の病気”(東京化学同人)  2007 

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  • 糖尿病-合併症の疫学

    カラー版糖尿病学 基礎と臨床(西村書店)  2007 

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  • 大血管症の克服をめざして 大規模臨床研究からの新しいエビデンス 大血管症リスクファクターとその管理

    糖尿病学の進歩2007 第41集(日本糖尿病学会編 診断と治療社)  2007 

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  • 日本人糖尿病患者の心血管疾患の実態は?

    現場の疑問に答える糖尿病診療Q&A (中外医学社)  2007 

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  • 糖尿病網膜症の一次予防のエビデンス-他の合併症との関連ならびにJDCS中間報告から-

    あたらしい眼科 24  2007 

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  • 生活習慣病の臨床エビデンス 運動とHDLコレステロール

    肥満と糖尿病6  2007 

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  • シリーズ危険因子 糖尿病:喫煙

    動脈硬化予防 6  2007 

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  • 運動による糖尿病予防・治療とQOLの向上

    体育の科学 57  2007 

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  • 禁煙の重要性―糖尿病患者を例にして―

    肥満と糖尿病 6  2007 

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  • 日本と世界における糖尿病網膜症の現状-大規模臨床研究JDCSの成果を含めて-

    医学のあゆみ 222  2007 

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  • 循環器病学の論点 メタボリックシンドロームは存在するか

    Therapeutic Research 28  2007 

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  • 生活習慣療法の理想と現実

    肥満と糖尿病 6  2007 

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  • 高脂血症がもたらす臓器障害 マルチプルリスク管理としての高脂血症

    Medical Practice 24  2007 

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  • JDCSからみた日本人2型糖尿病患者の特徴

    栄養学雑誌 65  2007 

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  • 歯周病と糖尿病

    肥満と糖尿病 6  2007 

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  • 血栓・塞栓症のリスクファクターとしてのメタボリックシンドローム

    Medical Technology 35  2007 

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  • メタボリックシンドロームと血管病はどのようにかかわるか?

    Vascular Medicine  2007 

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  • 生活習慣(ライフスタイル)変化とHDL-Cの改善

    Progress in Medicine 27  2007 

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  • 身体活動によって糖代謝はどう変わるか 慢性疾患と身体活動―QOL向上のための新しい具体策―

    臨床スポーツ医学臨時増刊号 24  2007 

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  • 低血糖

    スタンダード栄養・食料シリーズ4 “疾病の成り立ち II臓器別の病気”(東京化学同人)  2007 

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  • 糖尿病に対するわが国の取り組み

    Diabetes Team Now 24  2007 

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  • Exercise training for ameriorating cardiovascular risk factor Focusing on exercise intensity and amount

    Int J Sport Health Sci 4  2007 

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  • トピックス Japan Diabetes Complications Study (JDCS)

    BIO Clinica 22  2007 

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    糖尿病合併症学会誌19  2005 

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    公益信託日本動脈硬化予防研究基金平成14年度研究報告集  2003 

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    日本内科学会雑誌  1994 

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  • 【運動とアンチエイジング】運動による糖尿病予防・治療効果

    石黒 創, 曽根 博仁

    アンチ・エイジング医学   17 ( 5 )   418 - 422   2021.10

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  • イノツズマブによる再寛解導入に引き続いてブリナツモマブを投与し再移植できたB-ALLの1例

    米澤 穂高, 布施 香子, 水戸部 正樹, 武田 るい, 諏訪部 達也, 片桐 隆幸, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   62 ( 10 )   1526 - 1526   2021.10

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  • 副腎腫瘍とK低値で内分泌疾患を疑うもGitelman症候群と考えた1例

    中村 博至, 矢口 雄大, 佐藤 孝明, 山本 正彦, 石黒 創, 北澤 勝, 松林 泰弘, 石澤 正博, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( 2 )   559 - 559   2021.10

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  • 大規模医療データサイエンスが拓く新しい糖尿病網膜症学

    曽根 博仁

    糖尿病合併症   35 ( Suppl. )   94 - 94   2021.9

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  • 血清尿酸値と重症糖尿病網膜症との関係

    山本 正彦, 藤原 和哉, 矢口 雄大, 大澤 妙子, 山田 万祐子, 松林 泰弘, 長谷部 日, 山田 貴穂, 児玉 暁, 曽根 博仁

    糖尿病合併症   35 ( Suppl. )   268 - 268   2021.9

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  • 経口血糖降下薬(OHA)の服薬アドヒアランスおよび血糖コントロールと細小/大血管合併症発症の関連の検討

    矢口 雄大, 藤原 和哉, 山田 万祐子, 北澤 勝, 山本 正彦, 岩永 みどり, 山田 貴穂, 清田 浩康, 松林 泰弘, 児玉 暁, 曽根 博仁

    糖尿病合併症   35 ( Suppl. )   173 - 173   2021.9

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  • 日本人男性における耐糖能別にみた脳卒中既往がその後の脳卒中発症に与える影響

    山田 万祐子, 藤原 和哉, 大江 桃子, 大澤 妙子, 北澤 勝, 松林 泰弘, 佐藤 隆明, 矢口 雄大, 岩永 みどり, 山田 貴穂, 曽根 博仁

    糖尿病合併症   35 ( Suppl. )   174 - 174   2021.9

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  • 【脂質異常症の動向と治療の展望-ここまで到達した高コレステロール血症の治療】機能性表示食品と脂質異常

    鈴木 浩史, 渡辺 賢一, 曽根 博仁

    カレントテラピー   39 ( 9 )   871 - 875   2021.9

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    機能性表示食品は、科学的根拠に基づいた機能性を表示した食品とされ、必要な事項が事業者より消費者庁長官に届けられたものである。機能性表示食品は、特定保健用食品(トクホ)と異なり、消費者庁長官の個別の許可を受けたものではない。消費者庁のホームページで「中性脂肪」、「コレステロール」について機能性表示を行っている販売中の食品の機能性関与成分としては、リコピン、DHA・EPAが挙げられる。リコピンの脂質代謝改善作用については統一した見解がない。DHA・EPAについては、二次予防においてはエビデンスがあるが、一次予防についてはまだその有用性は証明されていない。その他にも脂質代謝改善作用が期待できる食品はあるが、いずれも実際に臨床現場で使用できるエビデンスが確立されているとは言い難い。今後、さまざまな食品によるヒト臨床試験が進んでいき、一次予防が可能な食品が現れることを期待したい。(著者抄録)

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  • 日本人2型糖尿病患者における野菜・果物摂取量の組合せと肥満リスク

    竹内 瑞希, 堀川 千嘉, 治田 麻理子, 武田 安永, 加藤 則子, 前川 聡, 斎藤 トシ子, 藤原 和哉, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   75回   145 - 145   2021.7

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  • 認知機能低下/治療中断による2型糖尿病の血糖増悪が急性発症1型糖尿病であった1例

    村井 幸四郎, 金子 正儀, 岸 裕太郎, 今西 明, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    糖尿病   64 ( 7 )   425 - 425   2021.7

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  • 粘液水腫性昏睡に急性膵炎を合併した一例

    齋藤 啓輔, 矢口 雄大, 滝澤 祥子, 西井 郁生, 竹内 亮, 山本 正彦, 川田 亮, 石黒 創, 北澤 勝, 松林 泰弘, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( Suppl.Update )   38 - 40   2021.7

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    72歳男性。入院6日前より近医にて低Na血症、甲状腺機能低下に対しレボチロキシン内服を開始されたが効果はなく、意識障害となって救急搬送された。20歳代よりBasedow病の既往がある。入院時現症、血液検査、画像検査各所見より、急性膵炎疑い、粘液水腫性昏睡の診断基準で確実例となり粘液水腫昏睡と診断した。ヒドロコルチゾン、レボチロキシン投与、ドパミン塩酸塩の持続静注、3%生理食塩水を開始し、低体温に対するウォームアップ、急性膵炎疑いに対する細胞外液大量投与とウリナスタチン投与を行った結果、全身状態は順調に改善した。経過中、腹痛や背部痛の訴えはなかった。甲状腺エコー所見より、粘液水腫性昏睡は甲状腺機能低下を伴う未治療橋本病により発症し、粘液水腫性昏睡による低体温、虚血障害に起因して急性膵炎を発症したと考えられた。

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01160&link_issn=&doc_id=20210811280012&doc_link_id=%2Fcq6naibu%2F2021%2F0097s1%2F013%2F0038-0040%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq6naibu%2F2021%2F0097s1%2F013%2F0038-0040%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • リアルワールドデータを糖尿病および合併症の臨床に生かす リアルワールドデータ(RWD)を活用した糖尿病合併症の臨床エビデンス創出

    曽根 博仁, 小田原 雅人, 山本 修一

    糖尿病合併症   35 ( 1 )   19 - 23   2021.7

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  • 同種造血幹細胞移植後の慢性GVHDとしての類上皮肉芽腫および多発筋炎

    諏訪部 達也, 布施 香子, 水戸部 正樹, 武田 ルイ, 米沢 穂高, 片桐 隆幸, 河本 啓介, 牛木 隆志, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 大島 孝一, 増子 正義

    臨床血液   62 ( 6 )   675 - 675   2021.6

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  • 【Webを利用した糖尿病管理】糖尿病合併症リスクエンジン

    曽根 博仁, 田中 司朗

    糖尿病・内分泌代謝科   52 ( 6 )   552 - 558   2021.6

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  • 陰茎・陰嚢病変を合併した精巣原発DLBCL

    水戸部 正樹, 武田 ルイ, 米沢 穂高, 田村 秀, 諏訪部 達也, 片桐 隆幸, 河本 啓介, 布施 香子, 柴崎 康彦, 増子 正義, 井上 佳菜子, 三好 寛明, 大島 孝一, 曽根 博仁, 瀧澤 淳

    臨床血液   62 ( 6 )   668 - 668   2021.6

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  • Genetically Reduced Chondroitin Sulfate Prevents the Progression of Diabetic Neuropathy via Pericyte Functions

    Hajime Ishiguro, Takashi Ushiki, Atsuko Honda, Tadahisa Mikami, Hiroshi Kitagawa, Kazunori Sango, Masayoshi Masuko, Michihiro Igarashi, Hirohito Sone

    DIABETES   70   2021.6

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    DOI: 10.2337/db21-421-P

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  • Sodium Intake and Incidence of Diabetes Retinopathy in Elderly Patients with Type 2 Diabetes: Analysis of Data from the Japanese Elderly Diabetes Intervention Study (J-EDIT)

    Chika Horikawa, Rei Aida, Shiro Tanaka, Chiemi Kamada, Sachiko Tanaka, Yukio Yoshimura, Remi Kodera, Kazuya Fujihara, Ryo Kawasaki, Tatsumi Moriya, Hirohito Sone, Atsushi Araki

    DIABETES   70   2021.6

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    DOI: 10.2337/db21-432-P

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  • Impact of Sodium Intake on the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: Analysis of Data from the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial

    Chika Horikawa, Rei Aida, Shiro Tanaka, Chiemi Kamada, Yukio Yoshimura, Remi Kodera, Kazuya Fujihara, Tatsumi Moriya, Atsushi Araki, Hirohito Sone

    DIABETES   70   2021.6

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    DOI: 10.2337/db21-371-P

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  • 糖尿病(DM)の有無別にみたeGFRと尿蛋白が透析開始に及ぼす影響

    大澤 妙子, 藤原 和哉, 山田 万祐子, 山本 正彦, 矢口 雄大, 北澤 勝, 松林 泰弘, 山田 貴穂, 曽根 博仁

    糖尿病   64 ( Suppl.1 )   I - 8   2021.5

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  • メトホルミン内服中の2型糖尿病患者に対するDPP4阻害薬またはSGLT2阻害薬の追加併用効果の多施設共同無作為化比較試験

    北澤 勝, 片桐 尚, 鈴木 裕美, 松永 佐澄志, 山田 万祐子, 五十嵐 智雄, 山本 正彦, 古川 和郎, 岩永 みどり, 治田 麻理子, 藤原 和哉, 山田 貴穂, 田中 司郎, 曽根 博仁, NISM研究グループ

    糖尿病   64 ( Suppl.1 )   I - 6   2021.5

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  • 健診の体力テスト結果を用いた総合体力指標の算出と生活習慣病との関連の検討

    佐藤 隆明, 藤原 和哉, 矢口 雄大, 山田 万祐子, 北澤 勝, 山本 正彦, 松林 泰弘, 岩永 みどり, 山田 貴穂, 加藤 公則, 曽根 博仁

    糖尿病   64 ( Suppl.1 )   III - 1   2021.5

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  • 糖尿病の悪化と視野障害により再発が疑われたCushing病

    今西 明, 北川 めぐみ, 渡辺 聖央, 小松 健, 北澤 優, 松林 泰弘, 岡田 正康, 山田 貴穂, 藤原 和哉, 曽根 博仁

    糖尿病   64 ( Suppl.1 )   P - 1   2021.5

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  • 服薬アドヒアランスと下肢切断のリスクに関する縦断的検討(第2報)

    金子 正儀, 藤原 和哉, 山田 万祐子, 北澤 勝, 矢口 雄大, 松林 泰弘, 山田 貴穂, 清田 浩康, 曽根 博仁

    糖尿病   64 ( Suppl.1 )   P - 4   2021.5

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  • ルキソルチニブ・ヒドロキシウレア併用療法が奏効した慢性好中球性白血病(CNL)の1例

    武田 ルイ, 布施 香子, 片桐 隆幸, 河本 啓介, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 野本 信彦, 曽根 博仁, 増子 正義

    臨床血液   62 ( 5 )   529 - 530   2021.5

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  • SGLT2阻害薬投与早期及び慢性期のヘモグロビン変化予測因子の検討 貧血・多血例における評価

    松林 泰弘, 吉田 明弘, 菅波 秀規, 矢口 雄大, 山本 正彦, 石黒 創, 北澤 勝, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   64 ( Suppl.1 )   II - 1   2021.5

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  • 機械学習による糖尿病専門医のインスリン選択の予測能の検討及び一般医との比較検討

    藤原 和哉, 松林 泰弘, 山田 万祐子, 山本 正彦, 飯塚 敏浩, 宮村 幸祐, 長谷川 好範, 山本 寛悟, 前川 聡, 山崎 達也, 曽根 博仁

    糖尿病   64 ( Suppl.1 )   III - 3   2021.5

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  • 日本人男性における耐糖能と脳卒中既往がその後の脳卒中発症に与える影響 リアルワールドデータによる検討

    山田 万祐子, 藤原 和哉, 大江 桃子, 大澤 妙子, 北澤 勝, 松林 泰弘, 佐藤 隆明, 矢口 雄大, 岩永 みどり, 清田 浩康, 山田 貴穂, 曽根 博仁

    糖尿病   64 ( Suppl.1 )   III - 2   2021.5

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  • 経口血糖降下薬(OHA)の服薬アドヒアランス(Ad)と生活習慣因子の関連

    矢口 雄大, 藤原 和哉, 山田 万祐子, 北澤 勝, 金子 正儀, 清田 浩康, 松林 泰弘, 曽根 博仁

    糖尿病   64 ( Suppl.1 )   III - 1   2021.5

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  • これからの糖尿病食事療法における課題と展望 大規模データサイエンスから見た新食事ガイドラインに残された課題と解決案 患者さんと指導現場の疑問に答えるには

    曽根 博仁, 堀川 千嘉, 藤原 和哉, 前川 聡, 荒木 厚, JDCSグループ, J-EDITグループ, JDDMグループ

    糖尿病   64 ( Suppl.1 )   S22 - 5   2021.5

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  • ビッグデータで切り開く糖尿病診療 リアルワールドデータを駆使した糖尿病診療・療養指導のエビデンス確立

    曽根 博仁

    糖尿病   64 ( Suppl.1 )   S12 - 6   2021.5

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  • GB療法施行中にHigh-grade B-cell lymphoma with MYC and BCL2 rearrangementsで再燃したFollicular lymphoma(Grade 3A)の2症例

    水戸部 正樹, 本宮 奈津子, 武田 ルイ, 米沢 穂高, 鈴木 隆晴, 諏訪部 達也, 片桐 隆幸, 河本 啓介, 布施 香子, 柴崎 康彦, 増子 正義, 井上 佳菜子, 三好 寛明, 大島 孝一, 曽根 博仁, 瀧澤 淳

    日本リンパ網内系学会会誌   61   114 - 114   2021.5

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  • 腎障害を有する高悪性度B細胞リンパ腫症例にDA-EPOCH-Rを施行した1例

    水戸部 正樹, 河本 啓介, 鈴木 隆晴, 米沢 穂高, 田村 秀, 諏訪部 達也, 根本 洋樹, 布施 香子, 柴崎 康彦, 増子 正義, 三好 寛明, 大島 孝一, 曽根 博仁, 瀧澤 淳

    臨床血液   62 ( 5 )   532 - 532   2021.5

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  • ニボルマブ投与後に同時期に破壊性甲状腺炎、1型糖尿病、下垂体機能低下症をきたした1例

    齋藤 啓輔, 矢口 雄大, 西井 郁生, 山本 正彦, 石黒 創, 北澤 勝, 松林 泰弘, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( 1 )   368 - 368   2021.4

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  • 心血管疾患既往の有無と耐糖能状態別に見たその後の心血管疾患発症リスク

    北澤 勝, 藤原 和哉, 山田 万祐子, 大澤 妙子, 矢口 雄大, 山本 正彦, 金子 正儀, 松林 泰弘, 山田 貴穂, 清田 浩康, 曽根 博仁

    日本内分泌学会雑誌   97 ( 1 )   274 - 274   2021.4

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  • 経口血糖降下薬(OHA)の服薬アドヒアランスに関連する因子および血糖コントロールとの関連

    矢口 雄大, 藤原 和哉, 山田 万祐子, 北澤 勝, 金子 正儀, 清田 浩康, 松林 泰弘, 曽根 博仁

    日本内分泌学会雑誌   97 ( 1 )   274 - 274   2021.4

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  • 【食事療法と運動療法】運動療法の基礎と臨床 糖尿病・脂質異常症予防・改善のための身体活動のエビデンス

    児玉 暁, 曽根 博仁

    The Lipid   32 ( 1 )   61 - 69   2021.4

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    多くの人々は、運動が糖尿病や脂質異常症予防・改善に有効であると当たり前のように受け入れているであろう。しかし、信頼性(エビデンスレベル)の高い、これまでの科学研究を系統的に分析したメタ解析研究の結果からみれば、運動には、糖尿病の予防・改善効果はあるものの、脂質異常症の予防・改善効果は明らかに不十分である。この検証結果は、巷に多くの健康情報が錯綜する昨今において、運動と糖尿病・脂質異常症という今回のテーマに限らず、「○○は体によい」というような多くの健康情報の真偽を自ら確認する習慣の重要性を示唆するといえる。このような観点から、本稿では、巷の健康情報の検証に役立てる目的で、情報源として信頼できる「エビデンスレベル」の高い研究の特長についても概説した。(著者抄録)

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  • ソマトスタチン受容体シンチグラフィが診断に有用であった肺カルチノイドによる周期性ACTH依存性クッシング症候群の1例

    金子 正儀, 佐藤 隆明, 福武 嶺一, 滝澤 祥子, 今西 明, 安楽 匠, 小松 健, 北澤 勝, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( 1 )   363 - 363   2021.4

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  • 遺伝子検査によりPendred症候群と考えられた一例

    竹内 亮, 岸 裕太郎, 山本 正彦, 山田 貴穂, 曽根 博仁

    日本内分泌学会雑誌   96 ( 4 )   983 - 983   2021.4

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  • ニボルマブ投与後に同時期に破壊性甲状腺炎、1型糖尿病、下垂体機能低下症をきたした1例

    齋藤 啓輔, 矢口 雄大, 西井 郁生, 山本 正彦, 石黒 創, 北澤 勝, 松林 泰弘, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( 1 )   368 - 368   2021.4

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  • ソマトスタチン受容体シンチグラフィが診断に有用であった肺カルチノイドによる周期性ACTH依存性クッシング症候群の1例

    金子 正儀, 佐藤 隆明, 福武 嶺一, 滝澤 祥子, 今西 明, 安楽 匠, 小松 健, 北澤 勝, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( 1 )   363 - 363   2021.4

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  • 心血管疾患既往の有無と耐糖能状態別に見たその後の心血管疾患発症リスク

    北澤 勝, 藤原 和哉, 山田 万祐子, 大澤 妙子, 矢口 雄大, 山本 正彦, 金子 正儀, 松林 泰弘, 山田 貴穂, 清田 浩康, 曽根 博仁

    日本内分泌学会雑誌   97 ( 1 )   274 - 274   2021.4

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  • 経口血糖降下薬(OHA)の服薬アドヒアランスに関連する因子および血糖コントロールとの関連

    矢口 雄大, 藤原 和哉, 山田 万祐子, 北澤 勝, 金子 正儀, 清田 浩康, 松林 泰弘, 曽根 博仁

    日本内分泌学会雑誌   97 ( 1 )   274 - 274   2021.4

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  • 【ダウンロードで今すぐ使える!初診・再診・重症化予防の3ステップ 最高で最強の糖尿病患者説明シート57】(第4章)運動療法の患者説明シート(ステップ1) これから運動を始めるあなたへ:まずはやってみよう!

    曽根 博仁

    糖尿病ケア   ( 2021春季増刊 )   176 - 180   2021.3

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  • 【ダウンロードで今すぐ使える!初診・再診・重症化予防の3ステップ 最高で最強の糖尿病患者説明シート57】(第4章)運動療法の患者説明シート(ステップ2) 場所も時間もないあなたへ おすすめの運動療法

    曽根 博仁

    糖尿病ケア   ( 2021春季増刊 )   182 - 186   2021.3

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  • 特定保健指導の最適介入法の同定を目指した前向き研究 新潟方式の試作とそのパイロットスタディによる効果の評価

    加藤 公則, 田代 稔, 鈴木 沙織, 大塚 政人, 小林 隆司, 三木 扶久子, 春木 匠, 小松原 祐介, 藤原 和哉, 津下 一代, 赤澤 宏平, 曽根 博仁

    人間ドック   35 ( 5 )   704 - 712   2021.3

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    目的:2018年度より特定健診・特定保健指導も第3期を迎え、「柔軟な運用による特定保健指導のモデル実施(以下モデル実施と略す)」が設けられた。このモデル実施を用いた新たな特定保健指導「新潟方式」を確立するために、現状の保健指導180ポイントにおいて、その効果に有効下限閾値があるのかを検証した。方法:対象は、2018年4月から12月までに特定健診を受けた人で、特定保健指導の積極的支援の対象者202人、A群0ポイント、B群20ポイント、C群100ポイント、D群180ポイントの4群に分け、保健指導終了の3ヵ月後の実績評価時に、腹囲2.0cm以上かつ体重2.0kg以上相当に減少した者(達成者)の割合を群間比較し、有効下限閾値の有無を検討した。また翌年の特定健診データとも比較検討し、その特定保健指導効果の持続性も確認した。結果:実績評価時の達成者の割合については、A群20.4%、B群36.0%、C群28.0%、D群12.5%であり、BとD群間のみ有意差が認められた。実績評価時の達成者が翌年も達成者のままでいた人はA群80.0%、B群88.9%、C群92.3%、D群100%であり、群間に有意差はなかった。結論:実績評価時において、保健指導の効果にはポイント数に依存する関係は存在せず、有効下限閾値は存在しなかった。また、翌年も特定保健指導の効果が持続していた。(著者抄録)

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  • 特定保健指導の最適介入法の同定を目指した前向き研究 新潟方式の試作とそのパイロットスタディによる効果の評価

    加藤 公則, 田代 稔, 鈴木 沙織, 大塚 政人, 小林 隆司, 三木 扶久子, 春木 匠, 小松原 祐介, 藤原 和哉, 津下 一代, 赤澤 宏平, 曽根 博仁

    人間ドック   35 ( 5 )   704 - 712   2021.3

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    目的:2018年度より特定健診・特定保健指導も第3期を迎え、「柔軟な運用による特定保健指導のモデル実施(以下モデル実施と略す)」が設けられた。このモデル実施を用いた新たな特定保健指導「新潟方式」を確立するために、現状の保健指導180ポイントにおいて、その効果に有効下限閾値があるのかを検証した。方法:対象は、2018年4月から12月までに特定健診を受けた人で、特定保健指導の積極的支援の対象者202人、A群0ポイント、B群20ポイント、C群100ポイント、D群180ポイントの4群に分け、保健指導終了の3ヵ月後の実績評価時に、腹囲2.0cm以上かつ体重2.0kg以上相当に減少した者(達成者)の割合を群間比較し、有効下限閾値の有無を検討した。また翌年の特定健診データとも比較検討し、その特定保健指導効果の持続性も確認した。結果:実績評価時の達成者の割合については、A群20.4%、B群36.0%、C群28.0%、D群12.5%であり、BとD群間のみ有意差が認められた。実績評価時の達成者が翌年も達成者のままでいた人はA群80.0%、B群88.9%、C群92.3%、D群100%であり、群間に有意差はなかった。結論:実績評価時において、保健指導の効果にはポイント数に依存する関係は存在せず、有効下限閾値は存在しなかった。また、翌年も特定保健指導の効果が持続していた。(著者抄録)

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  • 循環器病予防総説(シリーズ23) 対策編 循環器疾患予防のための糖尿病治療の基本

    岩永 みどり, 曽根 博仁

    日本循環器病予防学会誌   56 ( 1 )   18 - 30   2021.3

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  • メタ解析的アプローチによる塩分摂取と心不全発症リスクとの量-反応分析

    児玉 暁, 藤原 和哉, 渡辺 賢一, 加藤 公則, 曽根 博仁

    日本内科学会雑誌   110 ( Suppl. )   142 - 142   2021.2

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  • 糖尿病患者におけるIoT端末による食事運動記録と持続血糖測定器を用いた新しい食事運動療法の開発

    北澤 勝, 藤原 和哉, 石澤 正博, 松林 泰弘, 山田 貴穂, 曽根 博仁

    新潟県医師会報   ( 851 )   10 - 11   2021.2

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  • 【低血糖の病態と対策】心血管イベントおよび細小血管障害の危険因子としての低血糖

    矢口 雄大, 曽根 博仁

    月刊糖尿病   13 ( 1 )   26 - 33   2021.1

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  • バセドウ病合併妊婦において、分娩後に著しい甲状腺機能亢進症・無痛性甲状腺炎を呈した一例

    岩永 みどり, 松林 泰弘, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   96 ( 3 )   660 - 660   2021.1

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  • Evidence from large scale medical data science on the integrated effects of diet and exercise

    曽根博仁

    医学のあゆみ   276 ( 5 )   510 - 515   2021.1

  • GH産生下垂体腺腫へのソマトスタチンアナログ使用例におけるソマトスタチン受容体発現解析

    岡田 正康, 米岡 有一郎, 平石 哲也, 佐野 正和, 大石 誠, 石黒 創, 伊藤 崇子, 曽根 博仁, 藤井 幸彦

    日本内分泌学会雑誌   96 ( 3 )   651 - 651   2021.1

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  • 思春期年齢におけるGHRP2負荷試験のGH頂値の検討

    小貫 孝則, 廣嶋 省太, 澤野 堅太郎, 柴田 奈央, 入月 浩美, 小川 洋平, 米岡 有一郎, 岡田 正康, 曽根 博仁, 長崎 啓祐

    日本内分泌学会雑誌   96 ( 3 )   657 - 657   2021.1

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  • 日本人2型糖尿病患者における食事摂取状況の5年間の経過 Japan Diabetes Complications Study

    堀川 千嘉, 相田 麗, 田中 司朗, 田中 明, 井藤 英喜, 吉村 幸雄, 大橋 靖雄, 赤沼 安夫, 曽根 博仁

    Journal of Epidemiology   31 ( Suppl. )   125 - 125   2021.1

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  • 糖尿病と定期的な運動習慣が要介護発症へ及ぼす影響の検討

    藤原 和哉, 山田 万祐子, 北澤 勝, 松林 泰弘, 八尋 拓也, 筒井 歩, 加藤 公則, 曽根 博仁

    Journal of Epidemiology   31 ( Suppl. )   102 - 102   2021.1

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  • 臨床に活かす!日本発の栄養疫学研究からのエビデンス 2型糖尿病の合併症予防のための食事療法

    堀川千嘉, 曽根博仁

    臨床栄養   139 ( 2 )   175 - 183   2021

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  • Comparison of clinical outcomes among ATG and PTCY HLA-haploidentical HCT-single center analysis

    米沢穂高, 柴崎康彦, 武田ルイ, 片桐隆幸, 布施香子, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   43rd   2021

  • 腫瘍抗原特異的CTLがNK細胞に及ぼす影響

    相原瞳, 佐藤廣幸, 諏訪部達也, 柴崎康彦, 増子正義, 内山孝由, 佐藤英世, 富山智香子, 曽根博仁, 成田美和子

    日本免疫治療学会学術集会プログラム・抄録集   18th   2021

  • AML with Major & minor-bcr/abl co-expressing clone after second hematopoietic cell transplants

    本宮奈津子, 本宮奈津子, 片桐隆幸, 武田ルイ, 水戸部正樹, 米沢穂高, 諏訪部達也, 布施香子, 柴崎康彦, 瀧澤淳, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   43rd   2021

  • Comparison of allo-HSCT for Primary induction failure and relapse acute myeloid leukemia

    布施香子, 武田ルイ, 水戸部正樹, 米沢穂高, 諏訪部達也, 片桐隆幸, 柴崎康彦, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   43rd   2021

  • 【糖尿病網膜症診療ガイドライン(第1版)】

    瓶井 資弘, 石垣 泰, 島田 朗, 曽根 博仁, 池田 恒彦, 高村 佳弘, 舩津 英陽, 村田 敏規, 川崎 良, 後沢 誠, 佐々木 真理子, 佐藤 孝樹, 杉本 昌彦, 中尾 新太郎, 西田 健太郎, 平野 隆雄, 村上 智昭, 日本糖尿病眼学会診療ガイドライン委員会, 日本糖尿病眼学会

    日本眼科学会雑誌   124 ( 12 )   955 - 981   2020.12

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  • 白米と玄米および湿熱処理玄米米粉米菓摂取における血流依存性血管拡張反応値の比較検討

    鈴木 浩史, 渡辺 賢一, 曽根 博仁, 菅原 正義, 奥村 寿子, 本間 紀之, 藤井 義文, 室橋 直人, 大坪 研一, 加藤 久典, 平山 匡男

    機能性食品と薬理栄養   14 ( 3 )   173 - 173   2020.12

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  • 糖尿病・代謝疾患と機能性食品 糖尿病における食事療法のエビデンスと機能性食品

    曽根 博仁

    機能性食品と薬理栄養   14 ( 3 )   124 - 124   2020.12

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  • リアルワールドデータを糖尿病および合併症の臨床に生かす リアルワールドデータを活用した糖尿病合併症の臨床エビデンス創出

    曽根 博仁

    糖尿病合併症   34 ( Suppl.1 )   110 - 110   2020.11

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  • ビッグデータ解析に基づく網膜症予防のための内科的アプローチ

    曽根 博仁

    糖尿病合併症   34 ( Suppl.1 )   100 - 100   2020.11

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  • 眼科処置を要する糖尿病重症眼疾患発生と飲酒についての検討

    山本 正彦, 藤原 和哉, 矢口 雄大, 大澤 妙子, 山田 万祐子, 松林 泰弘, 長谷部 日, 曽根 博仁

    糖尿病合併症   34 ( Suppl.1 )   269 - 269   2020.11

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  • 心血管・動脈硬化 耐糖能別にみた収縮期血圧と冠動脈疾患、脳血管疾患発症との関連

    山田 万祐子, 藤原 和哉, 大澤 妙子, 矢口 雄大, 北澤 勝, 松林 泰弘, 岩永 みどり, 清田 浩康, 山中 菜詩, 山田 貴穂, 曽根 博仁

    糖尿病合併症   34 ( Suppl.1 )   219 - 219   2020.11

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  • 妊娠初期における糖代謝異常スクリーニング指標の検討

    谷内 洋子, 曽根 博仁

    糖尿病と妊娠   20 ( 3 )   S - 82   2020.11

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  • ビッグデータ解析に基づく網膜症予防のための内科的アプローチ

    曽根 博仁

    糖尿病合併症   34 ( Suppl.1 )   100 - 100   2020.11

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  • 第三期特定保健指導のモデル実施『新潟モデル』の構築について パイロットスタディ

    加藤 公則, 田代 稔, 鈴木 沙織, 小林 隆司, 春木 匠, 小松原 祐介, 佐藤 幸示, 赤澤 宏平, 曽根 博仁, 津下 一代

    人間ドック   35 ( 3 )   436 - 436   2020.11

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  • 眼科処置を要する糖尿病重症眼疾患発生と飲酒についての検討

    山本 正彦, 藤原 和哉, 矢口 雄大, 大澤 妙子, 山田 万祐子, 松林 泰弘, 長谷部 日, 曽根 博仁

    糖尿病合併症   34 ( Suppl.1 )   269 - 269   2020.11

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  • 健診・人間ドックビッグデータによるエビデンス構築と未来への伝承

    曽根 博仁

    人間ドック   35 ( 3 )   328 - 328   2020.11

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  • リアルワールドデータを糖尿病および合併症の臨床に生かす リアルワールドデータを活用した糖尿病合併症の臨床エビデンス創出

    曽根 博仁

    糖尿病合併症   34 ( Suppl.1 )   110 - 110   2020.11

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  • 心血管・動脈硬化 耐糖能別にみた収縮期血圧と冠動脈疾患、脳血管疾患発症との関連

    山田 万祐子, 藤原 和哉, 大澤 妙子, 矢口 雄大, 北澤 勝, 松林 泰弘, 岩永 みどり, 清田 浩康, 山中 菜詩, 山田 貴穂, 曽根 博仁

    糖尿病合併症   34 ( Suppl.1 )   219 - 219   2020.11

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  • Genetic Manipulation Resulting in Decreased Donor ChondroitinsulfateSynthesis Mitigates Gvhd Following Allogeneic Hematopoietic Cell Transplantation in a Murine Model

    Suguru Tamura, Takashi Ushiki, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Kyoko Fuse, Yasuhiko Shibasaki, Miwako Narita, Michihiro Igarashi, Hirohito Sone, Masayoshi Masuko

    BLOOD   136   2020.11

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  • 汎血球減少を伴ったバセドウ病の一例

    日向 裕大, 渡辺 聖央, 佐藤 隆明, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   96 ( 2 )   514 - 514   2020.10

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  • 人間ドックと職域健診におけるCKDの有病率の比較 加齢によるeGFR悪化を考慮した推定CKDによる解析

    加藤 公則, 小林 篤子, 高橋 克美, 田代 稔, 白井 彰, 小林 隆司, 井口 清太郎, 曽根 博仁

    臨床化学   49 ( Suppl.1 )   181 - 181   2020.10

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  • 粘液水腫性昏睡に急性膵炎を合併した一例

    齋藤 啓輔, 滝澤 祥子, 西井 郁生, 竹内 亮, 矢口 雄大, 山本 正彦, 川田 亮, 石黒 創, 北澤 勝, 松林 泰弘, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   96 ( 2 )   518 - 518   2020.10

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  • 大規模医療データサイエンスに基づく臨床栄養学 ビッグデータが変える食事栄養療法の未来

    曽根 博仁

    New Diet Therapy   36 ( 2 )   36 - 36   2020.9

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  • 慢性疾患治療のための運動療法up-to date 糖尿病の予防と治療のための身体活動と運動療法

    曽根 博仁

    日本臨床運動療法学会学術集会プログラム・抄録集   39回 ( 1 )   35 - 35   2020.9

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  • SGLT2阻害薬投与による肝インスリンクリアランス増加と血中トリグリセリド・βヒドロキシ酪酸レベルの変化との関連について

    松林 泰弘, 吉田 明弘, 菅波 秀規, 藤原 和哉, 加来 浩平, 曽根 博仁

    日本内分泌学会雑誌   96 ( 1 )   263 - 263   2020.8

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  • 下垂体機能低下症を併発した本態性高Na血症の一例

    岸 裕太郎, 竹内 亮, 山本 正彦, 松林 泰弘, 山田 貴穂, 岩永 みどり, 石黒 創, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   96 ( 1 )   256 - 256   2020.8

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  • 著明な嚥下障害を呈したKearns-Sayre症候群に合併した糖尿病の1例

    種村 聡, 山本 正彦, 石黒 創, 岩永 みどり, 松林 泰弘, 山田 貴穂, 藤原 和哉, 渡邊 賢一, 曽根 博仁

    糖尿病   63 ( 8 )   568 - 568   2020.8

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  • 1型糖尿病に対して膵腎同時移植を施行し透析およびインスリンを離脱した1例

    岸 裕太郎, 竹内 亮, 山本 正彦, 松林 泰弘, 藤原 和哉, 岩永 みどり, 山田 高穂, 曽根 博仁, 三浦 宏平, 小林 隆, 若井 俊文

    糖尿病   63 ( 8 )   558 - 558   2020.8

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  • 高齢になり副腎皮質機能低下症、甲状腺機能低下症が顕在化した下垂体茎離断症候群に甲状腺乳頭癌を合併した1例

    浅島 雄弥, 佐藤 隆明, 竹内 亮, 小松 健, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   96 ( 1 )   309 - 309   2020.8

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  • 指先穿刺による血糖およびHbA1c迅速測定をもちいた糖尿病啓発の取り組み(第2報)

    山田 貴穂, 武田 安永, 池田 和泉, 竹内 瑞希, 國米 純也, 中湊 大成, 滝澤 祥子, 村井 幸四郎, 竹内 亮, 今西 明, 安楽 匠, 岸 裕太郎, 小松 健, 佐藤 隆明, 矢口 雄大, 山田 万祐子, 川田 亮, 金子 正儀, 鈴木 浩史, 松林 泰弘, 藤原 和哉, 岩永 みどり, 鈴木 亜希子, 羽入 修, 曽根 博仁, 新潟県糖尿病協会

    糖尿病   63 ( Suppl.1 )   S - 349   2020.8

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  • 総合体力尺度から作成した体力年齢とメタボリックシンドローム(MetS)との関連

    佐藤 隆明, 藤原 和哉, 山田 万祐子, 矢口 雄大, 北澤 勝, 松林 泰弘, 岩永 みどり, 山田 貴穂, 加藤 公則, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 133   2020.8

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  • 糖尿病と定期的な運動習慣が要介護発症へ及ぼす影響の検討

    藤原 和哉, 山田 万祐子, 北澤 勝, 松林 泰弘, 矢口 雄大, 八尋 拓也, 筒井 歩, 山田 貴穂, 加藤 公則, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 148   2020.8

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  • ガイドラインからみた糖尿病の食事療法における課題 高齢者糖尿病の食事療法

    荒木 厚, 大村 卓也, 山岡 巧弥, 田村 嘉章, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 83   2020.8

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  • 糖尿病診療現場に活かせる日本人大規模医療データ解析 JDCSから大規模医療データサイエンスへ

    曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 86   2020.8

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  • 日本人2型糖尿病患者の肥満に対するエネルギー摂取と身体活動の複合効果

    治田 麻理子, 藤原 和哉, 森川 咲子, 武田 安永, 堀川 千嘉, 加藤 光敏, 横山 宏樹, 栗原 義夫, 岩崎 皓一, 宮澤 一裕, 山崎 勝也, 田中 四郎, 前川 聡, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 171   2020.8

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  • 糖尿病の有無別にみた収縮期血圧が透析開始に及ぼす影響

    大澤 妙子, 藤原 和哉, 山田 万祐子, 山本 正彦, 北澤 勝, 松林 泰弘, 岩永 みどり, 清田 浩康, 山田 貴穂, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 172   2020.8

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  • 糖尿病の有無別にみた日本人男性におけるBMI・腹囲と冠動脈疾患発症との関連

    上村 和樹, 藤原 和哉, 山田 万祐子, 北澤 勝, 矢口 雄大, 清田 浩康, 山中 菜詩, 松林 泰弘, 山田 貴穂, 児玉 暁, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 229   2020.8

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  • 2型糖尿病患者における野菜と果物の摂取と肥満との関連

    竹内 瑞希, 藤原 和哉, 治田 麻理子, 武田 安永, 堀川 千嘉, 斎藤 トシ子, 加藤 光敏, 加藤 則子, 横山 宏樹, 栗原 義夫, 岩崎 皓一, 宮澤 一裕, 山崎 勝也, 前川 聡, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 243   2020.8

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  • 経口血糖降下薬(OHA)の服薬アドヒアランス(Ad)と血糖コントロールとの関係

    矢口 雄大, 藤原 和哉, 山田 万祐子, 北澤 勝, 金子 正儀, 清田 浩康, 山中 菜詩, 松林 泰弘, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 222   2020.8

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  • SGLT2阻害薬52週投与及び投与中止2週後の推算血漿流量変化とBNPとの関連の検討

    松林 泰弘, 吉田 明弘, 野島 俊秋, 菅波 秀規, 石黒 創, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 223   2020.8

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  • 耐糖能別にみた収縮期血圧が冠動脈/脳血管疾患に及ぼす影響の検討

    山田 万祐子, 藤原 和哉, 大澤 妙子, 北澤 勝, 松林 泰弘, 矢口 雄大, 岩永 みどり, 山中 菜詩, 清田 浩康, 山田 貴穂, 小川 渉, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 206   2020.8

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  • 服薬アドヒアランスと下肢切断のリスクとの関連に関する縦断的検討

    金子 正儀, 藤原 和哉, 山田 万祐子, 北澤 勝, 矢口 雄大, 清田 浩康, 山中 菜詩, 松林 泰弘, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 207   2020.8

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  • スマートフォンを含むスクリーンタイムと小児の生活習慣、食品群別摂取量および肥満との関連

    池田 和泉, 藤原 和哉, 根立 梨奈, 森川 咲子, 石黒 創, 山田 万祐子, 松林 泰弘, 山田 貴穂, 曽根 博仁

    糖尿病   63 ( Suppl.1 )   S - 275   2020.8

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  • 糖尿病大血管症に対する多面的アプローチ リアルワールド・ビッグデータから見た糖尿病大血管症のリスクと管理

    曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   52回   105 - 105   2020.7

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  • 心不全患者に対する高尿酸血症治療薬の予後改善効果に関するネットワークメタ分析

    児玉 暁, 藤原 和哉, 渡辺 賢一, 加藤 公則, 曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   52回   234 - 234   2020.7

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  • A Prospective Cohort Study Of Physical Fitness And Incident Hearing Loss: The Niigata Wellness Study

    Ryoko Kawakami, Susumu S. Sawada, Kiminori Kato, Yuko Gando, Haruki Momma, Hideaki Oike, Motohiko Miyachi, I-Min Lee, Steven N. Blair, Minoru Tashiro, Hirohito Sone

    MEDICINE AND SCIENCE IN SPORTS AND EXERCISE   52 ( 17 )   421 - 421   2020.7

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    DOI: 10.1249/01.MSS.0000678444.92344.B1

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  • 糖尿病合併症の大規模研究 糖尿病患者の心血管イベントに対する血糖降下薬介入研究

    曽根 博仁

    糖尿病合併症   34 ( 1 )   122 - 126   2020.6

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  • Dietary Patterns Significantly Associated with Obesity in Japanese with Type 2 Diabetes: JDDM

    Mariko Hatta, Kazuya Fujihara, Izumi Ikeda, Mizuki Takeuchi, Rina Nedachi, Sakiko Y. Morikawa, Chika Horikawa, Mitsutoshi Kato, Noriko Kato, Hiroshi Maegawa, Hirohito Sone

    DIABETES   69   2020.6

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    DOI: 10.2337/db20-1541-P

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  • 【糖尿病エキスパートブック 食事療法・栄養指導に活かす最新情報】疫学と予防 2型糖尿病の予防

    曽根 博仁

    臨床栄養   136 ( 6 )   743 - 749   2020.5

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    <Key point>●糖尿病予防は、もっとも有効かつ確実な糖尿病合併症予防策である。●わずかな体重増加であっても、それが長年維持されると糖尿病発症リスクとなる。●多くの糖尿病発症リスク因子が解明されており、それらを組み合わせて糖尿病発症高リスク者をスクリーニングすることが、効率的な対策につながる。●多くの食品やその成分が、糖尿病発症リスク低下と関連している。●食事指導と運動指導は同時に行う必要がある。(著者抄録)

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  • 脳心血管病対策と合併症・重症化予防に役立つ食事療法 日本人患者のエビデンスに基づく糖尿病の合併症・重症化予防のための食事療法

    曽根 博仁

    日本栄養・食糧学会大会講演要旨集   74回   163 - 163   2020.4

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  • 妊娠初期の身体活動度および食事内容と耐糖能異常の関連 TWC Study

    田中 康弘, 谷内 洋子, 曽根 博仁

    日本産科婦人科学会雑誌   72 ( 臨増 )   S - 460   2020.3

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  • JDCS(Japan Diabetes Complications Study)

    曽根博仁

    糖尿病の最新治療   11 ( 2 )   68 - 74   2020.2

  • 甲状腺穿刺吸引細胞診後に一過性びまん性甲状腺腫脹を呈した1例

    山田 貴穂, 岸 裕太郎, 小松 健, 曽根 博仁

    日本内分泌学会雑誌   95 ( 4 )   1346 - 1346   2020.2

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  • 糖尿病、非糖尿患者における血糖、血圧、脂質、喫煙の管理目標の達成状況と冠動脈疾患発症の検討

    藤原 和哉, 山田 万佑子, 曽根 博仁

    日本内科学会雑誌   109 ( Suppl. )   240 - 240   2020.2

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  • 抗体陰性バセドウ病に合併した類もやもや病の1例

    滝澤 祥子, 今西 明, 安楽 匠, 川田 亮, 佐藤 隆明, 金子 正儀, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    新潟医学会雑誌   134 ( 2 )   75 - 76   2020.2

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  • 甲状腺穿刺吸引細胞診後に一過性びまん性甲状腺腫脹を呈した1例

    山田 貴穂, 岸 裕太郎, 小松 健, 黒崎 功, 曽根 博仁

    新潟医学会雑誌   134 ( 2 )   76 - 76   2020.2

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  • 日本人のやせと内分泌:エビデンスとこれからの対策 日本人若年女性におけるやせの実態と課題

    曽根 博仁

    日本内分泌学会雑誌   95 ( 3 )   960 - 960   2020.1

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  • 疫学と予防 2型糖尿病の予防

    曽根博仁

    臨床栄養   136 ( 6 )   743 - 749   2020

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    <Key point>●糖尿病予防は、もっとも有効かつ確実な糖尿病合併症予防策である。●わずかな体重増加であっても、それが長年維持されると糖尿病発症リスクとなる。●多くの糖尿病発症リスク因子が解明されており、それらを組み合わせて糖尿病発症高リスク者をスクリーニングすることが、効率的な対策につながる。●多くの食品やその成分が、糖尿病発症リスク低下と関連している。●食事指導と運動指導は同時に行う必要がある。(著者抄録)

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  • 白米と玄米および湿熱処理玄米米粉米菓摂取における血流依存性血管拡張反応値の比較検討

    鈴木浩史, 渡辺賢一, 曽根博仁, 菅原正義, 奥村寿子, 本間紀之, 藤井義文, 室橋直人, 大坪研一, 加藤久典, 平山匡男

    機能性食品と薬理栄養   14 ( 3 )   173 - 173   2020

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  • 健診・人間ドックビッグデータによるエビデンス構築と未来への伝承

    曽根博仁, 曽根博仁

    人間ドック   35 ( 3 )   328 - 328   2020

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  • 糖尿病における食事療法のエビデンスと機能性食品

    曽根博仁

    機能性食品と薬理栄養   14 ( 3 )   124 - 124   2020

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  • 第三期特定保健指導のモデル実施『新潟モデル』の構築について-パイロットスタディ

    加藤公則, 加藤公則, 田代稔, 鈴木沙織, 小林隆司, 春木匠, 小松原祐介, 佐藤幸示, 赤澤宏平, 曽根博仁, 津下一代

    人間ドック   35 ( 3 )   436 - 436   2020

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  • 運動の疫学を再考する 小児生活習慣病対策における体力の意義 新潟小児生活習慣病研究から得られた知見を中心として

    森川 咲子, 藤原 和哉, 曽根 博仁

    日本臨床運動療法学会雑誌   21 ( 2 )   17 - 20   2020

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  • ビッグデータ時代の臨床エビデンスに基づく運動療法

    曽根 博仁

    日本臨床運動療法学会雑誌   21 ( 2 )   1 - 4   2020

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  • 妊娠初期の身体活動度および食事内容と耐糖能異常の関連 TWC Study

    田中康弘, 谷内洋子, 谷内洋子, 曽根博仁

    日本産科婦人科学会雑誌   72 ( 臨増 )   S - 460   2020

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  • 糖尿病,非糖尿患者における血糖,血圧,脂質,喫煙の管理目標の達成状況と冠動脈疾患発症の検討

    藤原和哉, 山田万佑子, 曽根博仁

    日本内科学会雑誌   109 ( Suppl. )   240 - 240   2020

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  • 糖尿病患者の心血管イベントに対する血糖降下薬介入研究

    曽根博仁

    糖尿病合併症   34 ( 1 )   122 - 126   2020

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  • 糖尿病網膜症診療ガイドライン(第1版)

    瓶井資弘, 石垣泰, 島田朗, 曽根博仁, 池田恒彦, 高村佳弘, 舩津英陽, 村田敏規, 川崎良, 後沢誠, 佐々木真理子, 佐藤孝樹, 杉本昌彦, 中尾新太郎, 西田健太郎, 平野隆雄, 村上智昭

    日本眼科学会雑誌   124 ( 12 )   955 - 981   2020

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  • 著明な嚥下障害を呈したKearns-Sayre症候群に合併した糖尿病の1例

    種村聡, 山本正彦, 石黒創, 岩永みどり, 松林泰弘, 山田貴穂, 藤原和哉, 渡邊賢一, 曽根博仁

    糖尿病(Web)   63 ( 8 )   2020

  • A case of MDS with graft failure in HLA 1 locus-mismatch rPBSCT after graft failure in HLA-matched urBMT

    笠見卓哉, 柴崎康彦, 米沢穂高, 田村秀, 鈴木隆晴, 河本啓介, 布施香子, 瀧澤淳, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   42nd   2020

  • Successful treatment for MDS-EB2 using ATG for GVHD prophylaxis in allogenic BMT from HLA two loci mismatch unrelated donor

    米沢穂高, 柴崎康彦, 笠見卓哉, 鈴木隆晴, 田村秀, 河本啓介, 布施香子, 瀧澤淳, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   42nd   2020

  • 1型糖尿病に対して膵腎同時移植を施行し透析およびインスリンを離脱した1例

    岸裕太郎, 竹内亮, 山本正彦, 松林泰弘, 藤原和哉, 岩永みどり, 山田高穂, 曽根博仁, 三浦宏平, 小林隆, 若井俊文

    糖尿病(Web)   63 ( 8 )   2020

  • 加齢に伴う握力の変化と追跡期間中の握力に影響する要因:新潟ウェルネススタディ

    門間陽樹, 門間陽樹, 加藤公則, 加藤公則, 澤田亨, 丸藤祐子, 川上諒子, 宮地元彦, 永富良一, 田代稔, 藤原和哉, 曽根博仁

    日本疫学会学術総会講演集(Web)   30th   2020

  • IMiDsがCTLとNK細胞に及ぼす効果

    佐藤廣幸, 諏訪部達也, 柴崎康彦, 増子正義, 内山孝由, 富山智香子, 渡邉香奈子, 高橋益廣, 曽根博仁, 成田美和子

    日本免疫治療学会学術集会プログラム・抄録集   17th   2020

  • MDS/AML-MRC as a poor risk factor for primary graft failure in allogeneic hematopoietic cell transplantation

    田村秀, 柴崎康彦, 米沢穂高, 鈴木隆晴, 笠見卓哉, 河本啓介, 布施香子, 瀧澤淳, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   42nd   2020

  • 小中学生における体型の過大認識の現状および身体・精神的疲労度との関連の検討

    広瀬歩美, 広瀬歩美, 池田和泉, 竹内瑞希, 根立梨奈, 武田安永, 治田麻理子, 森川咲子, 堀川千嘉, 藤原かずや, 曽根博仁

    日本疫学会学術総会講演集(Web)   30th   2020

  • 2型糖尿病患者におけるカルシウム摂取量と腎症発症リスクとの関係:JDCS

    堀川千嘉, 相田麗, 田中司朗, 田中明, 井藤秀喜, 吉村幸雄, 大橋靖雄, 藤原和哉, 赤沼安夫, 曽根博仁

    日本疫学会学術総会講演集(Web)   30th   2020

  • 造血細胞と骨髄間質のコンドロイチン硫酸は異なる造血調節作用を示す

    片桐隆幸, 牛木隆志, 中島やえ子, 大島基彦, 三上雅久, 河嵜麻実, 石黒創, 田中智之, 曽根博仁, 北川裕之, 五十嵐道弘, 岩間厚志, 増子正義

    日本血液学会学術集会抄録(Web)   82nd   2020

  • 機能的なWT1特異的CD8陽性T細胞クローンは骨髄異形成症候群の骨髄内に集積する

    諏訪部達也, 柴崎康彦, 佐藤廣幸, 田村秀, 片桐隆幸, 根本洋樹, 笠見卓哉, 小堺貴司, 難波亜矢子, 北嶋俊樹, 布施香子, 牛木隆志, 曽根博仁, 成田美和子, 増子正義

    日本血液学会学術集会抄録(Web)   82nd   2020

  • 湿熱処理玄米米粉米菓摂取による血流依存性血管拡張反応値変動推移試験

    鈴木 浩史, 渡辺 賢一, 曽根 博仁, 菅原 正義, 奥村 寿子, 本間 紀之, 藤井 義文, 室橋 直人, 大坪 研一, 加藤 久典, 平山 匡男

    機能性食品と薬理栄養   13 ( 3 )   161 - 161   2019.12

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  • SGLT2阻害薬の大規模臨床研究

    曽根 博仁

    Diabetes Journal: 糖尿病と代謝   47 ( 4 )   119 - 124   2019.12

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    SGLT2阻害薬は体重減少効果も有する最新の経口血糖降下薬クラスである。最近のCardiovascular Outcome Trials(CVOTs)の結果によると、DPP-4阻害薬では認められなかった、心不全を含む心血管イベントや死亡の有意な低下が認められており、とくに二次予防を中心とした心血管疾患の高リスク患者において、欧米のガイドラインにおける推奨度が高まっている。SGLT2阻害薬のこれらの効果は、直接的な血糖降下作用以外による可能性もあり、今後わが国の糖尿病患者を対象とする一次予防臨床試験が期待される。(著者抄録)

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  • 妊娠中の身体活動レベルおよび食事内容と糖代謝異常リスクの関連TWC Study

    谷内 洋子, 田中 康弘, 曽根 博仁

    糖尿病と妊娠   19 ( 3 )   S - 90   2019.11

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  • 2型糖尿病発症予防のための妊娠糖尿病妊婦への非薬物的強化介入の試み

    川崎 麻紀, 荒田 尚子, 和栗 雅子, 飯村 祐子, 山本 周美, 川嵜 有紀, 牧 尉太, 玉田 祥子, 青山 友子, 田中 茂穂, 秦 健一郎, 宮越 敬, 橋本 貢士, 杉山 隆, 安日 一郎, 曽根 博仁, 菊池 透, 瀧本 秀美, 安田 和基, 小川 佳宏, 大田 えりか, 井上 永介, 平松 祐司

    糖尿病と妊娠   19 ( 3 )   S - 96   2019.11

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  • 小児1型糖尿病患児におけるFlash Glucose Monitoringの精度の検討

    北澤 勝, 小川 洋平, 宮澤 七穂, 長崎 啓祐, 佐々木 直, 齋藤 昭彦, 曽根 博仁

    日本先進糖尿病治療研究会雑誌   15   45 - 45   2019.11

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  • 局在診断に苦慮している周期性ACTH依存性クッシング症候群の1例

    金子 正儀, 佐藤 隆明, 福武 嶺一, 滝澤 祥子, 今西 明, 安楽 匠, 小松 健, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁, 岡田 正康, 小原 伸雅, 米岡 有一郎

    日本内分泌学会雑誌   95 ( 2 )   765 - 765   2019.10

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  • 骨髄異形成症候群と低悪性度B細胞リンパ腫を合併し、多彩な合併症を呈した1例

    海發 茜, 小堺 貴司, 田村 秀, 片桐 隆幸, 河本 啓介, 難波 亜矢子, 布施 香子, 牛木 隆志, 柴崎 康彦, 森山 雅人, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   60 ( 10 )   1503 - 1503   2019.10

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  • 【動脈硬化診療のすべて】(II章)動脈硬化を識る 危険因子・関連疾患とその予防・治療 糖尿病

    曽根 博仁

    日本医師会雑誌   148 ( 特別2 )   S110 - S115   2019.10

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  • 下垂体性と異所性の鑑別に苦慮したACTH依存性クッシング症候群の1例

    佐藤 隆明, 金子 正儀, 福武 嶺一, 小松 健, 今西 明, 安楽 匠, 竹内 真理, 竹内 亮, 岸 裕太郎, 矢口 雄大, 山本 正彦, 川田 亮, 石黒 創, 松林 康弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    新潟医学会雑誌   133 ( 9-10 )   352 - 352   2019.10

  • Effects of Single-intake of Rice Cracker Prepared from Heat-moisture-treated Brown Rice Flour on Vasodilator Response in Adults with Mild Endothelial Dysfunction

    渡辺賢一, 平山匡男, 中村澄子, 大坪研一, 本間紀之, 藤井義文, 室橋直人, AMURUGAM Somasundaram, 鈴木浩史, 曽根博仁, 菅原正義

    新潟医学会雑誌   133 ( 9-10 )   329 - 337   2019.10

  • 糖尿病治療の均てん化に向けて

    野田 光彦, 曽根 博仁, 能登 洋, 松久 宗英, 大西 勝也, 矢郷 祐三

    プラクティス   36 ( 5 )   581 - 586   2019.9

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  • 糖尿病合併症の大規模研究 糖尿病患者の心血管イベントに対する薬物介入研究

    曽根 博仁

    糖尿病合併症   33 ( Suppl.1 )   139 - 139   2019.9

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  • 糖尿病治療の均てん化に向けて

    野田 光彦, 曽根 博仁, 能登 洋, 松久 宗英, 大西 勝也, 矢郷 祐三

    プラクティス   36 ( 5 )   581 - 586   2019.9

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  • 今後知っておくべき"糖尿病網膜症診療ガイドライン" 内科から見た糖尿病網膜症診療ガイドラインの意義

    曽根 博仁

    糖尿病合併症   33 ( Suppl.1 )   158 - 158   2019.9

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  • ビッグデータ時代の臨床エビデンスに基づく運動療法

    曽根 博仁

    日本臨床運動療法学会学術集会プログラム・抄録集   38回   23 - 23   2019.8

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  • 運動の疫学を再考する 小児生活習慣病対策における体力の意義 新潟小児生活習慣病研究から得られた知見を中心として

    森川 咲子, 藤原 和哉, 曽根 博仁

    日本臨床運動療法学会学術集会プログラム・抄録集   38回   27 - 27   2019.8

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  • GDMのフォローアップ 2型糖尿病発症予防のための妊娠糖尿病妊婦への非薬物的強化介入の試み

    川崎 麻紀, 荒田 尚子, 和栗 雅子, 飯村 祐子, 山本 周美, 川嵜 有紀, 牧 尉太, 玉田 祥子, 青山 友子, 田中 茂穂, 秦 健一郎, 宮越 敬, 橋本 貢士, 杉山 隆, 安日 一郎, 曽根 博仁, 菊池 透, 瀧本 秀美, 安田 和基, 小川 佳宏, 大田 えりか, 井上 永介, 平松 祐司

    糖尿病と妊娠   19 ( 2 )   S - 38   2019.8

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    Language:Japanese   Publisher:(一社)日本糖尿病・妊娠学会  

    妊娠糖尿病と診断された女性のうち、2型糖尿病発症高リスク群((1)妊娠前肥満、または(2)妊娠前非肥満かつ妊娠糖尿病診断時の糖負荷試験での異常ポイント数が2ポイント以上)を対象に、妊娠中から食事・運動・母乳推進・教育介入を組み合わせた包括的な強化介入を行うことによる産後の糖尿病予防効果を明らかにする研究を開始した。現在、産後3ヵ月時点の耐糖能異常率および母乳栄養率をアウトカムとしたパイロット試験が、多施設共同オープンランダム化比較試験(デイジーマムスタディ)として進行中である。今後、パイロット試験における介入プログラムの実行可能性およびその効果を探索的に評価して本試験のデザインを決定する。(著者抄録)

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  • 医療との共存共栄を目指した機能性食品への期待

    曽根 博仁

    機能性食品と薬理栄養   13 ( 1 )   5 - 8   2019.8

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  • 生活習慣・肥満部会 昭和・平成から令和につなげる生活習慣改善の道-2022年ガイドライン改訂に向けて- 生活習慣教育・介入の効果

    曽根 博仁, 枇榔 貞利, 井上 郁夫, 井上 茂, 澤田 享, 木庭 新治, 船橋 徹, 藤岡 由夫, 丸山 千寿子, 武城 英明

    日本動脈硬化学会総会プログラム・抄録集   51回   ST1 - 5   2019.7

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  • 生活習慣・肥満部会 昭和・平成から令和につなげる生活習慣改善の道-2022年ガイドライン改訂に向けて- 肥満、特にメタボリックシンドローム(MetS)の概念の歴史的な流れ 日本独自の動脈硬化疾患予防施策へのあゆみ

    井上 郁夫, 船橋 徹, 井上 茂, 木庭 新治, 澤田 享, 曽根 博仁, 枇榔 貞利, 藤岡 由夫, 丸山 千寿子, 武城 英明

    日本動脈硬化学会総会プログラム・抄録集   51回   ST1 - 4   2019.7

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  • 生活習慣・肥満部会 昭和・平成から令和につなげる生活習慣改善の道-2022年ガイドライン改訂に向けて- 動脈硬化性心血管疾患予防における心肺身体能力・運動・身体活動のエビデンス

    木庭 新治, 井上 茂, 澤田 享, 井上 郁夫, 曽根 博仁, 船橋 徹, 枇榔 貞利, 藤岡 由夫, 丸山 千寿子, 武城 英明

    日本動脈硬化学会総会プログラム・抄録集   51回   ST1 - 3   2019.7

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  • 生活習慣・肥満部会 昭和・平成から令和につなげる生活習慣改善の道-2022年ガイドライン改訂に向けて- 食事療法の理解と実践

    藤岡 由夫, 丸山 千寿子, 井上 郁夫, 井上 茂, 木庭 新治, 澤田 享, 曽根 博仁, 船橋 徹, 枇榔 貞利, 武城 英明

    日本動脈硬化学会総会プログラム・抄録集   51回   ST1 - 2   2019.7

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  • 生活習慣・肥満部会 昭和・平成から令和につなげる生活習慣改善の道-2022年ガイドライン改訂に向けて- 食事療法の理解と実践

    藤岡 由夫, 丸山 千寿子, 井上 郁夫, 井上 茂, 木庭 新治, 澤田 享, 曽根 博仁, 船橋 徹, 枇榔 貞利, 武城 英明

    日本動脈硬化学会総会プログラム・抄録集   51回   ST1 - 2   2019.7

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  • Blake's pouch cystに伴う水頭症の治療により若年性認知症の改善を認めた糖尿病の1例

    種村 聡, 山本 正彦, 石黒 創, 岩永 みどり, 松林 泰弘, 山田 貴穂, 藤原 和哉, 渡邊 賢一, 曽根 博仁

    糖尿病   62 ( 7 )   441 - 441   2019.7

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  • 糖尿病と動脈硬化性疾患の最新の話題 ビッグデータ解析から見た2型糖尿病の動脈硬化合併症

    曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   51回   S8 - 1   2019.7

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  • 10年後の健康を守るプロジェクト Next 10の中間報告

    鈴木 沙織, 加藤 公則, 小林 篤子, 山浦 裕美, 田代 稔, 小林 隆司, 北川 寛, 佐藤 幸示, 笹川 力, 曽根 博仁

    人間ドック   34 ( 2 )   325 - 325   2019.7

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  • Factors Significantly Associated with Adherence to Diabetes Medications: Findings from a Large Japanese Claims Database

    Yuta Yaguchi, Kazuya Fujihara, Taeko Osawa, Masahiko Yamamoto, Masanori Kaneko, Masaru Kitazawa, Mayuko Harada, Yasuhiro Matsubayashi, Takaho Yamada, Nauta Yamanaka, Hiroyasu Seida, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-698-P

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  • Lower Hematocrit Is Predictive of Treatment -Required Eye Diseases in Japanese Patients with Diabetes Mellitus

    Masahiko Yamamoto, Kazuya Fujihara, Taeko Osawa, Mayuko Harada, Masahiro Ishizawa, Hiroshi Suzuki, Hajime Ishiguro, Hiroyasu Seida, Nauta Yamanaka, Yasuhiro Matsubayashi, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-598-P

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  • Association between Intake of Magnesium and Obesity in Japanese Patients with Type 2 Diabetes Mellitus

    Rina Nedachi, Kazuya Fujihara, Mariko Hatta, Yasuhiro Matsubayashi, Yasunaga Takeda, Dai Ishii, Chika Horikawa, Mitsutoshi Kato, Hiroshi Maegawa, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-2450-PUB

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  • SOCS3 Deficiency on a High-Fat Diet Accelerates Systemic Inflammation and Results in Lethal Myeloid Hematopoiesis without Obesity and Adiposity

    Kaori Cho, Takashi Ushiki, Hajime Ishiguro, Takayuki Katagiri, Tatsuya Suwabe, Hideyo Hirai, Yoshimi Nakagawa, Masayoshi Masuko, Warren Alexander, Hitoshi Shimano, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-1910-P

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  • Low Dietary Energy Density (DED) Diet Is Associated with Favorable Dietary Pattern in Japanese Patients with Type 2 Diabetes (T2DM)

    Yasunaga Takeda, Kazuya Fujihara, Mariko Hatta, Sakiko Y. Morikawa, Chika Horikawa, Dai Ishii, Rina Nedachi, Hiroshi Maegawa, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-764-P

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  • Personality, Self-Management Behaviors, and Glycemic Control among Japanese Patients with Type 2 Diabetes Mellitus (T2DM)

    Sakiko Y. Morikawa, Kazuya Fujihara, Mariko Hatta, Yasunaga Takeda, Dai Ishii, Junko Yachida, Chika Horikawa, Mitsutoshi Kato, Hiroshi Maegawa, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-854-P

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  • A Prospective Cohort Study of Physical Fitness and Incident Glaucoma: The Niigata Wellness Study

    Ryoko Kawakami, Susumu S. Sawada, Yuko Gando, Haruki Momma, Minoru Tashiro, I-Min Lee, Steven N. Blair, Motohiko Miyachi, Mitsuru Higuchi, Kiminori Kato, Hirohito Sone

    MEDICINE AND SCIENCE IN SPORTS AND EXERCISE   51 ( 6 )   222 - 222   2019.6

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    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1249/01.mss.0000561173.76263.2f

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  • Higher Calcium Intake Is Associated with Lower Incidence of Diabetic Nephropathy in Japanese Patients with Type 2 Diabetes

    Chika Horikawa, Rei Aida, Shiro Tanaka, Sachiko Tanaka, Chiemi Kamada, Yukio Yoshimura, Atsushi Araki, Tatsumi Moriya, Shigehiro Katayama, Yasuo Akanuma, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-1579-P

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  • Family Support for Medical Nutritional Therapy and Dietary Intake among Japanese Patients with Type 2 Diabetes

    Chika Horikawa, Yasunaga Takeda, Mariko Hatta, Dai Ishii, Sakiko Y. Morikawa, Kazuya Fujihara, Hiroshi Maegawa, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-767-P

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  • Association of Zinc Intake with Obesity in Japanese Patients with Type 2 Diabetes Mellitus (T2DM)

    Rina Nedachi, Kazuya Fujihara, Mariko Hatta, Yasuhiro Matsubayashi, Yasunaga Takeda, Dai Ishii, Chika Horikawa, Noriko Kato, Hiroshi Maegawa, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-789-P

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  • Significant Association of Food Group Intake with Obesity among Patients with Type 2 Diabetes Mellitus in Japan

    Mariko Hatta, Kazuya Fujihara, Yasunaga Takeda, Rina Nedachi, Dai Ishii, Sakiko Y. Morikawa, Chika Horikawa, Mitsutoshi Kato, Hiroshi Maegawa, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-775-P

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  • Association of Dietary Intake of Phosphorus with Obesity in Japanese Patients with Type 2 Diabetes Mellitus (T2DM)

    Mariko Hatta, Kazuya Fujihara, Yasuhiro Matsubayashi, Yasunaga Takeda, Rina Nedachi, Dai Ishii, Chika Horikawa, Mitsutoshi Kato, Hiroshi Maegawa, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-2078-P

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  • Intake of Fish and Related Nutrients in Association with Obesity in Japanese Patients with Type 2 Diabetes (T2D)

    Mariko Hatta, Kazuya Fujihara, Yasuhiro Matsubayashi, Yasunaga Takeda, Rina Nedachi, Dai Ishii, Chika Horikawa, Noriko Kato, Hiroshi Maegawa, Hirohito Sone

    DIABETES   68   2019.6

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    DOI: 10.2337/db19-1583-P

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  • 脳心血管病予防に関する包括的リスク管理チャート2019年版について

    寺本 民生, 荒井 秀典, 磯 博康, 野出 孝一, 松本 昌泰, 飯田 真美, 小熊 祐子, 井上 茂, 永富 良一, 庄司 哲雄, 楽木 宏実, 曽根 博仁, 宮崎 滋, 神崎 恒一, 脳心血管病協議会, 一般社団法人日本疫学会, 特定非営利活動法人日本高血圧学会, 一般社団法人日本循環器学会, 一般社団法人日本腎臓学会, 一般社団法人日本総合健診医学会, 一般社団法人日本体力医学会, 一般社団法人日本痛風, 核酸代謝学会, 一般社団法人日本糖尿病学会, 一般社団法人日本動脈硬化学会, 一般社団法人日本内科学会, 一般社団法人日本脳卒中学会, 一般社団法人日本肥満学会, 一般社団法人日本老年医学会, 一般社団法人日本神経学会, 一般社団法人日本医学会連合, 公益社団法人日本医師会

    日本内科学会雑誌   108 ( 5 )   1024 - 1074   2019.5

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  • 【糖尿病網膜症】糖尿病網膜症と大血管合併症のビッグデータ解析によるエビデンス

    山本 正彦, 藤原 和哉, 曽根 博仁

    内分泌・糖尿病・代謝内科   48 ( 5 )   332 - 337   2019.5

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  • 脳心血管病予防に関する包括的リスク管理チャート2019年版について

    寺本 民生, 荒井 秀典, 磯 博康, 野出 孝一, 松本 昌泰, 飯田 真美, 小熊 祐子, 井上 茂, 永富 良一, 庄司 哲雄, 楽木 宏実, 曽根 博仁, 宮崎 滋, 神崎 恒一, 脳心血管病協議会, 一般社団法人日本疫学会, 特定非営利活動法人日本高血圧学会, 一般社団法人日本循環器学会, 一般社団法人日本腎臓学会, 一般社団法人日本総合健診医学会, 一般社団法人日本体力医学会, 一般社団法人日本痛風, 核酸代謝学会, 一般社団法人日本糖尿病学会, 一般社団法人日本動脈硬化学会, 一般社団法人日本内科学会, 一般社団法人日本脳卒中学会, 一般社団法人日本肥満学会, 一般社団法人日本老年医学会, 一般社団法人日本神経学会, 一般社団法人日本医学会連合, 公益社団法人日本医師会

    日本内科学会雑誌   108 ( 5 )   1024 - 1074   2019.5

  • Hodgkin lymphomaとAnaplastic large cell lymphomaの鑑別が困難であった巨大縦隔腫瘤を呈した1例

    河本 啓介, 鈴木 隆晴, 海發 茜, 田村 秀, 片桐 隆之, 難波 亜矢子, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 三好 寛明, 大島 孝一, 瀧澤 淳

    日本リンパ網内系学会会誌   59   133 - 133   2019.5

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  • 日本では未分類である脾臓B細胞リンパ腫/白血病におけるBRAF遺伝子変異の分析(Analysis of BRAF mutation in splenic B-cell lymphoma/leukemia, unclassifiable in Japan)

    鈴木 隆晴, 三好 寛明, 河本 啓介, 荒川 文子, 古田 拓也, 下埜 城嗣, 山田 恭平, 柳田 恵理子, 瀬戸 加大, 曽根 博仁, 瀧澤 淳, 大島 孝一

    日本リンパ網内系学会会誌   59   145 - 145   2019.5

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  • 糖尿病の有無別にみた血糖・血圧・脂質・喫煙の各管理目標達成状況が冠動脈疾患発症に及ぼす影響

    原田 万祐子, 藤原 和哉, 大澤 妙子, 石澤 正博, 山本 正彦, 金子 正儀, 松林 泰弘, 清田 浩康, 山田 貴穂, 小川 渉, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 285   2019.4

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  • (わが国における)経口血糖降下薬の服薬アドヒアランスの現況とその関連因子

    矢口 雄大, 藤原 和哉, 原田 万祐子, 金子 正儀, 松林 泰弘, 北澤 勝, 清田 浩康, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 263   2019.4

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  • 糖尿病(DM)・冠動脈疾患(CAD)・脳血管疾患(CVD)の既往及び組み合わせがその後のリスクへ及ぼす影響の検討

    藤原 和哉, 松林 泰弘, 原田 万祐子, 大澤 妙子, 金子 正儀, 山本 正彦, 山田 高穂, 清田 浩康, 加藤 公則, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 254   2019.4

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  • 脂肪細胞インスリン抵抗性からみたSGLT2阻害薬投与によるケトン体上昇予測因子の検討

    松林 泰弘, 吉田 明弘, 野島 俊秋, 菅波 秀規, 石黒 創, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 126   2019.4

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  • 術前に経カテーテル動脈塞栓術(TAE)を施行した骨盤内IGF-2産生腫瘍による低血糖症の1例

    佐藤 隆明, 金子 正儀, 福武 嶺一, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁, 福田 いずみ, 長嶋 洋治

    日本内分泌学会雑誌   95 ( 1 )   495 - 495   2019.4

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  • 大規模医療データサイエンスの成果を現場臨床に活かす 医療・保健ビッグデータを活用した糖尿病とその合併症予防のエビデンス

    曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 13   2019.4

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  • 原発巣の特定に苦慮した甲状腺扁平上皮癌が疑われた一例

    今西 明, 安樂 匠, 三ツ間 友里恵, 矢口 雄大, 鈴木 達郎, 山田 貴穂, 曽根 博仁, 植木 雄志, 茂木 聡子, 梅津 哉, 大橋 瑠子, 佐々木 健太, 平田 哲大, 丸山 克也

    日本内分泌学会雑誌   95 ( 1 )   464 - 464   2019.4

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  • 糖尿病患者における運動療法の有効性に関する大規模臨床エビデンス

    曽根 博仁

    日本内分泌学会雑誌   95 ( 1 )   246 - 246   2019.4

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  • 機能性食品と栄養学の将来を考える 機能性食品・成分の医療分野への応用と期待

    曽根 博仁

    日本栄養・食糧学会大会講演要旨集   73回   330 - 330   2019.4

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  • 血清アミラーゼ値およびその経時変化が2型糖尿病発症に及ぼす影響の定量的検討

    石井 大, 藤原 和哉, 根立 梨奈, 原田 万佑子, 松林 泰弘, 斎藤 和美, 児玉 暁, 森 保道, 本田 律子, 荒瀬 康司, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 219   2019.4

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  • 脂肪細胞インスリン抵抗性からみたSGLT2阻害薬投与によるケトン体上昇予測因子の検討

    松林 泰弘, 吉田 明弘, 野島 俊秋, 菅波 秀規, 石黒 創, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 126   2019.4

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  • (わが国における)経口血糖降下薬の服薬アドヒアランスの現況とその関連因子

    矢口 雄大, 藤原 和哉, 原田 万祐子, 金子 正儀, 松林 泰弘, 北澤 勝, 清田 浩康, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 263   2019.4

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  • 血清アミラーゼ値およびその経時変化が2型糖尿病発症に及ぼす影響の定量的検討

    石井 大, 藤原 和哉, 根立 梨奈, 原田 万佑子, 松林 泰弘, 斎藤 和美, 児玉 暁, 森 保道, 本田 律子, 荒瀬 康司, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 219   2019.4

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  • 医療ビッグデータを用いた糖尿病患者の下肢切断に関するリスク因子の検討

    金子 正儀, 藤原 和哉, 原田 万祐子, 山本 正彦, 松林 泰弘, 北澤 勝, 石井 大, 清田 浩康, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 195   2019.4

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  • 糖尿病の有無別にみた高血圧が透析導入に及ぼす影響の検討

    大澤 妙子, 藤原 和哉, 山本 正彦, 原田 万祐子, 北澤 勝, 金子 正儀, 石黒 創, 石澤 正博, 松林 泰弘, 清田 浩康, 山中 菜詩, 山田 貴穂, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 219   2019.4

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  • 2型糖尿病患者における食事エネルギー密度と食事パターンとの関連

    武田 安永, 藤原 和哉, 治田 麻理子, 森川 咲子, 堀川 千嘉, 石井 大, 根立 梨奈, 加藤 光敏, 横山 宏樹, 栗原 義夫, 宮澤 一裕, 岩崎 晧一, 川井 紘一, 朝長 修, 屋宜 宣治, 前川 聡, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 116   2019.4

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  • 大規模医療データサイエンスの成果を現場臨床に活かす 医療・保健ビッグデータを活用した糖尿病とその合併症予防のエビデンス

    曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 13   2019.4

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  • 耐糖能状態と心血管疾患既往の有無別に見たその後の心血管疾患発症リスク

    北澤 勝, 藤原 和哉, 原田 万祐子, 大澤 妙子, 山本 正彦, 矢口 雄大, 金子 正儀, 松林 泰弘, 山田 貴穂, 清田 浩康, 曽根 博仁

    糖尿病   62 ( Suppl.1 )   S - 190   2019.4

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  • 【病気のしくみ・合併症・治療による変化がわかる 糖尿病の病態生理イラスト図鑑】 (第2章)糖尿病合併症のしくみ メタボリックシンドロームと糖尿病

    福武 嶺一, 曽根 博仁

    糖尿病ケア   ( 2019春季増刊 )   154 - 157   2019.3

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  • 日本人若年女性・妊婦におけるやせ過ぎとその弊害

    谷内 洋子, 曽根 博仁

    New Diet Therapy   34 ( 4 )   27 - 32   2019.3

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  • 【病気のしくみ・合併症・治療による変化がわかる 糖尿病の病態生理イラスト図鑑】(第2章)糖尿病合併症のしくみ メタボリックシンドロームと糖尿病

    福武 嶺一, 曽根 博仁

    糖尿病ケア   ( 2019春季増刊 )   154 - 157   2019.3

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  • 日本人若年女性・妊婦におけるやせ過ぎとその弊害

    谷内 洋子, 曽根 博仁

    New Diet Therapy   34 ( 4 )   27 - 32   2019.3

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  • 耐糖能別にみた肥満及び代謝異常が冠動脈疾患発症へ及ぼす影響の縦断的検討

    藤原 和哉, 松林 泰弘, 児玉 暁, 曽根 博仁

    日本内科学会雑誌   108 ( Suppl. )   187 - 187   2019.2

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  • メタ解析からみた糖尿病の心不全発症危険因子としての疫学的エビデンス

    児玉 暁, 藤原 和哉, 石澤 正博, 石黒 創, 松林 泰弘, 岩永 みどり, 山田 貴穂, 渡辺 賢一, 加藤 公則, 曽根 博仁

    日本内科学会雑誌   108 ( Suppl. )   270 - 270   2019.2

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  • 耐糖能別にみた肥満及び代謝異常が冠動脈疾患発症へ及ぼす影響の縦断的検討

    藤原 和哉, 松林 泰弘, 児玉 暁, 曽根 博仁

    日本内科学会雑誌   108 ( Suppl. )   187 - 187   2019.2

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  • メタ解析からみた糖尿病の心不全発症危険因子としての疫学的エビデンス

    児玉 暁, 藤原 和哉, 石澤 正博, 石黒 創, 松林 泰弘, 岩永 みどり, 山田 貴穂, 渡辺 賢一, 加藤 公則, 曽根 博仁

    日本内科学会雑誌   108 ( Suppl. )   270 - 270   2019.2

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  • 2型糖尿病患者における食事エネルギー密度とエネルギー、マクロ栄養素の肥満との関連

    武田 安永, 根立 梨奈, 石井 大, 治田 麻理子, 森川 咲子, 堀川 千嘉, 藤原 和哉, 曽根 博仁

    日本病態栄養学会誌   22 ( Suppl. )   S - 1   2019.1

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  • 2型糖尿病患者における食事エネルギー密度とエネルギー、マクロ栄養素の肥満との関連

    武田 安永, 根立 梨奈, 石井 大, 治田 麻理子, 森川 咲子, 堀川 千嘉, 藤原 和哉, 曽根 博仁

    日本病態栄養学会誌   22 ( Suppl. )   S - 1   2019.1

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  • 非寛解期末梢血幹細胞移植後に通常量5‐AZA療法を施行し,寛解を維持しているEVI‐1陽性AMLの一例

    田村秀, 柴崎康彦, 上村駿, 笠見卓哉, 海發茜, 今西明, 片桐隆幸, 難波亜矢子, 河本啓介, 牛木隆志, 布施香子, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   41st   296   2019

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  • 3度目の同種造血細胞移植後ポナチニブ維持療法を行い,寛解を維持している再発・難治Ph陽性ALL

    海發茜, 柴崎康彦, 諏訪部達也, 笠見卓哉, 田村秀, 片桐隆幸, 河本啓介, 難波亜矢子, 布施香子, 牛木隆志, 森山雅人, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   41st   173   2019

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  • 骨髄異形成症候群と低悪性度B細胞リンパ腫を合併し、多彩な合併症を呈した1例

    海發 茜, 小堺 貴司, 田村 秀, 片桐 隆幸, 河本 啓介, 難波 亜矢子, 布施 香子, 牛木 隆志, 柴崎 康彦, 森山 雅人, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   60 ( 10 )   1503 - 1503   2019

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  • Hodgkin lymphomaとAnaplastic large cell lymphomaの鑑別が困難であった巨大縦隔腫瘤を呈した1例

    河本 啓介, 鈴木 隆晴, 海發 茜, 田村 秀, 片桐 隆之, 難波 亜矢子, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 三好 寛明, 大島 孝一, 瀧澤 淳

    日本リンパ網内系学会会誌   59   133 - 133   2019

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  • GDMのフォローアップ 2型糖尿病発症予防のための妊娠糖尿病妊婦への非薬物的強化介入の試み

    川崎 麻紀, 荒田 尚子, 和栗 雅子, 飯村 祐子, 山本 周美, 川嵜 有紀, 牧 尉太, 玉田 祥子, 青山 友子, 田中 茂穂, 秦 健一郎, 宮越 敬, 橋本 貢士, 杉山 隆, 安日 一郎, 曽根 博仁, 菊池 透, 瀧本 秀美, 安田 和基, 小川 佳宏, 大田 えりか, 井上 永介, 平松 祐司

    糖尿病と妊娠   19 ( 2 )   S - 35   2019

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    妊娠糖尿病と診断された女性のうち、2型糖尿病発症高リスク群((1)妊娠前肥満、または(2)妊娠前非肥満かつ妊娠糖尿病診断時の糖負荷試験での異常ポイント数が2ポイント以上)を対象に、妊娠中から食事・運動・母乳推進・教育介入を組み合わせた包括的な強化介入を行うことによる産後の糖尿病予防効果を明らかにする研究を開始した。現在、産後3ヵ月時点の耐糖能異常率および母乳栄養率をアウトカムとしたパイロット試験が、多施設共同オープンランダム化比較試験(デイジーマムスタディ)として進行中である。今後、パイロット試験における介入プログラムの実行可能性およびその効果を探索的に評価して本試験のデザインを決定する。(著者抄録)

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  • 生活習慣・肥満部会 昭和・平成から令和につなげる生活習慣改善の道-2022年ガイドライン改訂に向けて- 動脈硬化性心血管疾患予防における心肺身体能力・運動・身体活動のエビデンス

    木庭 新治, 井上 茂, 澤田 享, 井上 郁夫, 曽根 博仁, 船橋 徹, 枇榔 貞利, 藤岡 由夫, 丸山 千寿子, 武城 英明

    日本動脈硬化学会総会プログラム・抄録集   51st   ST1 - 3   2019

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  • 生活習慣・肥満部会 昭和・平成から令和につなげる生活習慣改善の道-2022年ガイドライン改訂に向けて- 生活習慣教育・介入の効果

    曽根 博仁, 枇榔 貞利, 井上 郁夫, 井上 茂, 澤田 享, 木庭 新治, 船橋 徹, 藤岡 由夫, 丸山 千寿子, 武城 英明

    日本動脈硬化学会総会プログラム・抄録集   51st   ST1 - 5   2019

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  • 生活習慣・肥満部会 昭和・平成から令和につなげる生活習慣改善の道-2022年ガイドライン改訂に向けて- 肥満、特にメタボリックシンドローム(MetS)の概念の歴史的な流れ 日本独自の動脈硬化疾患予防施策へのあゆみ

    井上 郁夫, 船橋 徹, 井上 茂, 木庭 新治, 澤田 享, 曽根 博仁, 枇榔 貞利, 藤岡 由夫, 丸山 千寿子, 武城 英明

    日本動脈硬化学会総会プログラム・抄録集   51st   ST1 - 4   2019

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  • 糖尿病と動脈硬化性疾患の最新の話題 ビッグデータ解析から見た2型糖尿病の動脈硬化合併症

    曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   51st   S8 - 1   2019

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  • 【わが国の最近の生活習慣病コホート/ビッグデータ研究と臨床試験】患者コホート研究 糖尿病リスクエンジンの開発と費用効果分析への応用 Japan Diabetes Complications Study(JDCS)

    田中 司朗, 相田 麗, 曽根 博仁

    The Lipid   30 ( 3 )   267 - 275   2019

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    医療の質の向上、財政維持、医薬品・医療機器開発は、経済学的な意味でしばしば対立する課題であり、その解決策の1つとして費用対効果評価の導入が進められている。JJリスクエンジンは、日本人2型糖尿病コホート研究から得られたデータに基づいて、血糖・血圧・脂質コレステロールを通じて、薬剤がどれくらい合併症を予防できるか、別の薬剤に比べ、どの程度費用対効果があるかをシミュレートすることができるExcelツールである。JJリスクエンジンの入力項目のうち重要なのは、比較する二種類の薬剤がもたらすHbA1c、収縮期血圧、BMI、non-HDLコレステロールの変化と薬剤コストの指定である。これらを入力することによって、糖尿病合併症が発生する確率を計算し、生存年、QALY、コスト、ICERといった費用対効果の指標を出力することができる。(著者抄録)

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  • 【糖尿病の運動指導:すぐに役立つ効果的アプローチ-最新のエビデンスと基礎データを活かす-】糖尿病と運動・身体活動についての疫学・大規模臨床研究エビデンス

    石黒 創, 曽根 博仁

    プラクティス   36 ( 4 )   410 - 415   2019

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  • 2型糖尿病患者における食事エネルギー密度と食事パターンとの関連

    武田安永, 藤原和哉, 治田麻理子, 森川咲子, 森川咲子, 堀川千嘉, 堀川千嘉, 石井大, 根立梨奈, 加藤光敏, 横山宏樹, 栗原義夫, 宮澤一裕, 岩崎晧一, 川井紘一, 朝長修, 屋宜宣治, 前川聡, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 術前に経カテーテル動脈塞栓術(TAE)を施行した骨盤内IGF-2産生腫瘍による低血糖症の1例

    佐藤 隆明, 金子 正儀, 福武 嶺一, 松林 泰弘, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁, 福田 いずみ, 長嶋 洋治

    日本内分泌学会雑誌   95 ( 1 )   495 - 495   2019

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  • 原発巣の特定に苦慮した甲状腺扁平上皮癌が疑われた一例

    今西 明, 安樂 匠, 三ツ間 友里恵, 矢口 雄大, 鈴木 達郎, 山田 貴穂, 曽根 博仁, 植木 雄志, 茂木 聡子, 梅津 哉, 大橋 瑠子, 佐々木 健太, 平田 哲大, 丸山 克也

    日本内分泌学会雑誌   95 ( 1 )   464 - 464   2019

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  • 10年後の健康を守るプロジェクト Next 10の中間報告

    鈴木 沙織, 加藤 公則, 小林 篤子, 山浦 裕美, 田代 稔, 小林 隆司, 北川 寛, 佐藤 幸示, 笹川 力, 曽根 博仁

    人間ドック   34 ( 2 )   325 - 325   2019

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  • Analysis of BRAF mutation in splenic B-cell lymphoma/leukemia, unclassifiable in Japan

    鈴木隆晴, 鈴木隆晴, 三好寛明, 河本啓介, 荒川文子, 古田拓也, 下埜城嗣, 山田恭平, 柳田恵理子, 瀬戸加大, 曽根博仁, 瀧澤淳, 大島孝一

    日本リンパ網内系学会会誌   59   145 - 145   2019

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  • 医療との共存共栄を目指した機能性食品への期待

    曽根 博仁

    機能性食品と薬理栄養   13 ( 1 )   5 - 8   2019

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  • 同種造血幹細胞移植後に再発した急性白血病の全生存とTRMの予後因子の検討

    布施香子, 諏訪部達也, 片桐隆幸, 柴崎康彦, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   41st   2019

  • 医療ビッグデータと大規模臨床データを用いた糖尿病研究

    曽根博仁

    糖尿病学の進歩   53rd   2019

  • 糖尿病の疫学・大規模臨床研究-過去と未来

    曽根博仁

    糖尿病学の進歩   53rd   2019

  • 糖尿病(DM)・冠動脈疾患(CAD)・脳血管疾患(CVD)の既往及び組み合わせがその後のリスクへ及ぼす影響の検討

    藤原和哉, 松林泰弘, 原田万祐子, 大澤妙子, 金子正儀, 山本正彦, 山田高穂, 清田浩康, 加藤公則, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 脂肪細胞インスリン抵抗性からみたSGLT2阻害薬投与によるケトン体上昇予測因子の検討

    松林泰弘, 吉田明弘, 吉田明弘, 野島俊秋, 野島俊秋, 菅波秀規, 石黒創, 岩永みどり, 山田貴穂, 藤原和哉, 加来浩平, 加来浩平, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • サルコペニアの疫学~人間ドックのデータの検討から

    石澤正博, 石澤正博, 曽根博仁

    日本サルコペニア・フレイル学会誌   3 ( 2 )   2019

  • Blake’s pouch cystに伴う水頭症の治療により若年性認知症の改善を認めた糖尿病の1例

    種村聡, 山本正彦, 石黒創, 岩永みどり, 松林泰弘, 山田貴穂, 藤原和哉, 渡邊賢一, 曽根博仁

    糖尿病(Web)   62 ( 7 )   2019

  • 医療・保健ビッグデータを活用した糖尿病とその合併症予防のエビデンス

    曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 小児1型糖尿病キャンプにおける低血糖発現状況の検討

    北澤勝, 小川洋平, 佐々木直, 佐藤英利, 長崎啓祐, 斉藤昭彦, 曽根博仁

    日本小児・思春期糖尿病学会年次学術集会プログラム・抄録集   25th   2019

  • 同種造血細胞移植前のCT断面像による大腰筋面積測定は予後予測に有用である

    小林健太, 柴崎康彦, 柴崎康彦, 布施香子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   41st   2019

  • 食事療法の理解と実践

    藤岡由夫, 丸山千寿子, 井上郁夫, 井上茂, 木庭新治, 澤田享, 曽根博仁, 船橋徹, 枇榔貞利, 武城英明, 武城英明

    日本動脈硬化学会総会・学術集会プログラム・抄録集(Web)   51st   2019

  • 抗原特異的細胞障害性T細胞の増幅に及ぼすIMidの効果の検討

    小川彩空, 諏訪部達也, 柴崎康裕, 後藤若奈, 増子正義, 内山孝由, 瀧澤淳, 曽根博仁, 高橋益廣, 成田美和子

    日本免疫治療学会学術集会プログラム・抄録集   16th   2019

  • (わが国における)経口血糖降下薬の服薬アドヒアランスの現況とその関連因子

    矢口雄大, 藤原和哉, 原田万祐子, 金子正儀, 松林泰弘, 北澤勝, 清田浩康, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 糖尿病の有無別にみた血糖・血圧・脂質・喫煙の各管理目標達成状況が冠動脈疾患発症に及ぼす影響

    原田万祐子, 原田万祐子, 藤原和哉, 大澤妙子, 石澤正博, 山本正彦, 金子正儀, 松林泰弘, 清田浩康, 山田貴徳, 小川渉, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 医療ビッグデータを用いた糖尿病患者の下肢切断に関するリスク因子の検討

    金子正儀, 藤原和哉, 原田万祐子, 山本正彦, 松林泰弘, 北澤勝, 石井大, 清田浩康, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 血清アミラーゼ値およびその経時変化が2型糖尿病発症に及ぼす影響の定量的検討

    石井大, 藤原和哉, 根立梨奈, 原田万佑子, 松林泰弘, 斎藤和美, 児玉暁, 森保道, 本田律子, 荒瀬康司, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 糖尿病の有無別にみた高血圧が透析導入に及ぼす影響の検討

    大澤妙子, 藤原和哉, 山本正彦, 原田万祐子, 北澤勝, 金子正儀, 石黒創, 石澤正博, 松林泰弘, 清田浩康, 山中菜詩, 山田貴徳, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 耐糖能状態と心血管疾患既往の有無別に見たその後の心血管疾患発症リスク

    北澤勝, 北澤勝, 藤原和哉, 原田万祐子, 大澤妙子, 山本正彦, 矢口雄大, 金子正儀, 松林泰弘, 山田貴穂, 清田浩康, 曽根博仁

    糖尿病(Web)   62 ( Suppl )   2019

  • 糖尿病患者における運動療法の有効性に関する大規模臨床エビデンス

    曽根 博仁

    日本内分泌学会雑誌   95 ( 1 )   246 - 246   2019

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  • 日本人若年女性・妊婦におけるやせ過ぎとその弊害

    谷内洋子, 谷内洋子, 曽根博仁

    New Diet Therapy   34 ( 4 )   2019

  • 無痛性甲状腺炎の経過中に低Ca血症が顕在化した22q11.2欠失症候群による副甲状腺機能低下症の成人例

    廣嶋 省太, 柴田 奈央, 入月 浩美, 佐々木 直, 小川 洋平, 長崎 啓祐, 曽根 博仁

    新潟医学会雑誌   132 ( 11-12 )   401 - 402   2018.12

  • バセドウ病治療に伴う無顆粒球症の治療中、血球貪食症候群を発症した一例

    三ツ間 友里恵, 橋本 浩平, 山本 正彦, 金子 正儀, 松林 泰弘, 山田 貴穂, 岩永 みどり, 藤原 和哉, 曽根 博仁, 福武 嶺一

    日本内分泌学会雑誌   94 ( 3 )   846 - 846   2018.12

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  • 医療との共存共栄を目指した機能性食品への期待

    曽根 博仁

    機能性食品と薬理栄養   12 ( 3 )   122 - 122   2018.12

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  • 無痛性甲状腺炎の回復期に低Ca血症が顕在化した22q11.2欠失症候群による副甲状腺機能低下症の成人例

    廣嶋 省太, 柴田 奈央, 佐々木 直, 入月 浩美, 小川 洋平, 長崎 啓祐, 曽根 博仁

    日本内分泌学会雑誌   94 ( 3 )   887 - 887   2018.12

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  • バセドウ病治療に伴う無顆粒球症の治療中、血球貪食症候群を発症した一例

    三ツ間 友里恵, 橋本 浩平, 山本 正彦, 金子 正儀, 松林 泰弘, 山田 貴穂, 岩永 みどり, 藤原 和哉, 曽根 博仁, 福武 嶺一

    日本内分泌学会雑誌   94 ( 3 )   846 - 846   2018.12

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  • 無痛性甲状腺炎の回復期に低Ca血症が顕在化した22q11.2欠失症候群による副甲状腺機能低下症の成人例

    廣嶋 省太, 柴田 奈央, 佐々木 直, 入月 浩美, 小川 洋平, 長崎 啓祐, 曽根 博仁

    日本内分泌学会雑誌   94 ( 3 )   887 - 887   2018.12

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  • 胃亜全摘術後の2型糖尿病患者における治療強化の手段として、DPP-4阻害薬からGLP-1受容体作動薬への変更は有効か

    白石 友信, 吉岡 大志, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本先進糖尿病治療研究会雑誌   14   44 - 44   2018.11

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  • 人工知能を用いて患者の病態に合わせた最も効果的な同種造血細胞移植法を選択する試み

    布施 香子, 柴崎 康彦, 古川 達雄, 曽根 博仁, 増子 正義

    新潟県医師会報   ( 824 )   9 - 10   2018.11

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  • 【眼科医のための糖尿病トータルガイド】糖尿病の疫学

    山本 正彦, 曽根 博仁

    OCULISTA   ( 68 )   1 - 9   2018.11

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    糖尿病網膜症の有病率は2000年以降の研究において低下傾向にあるというメタ解析による報告はあるものの、糖尿病患者数は全世界的に増加傾向にある。そのため、全体として、糖尿病網膜症の患者数は増加傾向にあると推測される。一方で、眼科精査を受けずに、糖尿病網膜症に罹患していることに気がつかないまま放置された結果、失明や重度の視力障害に至り、生活の質が大きく低下することもある。そこで、本稿では、主として、糖尿病網膜症の有病率や主要なリスク因子、糖尿病網膜症の発症・進展防止と血糖・血圧・脂質管理について、これまでの代表的な研究を中心に概説し、糖尿病網膜症の発症・進展抑制のためのエビデンスを紹介する。(著者抄録)

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  • ATRA・ATO併用療法により寛解を維持している再発性治療関連急性前骨髄白血病の1例

    前田 愁一郎, 布施 香子, 諏訪部 達也, 笠見 卓哉, 河本 啓介, 田中 智之, 難波 亜矢子, 小林 弘典, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   59 ( 11 )   2496 - 2496   2018.11

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  • 入院下と外来でCGMを装着し血糖変化を確認した1型糖尿病の一例

    橋本 浩平, 金子 正儀, 三ツ間 友里恵, 山本 正彦, 松林 泰弘, 岩永 みどり, 松永 佐澄志, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本先進糖尿病治療研究会雑誌   14   39 - 39   2018.11

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  • ビッグデータ解析を活かした糖尿病の予防と治療の新しい戦略

    曽根 博仁

    日本先進糖尿病治療研究会雑誌   14   25 - 25   2018.11

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  • 胃亜全摘術後の2型糖尿病患者における治療強化の手段として、DPP-4阻害薬からGLP-1受容体作動薬への変更は有効か

    白石 友信, 吉岡 大志, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本先進糖尿病治療研究会雑誌   14   44 - 44   2018.11

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  • 入院下と外来でCGMを装着し血糖変化を確認した1型糖尿病の一例

    橋本 浩平, 金子 正儀, 三ツ間 友里恵, 山本 正彦, 松林 泰弘, 岩永 みどり, 松永 佐澄志, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本先進糖尿病治療研究会雑誌   14   39 - 39   2018.11

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  • ビッグデータ解析を活かした糖尿病の予防と治療の新しい戦略

    曽根 博仁

    日本先進糖尿病治療研究会雑誌   14   25 - 25   2018.11

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  • ATRA・ATO併用療法により寛解を維持している再発性治療関連急性前骨髄白血病の1例

    前田 愁一郎, 布施 香子, 諏訪部 達也, 笠見 卓哉, 河本 啓介, 田中 智之, 難波 亜矢子, 小林 弘典, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   59 ( 11 )   2496 - 2496   2018.11

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  • Clinical Features and Risk Factors of Post-Engraftment Bloodstream Infection in Allogeneic HCT

    Tatsuya Suwabe, Kyoko Fuse, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    BLOOD   132   2018.11

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    DOI: 10.1182/blood-2018-99-115844

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  • Marker Chromosomes Are a New Cytogenetic Adverse Risk Factor in AML after Allo-HCT

    Kyoko Fuse, Tomoyuki Tanaka, Shun Uemura, Tatsuya Suwabe, Takayuki Katagiri, Takashi Ushiki, Yasuhiko Shibasaki, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Tastuo Furukawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    BLOOD   132   2018.11

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    DOI: 10.1182/blood-2018-99-113251

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  • Distinct Effects of Chondroitin Sulfate on Hematopoietic Cells and the Stromal Microenvironment in Bone Marrow Hematopoiesis

    Takayuki Katagiri, Takashi Ushiki, Asami Kawasaki, Shun Uemura, Tatsuya Suwabe, Tomoyuki Tanaka, Kyoko Fuse, Yasuhiko Shibasaki, Hirohito Sone, Michihiro Igarashi, Masayoshi Masuko

    BLOOD   132   2018.11

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    DOI: 10.1182/blood-2018-99-115796

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  • 脈圧が透析導入に及ぼす影響の検討

    大澤妙子, 藤原和哉, 山本正彦, 原田万由子, 石澤正博, 清田浩康, 山中菜詩, 松林泰弘, 松永佐澄志, 山田貴穂, 曽根博仁

    糖尿病合併症   32 ( Suppl.1 )   245 - 245   2018.10

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  • 耐糖能別にみた肥満及び代謝異常が冠動脈疾患発症へ及ぼす影響の検討

    藤原和哉, 松林泰弘, 原田万祐子, 山本正彦, 大澤妙子, 金子正儀, 松永佐澄志, 山田貴穂, 清田浩康, 山中菜詩, 児玉暁, 曽根博仁

    糖尿病合併症   32 ( Suppl.1 )   206 - 206   2018.10

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  • 糖尿病患者の下肢切断の頻度とリスク因子の検討

    金子正儀, 藤原和哉, 原田万祐子, 松林泰弘, 北澤勝, 石井大, 清田浩康, 山中菜詩, 児玉暁, 曽根博仁

    糖尿病合併症   32 ( Suppl.1 )   291 - 291   2018.10

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  • 糖尿病患者における心不全発症リスクの系統レビュー・メタ解析

    児玉暁, 藤原和哉, 岩永みどり, 鈴木浩史, 山田貴穂, 渡辺賢一, 加藤公則, 曽根博仁

    糖尿病合併症   32 ( Suppl.1 )   287 - 287   2018.10

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  • 糖尿病腎症が重症糖尿病性眼疾患の発生に及ぼす影響

    山本正彦, 藤原和哉, 石澤正博, 大澤妙子, 石黒創, 岩永みどり, 松林泰弘, 清田浩康, 山中菜詩, 山田貴穂, 長谷部日, 曽根博仁

    糖尿病合併症   32 ( Suppl.1 )   299 - 299   2018.10

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  • 胃亜全摘後の糖尿病患者において、DPP-4阻害薬からGLP-1受容体作動薬への変更は有効か

    白石 友信, 吉岡 大志, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    糖尿病   61 ( 10 )   721 - 721   2018.10

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  • 1型糖尿病の発症以前にバセドウ病が先行したと考えられる14歳女児の1例

    橋本 浩平, 金子 正儀, 三ツ間 友里恵, 山本 正彦, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    糖尿病   61 ( 10 )   700 - 700   2018.10

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  • 高齢発症の劇症1型糖尿病の1例

    吉岡 大志, 小松 健, 皆川 真一, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 今川 彰久, 曽根 博仁

    糖尿病   61 ( 10 )   726 - 726   2018.10

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  • 網膜症と大血管障害 糖尿病網膜症と大血管合併症のビッグデータ解析によるエビデンス

    曽根 博仁

    糖尿病合併症   32 ( Suppl.1 )   160 - 160   2018.10

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  • 肥満境界型糖尿病患者に対する血糖自己測定と「血糖に変わる速度と割合」の理解度との関係

    長谷川美代, 堀川千嘉, 藤原和哉, 曽根博仁

    栄養学雑誌   76 ( 5 Supplement )   189   2018.9

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  • 大規模臨床データ解析が開く新しい糖尿病合併症学

    曽根 博仁

    日本糖尿病眼学会誌   22   2 - 2   2018.9

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  • 当科で経験した下垂体茎断裂症候群の1例

    佐藤隆明, 福武嶺一, 金子正儀, 岩永みどり, 松林泰弘, 山田貴徳, 藤原和哉, 曽根博仁

    日本内分泌学会雑誌   94 ( 2 )   680 - 680   2018.9

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  • ACTH依存性に増大を認めた,クッシング症候群を伴う副腎癌の1例

    北澤勝, 北澤勝, 張かおり, 矢口雄大, 鈴木達郎, 金子正儀, 松林泰弘, 藤原和哉, 八幡和明, 曽根博仁

    日本内分泌学会雑誌   94 ( 2 )   716 - 716   2018.9

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  • 寛解期急性白血病に対する同種移植のドナーソース別入院費の比較(Hospitalization costs of allo-HCT among donor sources for acute leukemia in complete remission)

    難波 亜矢子, 柴崎 康彦, 上村 駿, 諏訪部 達也, 片桐 隆幸, 田中 智之, 布施 香子, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   59 ( 9 )   1680 - 1680   2018.9

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  • 下肢皮膚潰瘍から骨髄炎に至った2型糖尿病の1例

    張 かおり, 金子 正儀, 佐藤 陽子, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 羽入 修, 曽根 博仁

    糖尿病   61 ( 9 )   646 - 646   2018.9

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  • 同種造血幹細胞移植における強化口腔ケアは生着後の血流感染を減少させる(Intensive oral care can reduce blood stream infection post neutrophil engraftment in allogeneic HCT)

    諏訪部 達也, 布施 香子, 勝良 剛詞, 田中 恵子, 片桐 隆幸, 田中 智之, 牛木 隆志, 柴崎 康彦, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   59 ( 9 )   1536 - 1536   2018.9

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  • ob/obマウスにおけるSREBP-1a過剰発現はリポジストロフィーとインスリン抵抗性の増悪を示す

    大野 博, 松坂 賢, 唐 ネ, Rahul Sharma, 本村 香織, 志村 拓哉, 佐藤 葵, 鈴木 浩明, 関谷 元博, 中川 嘉, 曽根 博仁, 矢作 直也, 山田 信博, 樋上 賀一, 島野 仁

    肥満研究   24 ( Suppl. )   179 - 179   2018.9

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  • 寛解期急性白血病に対する同種移植のドナーソース別入院費の比較(Hospitalization costs of allo-HCT among donor sources for acute leukemia in complete remission)

    難波 亜矢子, 柴崎 康彦, 上村 駿, 諏訪部 達也, 片桐 隆幸, 田中 智之, 布施 香子, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   59 ( 9 )   1680 - 1680   2018.9

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  • 単一施設におけるATGとPTCYを用いた半合致移植の後方視解析(Clinical analysis of haploidentical transplantation using ATG and PTCY in single institute)

    田中 智之, 上村 駿, 海發 茜, 田村 秀, 諏訪部 達也, 片桐 隆幸, 河本 啓介, 布施 香子, 牛木 隆志, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   59 ( 9 )   1678 - 1678   2018.9

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  • 濾胞性リンパ腫初回診断時におけるアグレッシブリンパ腫への形質転換予測(MYC copy number predicts histologic transformation of follicular lymphoma to aggressive lymphoma)

    桐生 真依子, 河本 啓介, 鈴木 隆晴, 田村 秀, 上村 駿, 海發 茜, 諏訪部 達也, 今西 明, 笠見 卓哉, 根本 洋樹, 片桐 隆幸, 田中 智之, 難波 亜矢子, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 三好 寛明, 瀬戸 加大, 大島 孝一, 瀧澤 淳

    臨床血液   59 ( 9 )   1593 - 1593   2018.9

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  • 濾胞性リンパ腫初回診断時におけるアグレッシブリンパ腫への形質転換予測(MYC copy number predicts histologic transformation of follicular lymphoma to aggressive lymphoma)

    桐生 真依子, 河本 啓介, 鈴木 隆晴, 田村 秀, 上村 駿, 海發 茜, 諏訪部 達也, 今西 明, 笠見 卓哉, 根本 洋樹, 片桐 隆幸, 田中 智之, 難波 亜矢子, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 三好 寛明, 瀬戸 加大, 大島 孝一, 瀧澤 淳

    臨床血液   59 ( 9 )   1593 - 1593   2018.9

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  • 単一施設におけるATGとPTCYを用いた半合致移植の後方視解析(Clinical analysis of haploidentical transplantation using ATG and PTCY in single institute)

    田中 智之, 上村 駿, 海發 茜, 田村 秀, 諏訪部 達也, 片桐 隆幸, 河本 啓介, 布施 香子, 牛木 隆志, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   59 ( 9 )   1678 - 1678   2018.9

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  • 妊娠初期の栄養摂取状況と低出生体重児出産リスクとの関連の検討

    飯島 春香, 田中 康弘, 津野 和, 小松 弥生, 安見 真奈, 田島 諒子, 広瀬 歩美, 曽根 博仁, 谷内 洋子

    New Diet Therapy   34 ( 2 )   173 - 173   2018.9

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  • 【患者に楽しく継続してもらえるコツが満載!糖尿病食事療法 パーフェクト指導BOOK ダウンロードできる簡単レシピ&綴じ込み食事指導ツールつき】(第1章)基本をおさらい!糖尿病食事療法 妊娠糖尿病の食事療法の基本

    谷内 洋子, 曽根 博仁

    糖尿病ケア   ( 2018秋季増刊 )   24 - 26   2018.9

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  • 高齢者の生活習慣病 高齢者の生活習慣修正 高齢者の身体活動と生活習慣病

    北澤勝, 藤原和哉, 曽根博仁

    日本臨床   76 ( 増刊7 老年医学(下) )   139 - 143   2018.8

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  • 人間ドックのビッグデータが教える健康長寿エビデンス

    曽根 博仁

    人間ドック   33 ( 2 )   216 - 216   2018.8

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  • 尿酸高値は非アルコール性脂肪性肝疾患発症の独立したリスク因子である

    原 茂子, 戸田 晶子, 大本 由樹, 辻 裕之, 斎藤 和美, 児玉 暁, 曽根 博仁, 荒瀬 康司

    人間ドック   33 ( 2 )   321 - 321   2018.8

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  • 脂質異常症の簡便な予測因子としての体力テストの可能性 コホート研究 Niigata Wellness Study

    門間 陽樹, 澤田 亨, 丸藤 祐子, 宮地 元彦, 永富 良一, 田代 稔, 加藤 公則, 曽根 博仁

    人間ドック   33 ( 2 )   277 - 277   2018.8

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  • 余暇身体活動時間および歩行業務時間と尿路結石症発症の関係 新潟ウェルネス・スタディ

    澤田 亨, 川上 諒子, 丸藤 祐子, 田代 稔, 加藤 公則, 曽根 博仁

    人間ドック   33 ( 2 )   346 - 346   2018.8

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  • 日本人における柔軟性と高血圧罹患の関係 コホート研究 Niigata Wellness Study

    丸藤 祐子, 澤田 亨, 門間 陽樹, 川上 諒子, 宮地 元彦, 田代 稔, 加藤 公則, 曽根 博仁

    人間ドック   33 ( 2 )   334 - 334   2018.8

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  • 余暇身体活動時間および歩行業務時間と尿路結石症発症の関係 新潟ウェルネス・スタディ

    澤田 亨, 川上 諒子, 丸藤 祐子, 田代 稔, 加藤 公則, 曽根 博仁

    人間ドック   33 ( 2 )   346 - 346   2018.8

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  • 人間ドックのビッグデータが教える健康長寿エビデンス

    曽根 博仁

    人間ドック   33 ( 2 )   216 - 216   2018.8

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  • 脂質異常症の簡便な予測因子としての体力テストの可能性 コホート研究 Niigata Wellness Study

    門間 陽樹, 澤田 亨, 丸藤 祐子, 宮地 元彦, 永富 良一, 田代 稔, 加藤 公則, 曽根 博仁

    人間ドック   33 ( 2 )   277 - 277   2018.8

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  • 尿酸高値は非アルコール性脂肪性肝疾患発症の独立したリスク因子である

    原 茂子, 戸田 晶子, 大本 由樹, 辻 裕之, 斎藤 和美, 児玉 暁, 曽根 博仁, 荒瀬 康司

    人間ドック   33 ( 2 )   321 - 321   2018.8

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  • 日本人における柔軟性と高血圧罹患の関係 コホート研究 Niigata Wellness Study

    丸藤 祐子, 澤田 亨, 門間 陽樹, 川上 諒子, 宮地 元彦, 田代 稔, 加藤 公則, 曽根 博仁

    人間ドック   33 ( 2 )   334 - 334   2018.8

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  • Effect of Number of Achieved Targets for Risk Factors on Coronary Artery Disease (CAD) in Those With and Without Diabetes Mellitus (DM)

    Kazuya Fujihara, Yasuhiro Matsubayashi, Masaru Kitazawa, Masahiko Yamamoto, Taeko Osawa, Masanori Kaneko, Nauta Yamanaka, Hiroyasu Seida, Kiminori Kato, Satoru Kodama, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-442-P

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  • Incidence and Risk Factors for Amputation in Patients with Diabetes in Japan-Historical Cohort Study Using a Nationwide Claims Database

    Masanori Kaneko, Kazuya Fujihara, Masahiko Yamamoto, Masaru Kitazawa, Masahiro Ishizawa, Taeko Osawa, Mayuko Harada, Yasuhiro Matsubayashi, Takaho Yamada, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-637-P

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  • Test Strip-Positive Proteinuria and Its Combination with Low eGFR Are Predictive of Treatment-Required Eye Diseases in Japanese Patients with Diabetes Mellitus

    Masahiko Yamamoto, Kazuya Fujihara, Taeko Osawa, Mayuko Harada, Masahiro Ishizawa, Hajime Ishiguro, Hiroshi Suzuki, Hiroyasu Seida, Nauta Yamanaka, Yasuhiro Matsubayashi, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-594-P

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  • Effects of Treatment-Achieved HbA1c on Incidence of Micro-/Macrovascular Complications in Patients with Diabetes Mellitus

    Mayuko Harada, Kazuya Fujihara, Taeko Osawa, Masahiko Yamamoto, Masanori Kaneko, Yasuhiro Matsubayashi, Satoshi Matsunaga, Takaho Yamada, Nauta Yamanaka, Hiroyasu Seida, Satoru Kodama, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-444-P

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  • Dipstick Proteinuria as a Predictor of End-Stage Renal Disease in Japanese Adults With and Without Diabetes Mellitus (DM)

    Atsushi Furuya, Kazuya Fujihara, Taeko Osawa, Masahiko Yamamoto, Mayuko Harada, Masahiro Ishizawa, Hiroyasu Seida, Nauta Yamanaka, Yasuhiro Matsubayashi, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-2384-PUB

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  • 【診療所外来における生活療養指導】 糖尿病に対する療養指導

    古川 和郎, 曽根 博仁

    地域医学   32 ( 7 )   563 - 568   2018.7

  • 当科で経験した小児クッシング症候群の1例

    三ツ間 友里恵, 金子 正儀, 山本 正彦, 橋本 浩平, 矢口 雄大, 鈴木 達郎, 石黒 創, 松林 泰弘, 山田 貴穂, 岩永 みどり, 藤原 和哉, 曽根 博仁, 長崎 啓祐, 齋藤 和英, 羽入 修

    新潟医学会雑誌   132 ( 7 )   287 - 287   2018.7

  • Developing a Health Economic Model for Asians with Type 2 Diabetes Based on the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial

    Shiro Tanaka, Jakob Langer, Tim Morton, Lars Wilkinson, Sachiko Tanaka, Ryo Kawasaki, Tatsumi Moriya, Chika Horikawa, Rei Aida, Atsushi Araki, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-2319-PUB

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  • Genetically Reduced Chondroitin Sulfate Prevents the Progression of Diabetic Neuropathy

    Hajime Ishiguro, Takashi Ushiki, Asami Kawasaki, Kaori Cho, Masayoshi Masuko, Kazunori Sango, Michihiro Igarashi, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-547-P

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  • Higher Dietary Intake of Vitamin D Is Associated with Lower Incidence of Diabetic Nephropathy in Japanese Patients with Type 2 Diabetes

    Chika Horikawa, Rei Aida, Shiro Tanaka, Sachiko Tanaka, Chiemi Kamada, Yukio Yoshimura, Atsushi Araki, Tatsumi Moriya, Shigehiro Katayama, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-1561-P

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  • Impact of Vitamin B6 Intake on the Risk of Diabetic Retinopathy-Analysis from Multicenter Prospective Study of Japanese Patients with Type 2 Diabetes

    Chika Horikawa, Rei Aida, Shiro Tanaka, Yukio Yoshimura, Ryo Kawasaki, Tatsumi Moriya, Atsushi Araki, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-597-P

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  • Education for Family Members Is Effective for Improved Glycemic Control of Patients with Type 2 Rather than Type 1 Diabetes Mellitus-A Meta-analysis

    Satoru Kodama, Kazuya Fujihara, Hajime Ishiguro, Chika Horikawa, Yoko Yachi, Masahiro Ishizawa, Satoshi Matsunaga, Shiro Tanaka, Kiminori Kato, Hirohito Sone

    DIABETES   67   2018.7

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    DOI: 10.2337/db18-823-P

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  • 耐糖能及び肥満の有無別にみた代謝異常が冠動脈疾患発症に及ぼす影響の検討

    藤原 和哉, 松林 泰弘, 山本 正彦, 金子 正儀, 松永 佐澄志, 山田 貴穂, 清田 浩康, 山中 菜詩, 児玉 暁, 曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   50回   336 - 336   2018.6

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  • 【Real World Data(実臨床データ)を用いた臨床疫学研究】 大規模臨床研究からみた日本人2型糖尿病患者の食事療法

    堀川 千嘉, 曽根 博仁

    医学のあゆみ   265 ( 11 )   939 - 943   2018.6

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    食事療法は2型糖尿病患者の血糖コントロールや合併症発症予防・遅延のための治療の基本であるが、その根拠はいまだに一般対象者による研究や少人数の糖尿病患者を対象とした観察・介入研究が多く、糖尿病患者を対象とする大規模臨床研究からのエビデンス創出が求められている。また、食事療法は、食習慣や食文化などの観点から人種・民族差が大きく影響するため、わが国発の日本人2型糖尿病患者のための食事療法に関するエビデンス構築が必要である。そこでわが国では国際的にいち早く、1996年から糖尿病専門医療機関59施設の2型糖尿病患者2,033名を追跡するJapan Diabetes Complications Study(JDCS)を実施し、糖尿病の臨床像を明らかにしてきた。本稿では、JDCSでこれまでに得られた日本人2型糖尿病患者の食事摂取状況や食品・栄養素摂取状況と合併症発症リスクの関係を整理し、紹介していく。(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00060&link_issn=&doc_id=20180619030005&doc_link_id=%2Faa7ayuma%2F2018%2F026511%2F006%2F0939-0943%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2018%2F026511%2F006%2F0939-0943%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 【糖尿病と栄養】 医療ビッグデータ解析に基づく糖尿病患者の食事と合併症との関連

    曽根 博仁

    栄養   3 ( 2 )   95 - 99   2018.6

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    食事療法は総ての糖尿病(DM)患者にとって必須の基本的治療であるが、食事は食文化や食習慣による違いが大きいため、食事療法のエビデンスは自国の患者のデータに基づくものでなければならない。わが国の59ヶ所のDM専門医療施設における40〜70歳の2型DM患者2033名を対象に8年間の追跡調査を行い、その解析結果を基に、下記について概説した。1)日本人2型DM患者の食事摂取状況の実態、2)食事摂取状況と合併症発症リスクとの関係(果実摂取量と網膜症発症リスク、食物繊維摂取量と脳卒中発症リスク、食塩摂取量と心血管疾患発症リスク、炭水化物摂取比率と合併症発症リスク)、について述べた。

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  • G-CSFを産生し初回治療中に再発したびまん性大細胞型B細胞性リンパ腫の1例

    笠見 卓哉, 河本 啓介, 鈴木 隆晴, 田中 智之, 布施 香子, 柴崎 康彦, 増子 正義, 成田 美和子, 曽根 博仁, 大島 孝一, 瀧澤 淳

    日本リンパ網内系学会会誌   58   114 - 114   2018.5

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  • 【血糖変動】 血糖の日内変動の血管合併症への影響

    山田 貴穂, 曽根 博仁

    内分泌・糖尿病・代謝内科   46 ( 5 )   316 - 322   2018.5

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  • ビタミンD3産生性と考えられるALK陰性未分化大細胞リンパ腫の1例

    水戸部 正樹, 河本 啓介, 鈴木 隆晴, 難波 亜矢子, 柴崎 康彦, 増子 正義, 曽根 博仁, 三好 寛明, 大島 孝一, 瀧澤 淳

    日本リンパ網内系学会会誌   58   121 - 121   2018.5

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  • ビタミンD3産生性と考えられるALK陰性未分化大細胞リンパ腫の1例

    水戸部 正樹, 河本 啓介, 鈴木 隆晴, 難波 亜矢子, 柴崎 康彦, 増子 正義, 曽根 博仁, 三好 寛明, 大島 孝一, 瀧澤 淳

    日本リンパ網内系学会会誌   58   121 - 121   2018.5

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  • GDP療法がtriple-hit lymphomaの救援療法として有効であった1例

    水戸部 正樹, 河本 啓介, 鈴木 隆晴, 田村 秀, 小堺 貴司, 難波 亜矢子, 諏訪部 達也, 笠見 卓哉, 田中 智之, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 大島 孝一, 瀧澤 淳

    臨床血液   59 ( 5 )   620 - 621   2018.5

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  • 【血糖変動】血糖の日内変動の血管合併症への影響

    山田 貴穂, 曽根 博仁

    内分泌・糖尿病・代謝内科   46 ( 5 )   316 - 322   2018.5

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  • G-CSFを産生し初回治療中に再発したびまん性大細胞型B細胞性リンパ腫の1例

    笠見 卓哉, 河本 啓介, 鈴木 隆晴, 田中 智之, 布施 香子, 柴崎 康彦, 増子 正義, 成田 美和子, 曽根 博仁, 大島 孝一, 瀧澤 淳

    日本リンパ網内系学会会誌   58   114 - 114   2018.5

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  • Leisure-time Physical Activity, Work-related Walking and Incidence of Kidney Stones In Japanese Workers: The Niigata Wellness Study

    Susumu S. Sawada, Yuko Gando, Ryoko Kawakami, Minoru Tashiro, I-Min Lee, Steven N. Blair, Motohiko Miyachi, Hirohito Sone, Kiminori Kato

    MEDICINE AND SCIENCE IN SPORTS AND EXERCISE   50 ( 5 )   392 - 392   2018.5

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  • 糖尿病合併妊娠の妊娠転帰に関する多施設前向き研究(DREAMBeeスタディ)について

    川崎 麻紀, 荒田 尚子, 宮越 敬, 菊池 透, 曽根 博仁, 守屋 達美, 杉山 隆, 佐川 典正, 内潟 安子, 難波 光義, 平松 祐司

    糖尿病   61 ( Suppl.1 )   S - 270   2018.4

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  • 小児1型糖尿病におけるFlash Glucose monitoringの測定精度の検討

    北澤 勝, 齋藤 七穂, 小川 洋平, 長崎 啓祐, 佐々木 直, 齋藤 昭彦, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 268   2018.4

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  • 日本人2型糖尿病における栄養摂取と身体活動の現状 JDCP studyにおける登録時データより

    松永 佐澄志, 曽根 博仁, 津田 謹輔, 押田 芳治, 佐々木 敏, 佐藤 譲, 林野 泰明, 西村 理明, 田嶼 尚子

    糖尿病   61 ( Suppl.1 )   S - 407   2018.4

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  • 指先穿刺による血糖およびHbA1c迅速測定をもちいた糖尿病啓発の取り組み

    山田 貴穂, 石井 大, 武田 安永, 橋本 浩平, 三ツ間 友里恵, 張 かおり, 原田 万祐子, 白石 友信, 吉岡 大志, 山本 正彦, 大澤 妙子, 石黒 創, 金子 正儀, 鈴木 浩史, 松林 泰弘, 松永 佐澄志, 藤原 和哉, 岩永 みどり, 鈴木 亜希子, 羽入 修, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 377   2018.4

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  • 肥満境界型糖尿病患者に対する血糖自己測定と栄養指導媒体を用いた栄養教育の併用効果について

    長谷川 美代, 堀川 千嘉, 田代 稔, 鈴木 沙織, 藤原 和哉, 北澤 勝, 加藤 公則, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 267   2018.4

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  • 2型糖尿病患者における食事エネルギー密度と肥満との関連 JDDMにおける検討

    武田 安永, 藤原 和哉, 治田 麻理子, 森川 咲子, 堀川 千嘉, 石井 大, 加藤 光敏, 横山 宏樹, 栗原 義夫, 宮澤 一裕, 岩崎 晧一, 川井 紘一, 朝長 修, 屋宜 宣治, 前川 聡, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 265   2018.4

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  • SGLT2阻害薬が安静時心拍数(Resting Heart Rate:RHR)に及ぼす影響とその関連因子の検討

    松林 泰弘, 阿部 孝洋, 吉田 明弘, 野島 俊秋, 菅波 秀規, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 158   2018.4

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  • 肥満と肝インスリンクリアランス(Hepatic insulin clearance:HIC)低下の関係における脂肪肝(Fatty Liver:FL)の役割

    松林 泰弘, 吉田 明弘, 菅波 秀規, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    日本内分泌学会雑誌   94 ( 1 )   432 - 432   2018.4

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  • 原発性アルドステロン症と原発性副甲状腺機能亢進症を併発した1例

    白石 友信, 吉岡 大志, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   94 ( 1 )   430 - 430   2018.4

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  • 菌状息肉症に対するベキサロテン治療後に出現した副作用例の検討

    山本 正彦, 棚橋 怜生, 松林 泰弘, 藤原 和哉, 北澤 勝, 松永 佐澄志, 金子 正儀, 鈴木 浩史, 石澤 正博, 岩永 みどり, 山田 貴穂, 曽根 博仁

    日本内分泌学会雑誌   94 ( 1 )   420 - 420   2018.4

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  • 日本人2型糖尿病患者における、ビタミンB6摂取量と糖尿病網膜症発症との関係 JDCSによる報告

    堀川 千嘉, 相田 麗, 田中 司朗, 鎌田 智恵実, 田中 佐智子, 吉村 幸雄, 川崎 良, 山下 英俊, 大橋 靖雄, 井藤 英喜, 赤沼 安夫, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 141   2018.4

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  • 糖尿病患者の受診中断に関連する因子の1年間追跡調査 糖尿病データマネジメント研究会(JDDM)より

    谷内田 潤子, 藤原 和哉, 武田 安永, 治田 麻里子, 石井 大, 和井田 結佳子, 大石 まり子, 川井 紘一, 横山 宏樹, 前川 聡, 曽根 博仁, 糖尿病データマネジメント研究会

    糖尿病   61 ( Suppl.1 )   S - 139   2018.4

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  • 糖尿病における栄養疫学のエビデンス

    曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 121   2018.4

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  • JDCP研究が示す我が国の糖尿病診療の現状 JDCP研究における食事・運動療法について

    曽根 博仁, 松永 佐澄志, 佐々木 敏, 押田 芳治, 佐藤 譲, 津田 謹輔

    糖尿病   61 ( Suppl.1 )   S - 87   2018.4

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  • 腎臓病・糖尿病領域コホート研究の最新知見 Japan Diabetes Complications Study(JDCS)における腎臓病・糖尿病領域の結果

    守屋 達美, 曽根 博仁

    日本腎臓学会誌   60 ( 3 )   293 - 293   2018.4

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  • 耐糖能及び肥満の有無に関わらず代謝異常は冠動脈疾患発症リスクを増大させる

    藤原 和哉, 松林 泰弘, 山本 正彦, 松永 佐澄志, 清田 浩康, 山中 菜詩, 児玉 暁, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 260   2018.4

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  • コンドロイチン硫酸減少を介した糖尿病性神経障害の抑制効果

    石黒 創, 牛木 隆志, 河嵜 麻実, 張 かおり, 増子 正義, 三五 一憲, 五十嵐 道弘, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 240   2018.4

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  • 当院における糖尿病合併妊娠及び妊娠糖尿病患者への分割食の栄養指導の実態と指導方法の検討

    治田 麻理子, 深沢 尚子, 桜井 健一, 津野 菜津美, 佐藤 かえで, 西山 陽子, 藤原 和哉, 曽根 博仁, 鈴木 克典

    糖尿病   61 ( Suppl.1 )   S - 214   2018.4

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  • 糖尿病治療薬別にみたHbA1cと冠動脈疾患(CAD)発症リスクとの関連

    原田 万祐子, 藤原 和哉, 大澤 妙子, 石澤 正博, 山本 正彦, 金子 正儀, 松林 泰弘, 松永 佐澄志, 山中 菜詩, 清田 浩康, 山田 貴穂, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 258   2018.4

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  • DPP-4阻害薬アナグリプチン(ANA)の12週間投与時におけるインスリンクリアランスに及ぼす影響

    阿部 孝洋, 松林 泰弘, 村岸 沙也加, 吉田 明弘, 菅波 秀規, 古澤 研一, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 246   2018.4

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  • 眼科処置を要する重症糖尿病性眼疾患の発生リスクに対する腎症の影響についての検討

    山本 正彦, 藤原 和哉, 大澤 妙子, 原田 万祐子, 石黒 創, 石澤 正博, 岩永 みどり, 松永 佐澄志, 松林 泰弘, 清田 浩康, 山中 菜詩, 山田 貴穂, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 161   2018.4

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  • 糖尿病患者における脈圧が透析導入に及ぼす影響の検討

    大澤 妙子, 藤原 和哉, 山本 正彦, 原田 万由子, 石澤 正博, 清田 浩康, 山中 菜詩, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 160   2018.4

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  • 診断に難渋した再発性重症低血糖の原因特定に薬物血中濃度測定が有用であった一例

    三ツ間 友里恵, 山本 正彦, 橋本 浩平, 金子 正儀, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 岩永 みどり, 藤原 和哉, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 181   2018.4

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  • 年齢層別に見た血清アミラーゼ値と2型糖尿病発症との関連

    石井 大, 藤原 和哉, 治田 麻理子, 原田 万佑子, 松林 泰弘, 斎藤 和美, 児玉 暁, 森 保道, 本田 律子, 荒瀬 康司, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 161   2018.4

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  • コンドロイチン硫酸減少を介した糖尿病性神経障害の抑制効果

    石黒 創, 牛木 隆志, 河嵜 麻実, 張 かおり, 増子 正義, 三五 一憲, 五十嵐 道弘, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 240   2018.4

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  • 医療ビックデータを活用した新潟発の臨床疫学研究

    藤原和哉, 曽根博仁

    新潟医学会雑誌   132 ( 4 )   123 - 126   2018.4

  • 糖尿病合併妊娠の妊娠転帰に関する多施設前向き研究(DREAMBeeスタディ)について

    川崎 麻紀, 荒田 尚子, 宮越 敬, 菊池 透, 曽根 博仁, 守屋 達美, 杉山 隆, 佐川 典正, 内潟 安子, 難波 光義, 平松 祐司

    糖尿病   61 ( Suppl.1 )   S - 270   2018.4

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  • 腎臓病・糖尿病領域コホート研究の最新知見 Japan Diabetes Complications Study(JDCS)における腎臓病・糖尿病領域の結果

    守屋 達美, 曽根 博仁

    日本腎臓学会誌   60 ( 3 )   293 - 293   2018.4

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  • 糖尿病患者の受診中断に関連する因子の1年間追跡調査 糖尿病データマネジメント研究会(JDDM)より

    谷内田 潤子, 藤原 和哉, 武田 安永, 治田 麻里子, 石井 大, 和井田 結佳子, 大石 まり子, 川井 紘一, 横山 宏樹, 前川 聡, 曽根 博仁, 糖尿病データマネジメント研究会

    糖尿病   61 ( Suppl.1 )   S - 139   2018.4

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  • 日本人2型糖尿病における栄養摂取と身体活動の現状 JDCP studyにおける登録時データより

    松永 佐澄志, 曽根 博仁, 津田 謹輔, 押田 芳治, 佐々木 敏, 佐藤 譲, 林野 泰明, 西村 理明, 田嶼 尚子

    糖尿病   61 ( Suppl.1 )   S - 407   2018.4

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  • 当院における糖尿病合併妊娠及び妊娠糖尿病患者への分割食の栄養指導の実態と指導方法の検討

    治田 麻理子, 深沢 尚子, 桜井 健一, 津野 菜津美, 佐藤 かえで, 西山 陽子, 藤原 和哉, 曽根 博仁, 鈴木 克典

    糖尿病   61 ( Suppl.1 )   S - 214   2018.4

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  • 年齢層別に見た血清アミラーゼ値と2型糖尿病発症との関連

    石井 大, 藤原 和哉, 治田 麻理子, 原田 万佑子, 松林 泰弘, 斎藤 和美, 児玉 暁, 森 保道, 本田 律子, 荒瀬 康司, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 161   2018.4

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  • 小児1型糖尿病におけるFlash Glucose monitoringの測定精度の検討

    北澤 勝, 齋藤 七穂, 小川 洋平, 長崎 啓祐, 佐々木 直, 齋藤 昭彦, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 268   2018.4

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  • DPP-4阻害薬アナグリプチン(ANA)の12週間投与時におけるインスリンクリアランスに及ぼす影響

    阿部 孝洋, 松林 泰弘, 村岸 沙也加, 吉田 明弘, 菅波 秀規, 古澤 研一, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 246   2018.4

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  • 糖尿病における栄養疫学のエビデンス

    曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 121   2018.4

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  • JDCP研究が示す我が国の糖尿病診療の現状 JDCP研究における食事・運動療法について

    曽根 博仁, 松永 佐澄志, 佐々木 敏, 押田 芳治, 佐藤 譲, 津田 謹輔

    糖尿病   61 ( Suppl.1 )   S - 87   2018.4

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  • SGLT2阻害薬が安静時心拍数(Resting Heart Rate:RHR)に及ぼす影響とその関連因子の検討

    松林 泰弘, 阿部 孝洋, 吉田 明弘, 野島 俊秋, 菅波 秀規, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   61 ( Suppl.1 )   S - 158   2018.4

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  • 肥満と肝インスリンクリアランス(Hepatic insulin clearance:HIC)低下の関係における脂肪肝(Fatty Liver:FL)の役割

    松林 泰弘, 吉田 明弘, 菅波 秀規, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 加来 浩平, 曽根 博仁

    日本内分泌学会雑誌   94 ( 1 )   432 - 432   2018.4

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  • 原発性アルドステロン症と原発性副甲状腺機能亢進症を併発した1例

    白石 友信, 吉岡 大志, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   94 ( 1 )   430 - 430   2018.4

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  • 菌状息肉症に対するベキサロテン治療後に出現した副作用例の検討

    山本 正彦, 棚橋 怜生, 松林 泰弘, 藤原 和哉, 北澤 勝, 松永 佐澄志, 金子 正儀, 鈴木 浩史, 石澤 正博, 岩永 みどり, 山田 貴穂, 曽根 博仁

    日本内分泌学会雑誌   94 ( 1 )   420 - 420   2018.4

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  • 【検査機器・試薬・技術の新たな展開】 医療ビッグデータとしての臨床検査データの利活用 糖尿病を中心とした生活習慣病分野を例に

    曽根 博仁

    生物試料分析   41 ( 2 )   73 - 78   2018.3

  • SGLT2阻害薬による腟カンジダ発現頻度とその臨床的特徴

    長尾 有未, 小原 信, 木村 祐之, 大内 基司, 清水 平, 山田 大志郎, 首藤 龍人, 曽根 博仁, 本庄 潤, 横山 宏樹

    糖尿病   61 ( 3 )   141 - 141   2018.3

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  • CpG-Bを用いた白血病性形質細胞様樹状細胞(PMDC11)における抗原特異的CTL誘導能の増強

    後藤 若奈, 山田 峻也, 橋本 誠雄, 増子 正義, 小林 果歩, 小川 彩空, 柴崎 康彦, 曽根 博仁, 高橋 益廣, 成田 美和子

    新潟大学保健学雑誌   15 ( 1 )   1 - 8   2018.3

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    本研究室では、樹立した白血病性形質細胞様樹状細胞株PMDC05へCD80遺伝子を導入することにより強力な抗原提示能をもつPMDC11を作成している。腫瘍細胞とその腫瘍に対する抗原特異的細胞傷害性T細胞(CTL)との間の免疫チェックポイントの強度に関する検査法開発を目指した基礎的研究としてPMDC11のCpG-Bによる機能の変化の有無と腫瘍抗原特異的CTLの増幅効果を検討した。CpG-B刺激は共抑制因子PD-L1及びPD-L2の発現を増加させることなく共刺激因子CD40及びCD83をわずかに高めた。WT1ペプチドパルスに加えてCpG-B刺激したPMDC11とWT1/MHC-tetramer+細胞との共培養を行ったところ、WT1ペプチド抗原特異的CTLの著しい増加が認められた。この培養法は、腫瘍抗原特異的CTLの機能解析において応用可能と考えられた。(著者抄録)

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  • 樹状細胞由来細胞株を用いて増幅したWT1特異的細胞傷害性T細胞(CTL)のINF-γ産生能の検討

    山田 峻也, 後藤 若奈, 小川 彩空, 増子 正義, 小林 果歩, 柴崎 康彦, 内山 孝由, 瀧澤 惇, 曽根 博仁, 高橋 益廣, 成田 美和子

    新潟大学保健学雑誌   15 ( 1 )   9 - 17   2018.3

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    免疫チェックポイント阻害薬の臨床的効果により、抗原特異的細胞傷害性T細胞(CTL)が抗腫瘍作用において重要な役割を果たしていることが明らかとなった。腫瘍に対するCTLの臨床効果を予測する解析のためには、個別のヒトCTLの簡便なクローン性の増幅方法の開発が必要である。我々は、MLPC法と強力な抗原提示能を有する樹状細胞株PMDC11を用いてWT1特異的CTLのクローン性増幅を試みた。数個のCTLから4週間の培養によって増幅した細胞群にはWT1特異的IFN-γ産生が確認された。この抗原特異的CTLの簡便で効率的な増幅方法は、免疫チェックポイント阻害因子、T細胞受容体(TCR)や腫瘍特異的表面抗原の解析に応用可能と思われた。(著者抄録)

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  • 歯磨き回数と早食い その糖尿病やメタボ因子との関連

    佐藤 未希, 渡邊 真恵, 高橋 直穂, 清水 平, 山田 大志郎, 首藤 龍人, 曽根 博仁, 本庄 潤, 横山 宏樹

    糖尿病   61 ( 3 )   138 - 138   2018.3

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  • CpG-Bを用いた白血病性形質細胞様樹状細胞(PMDC11)における抗原特異的CTL誘導能の増強

    後藤 若奈, 山田 峻也, 橋本 誠雄, 増子 正義, 小林 果歩, 小川 彩空, 柴崎 康彦, 曽根 博仁, 高橋 益廣, 成田 美和子

    新潟大学保健学雑誌   15 ( 1 )   1 - 8   2018.3

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    本研究室では、樹立した白血病性形質細胞様樹状細胞株PMDC05へCD80遺伝子を導入することにより強力な抗原提示能をもつPMDC11を作成している。腫瘍細胞とその腫瘍に対する抗原特異的細胞傷害性T細胞(CTL)との間の免疫チェックポイントの強度に関する検査法開発を目指した基礎的研究としてPMDC11のCpG-Bによる機能の変化の有無と腫瘍抗原特異的CTLの増幅効果を検討した。CpG-B刺激は共抑制因子PD-L1及びPD-L2の発現を増加させることなく共刺激因子CD40及びCD83をわずかに高めた。WT1ペプチドパルスに加えてCpG-B刺激したPMDC11とWT1/MHC-tetramer+細胞との共培養を行ったところ、WT1ペプチド抗原特異的CTLの著しい増加が認められた。この培養法は、腫瘍抗原特異的CTLの機能解析において応用可能と考えられた。(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J06421&link_issn=&doc_id=20180420580001&doc_link_id=http%3A%2F%2Fhdl.handle.net%2F10191%2F49818&url=http%3A%2F%2Fhdl.handle.net%2F10191%2F49818&type=%90V%8A%83%91%E5%8Aw%81F%90V%8A%83%91%E5%8Aw%8Aw%8Fp%83%8A%83%7C%83W%83g%83%8A_Nuar&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80230_3.gif

  • 樹状細胞由来細胞株を用いて増幅したWT1特異的細胞傷害性T細胞(CTL)のINF-γ産生能の検討

    山田 峻也, 後藤 若奈, 小川 彩空, 増子 正義, 小林 果歩, 柴崎 康彦, 内山 孝由, 瀧澤 惇, 曽根 博仁, 高橋 益廣, 成田 美和子

    新潟大学保健学雑誌   15 ( 1 )   9 - 17   2018.3

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    免疫チェックポイント阻害薬の臨床的効果により、抗原特異的細胞傷害性T細胞(CTL)が抗腫瘍作用において重要な役割を果たしていることが明らかとなった。腫瘍に対するCTLの臨床効果を予測する解析のためには、個別のヒトCTLの簡便なクローン性の増幅方法の開発が必要である。我々は、MLPC法と強力な抗原提示能を有する樹状細胞株PMDC11を用いてWT1特異的CTLのクローン性増幅を試みた。数個のCTLから4週間の培養によって増幅した細胞群にはWT1特異的IFN-γ産生が確認された。この抗原特異的CTLの簡便で効率的な増幅方法は、免疫チェックポイント阻害因子、T細胞受容体(TCR)や腫瘍特異的表面抗原の解析に応用可能と思われた。(著者抄録)

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J06421&link_issn=&doc_id=20180420580002&doc_link_id=http%3A%2F%2Fhdl.handle.net%2F10191%2F49822&url=http%3A%2F%2Fhdl.handle.net%2F10191%2F49822&type=%90V%8A%83%91%E5%8Aw%81F%90V%8A%83%91%E5%8Aw%8Aw%8Fp%83%8A%83%7C%83W%83g%83%8A_Nuar&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80230_3.gif

  • 勤労世代男性における各耐糖能が冠動脈疾患発症に及ぼす影響の検討

    藤原和哉, 松林泰弘, 石澤正博, 山本正彦, 松永佐澄志, 山田貴穂, 山中菜詩, 清田浩康, 児玉暁, 曽根博仁

    日本疫学会学術総会講演集(Web)   28th   76 (WEB ONLY)   2018.2

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  • 【肥満症 概念・診断・治療の現状と展望】 セミナー 肥満症に対処するための具体的知識 肥満症に対する介入試験のエビデンス

    山本 正彦, 曽根 博仁

    Medical Practice   35 ( 2 )   231 - 235   2018.2

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  • 【患者説明にそのまま使える糖尿病の重要数字35】 そのほか 重要数字 脂質、血糖、血圧を包括的に早期から治療することで延びる寿命→約8年

    山本 正彦, 曽根 博仁

    糖尿病ケア   15 ( 2 )   135 - 135   2018.2

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  • 【患者説明にそのまま使える糖尿病の重要数字35】 三大療法 重要数字 インスリン治療を受ける際の年間医療費→約120,000〜360,000円(自己負担3割分として)

    川田 亮, 曽根 博仁

    糖尿病ケア   15 ( 2 )   114 - 114   2018.2

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  • 【ポリファーマシーの問題点と解決策】 糖尿病患者における薬物処方の現状と多剤処方

    藤原 和哉, 曽根 博仁

    カレントテラピー   36 ( 2 )   163 - 168   2018.2

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  • 【患者説明にそのまま使える糖尿病の重要数字35】 三大療法 重要数字 経口血糖降下薬治療を受ける際の年間医療費→約20,000〜70,000円(自己負担3割分として)

    鈴木 達郎, 曽根 博仁

    糖尿病ケア   15 ( 2 )   113 - 113   2018.2

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  • 【新薬展望2018】(第III部)治療における最近の新薬の位置付け<薬効別>〜新薬の広場〜 糖尿病治療薬

    阿部 孝洋, 曽根 博仁

    医薬ジャーナル   54 ( 増刊 )   587 - 594   2018.2

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    <文献概要>わが国において,2009年のDPP-4(dipeptidyl peptidase-4)阻害薬,2010年のGLP-1(glucagon-like peptide 1)受容体作動薬,2014年のSGLT2(sodium-glucose co-transporter 2)阻害薬と,次々に新規作用機序の糖尿病薬が登場した。そして,2015年以降,SGLT2阻害薬(EMPA-REG OUTCOME試験,CANVAS試験・CANVAS-R試験)やGLP-1受容体作動薬(LEADER試験,SUSTAIN-6試験)による心血管イベント予防効果が報告されるようになった。今のところ,新たな作用機序の新薬が上市される予定はないが,上記のDPP-4阻害薬・GLP-1アナログ・SGLT2阻害薬を含む配合薬は多数開発されている。また,インスリンにおいては,従来のInslin Aspart(従来型インスリンアスパルト)の作用発現をさらに速めた超々速効型インスリン(Fast-Acting Inslin Aspart)が開発されている。

    DOI: 10.20837/1201813587

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  • 原発巣の同定に至らなかった癌の1例

    橋本 浩平, 三ツ間 友里恵, 山本 正彦, 金子 正儀, 松林 泰弘, 山田 貴穂, 岩永 みどり, 松永 佐澄志, 藤原 和哉, 曽根 博仁

    新潟医学会雑誌   132 ( 1 )   31 - 31   2018.1

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  • 動脈硬化予防と脂質代謝 糖尿病患者における脂質異常症と動脈硬化疾患

    曽根 博仁

    日本病態栄養学会誌   21 ( Suppl. )   S - 62   2018.1

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  • 脳心血管病予防のための糖尿病管理

    曽根 博仁

    総合健診   45 ( 1 )   157 - 157   2018.1

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    DOI: 10.7143/jhep.45.156

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  • 【エビデンスを2型糖尿病臨床にどう生かせばいい?-Evidence Based MedicineをReal Worldへ】 大規模臨床試験の結果を糖尿病臨床に生かす際の注意点

    北澤 勝, 藤原 和哉, 曽根 博仁

    内科   121 ( 1 )   11 - 15   2018.1

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    日本人を含む東アジア人と欧米人では,インスリン感受性や分泌能など糖尿病の基本的な病態,大血管障害の頻度が大きく異なることに留意する必要がある.大血管障害などのアウトカムは,試験の対象患者の背景(大血管障害の既往の有無,糖尿病罹病期間など),試験期間などの影響を受けることに留意する必要がある.大規模臨床試験の結果をリスク比,リスク差などを含め定量的に把握し,実臨床へのインパクトがどの程度なのか考慮する必要がある.(著者抄録)

    DOI: 10.15106/j_naika121_11

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  • 原発巣の同定に至らなかった癌の1例

    橋本 浩平, 三ツ間 友里恵, 山本 正彦, 金子 正儀, 松林 泰弘, 山田 貴穂, 岩永 みどり, 松永 佐澄志, 藤原 和哉, 曽根 博仁

    新潟医学会雑誌   132 ( 1 )   31 - 31   2018.1

  • GDP療法がtriple-hit lymphomaの救援療法として有効であった1例

    水戸部 正樹, 河本 啓介, 鈴木 隆晴, 田村 秀, 小堺 貴司, 難波 亜矢子, 諏訪部 達也, 笠見 卓哉, 田中 智之, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 大島 孝一, 瀧澤 淳

    臨床血液   59 ( 5 )   620 - 621   2018

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  • 【糖尿病と栄養】 医療ビッグデータ解析に基づく糖尿病患者の食事と合併症との関連

    曽根 博仁

    栄養   3 ( 2 )   95 - 99   2018

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    食事療法は総ての糖尿病(DM)患者にとって必須の基本的治療であるが、食事は食文化や食習慣による違いが大きいため、食事療法のエビデンスは自国の患者のデータに基づくものでなければならない。わが国の59ヶ所のDM専門医療施設における40〜70歳の2型DM患者2033名を対象に8年間の追跡調査を行い、その解析結果を基に、下記について概説した。1)日本人2型DM患者の食事摂取状況の実態、2)食事摂取状況と合併症発症リスクとの関係(果実摂取量と網膜症発症リスク、食物繊維摂取量と脳卒中発症リスク、食塩摂取量と心血管疾患発症リスク、炭水化物摂取比率と合併症発症リスク)、について述べた。

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  • メタ解析を用いた,2型糖尿病患者におけるレジスタンストレーニングの有用性の検討

    石黒創, 児玉暁, 森川咲子, 堀川千嘉, 石井大, 治田麻理子, 張かおり, 山田貴穂, 藤原和哉, 曽根博仁

    日本臨床運動療法学会雑誌   20 ( 1 )   53 - 53   2018

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  • 下肢皮膚潰瘍から骨髄炎に至った2型糖尿病の1例

    張かおり, 金子正儀, 佐藤陽子, 松林泰弘, 松永佐澄志, 岩永みどり, 山田貴穂, 藤原和哉, 羽入修, 曽根博仁

    糖尿病(Web)   61 ( 9 )   646(J‐STAGE)   2018

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  • 胃亜全摘後の糖尿病患者において,DPP‐4阻害薬からGLP‐1受容体作動薬への変更は有効か

    白石友信, 吉岡大志, 松林泰弘, 松永佐澄志, 岩永みどり, 山田貴穂, 藤原和哉, 曽根博仁

    糖尿病(Web)   61 ( 10 )   721(J‐STAGE)   2018

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  • 高齢発症の劇症1型糖尿病の1例

    吉岡大志, 小松健, 皆川真一, 松林泰弘, 松永佐澄志, 岩永みどり, 山田貴穂, 藤原和哉, 今川彰久, 曽根博仁

    糖尿病(Web)   61 ( 10 )   726(J‐STAGE)   2018

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  • ステロイド糖尿病を合併し歯性感染から上顎の骨髄炎を発症した2型糖尿病の1例

    棚橋怜生, 山本正彦, 松林泰弘, 松永佐澄志, 山田貴穂, 岩永みどり, 藤原和哉, 羽入修, 曽根博仁

    糖尿病(Web)   61 ( 9 )   644(J‐STAGE)   2018

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  • 1型糖尿病の発症以前にバセドウ病が先行したと考えられる14歳女児の1例

    橋本浩平, 金子正儀, 三ツ間友里恵, 山本正彦, 松林泰弘, 松永佐澄志, 岩永みどり, 山田貴穂, 藤原和哉, 曽根博仁

    糖尿病(Web)   61 ( 10 )   700(J‐STAGE)   2018

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  • 青少年の心肺持久力及び筋力と代謝異常リスクの関連

    森川咲子, 森川咲子, 石黒創, 堀川千嘉, 堀川千嘉, 石井大, 武田安永, 治田麻里子, 松林泰弘, 山田貴穂, 藤原和哉, 曽根博仁

    日本臨床運動療法学会雑誌   20 ( 1 )   43 - 43   2018

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  • SGLT2阻害薬が安静時心拍数(Resting Heart Rate:RHR)に及ぼす影響とその関連因子の検討

    松林泰弘, 阿部孝洋, 吉田明弘, 吉田明弘, 野島俊秋, 野島俊秋, 菅波秀規, 松永佐澄志, 岩永みどり, 山田貴穂, 藤原和哉, 加来浩平, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 糖尿病合併妊娠の妊娠転帰に関する多施設前向き研究(DREAMBeeスタディ)について

    川崎麻紀, 荒田尚子, 宮越敬, 菊池透, 曽根博仁, 守屋達美, 杉山隆, 佐川典正, 内潟安子, 難波光義, 平松祐司

    糖尿病(Web)   61 ( Suppl )   2018

  • 眼科処置を要する重症糖尿病性眼疾患の発生リスクに対する腎症の影響についての検討

    山本正彦, 藤原和哉, 大澤妙子, 原田万祐子, 石黒創, 石澤正博, 岩永みどり, 松永佐澄志, 松林泰弘, 清田浩康, 山中菜詩, 山田貴穂, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 指先穿刺による血糖およびHbA1c迅速測定をもちいた糖尿病啓発の取り組み

    山田貴穂, 山田貴穂, 石井大, 武田安永, 橋本浩平, 三ツ間友里恵, 張かおり, 原田万祐子, 白石友信, 吉岡大志, 山本正彦, 大澤妙子, 石黒創, 金子正儀, 鈴木浩史, 松林泰弘, 松林泰弘, 松永佐澄志, 藤原和哉, 岩永みどり, 鈴木亜希子, 鈴木亜希子, 羽入修, 羽入修, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 肥満境界型糖尿病患者に対する血糖自己測定と栄養指導媒体を用いた栄養教育の併用効果について

    長谷川美代, 堀川千嘉, 田代稔, 鈴木沙織, 藤原和哉, 北澤勝, 加藤公則, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • Methotrexate大量療法後の高度排泄遅延および急性腎障害に対して血液浄化法が有用であったALL患者の1例

    森紗世子, 難波亜矢子, 後藤千尋, 柴崎康彦, 柴崎康彦, 増子正義, 曽根博仁, 後藤佐和子, 細島康宏, 山本卓, 成田一衛, 島田泉, 鈴木直人, 外山聡

    日本医療薬学会年会講演要旨集(Web)   28   2018

  • SGLT2阻害薬による膣カンジダ発現頻度とその臨床的特徴

    長尾有未, 小原信, 木村祐之, 大内基司, 清水平, 山田大志郎, 首藤龍人, 曽根博仁, 本庄潤, 横山宏樹

    糖尿病(Web)   61 ( 3 )   2018

  • 歯磨き回数と早食い-その糖尿病やメタボ因子との関連

    佐藤未希, 渡邊真恵, 高橋直穂, 清水平, 山田大志郎, 首藤龍人, 曽根博仁, 本庄潤, 横山宏樹

    糖尿病(Web)   61 ( 3 )   2018

  • 糖尿病患者の受診中断に関連する因子の1年間追跡調査~糖尿病データマネジメント研究会(JDDM)より~

    谷内田潤子, 谷内田潤子, 藤原和哉, 武田安永, 治田麻里子, 石井大, 和井田結佳子, 大石まり子, 川井紘一, 横山宏樹, 前川聡, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 糖尿病における栄養疫学のエビデンス

    曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 年齢層別に見た血清アミラーゼ値と2型糖尿病発症との関連

    石井大, 藤原和哉, 藤原和哉, 治田麻理子, 原田万佑子, 松林泰弘, 斎藤和美, 児玉暁, 児玉暁, 森保道, 本田律子, 荒瀬康司, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 小児1型糖尿病におけるFlash Glucose monitoringの測定精度の検討

    北澤勝, 北澤勝, 齋藤七穂, 小川洋平, 長崎啓祐, 佐々木直, 齋藤昭彦, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 2型糖尿病患者における食事エネルギー密度と肥満との関連-JDDMにおける検討-

    武田安永, 藤原和哉, 治田麻理子, 森川咲子, 森川咲子, 堀川千尋, 堀川千尋, 石井大, 加藤光敏, 横山宏樹, 栗原義夫, 宮澤一裕, 岩崎皓一, 川井紘一, 朝長修, 屋宜宣治, 前川聡, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 診断に難渋した再発性重症低血糖の原因特定に薬物血中濃度測定が有用であった一例

    三ツ間友里恵, 山本正彦, 橋本浩平, 金子正儀, 松林泰弘, 松永佐澄志, 山田貴穂, 岩永みどり, 藤原和哉, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 日本人2型糖尿病における栄養摂取と身体活動の現状~JDCP studyにおける登録時データより~

    松永佐澄志, 曽根博仁, 津田謹輔, 押田芳治, 佐々木敏, 佐藤譲, 林野泰明, 西村理明, 田嶼尚子

    糖尿病(Web)   61 ( Suppl )   2018

  • 耐糖能及び肥満の有無に関わらず代謝異常は冠動脈疾患発症リスクを増大させる

    藤原和哉, 松林泰弘, 山本正彦, 松永佐澄志, 清田浩康, 山中菜詩, 児玉暁, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • 当院における糖尿病合併妊娠及び妊娠糖尿病患者への分割食の栄養指導の実態と指導方法の検討

    治田麻理子, 治田麻理子, 深沢向子, 桜井健一, 津野菜津美, 佐藤かえで, 西山陽子, 藤原和哉, 曽根博仁, 鈴木克典

    糖尿病(Web)   61 ( Suppl )   2018

  • DPP-4阻害薬アナグリプチン(ANA)の12週間投与時におけるインスリンクリアランスに及ぼす影響

    阿部孝洋, 松林泰弘, 村岸沙也加, 吉田明弘, 吉田明弘, 菅波秀規, 古澤研一, 松永佐澄志, 岩永みどり, 山田貴穂, 藤原和哉, 加来浩平, 曽根博仁

    糖尿病(Web)   61 ( Suppl )   2018

  • Methotrexate大量療法後の高度排泄遅延および急性腎障害に対して血液浄化療法が有用であったALL患者の1例

    森紗世子, 後藤佐和子, 細島康宏, 山本卓, 成田一衛, 難波亜矢子, 後藤千尋, 柴崎康彦, 柴崎康彦, 増子正義, 曽根博仁, 島田泉, 鈴木直人, 外山聡

    東北腎不全研究会プログラム・抄録集   45th   2018

  • 妊娠初期の栄養摂取状況と低出生体重児出産リスクとの関連の検討

    飯島春香, 田中康弘, 津野和, 小松弥生, 安見真奈, 田島諒子, 広瀬歩美, 曽根博仁, 谷内洋子

    New Diet Therapy   34 ( 2 )   2018

  • マーカー染色体が急性骨髄性白血病に対する同種造血細胞移植成績に与える影響

    田中智之, 布施香子, 諏訪部達也, 笠見卓哉, 河本啓介, 河本啓介, 牛木隆志, 森山雅人, 柴崎康彦, 柴崎康彦, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   40th   239   2017.12

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  • 多職種連携チーム医療が著効した食道慢性GVHDの一例

    難波亜矢子, 上村駿, 諏訪部達也, 笠見卓哉, 河本啓介, 河本啓介, 田中智之, 小林弘典, 布施香子, 小師優子, 真柄仁, 高昌良, 冨永顕太郎, 橋本哲, 横山純二, 柴崎康彦, 柴崎康彦, 瀧澤淳, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   40th   305   2017.12

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  • 最終糖化産物(AGEs)はヒト血小板において、Srcファミリーキナーゼの活性化を介して脳由来神経栄養因子(BDNF)の放出を促進させる

    古川 和郎, 布施 一郎, 岩倉 百合子, 外山 英和, 羽入 修, 那波 宏之, 曽根 博仁, 武井 延之

    生命科学系学会合同年次大会   2017年度   [2P - 1016]   2017.12

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  • FHHとPHPTの鑑別に苦慮している一例

    棚橋 怜生, 山本 正彦, 松林 泰弘, 張 かおり, 佐藤 陽子, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   93 ( 3 )   753 - 753   2017.12

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  • 【糖尿病介入研究と動脈硬化】 Japan Diabetes Complications Study(JDCS) 長期間の生活習慣介入

    松永 佐澄志, 田中 司朗, 曽根 博仁

    動脈硬化予防   16 ( 4 )   38 - 45   2017.12

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    JDCSは日本人2型糖尿病患者を対象に長期間の生活習慣介入が心血管疾患予防に及ぼす影響について検証したわが国を代表する大規模臨床試験である。食事・運動療法を中心とした生活習慣強化介入によりHbA1cや血圧、脂質の改善は得られなかったが、脳卒中の発症を有意に抑制できることが示された。生活習慣強化介入群で心血管疾患発症の危険因子に改善が認められなかったにもかかわらず脳卒中が抑制された理由は定かではないが、生活習慣介入後に各種検査結果に改善が認められない場合でも合併症予防効果がある可能性を示している点は重要である。本稿では、JDCSから得られた動脈硬化性疾患予防に関するエビデンスについて解説したい。(著者抄録)

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  • 血小板凝集能低下により止血が困難であった骨髄異形成症候群

    田中 智之, 小堺 貴司, 北嶋 俊樹, 布施 香子, 小林 弘典, 牛木 隆志, 柴崎 康彦, 森山 雅人, 瀧澤 淳, 曽根 博仁, 布施 一郎, 増子 正義

    臨床血液   58 ( 12 )   2402 - 2405   2017.12

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    症例は75歳の女性。血液検査で貧血と末梢血に芽球を認められたため、当院を紹介受診した。骨髄穿刺で骨髄異形成症候群(myelodysplastic syndrome with excess blasts 2, MDS-EB-2)と診断された。血球減少の進行や芽球の増加、および出血症状はなく経過していた。診断から10ヵ月後、左手母指球に外傷を負い、内出血が持続し、止血困難となったため緊急入院した。血小板数は正常範囲であったが、血小板機能検査でコラーゲン凝集能とアラキドン酸凝集能の低下を認められた。抗血小板薬の内服はなく、またこれまで出血傾向の既往もなかったことから、MDSによる二次性の血小板機能低下による出血と判断し、血小板輸血を行い止血した。MDSの患者では、潜在的に血小板凝集能が低下していることが多く、血小板数の割に出血傾向が強い場合には血小板凝集能を調べ、血小板輸血などの治療介入を検討する必要がある。(著者抄録)

    DOI: 10.11406/rinketsu.58.2402

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01540&link_issn=&doc_id=20180112380008&doc_link_id=130006308822&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130006308822&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • 【糖尿病診療 今後の展望-next decade】 糖尿病診療および疾病管理におけるビッグデータの活用 今後の展望

    山田 貴穂, 曽根 博仁

    糖尿病診療マスター   15 ( 12 )   1042 - 1047   2017.12

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    <POINT>日本人糖尿病へのエビデンス構築と糖尿病発症予防の重要性.従来の大規模臨床研究と新しいビッグデータを活用した研究への期待.(著者抄録)

    DOI: 10.11477/mf.1415200817

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  • JDCSにおける食事と運動

    堀川 千嘉, 曽根 博仁

    Diabetes Journal: 糖尿病と代謝   45 ( 4 )   131 - 137   2017.12

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    食事療法は2型糖尿病患者の治療の要であるが、その科学的エビデンスは一般対象者の研究や、糖尿病患者では比較的少人数の短期介入研究が多く、多数の糖尿病患者を長期的に追跡した科学的エビデンスの不足が指摘されている。さらに、食事療法の実践にあたっては、臨床像・病態・食習慣を含む生活習慣や文化などの観点から、人種や民族差が大きな影響を及ぼし得る。したがって、わが国独自の2型糖尿病患者における食事療法のエビデンス構築は、われわれ自身によって解決されなければならない課題である。そこでわが国では、東アジアや世界に先駆けて、全国糖尿病専門医療機関59施設に登録された2型糖尿病患者2,033名を追跡するJapan Diabetes Complications Study(JDCS)が1996年から実施され、食事摂取状況や運動量を含む生活習慣を含む糖尿病の臨床像を明らかにしてきた。本稿では、JDCS研究で報告された日本人2型糖尿病患者の食事摂取状況・運動量や、これらと合併症発症リスクの関係性が認められた食事・運動について整理を行った。(著者抄録)

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  • 最終糖化産物(AGEs)はヒト血小板において、Srcファミリーキナーゼの活性化を介して脳由来神経栄養因子(BDNF)の放出を促進させる

    古川 和郎, 布施 一郎, 岩倉 百合子, 外山 英和, 羽入 修, 那波 宏之, 曽根 博仁, 武井 延之

    生命科学系学会合同年次大会   2017年度   [2P - 1016]   2017.12

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  • Further Prognostic Factors for Stratification of Patients in the High-Risk HCT-CI Group Undergoing Allogeneic HCT

    Yasuhiko Shibasaki, Tatsuya Suwabe, Shun Uemura, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Kyoko Fuse, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    BLOOD   130   2017.12

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  • Patient-Based Prediction Algorithm of Relapse after Allo-HSCT for Acute Leukemia Using Machine Learning Approach

    Kyoko Fuse, Shun Uemura, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Yasuhiko Shibasaki, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Tastuo Furukawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    BLOOD   130   2017.12

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  • 重症低血糖を契機に発見されたIGF-2産生腫瘍によるNICTHの1例

    張 かおり, 金子 正儀, 佐藤 陽子, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 羽入 修, 曽根 博仁, 福田 いずみ, 長嶋 洋治

    新潟医学会雑誌   131 ( 11 )   667 - 667   2017.11

  • 【肥満は病気である】 肥満と冠動脈疾患、脳梗塞

    石黒 創, 曽根 博仁

    成人病と生活習慣病   47 ( 11 )   1395 - 1399   2017.11

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    BMIが25以上で「肥満」と診断する。また「肥満」の中でも、種々の健康障害と関連し医学的に減量を必要とする病態を「肥満症」と定義する。肥満によって、冠動脈疾患や脳梗塞の発症率や死亡率は上昇する。心筋梗塞後のイベント再発率や生存率については、BMI高値の人の方が低値の人よりも良好であるという&quot;obesity paradox&quot;は、解釈に注意を要する。減量によって冠動脈疾患や脳梗塞の発症率や死亡率が改善するか、については、適切な大規模前向き研究はないが、種々の観察研究からは減量の効果が認められており推奨される。特に脳梗塞は、高血圧や糖尿病などが非常に強い危険因子であり、減量とともにこれらの因子の改善も重要である。脳出血とBMIの関連は現在のところ、相反する報告があり不明である。(著者抄録)

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  • HLA半合致移植後AMLとして再発したB-ALLの1例

    小堺 貴司, 田村 秀, 布施 香子, 柴崎 康彦, 瀧澤 淳, 曽根 博仁, 増子 正義

    臨床血液   58 ( 11 )   2270 - 2271   2017.11

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  • 知っておきたい糖尿病情報 Q‐1 糖尿病患者数が頭打ちになっているというのは本当ですか?

    石澤正博, 曽根博仁

    臨床栄養   1‐4   2017.10

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  • 心血管疾患 糖尿病が冠動脈疾患発症へ与える影響は若年者と中年では大きく異なる

    藤原 和哉, 松林 泰弘, 山本 正彦, 石澤 正博, 松永 佐澄志, 山田 貴穂, 清田 浩康, 山中 菜詩, 児玉 暁, 曽根 博仁

    糖尿病合併症   31 ( Suppl.1 )   202 - 202   2017.10

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  • 【栄養指導・管理のためのスキルアップシリーズvol.7 糖尿病の最新食事療法のなぜに答える 基礎編】 妊娠糖尿病や糖尿病合併妊娠では、何を食事療法の評価指標とし、どのような指導・管理をすればよいでしょうか?

    谷内 洋子, 曽根 博仁

    臨床栄養   別冊 ( 栄養指導・管理のためのスキルアップシリーズ7 )   124 - 127   2017.10

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  • 【栄養指導・管理のためのスキルアップシリーズvol.7 糖尿病の最新食事療法のなぜに答える 基礎編】 糖尿病の診断は何を目的として、どのような基準で行うのでしょうか?

    岩永 みどり, 曽根 博仁

    臨床栄養   別冊 ( 栄養指導・管理のためのスキルアップシリーズ7 )   5 - 8   2017.10

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  • 【栄養指導・管理のためのスキルアップシリーズvol.7 糖尿病の最新食事療法のなぜに答える 基礎編】 糖尿病患者数が頭打ちになっているというのは本当ですか?

    石澤 正博, 曽根 博仁

    臨床栄養   別冊 ( 栄養指導・管理のためのスキルアップシリーズ7 )   1 - 4   2017.10

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  • 【栄養指導・管理のためのスキルアップシリーズvol.7 糖尿病の最新食事療法のなぜに答える 基礎編】 血糖コントロールにより、境界型からの糖尿病発症や、糖尿病からの合併症発症をどのくらい予防できるのでしょうか?

    鈴木 裕美, 曽根 博仁

    臨床栄養   別冊 ( 栄養指導・管理のためのスキルアップシリーズ7 )   9 - 12   2017.10

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  • 当科におけるMTX関連リンパ増殖性疾患の後方視的解析

    笠見 卓哉, 河本 啓介, 鈴木 隆晴, 田中 智之, 難波 亜矢子, 小林 弘典, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 瀧澤 淳

    新潟医学会雑誌   131 ( 10 )   618 - 618   2017.10

  • 【糖尿病と心合併症2017〜循環器専門医との連携を図る】 大規模臨床試験から明らかになった心血管イベントの予防・治療戦略 糖尿病患者における心血管イベント抑制についてのエビデンスのOverview

    北澤 勝, 曽根 博仁

    Diabetes Frontier   28 ( 5 )   538 - 543   2017.10

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  • 原発巣の同定に至らなかった癌の一例

    橋本 浩平, 金子 正儀, 三ツ間 友里恵, 山本 正彦, 松林 泰弘, 山田 貴穂, 松永 佐澄志, 岩永 みどり, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   93 ( 2 )   642 - 642   2017.10

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  • 膵島細胞症とインスリノーマの合併が疑われ診断に難渋した一例

    山本 正彦, 棚橋 怜生, 松林 泰弘, 松永 佐澄志, 藤原 和哉, 林 和直, 岩永 みどり, 山田 貴穂, 高野 徹, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   93 ( 2 )   589 - 589   2017.10

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  • 【生産年齢期の身体活動による生活習慣病予防】 糖尿病予防に対する身体活動エビデンス

    児玉 暁, 曽根 博仁

    体育の科学   67 ( 10 )   675 - 681   2017.10

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  • Comprehensive risk management for the prevention of cerebro- cardiovascular diseases in Japan

    Tamio Teramoto, Masayuki Yokode, Hiroyasu Iso, Akihiko Kitamura, Hiroki Shiomi, Tsuyoshi Kimura, Masayasu Matsumoto, Mami Lida, Jun Sasaki, Shigeru Inoue, Ryouichi Nagatomi, Tetsuo Shoji, Hidenori Arai, Hiromi Rakugi, Hirohito Sone, Shizuya Yamashita, Shigeru Mizyzaki

    HYPERTENSION RESEARCH   40 ( 10 )   847 - 855   2017.10

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    DOI: 10.1038/hr.2016.155

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  • 妊娠初期HbA1c値および空腹時血糖値と妊娠糖尿病発症予測能の検討<TWC Study>

    谷内 洋子, 田中 康弘, 広瀬 歩美, 伊部 陽子, 藤原 和哉, 曽根 博仁

    New Diet Therapy   33 ( 2 )   194 - 194   2017.9

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  • 当院の心臓リハビリテーション患者における減塩生活の現状

    治田 麻理子, 曽根 博仁

    New Diet Therapy   33 ( 2 )   199 - 199   2017.9

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  • 単一施設における末梢性T細胞リンパ腫、非特定型の後方視的解析

    鈴木 隆晴, 河本 啓介, 田村 秀, 上村 駿, 海發 茜, 根本 洋樹, 小林 弘典, 牛木 隆志, 布施 香子, 柴崎 康彦, 森山 雅人, 増子 正義, 成田 美和子, 曽根 博仁, 青木 定夫, 中村 直哉, 大島 孝一, 瀧澤 淳

    臨床血液   58 ( 8 )   905 - 911   2017.8

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    1998年から2015年までに新潟大学医歯学総合病院血液内科で診断したPTCL,NOS 28例について臨床像,病理学的特徴,治療内容,予後を後方視的に解析した。性別は男性16例,女性12例で年齢中央値62.5(26〜88)歳。IPIはHIが10例,Hが9例であり高リスク群が68%を占めていた。初回治療としてCHOPまたはTHP-COP療法が12例に行われ,第三世代化学療法が9例に行われた。予後の確認ができた26例の観察期間中央値30ヵ月(範囲1〜164ヵ月)における2年OSは61%,2年PFSは44%であった。初回治療における効果がCRであった11例は5年OS 83%,5年PFS 75%であり,CRに至らなかった9例に比べ予後良好であった(p&lt;0.005)。PTCL,NOSに対する新規薬剤を用いた治療法の開発が望まれる。(著者抄録)

    DOI: 10.11406/rinketsu.58.905

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  • 【臨床研究の壺】 コホート研究と大規模臨床疫学研究

    岩永 みどり, 曽根 博仁

    内分泌・糖尿病・代謝内科   45 ( 2 )   115 - 121   2017.8

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    Other Link: http://search.jamas.or.jp/link/ui/2017341771

  • 骨粗鬆症検診と体力測定の関係についての縦断的解析

    加藤 公則, 石澤 正博, 児玉 暁, 藤原 和哉, 小林 隆司, 田代 稔, 佐藤 幸示, 北川 寛, 笹川 力, 曽根 博仁

    人間ドック   32 ( 2 )   308 - 308   2017.8

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  • 骨粗鬆症検診と体力測定の関係についての横断的解析

    加藤 公則, 石澤 正博, 児玉 暁, 藤原 和哉, 小林 隆司, 田代 稔, 佐藤 幸示, 北川 寛, 笹川 力, 曽根 博仁

    人間ドック   32 ( 2 )   307 - 307   2017.8

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  • 臍帯血移植後にヒトパルボウイルスB19感染による自己免疫性溶血性貧血と赤芽球癆を発症した1例

    海發 茜, 柴崎 康彦, 上村 駿, 田村 秀, 小堺 貴司, 難波 亜矢子, 小林 弘典, 布施 香子, 牛木 隆志, 森山 雅人, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   58 ( 8 )   1078 - 1078   2017.8

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  • Pulse Pressure and HbA1c Levels Are Significant Predictors of Vision-Threatening Eye Diseases in Japanese Patients with Diabetes Mellitus

    Masahiko Yamamoto, Kazuya Fujihara, Risa Igarashi, Sakiko Yoshizawa, Yasuhiro Matsubayashi, Takaho Yamada, Satoshi Mat-Sunaga, Chie Ito, Nauta Yamanaka, Hiruma Hasebe, Takeo Fukuchi, Shiro Tanaka, Kiminori Katou, Satoru Kodama, Hirohito Sone

    DIABETES   66   A431 - A431   2017.6

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  • Impact of Individual Components and Their Combinations within a Family History (FH) of Diabetes on the Development of Diabetes

    Risa Igarashi, Dai Ishii, Yasunaga Takeda, Kazuya Fujihara, Mariko Hatta, Yoshie Oshikane, Yasuhiro Matsubayashi, Kazumi Saito, Satoru Kodama, Ritsuko Honda, Yasuji Arase, Hirohito Sone

    DIABETES   66   A418 - A418   2017.6

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  • Trends In Dietary Intake by Patients with Type 2 Diabetes (T2DM) in Japan, 1996-2016

    Yasunaga Takeda, Chika Horikawa, Megumi Tsuruta, Kazuya Fujihara, Sakiko Yoshizawa, Risa Igarashi, Mariko Hatta, Dai Ishii, Mitsutoshi Kato, Hiroki Yokoyama, Yoshio Kurihara, Kazuhiro Miyazawa, Koichi Iwasaki, Koichi Kawai, Osamu Tomonaga, Noriharu Yagi, Hiroshi Maegawa, Hirohito Sone

    DIABETES   66   A441 - A441   2017.6

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  • Effects on Fasting Free Fatty Acid (F-FFA) and Adipose-Tissue Insulin Resistance (Adipo-IR) after Long-Term Treatment of Type 2 Diabetes Mellitus (T2DM) with the SGLT2 inhibitor (SGLT2i) Tofogliflozin (TOFO)

    Yasuhiro Matsubayashi, Akihiro Yoshida, Hideki Suganami, Kazuya Fujihara, Kohei Kaku, Hirohito Sone

    DIABETES   66   A328 - A328   2017.6

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  • 液剤の硫酸プロタミンを用いた簡便かつ効果的なプロタミン補充APTT測定手順の検討

    松田 将門, 松戸 隆之, 高野 操, 曽根 博仁

    臨床病理   65 ( 6 )   640 - 645   2017.6

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    APTT延長の原因として、ヘパリン混入の有無を鑑別するためのプロタミン補充APTTの測定手順について検討した。その結果、簡便かつ効果的なプロタミン補充APTTの測定方法として、液剤であるノボ・硫酸プロタミン注を用い、第一選択するプロタミン終濃度を10μg/mLとする測定手順を確立した。本法を用いることで、ヘパリン混入によるAPTT偽延長を検査室で発見し、診療上の混乱を未然に防ぐことが期待される。

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01563&link_issn=&doc_id=20170718080002&doc_link_id=%2Fco3labor%2F2017%2F006506%2F002%2F0640-0645%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fco3labor%2F2017%2F006506%2F002%2F0640-0645%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 【高血圧と機能性食品】 疫学研究からみた、塩分制限と高血圧・心血管病の関係と今後の展望

    堀川 千嘉, 石井 大, 村山 伸子, 曽根 博仁

    機能性食品と薬理栄養   11 ( 1 )   12 - 18   2017.6

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  • 【糖尿病の日本人特異性〜日本的糖尿病学の確立へ〜】 日本人糖尿病合併症の特徴

    藤原 和哉, 曽根 博仁

    月刊糖尿病   9 ( 6 )   93 - 102   2017.6

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    Other Link: http://search.jamas.or.jp/link/ui/2017252406

  • 生活習慣病の運動療法 糖尿病・動脈硬化症を中心とした生活習慣病に対する運動の効果

    曽根 博仁

    日本抗加齢医学会総会プログラム・抄録集   17回   125 - 125   2017.6

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  • 凝固検査の標準化における遠心条件の重要性 高速遠心による凝固活性化の可能性

    森山 雅人, 松田 将門, 鈴木 健史, 小宮山 豊, 末武 司, 井藤 ヒロミ, 高野 操, 西條 康夫, 松戸 隆之, 曽根 博仁

    日本検査血液学会雑誌   18 ( 学術集会 )   S169 - S169   2017.6

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  • ELISAを測定原理とする抗凝固第VIII因子抗体測定キットZYMUTEST Anti VIII IgGの第VIII因子インヒビター検出能の評価

    松田 将門, 森山 雅人, 鈴木 健史, 小宮山 豊, 末武 司, 星山 良樹, 高野 操, 松戸 隆之, 曽根 博仁

    日本検査血液学会雑誌   18 ( 学術集会 )   S132 - S132   2017.6

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  • Potential protective effect of lactation against incidence of type 2 diabetes mellitus in women with previous gestational diabetes mellitus: A systematic review and meta-analysis

    Kanako Tanase-Nakao, Naoko Arata, Maki Kawasaki, Ichiro Yasuhi, Hirohito Sone, Rintaro Mori, Erika Ota

    DIABETES-METABOLISM RESEARCH AND REVIEWS   33 ( 4 )   2017.5

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    Lactation may protect women with previous gestational diabetes mellitus (GDM) from developing type 2 diabetes mellitus, but the results of existing studies are inconsistent, ranging from null to beneficial. We aimed to conduct a systematic review to gather available evidence. Databases MEDLINE, CINAHL, PubMed, and EMBASE were searched on December 15, 2015, without restriction of language or publication year. A manual search was also conducted. We included observational studies (cross-sectional, case-control, and cohort study) with information on lactation and type 2 diabetes mellitus incidence among women with previous GDM. We excluded case studies without control data. Data synthesis was conducted by random-effect meta-analysis. Fourteen reports of 9 studies were included. Overall risk of bias using RoBANS ranged from low to unclear. Longer lactation for more than 4 to 12weeks postpartum had risk reduction of type 2 diabetes mellitus compared with shorter lactation (OR 0.77, 95% CI 0.01-55.86; OR 0.56, 95% CI 0.35-0.89; OR 0.22, 95% CI 0.13-0.36; type 2 diabetes mellitus evaluation time &lt;2y, 2-5y, and &gt;5y, respectively). Exclusive lactation for more than 6 to 9weeks postpartum also had lower risk of type 2 diabetes mellitus compared with exclusive formula (OR 0.42, 95% CI 0.22-0.81). The findings support the evidence that longer and exclusive lactation may be beneficial for type 2 diabetes mellitus prevention in women with previous GDM. However, the evidence relies only on observational studies. Therefore, further studies are required to address the true causal effect.

    DOI: 10.1002/dmrr.2875

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  • 大規模臨床データ解析研究が開く新しい糖尿病合併症学 網膜症を中心に

    曽根 博仁

    糖尿病合併症   31 ( 2 )   113 - 120   2017.5

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    網膜症を含む糖尿病合併症は、健康寿命と国民医療費に甚大な悪影響を及ぼしている。長期経過後に発症する糖尿病合併症のリスクを早期かつ的確に予測できれば、糖尿病診療の改善に貢献できる。そのためには大規模臨床データ解析に基づく科学的エビデンスが不可欠であるが、近年の情報技術の発達により従来のコホート研究に加え、検診やレセプトデータなどのいわゆる医療ビッグデータが研究に活用しやすくなってきた。このような手段により、糖尿病合併症はもちろん、糖尿病そのものの発症のリスクを評価・予測し、診療、予防活動や政策立案に応用可能である。糖尿病と網膜症を中心とした糖尿病合併症の発症リスク評価について自験例を中心に紹介する。(著者抄録)

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  • 生活習慣への介入と合併症進展予防 生活習慣と糖尿病合併症 大規模臨床研究のエビデンス

    曽根 博仁

    糖尿病合併症   31 ( 2 )   147 - 150   2017.5

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  • 顆粒球肉腫におけるPD-1/PD-L1発現の臨床病理学的検討

    河本 啓介, 三好 寛明, 喜安 純一, 佐々木 裕哉, 栗田 大輔, 鈴木 隆晴, 曽根 博仁, 瀬戸 加大, 瀧澤 淳, 大島 孝一

    日本リンパ網内系学会会誌   57   108 - 108   2017.5

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  • 重症低血糖を契機に発見されたIGF-II産生腫瘍の1例

    佐藤 陽子, 金子 正儀, 張 かおり, 棚橋 怜生, 山本 正彦, 松林 康弘, 松永 佐登志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 羽入 修, 曽根 博仁

    新潟医学会雑誌   131 ( 5 )   320 - 320   2017.5

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  • 顆粒球肉腫におけるPD-1/PD-L1発現の臨床病理学的検討

    河本 啓介, 三好 寛明, 喜安 純一, 佐々木 裕哉, 栗田 大輔, 鈴木 隆晴, 曽根 博仁, 瀬戸 加大, 瀧澤 淳, 大島 孝一

    日本リンパ網内系学会会誌   57   90 - 90   2017.5

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  • 糖尿病合併症の疫学と最新の診断法について 大血管障害の疫学と診断、リスク評価

    曽根 博仁

    日本糖尿病眼学会誌   21   68 - 68   2017.4

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  • 糖尿病に起因する重症視力障害発症のリスク因子およびHbA1cの閾値に関する検討

    山本正彦, 藤原和哉, 伊藤知恵, 錦野理絵, 山中菜詩, 児玉暁, 長谷部日, 田中司朗, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.140(J‐STAGE) - 140   2017.4

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  • 糖尿病の詳細な家族歴が2型糖尿病発症リスクに与える影響の定量的検討

    石井大, 五十嵐理沙, 藤原和哉, 藤原和哉, 治田麻理子, 押鐘芳恵, 松林泰弘, 斎藤和美, 児玉暁, 本田律子, 荒瀬康司, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.281(J‐STAGE) - 281   2017.4

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  • 糖尿病患者における透析導入のリスク因子の検討

    大澤妙子, 山本正彦, 石澤正博, 松林泰弘, 松永佐澄志, 藤原和哉, 山田貴穂, 小石美恵子, 伊藤知恵, 山中菜詩, 児玉暁, 加藤公則, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.245(J‐STAGE) - 245   2017.4

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  • 骨粗鬆症検診と体力測定の関係—人間ドック受診者では糖代謝異常と骨密度と関連しない—

    加藤公則, 加藤公則, 石澤正博, 岩永みどり, 児玉暁, 藤原和哉, 小林隆司, 田代稔, 田代稔, 小林篤子, 上村伯人, 佐藤幸示, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.216(J‐STAGE) - 216   2017.4

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  • 耐糖能別にみた収縮期血圧が透析導入に及ぼす影響の検討

    古谷篤, 藤原和哉, 五十嵐理沙, 山本正彦, 石澤正博, 松林泰弘, 松永佐澄志, 加藤公則, 伊藤知恵, 小石美恵子, 山中菜詩, 児玉暁, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.287(J‐STAGE) - 287   2017.4

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  • 診断に難渋した低血糖症

    山本 正彦, 棚橋 怜生, 松林 泰弘, 張 かおり, 佐藤 陽子, 金子 正儀, 松永 佐澄志, 藤原 和哉, 林 和直, 岩永 みどり, 山田 貴穂, 高野 徹, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   93 ( 1 )   328 - 328   2017.4

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  • 骨密度に影響する身体測定値 人間ドックのデータ解析から

    石澤 正博, 藤原 和哉, 田代 稔, 加藤 公則, 松永 佐澄志, 山田 貴穂, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   93 ( 1 )   332 - 332   2017.4

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  • 勤労世代男性における耐糖能の冠動脈疾患発症への影響の検討

    藤原 和哉, 山本 正彦, 石澤 正博, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 加藤 公則, 伊藤 知恵, 小石 美恵子, 山中 菜詩, 曽根 博仁

    日本内分泌学会雑誌   93 ( 1 )   260 - 260   2017.4

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  • グルカゴン/インスリン比の糖尿病病態評価における有用性 SLGT2阻害薬投与前後の変化も踏まえて

    松林 泰弘, 菅波 秀規, 加来 浩平, 曽根 博仁

    日本内分泌学会雑誌   93 ( 1 )   260 - 260   2017.4

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  • 重症低血糖を契機に発見されたIGF-2産生腫瘍によるNICTHの一例

    張 かおり, 金子 正儀, 佐藤 陽子, 松林 泰弘, 山田 貴穂, 松永 佐澄志, 藤原 和哉, 羽入 修, 曽根 博仁, 福田 いずみ, 長嶋 洋治

    日本内分泌学会雑誌   93 ( 1 )   329 - 329   2017.4

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  • グルカゴン/インスリン比の糖尿病病態評価における有用性 SLGT2阻害薬投与前後の変化も踏まえて

    松林 泰弘, 菅波 秀規, 加来 浩平, 曽根 博仁

    日本内分泌学会雑誌   93 ( 1 )   260 - 260   2017.4

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  • 診断に難渋した低血糖症

    山本 正彦, 棚橋 怜生, 松林 泰弘, 張 かおり, 佐藤 陽子, 金子 正儀, 松永 佐澄志, 藤原 和哉, 林 和直, 岩永 みどり, 山田 貴穂, 高野 徹, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   93 ( 1 )   328 - 328   2017.4

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  • 勤労世代男性における耐糖能の冠動脈疾患発症への影響の検討

    藤原 和哉, 山本 正彦, 石澤 正博, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 加藤 公則, 伊藤 知恵, 小石 美恵子, 山中 菜詩, 曽根 博仁

    日本内分泌学会雑誌   93 ( 1 )   260 - 260   2017.4

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  • 骨密度に影響する身体測定値 人間ドックのデータ解析から

    石澤 正博, 藤原 和哉, 田代 稔, 加藤 公則, 松永 佐澄志, 山田 貴穂, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   93 ( 1 )   332 - 332   2017.4

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  • 重症低血糖を契機に発見されたIGF-2産生腫瘍によるNICTHの一例

    張 かおり, 金子 正儀, 佐藤 陽子, 松林 泰弘, 山田 貴穂, 松永 佐澄志, 藤原 和哉, 羽入 修, 曽根 博仁, 福田 いずみ, 長嶋 洋治

    日本内分泌学会雑誌   93 ( 1 )   329 - 329   2017.4

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  • 妊娠中の食事および出産前後の体重歴とやせ願望との関連の検討

    浅井 彩矢香, 谷内 洋子, 田中 康弘, 小倉 秋乃, 春原 華歩, 西端 泉, 広瀬 歩美, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   71回   355 - 355   2017.4

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  • 小児期の運動能力と心血管リスクに関する検討

    柴田 健継, 松永 佐澄志, 五十嵐 理沙, 由澤 咲子, 古川 和郎, 山田 貴穂, 藤原 和哉, 曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 364   2017.4

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  • 日本人2型糖尿病患者における身体活動と臨床指標との関連 JDCP study

    松永 佐澄志, 曽根 博仁, 押田 芳治, 林野 泰明, 西村 理明, 田嶼 尚子

    糖尿病   60 ( Suppl.1 )   S - 254   2017.4

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  • 糖尿病患者における透析導入のリスク因子の検討

    大澤 妙子, 山本 正彦, 石澤 正博, 松林 泰弘, 松永 佐澄志, 藤原 和哉, 山田 貴穂, 小石 美恵子, 伊藤 知恵, 山中 菜詩, 児玉 暁, 加藤 公則, 曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 245   2017.4

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  • SGLT2阻害薬の腎庇護作用 アルブミン尿、eGFRへ及ぼす効果の解析

    樋詰 友香, 渡邉 真恵, 高橋 直穂, 木村 祐之, 大内 基司, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   60 ( Suppl.1 )   S - 269   2017.4

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  • SGLT2阻害薬による腟カンジダ症の発症頻度とその臨床的特徴

    長尾 有未, 樋詰 友香, 渡邉 真恵, 高橋 直穂, 木村 祐之, 大内 基司, 清水 平, 山田 大志郎, 首藤 龍人, 曽根 博仁, 本庄 潤, 横山 宏樹

    糖尿病   60 ( Suppl.1 )   S - 146   2017.4

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  • 糖尿病に起因する重症視力障害発症のリスク因子およびHbA1cの閾値に関する検討

    山本 正彦, 藤原 和哉, 伊藤 知恵, 錦野 理絵, 山中 菜詩, 児玉 暁, 長谷部 日, 田中 司朗, 曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 140   2017.4

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  • 糖尿病専門医の治療を受ける2型糖尿病患者の食事摂取状態の実態と時代的変遷 JDDMによる報告(第二報)

    武田 安永, 堀川 千嘉, 鶴田 恵, 藤原 和哉, 由澤 咲子, 五十嵐 理沙, 治田 麻理子, 石井 大, 加藤 光敏, 横山 宏樹, 栗原 義夫, 宮澤 一裕, 岩崎 皓一, 川井 紘一, 朝長 修, 屋宜 宣治, 前川 聡, 曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 244   2017.4

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  • 骨粗鬆症検診と体力測定の関係 人間ドック受診者では糖代謝異常と骨密度と関連しない

    加藤 公則, 石澤 正博, 岩永 みどり, 児玉 暁, 藤原 和哉, 小林 隆司, 田代 稔, 小林 篤子, 上村 伯人, 佐藤 幸示, 曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 216   2017.4

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  • 世界と日本の大規模臨床研究の現在 日本人糖尿病の予防と治療に関するビッグデータ解析の可能性

    曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 97   2017.4

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  • DPP4阻害剤の週1製剤変更希望者と非希望者の比較

    高橋 望美, 本庄 潤, 山田 大志郎, 首藤 龍人, 清水 平, 大内 基司, 木村 祐之, 山下 りさ, 高橋 直穂, 刀禰谷 雅之, 曽根 博仁, 横山 宏樹

    糖尿病   60 ( Suppl.1 )   S - 455   2017.4

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  • SGLT2阻害薬とピオグリタゾンの併用による脂肪肝・体脂肪への効果の比較

    中井 伸江, 樋詰 友香, 高橋 直穂, 木村 祐之, 大内 基司, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   60 ( Suppl.1 )   S - 407   2017.4

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  • トホグリフロジン(TOFO)長期投与が遊離脂肪酸及び脂肪細胞インスリン抵抗性に与える影響の検討

    松林 泰弘, 吉田 明弘, 田中 司郎, 菅波 秀規, 阿部 孝洋, 山本 正彦, 大澤 妙子, 松永 佐澄志, 藤原 和哉, 加来 浩平, 曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 491   2017.4

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  • わが国の糖尿病専門医の薬物療法における処方と患者背景の解析(第3報)

    藤原 和哉, 五十嵐 理沙, 松永 佐澄志, 松林 泰弘, 山田 貴穂, 横山 宏樹, 田中 司朗, 島野 仁, 前川 聡, 山崎 勝也, 川井 紘一, 曽根 博仁, 糖尿病データマネジメント研究会

    糖尿病   60 ( Suppl.1 )   S - 457   2017.4

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  • 耐糖能別にみた収縮期血圧が透析導入に及ぼす影響の検討

    古谷 篤, 藤原 和哉, 五十嵐 理沙, 山本 正彦, 石澤 正博, 松林 泰弘, 松永 佐澄志, 加藤 公則, 伊藤 知恵, 小石 美恵子, 山中 菜詩, 児玉 暁, 曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 287   2017.4

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  • 糖尿病の詳細な家族歴が2型糖尿病発症リスクに与える影響の定量的検討

    五十嵐 理沙, 藤原 和哉, 治田 麻理子, 押鐘 芳恵, 松林 泰弘, 斎藤 和美, 児玉 暁, 本田 律子, 荒瀬 康司, 曽根 博仁

    糖尿病   60 ( Suppl.1 )   S - 281   2017.4

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  • LiraglutideとSGLT2阻害薬の併用による体重および血糖への効果の検討

    小川 真弓, 樋詰 友香, 高橋 直穂, 木村 祐之, 大内 基司, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   60 ( Suppl.1 )   S - 401   2017.4

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  • 健常女性における思春期のやせの要因解明および予防プログラムの構築の検討

    谷内 洋子, 広瀬 歩美, 平澤 玲子, 児玉 暁, 曽根 博仁

    千葉県立保健医療大学紀要   8 ( 1 )   101 - 101   2017.3

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  • 移植後長期フォローアップにおける再発の早期発見を目的とした末梢血STR法の有用性

    海發茜, 柴崎康彦, 中村岳史, 椎谷恵子, 和田玲子, 田村秀, 鈴木隆晴, 上村駿, 片桐隆幸, 根元洋樹, 小林弘典, 布施香子, 牛木隆志, 森山雅人, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   39th   252   2017.2

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  • 同種造血幹細胞移植において生着後早期の免疫再構築はドナーソースや移植法により異なる

    上村駿, 柴崎康彦, 片桐隆幸, 井藤ヒロミ, 海發茜, 田村秀, 鈴木隆晴, 根本洋樹, 小林弘典, 布施香子, 牛木隆志, 森山雅人, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   39th   237   2017.2

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  • 樹木構造接近法を用いた急性白血病,骨髄異形成症候群に対する造血細胞移植後の予後因子の解析

    布施香子, 上村駿, 海發茜, 鈴木隆晴, 田村秀, 片桐隆幸, 根本洋樹, 小林弘典, 牛木隆志, 柴崎康彦, 森山雅人, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   39th   247   2017.2

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  • 糖尿病患者の家族に対する教育が患者血糖に及ぼす効果のメタ分析

    児玉 暁, 藤原 和哉, 山本 正彦, 石澤 正博, 石黒 創, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 加藤 公則, 曽根 博仁

    日本内科学会雑誌   106 ( Suppl. )   211 - 211   2017.2

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  • 糖尿病患者の家族に対する教育が患者血糖に及ぼす効果のメタ分析

    児玉 暁, 藤原 和哉, 山本 正彦, 石澤 正博, 石黒 創, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 加藤 公則, 曽根 博仁

    日本内科学会雑誌   106 ( Suppl. )   211 - 211   2017.2

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  • 日本人男女における2型糖尿病発症予測のためのBMIおよびウエスト周囲径(WC)閾値の検討:NIWELLS

    五十嵐理沙, 藤原和哉, 藤原和哉, 平安座依子, 平安座依子, 石澤正博, 鶴田恵, 治田麻理子, 治田麻理子, 由澤咲子, 堀川千嘉, 堀川千嘉, 松永佐澄志, 羽入修, 児玉暁, 児玉暁, 佐藤幸示, 加藤公則, 加藤公則, 曽根博仁

    日本疫学会学術総会講演集(Web)   27th   74 (WEB ONLY)   2017.1

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  • 抗CCR4抗体併用化学療法による寛解後の臍帯血移植が奏効した成人T細胞白血病リンパ腫

    諏訪部 達也, 柴崎 康彦, 海發 茜, 片桐 隆幸, 宮腰 淑子, 布施 香子, 小林 弘典, 牛木 隆志, 森山 雅人, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   58 ( 1 )   32 - 36   2017.1

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    症例は成人T細胞白血病/リンパ腫(ATLL)急性型の62歳男性。CHOP療法単独では治療抵抗性であったが,抗CCR4抗体mogamulizumab併用CHOP療法が奏効し寛解を得た。HLA一致血縁・非血縁ドナーが得られず,mogamulizumab最終投与後71日目に骨髄非破壊的前処置を用いた臍帯血移植を施行した。急性移植片対宿主病(GVHD)grade II(皮膚stage2)を発症したが,methylprednisolone投与により制御可能であり,移植後9ヵ月時点まで寛解を維持している。経過中,制御性T細胞(Treg)は著減したままの状態であった。同種造血幹細胞移植はATLLの根治的治療であるが,移植前にmogamulizumabを使用する際,Tregの減少による急性GVHDの発症頻度・重症度が増加する可能性が報告されている。寛解期移植を目指すためにmogamulizumabを使用せざるを得ない症例における至適なドナーソースや移植時期,GVHD予防法に関して,更なる症例の蓄積が望まれる。(著者抄録)

    DOI: 10.11406/rinketsu.58.32

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  • 【これからの高トリグリセライド(TG)血症治療】 リスクとしての高TG血症 疫学研究からみた高TG血症の意義

    山田 貴穂, 曽根 博仁

    The Lipid   28 ( 1 )   11 - 18   2017.1

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    動脈硬化性心血管疾患は、LDL低下治療だけではまだ完全に防止できず、その「残存リスク」への介入が今後の課題である。近年の疫学研究から、トリグリセライド(TG)もそのひとつであることが判明しており、特に非空腹時TG値と心血管疾患との関連が注目されている。高TG血症の背景のひとつにはインスリン抵抗性があるため、肥満の有無にかかわらず、将来、耐糖能異常の発症も危惧される。また、2型糖尿病患者では心血管疾患(大血管障害)予防のため、両病態の根底にあるインスリン抵抗性改善が重要と考えられる。(著者抄録)

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  • 当院における抗MRSA薬の薬剤感受性推移と測定法による影響

    横山 和弘, 草間 文子, 小林 めぐみ, 吉田 彩, 近藤 千草, 古川 久美子, 町田 良子, 高野 操, 茂呂 寛, 松戸 隆之, 曽根 博仁

    新潟医学会雑誌   131 ( 1 )   58 - 59   2017.1

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    Other Link: http://search.jamas.or.jp/link/ui/2017250972

  • 同種造血細胞移植後の免疫再構築に関与する因子の同定および、それらの因子を用いた予後予測モデルの構築

    柴崎 康彦, 曽根 博仁, 増子 正義

    新潟県医師会報   ( 802 )   9 - 10   2017.1

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  • 医療ビッグデータとしての臨床検査データの利活用 糖尿病を中心とした生活習慣病分野を例に

    曽根 博仁

    生物試料分析   40 ( 1 )   7 - 7   2017.1

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  • 生活習慣への介入と合併症進展予防 糖尿病における生活習慣と心血管イベント予防 JDCS研究から

    曽根 博仁

    Diabetes Update   6 ( 1 )   50 - 51   2017.1

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  • 働き盛り世代男性における耐糖能の冠動脈疾患発症への影響の検討

    藤原 和哉, 五十嵐 理沙, 山本 正彦, 石澤 正博, 松林 泰弘, 松永 佐澄志, 加藤 公則, 伊藤 知恵, 小石 美恵子, 山中 菜詩, 児玉 暁, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   43   79 - 79   2017.1

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  • 科学的エビデンスに基づく運動療法と指導 共生社会実現を目指して

    曽根 博仁

    日本障害者スポーツ学会誌   ( 25 )   14 - 14   2017.1

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  • 破壊性甲状腺炎をともなったMYC転座陽性甲状腺悪性リンパ腫の1例

    山田 貴穂, 布施 香子, 柴崎 康彦, 河本 啓介, 羽入 修, 瀧澤 淳, 大島 孝一, 曽根 博仁

    日本内分泌学会雑誌   92 ( 3 )   635 - 635   2017.1

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  • 甲状腺全摘術後に腎細胞癌の甲状腺転移が判明した腺腫様甲状腺腫合併T3優位型Basedow病の一例

    羽入 修, 山田 貴穂, 金子 正儀, 松林 泰弘, 松永 佐澄志, 藤原 和哉, 岩永 みどり, 伊藤 崇子, 鈴木 亜希子, 曽根 博仁

    日本内分泌学会雑誌   92 ( 3 )   638 - 638   2017.1

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  • 糖尿病専門医の治療を受ける2型糖尿病患者の食事摂取状態の実態と時代的変遷~JDDMによる報告~(第二報)

    武田安永, 堀川千嘉, 堀川千嘉, 鶴田恵, 藤原和哉, 由澤咲子, 五十嵐理沙, 治田麻理子, 石井大, 加藤光敏, 横山宏樹, 栗原義夫, 宮澤一裕, 岩崎皓一, 川井紘一, 朝長修, 屋宜宣治, 前川聡, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.244(J‐STAGE)   2017

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  • FHHとPHPTの鑑別に苦慮している一例

    棚橋怜生, 山本正彦, 松林泰弘, 張かおり, 佐藤陽子, 松永佐澄志, 岩永みどり, 山田貴穂, 藤原和哉, 曽根博仁

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   18th   78   2017

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  • Comprehensive Risk Management for the Prevention of CerebroCardiovascular Diseases in Japan

    Tamio Teramoto, Masayuki Yokode, Hiroyasu Iso, Akihiko Kitamura, Hiroki Shiomi, Tsuyoshi Kimura, Masayasu Matsumoto, Mami Iida, Jun Sasaki, Shigeru Inoue, Ryouichi Nagatomi, Tetsuo Shoji, Hidenori Arai, Hiromi Rakugi, Hirohito Sone, Shizuya Yamashita, Shigeru Miyazaki

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   24 ( 7 )   749 - 760   2017

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    DOI: 10.5551/jat.CR001

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  • わが国の糖尿病専門医の薬物療法における処方と患者背景の解析(第3報)

    藤原和哉, 五十嵐理沙, 松永佐澄志, 松林泰弘, 山田貴穂, 横山宏樹, 田中司朗, 島野仁, 前川聡, 山崎勝也, 川井紘一, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.457(J‐STAGE)   2017

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  • トホグリフロジン(TOFO)長期投与が遊離脂肪酸及び脂肪細胞インスリン抵抗性に与える影響の検討

    松林泰弘, 吉田明弘, 吉田明弘, 田中司郎, 菅波秀規, 阿部孝洋, 山本正彦, 大澤妙子, 松永佐澄志, 藤原和哉, 加来浩平, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.491(J‐STAGE)   2017

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  • 小児期の運動能力と心血管リスクに関する検討

    柴田健継, 松永佐澄志, 五十嵐理沙, 由澤咲子, 古川和郎, 山田貴穂, 藤原和哉, 曽根博仁

    糖尿病(Web)   60 ( Suppl )   S.364(J‐STAGE)   2017

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  • 機械学習を用いた急性白血病における造血幹細胞移植後の患者ベースの再発予測モデルと個別化治療への応用

    布施香子, 上村駿, 諏訪部達也, 片桐隆幸, 笠見卓哉, 田中智之, 難波亜矢子, 牛木隆志, 柴崎康彦, 柴崎康彦, 佐藤直子, 矢野敏雄, 黒羽高志, 橋本誠雄, 古川達雄, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   40th   2017

  • 妊娠初期HbA1c値および空腹時血糖値と妊娠糖尿病発症予測能の検討〈TWC Study〉

    谷内洋子, 谷内洋子, 田中康弘, 広瀬歩美, 広瀬歩美, 伊部陽子, 藤原和哉, 曽根博仁

    New Diet Therapy   33 ( 2 )   2017

  • その他の合併症への対応 Q-27 妊娠糖尿病や糖尿病合併妊娠では,何を食事療法の評価指標とし,どのような指導・管理をすればよいでしょうか?

    谷内洋子, 曽根博仁

    臨床栄養   2017

  • The Predictive Factors of Favorable Prognosis after Allo-HSCT for Refractory Acute Leukemia

    Kyoko Fuse, Takayuki Katagiri, Yasuhiko Shibasaki, Tomoyuki Tanaka, Miwako Narita, Hirohito Sone, Masayoshi Masuko, Tatsuo Furukawa, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Takashi Ushiki

    BLOOD   128 ( 22 )   2016.12

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    DOI: 10.1182/blood.V128.22.2297.2297

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  • Evaluation of Liver Iron Deposition in Transfusion-Dependent Patients By Dual-Energy CT

    Hironori Kobayashi, Norihiko Yoshimura, Takayuki Katagiri, Takashi Ushiki, Kyoko Fuse, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    BLOOD   128 ( 22 )   2016.12

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    DOI: 10.1182/blood.V128.22.3619.3619

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  • 診断に難渋した褐色細胞腫の1例

    横川 かおり, 佐藤 陽子, 金子 正儀, 棚橋 怜生, 山本 正彦, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 羽入 修, 曽根 博仁

    新潟医学会雑誌   130 ( 12 )   714 - 714   2016.12

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  • 臨床研究の進め方 ビッグデータの活用と解析 医療ビッグデータの病態栄養学研究への活用

    曽根 博仁

    日本病態栄養学会誌   20 ( Suppl. )   S - 62   2016.12

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  • 2型糖尿病患者の代謝指標と食事摂取状況の変化 2年間の追跡調査

    鶴田 恵, 飯塚 つかさ, 近藤 桜香, 小野 康子, 米岡 裕美, 藤原 和哉, 金胎 芳子, 山谷 恵一, 曽根 博仁

    日本病態栄養学会誌   20 ( Suppl. )   S - 97   2016.12

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  • 炭水化物摂取比率は、日本人2型糖尿病患者の合併症発症リスクに関連するか? JDCSによる報告

    堀川 千嘉, 鎌田 智恵実, 奥村 亮太, 田中 司朗, 田中 佐智子, 井藤 英喜, 赤沼 安夫, 吉村 幸雄, 曽根 博仁

    日本病態栄養学会誌   20 ( Suppl. )   S - 70   2016.12

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  • 2型糖尿病患者の代謝指標と食事摂取状況の変化 2年間の追跡調査

    鶴田 恵, 飯塚 つかさ, 近藤 桜香, 小野 康子, 米岡 裕美, 藤原 和哉, 金胎 芳子, 山谷 恵一, 曽根 博仁

    日本病態栄養学会誌   20 ( Suppl. )   S - 97   2016.12

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  • 炭水化物摂取比率は、日本人2型糖尿病患者の合併症発症リスクに関連するか? JDCSによる報告

    堀川 千嘉, 鎌田 智恵実, 奥村 亮太, 田中 司朗, 田中 佐智子, 井藤 英喜, 赤沼 安夫, 吉村 幸雄, 曽根 博仁

    日本病態栄養学会誌   20 ( Suppl. )   S - 70   2016.12

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  • 臨床研究の進め方 ビッグデータの活用と解析 医療ビッグデータの病態栄養学研究への活用

    曽根 博仁

    日本病態栄養学会誌   20 ( Suppl. )   S - 62   2016.12

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  • 診断に難渋した褐色細胞腫の1例

    横川 かおり, 佐藤 陽子, 金子 正儀, 棚橋 怜生, 山本 正彦, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 羽入 修, 曽根 博仁

    新潟医学会雑誌   130 ( 12 )   714 - 714   2016.12

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  • 無症候性褐色細胞腫の一例

    横川 かおり, 佐藤 陽子, 金子 正儀, 棚橋 怜生, 山本 正彦, 松林 泰弘, 松永 佐澄志, 岩永 みどり, 山田 貴穂, 藤原 和哉, 羽生 修, 曽根 博仁, 山名 一寿, 田崎 正行

    日本内分泌学会雑誌   92 ( S.Branc )   111 - 111   2016.12

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  • 当科におけるPTCL、NOS 28例の臨床病理学的解析

    鈴木 隆晴, 田村 秀, 上村 俊, 海發 茜, 河本 啓介, 根本 洋樹, 小林 弘典, 牛木 隆志, 布施 香子, 柴崎 康彦, 森山 雅人, 増子 正義, 成田 美和子, 曽根 博仁, 青木 定夫, 中村 直哉, 大島 孝一, 瀧澤 淳

    臨床血液   57 ( 11 )   2426 - 2426   2016.11

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  • 当科におけるPTCL、NOS 28例の臨床病理学的解析

    鈴木 隆晴, 田村 秀, 上村 俊, 海發 茜, 河本 啓介, 根本 洋樹, 小林 弘典, 牛木 隆志, 布施 香子, 柴崎 康彦, 森山 雅人, 増子 正義, 成田 美和子, 曽根 博仁, 青木 定夫, 中村 直哉, 大島 孝一, 瀧澤 淳

    臨床血液   57 ( 11 )   2426 - 2426   2016.11

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  • 多発血栓を来したTAFRO症候群の1例

    上村 駿, 小林 弘典, 田村 秀, 鈴木 隆晴, 海發 茜, 河本 啓介, 笠見 卓哉, 根本 洋樹, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 大島 孝一, 瀧澤 淳

    臨床血液   57 ( 11 )   2423 - 2423   2016.11

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  • HLA半合致移植を施行した最重症再生不良性貧血の1例

    宮腰 淑子, 柴崎 康彦, 諏訪部 達也, 片桐 隆幸, 小林 弘典, 布施 香子, 森山 雅人, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   57 ( 11 )   2416 - 2416   2016.11

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  • 扁桃・リンパ節に多発性myeloid sarcomaを生じたMDSの1例

    片桐 隆幸, 牛木 隆志, 田中 智之, 宮腰 淑子, 難波 亜矢子, 河本 啓介, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 青木 定夫, 増子 正義

    臨床血液   57 ( 11 )   2415 - 2415   2016.11

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  • 糖尿病患者の脂質はどのようにコントロールするのか

    矢部 大介, 岡崎 啓明, 曽根 博仁, 平野 勉, 高瀬 暁, 藤原 和哉, 山田 穂高

    Diabetes Strategy   6 ( 4 )   151 - 168   2016.11

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    Other Link: http://search.jamas.or.jp/link/ui/2017082741

  • 扁桃・リンパ節に多発性myeloid sarcomaを生じたMDSの1例

    片桐 隆幸, 牛木 隆志, 田中 智之, 宮腰 淑子, 難波 亜矢子, 河本 啓介, 柴崎 康彦, 瀧澤 淳, 成田 美和子, 曽根 博仁, 青木 定夫, 増子 正義

    臨床血液   57 ( 11 )   2415 - 2415   2016.11

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  • HLA半合致移植を施行した最重症再生不良性貧血の1例

    宮腰 淑子, 柴崎 康彦, 諏訪部 達也, 片桐 隆幸, 小林 弘典, 布施 香子, 森山 雅人, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   57 ( 11 )   2416 - 2416   2016.11

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  • 多発血栓を来したTAFRO症候群の1例

    上村 駿, 小林 弘典, 田村 秀, 鈴木 隆晴, 海發 茜, 河本 啓介, 笠見 卓哉, 根本 洋樹, 布施 香子, 柴崎 康彦, 増子 正義, 曽根 博仁, 大島 孝一, 瀧澤 淳

    臨床血液   57 ( 11 )   2423 - 2423   2016.11

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  • 大動脈弁狭窄症を合併した閉塞性肥大型心筋症に対するPTSMAの一例

    齋藤 優紀, 中坊 亜由美, 加藤 靖彦, 星山 良樹, 松戸 隆之, 尾崎 和幸, 曽根 博仁, 南野 徹

    日臨技北日本支部医学検査学会抄録集   5回   107 - 107   2016.10

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  • 大規模臨床データ解析が開く新しい糖尿病合併症学

    曽根 博仁

    糖尿病合併症   30 ( Suppl.1 )   95 - 95   2016.9

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  • 糖尿病重症視力障害発症とHbA1cの関連性についての検討

    山本 正彦, 藤原 和哉, 五十嵐 理沙, 石澤 正博, 松林 泰弘, 松永 佐澄志, 伊藤 知恵, 錦野 理絵, 山中 菜詩, 児玉 暁, 曽根 博仁

    糖尿病合併症   30 ( Suppl.1 )   251 - 251   2016.9

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  • 生活習慣への介入と合併症進展予防 生活習慣と糖尿病合併症 大規模臨床研究のエビデンス

    曽根 博仁

    糖尿病合併症   30 ( Suppl.1 )   131 - 131   2016.9

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  • 日本人の食事摂取基準(2015年版)の概要

    平澤 玲子, 曽根 博仁

    内分泌・糖尿病・代謝内科   43 ( 3 )   231 - 236   2016.9

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    Other Link: http://search.jamas.or.jp/link/ui/2017006851

  • EMPA-REG OUTCOME studyから学ぶこと、残した課題

    古川 和郎, 藤原 和哉, 曽根 博仁

    Diabetes Journal: 糖尿病と代謝   44 ( 3 )   120 - 123   2016.9

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  • ネットワークメタ分析を用いた肥満外科手術による糖尿病寛解効果の検討

    児玉 暁, 加藤 公則, 曽根 博仁

    肥満研究   22 ( Suppl. )   181 - 181   2016.9

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  • Distance between dietary intake and self-rated dietary behavior in patients with diabetes: analysis from National Health and Nutrition survey in Japan

    C. Horikawa, N. Murayama, M. Tsumta, Y. Oshikane, R. Hiasawa, Y. Yachi, K. Fujihara, O. Hanyu, H. Sone

    DIABETOLOGIA   59   S336 - S336   2016.8

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  • Impact of glucose tolerance status on development of coronary artery disease among working aged men in Japan

    K. Fujihara, N. Yamanaka, R. Nishikino, M. Yamamoto, Y. Matsubayashi, S. Matsunaga, T. Yamada, H. Ishiguro, C. Horikawa, M. Ishizawa, N. Ohara, K. Kato, H. Sone

    DIABETOLOGIA   59   S514 - S515   2016.8

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  • Meta-analysis of improvement in glycaemic control by family intervention in patients with diabetes

    M. Tsuruta, S. Kodama, K. Hujihara, H. Ishiguro, R. Igarashi, M. Yamamoto, M. Ishizawa, C. Horikawa, S. Yoshizawa, H. Sone

    DIABETOLOGIA   59   S397 - S398   2016.8

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  • PCNSL寛解後12年を経て発症した副鼻腔DLBCLで、繰り返す皮膚再発に対して少量経口エトポシド療法が有効であった1症例

    田村 秀, 大橋 瑠子, 梅津 哉, 諏訪部 達也, 片桐 隆幸, 河本 啓介, 宮腰 淑子, 北嶋 俊樹, 柴崎 康彦, 曽根 博仁, 青木 洋, 大島 孝一, 瀧澤 淳

    日本リンパ網内系学会会誌   56   98 - 98   2016.8

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  • 当科におけるIVLBCL 14例の臨床病理学的検討

    諏訪部 達也, 河本 啓介, 片桐 隆幸, 宮腰 淑子, 小林 弘典, 牛木 隆志, 布施 香子, 柴崎 康彦, 森山 雅人, 増子 正義, 成田 美和子, 曽根 博仁, 瀧澤 淳, 中村 直哉, 大島 孝一

    日本リンパ網内系学会会誌   56   92 - 92   2016.8

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  • 高血糖を放置した結果、巨大後腹膜膿瘍を発症した1例

    田村 秀, 石澤 正博, 福武 嶺一, 吉岡 大志, 阿部 孝洋, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 鈴木 亜希子, 羽入 修, 曽根 博仁

    糖尿病   59 ( 8 )   599 - 599   2016.8

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  • 高血糖を放置した結果,巨大後腹膜膿瘍を発症した1例

    田村秀, 石澤正博, 福武嶺一, 吉岡大志, 阿部孝洋, 松林泰弘, 松永佐澄志, 山田貴穂, 鈴木亜希子, 羽入修, 曽根博仁

    糖尿病(Web)   59 ( 8 )   599(J‐STAGE) - 599   2016.8

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  • 【糖尿病神経障害の早期診断と薬物療法】 糖尿病神経障害の特殊な病型、病態 糖尿病神経障害と睡眠時無呼吸症候群

    松林 泰弘, 曽根 博仁

    月刊糖尿病   8 ( 8 )   67 - 71   2016.8

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    Other Link: http://search.jamas.or.jp/link/ui/2016309016

  • 【糖尿病の遺伝素因の解明研究】 遺伝素因と環境素因の相互作用 糖尿病罹患体質への食生活と運動の影響 疫学的解析から

    児玉 暁, 曽根 博仁

    Diabetes Frontier   27 ( 4 )   448 - 455   2016.8

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  • 新指標「握力体重比」は糖尿病発症を予測できる

    加藤 公則, 門間 陽樹, 小林 篤子, 小林 隆司, 田代 稔, 佐藤 幸示, 北川 寛, 笹川 力, 澤田 亨, 曽根 博仁

    人間ドック   31 ( 2 )   234 - 234   2016.7

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  • 【糖尿病診療における心血管合併症の診かたup to date】 糖尿病患者における冠動脈疾患、大動脈・末梢動脈疾患のマネジメント 糖尿病内科医の立場から

    藤原 和哉, 松永 佐澄志, 曽根 博仁

    月刊糖尿病   8 ( 7 )   19 - 29   2016.7

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  • 血漿中マイクロパーティクルの凝固活性を指標としたクロスミキシングテスト用正常血漿の評価

    松田 将門, 森山 雅人, 鈴木 健史, 小宮山 豊, 末武 司, 松戸 隆之, 高野 操, 曽根 博仁

    日本検査血液学会雑誌   17 ( 学術集会 )   S150 - S150   2016.7

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  • 【糖尿病の大血管症-疫学・現況・最新知見-】 糖尿病患者における大血管症の疫学と大規模臨床試験

    藤原 和哉, 曽根 博仁

    プラクティス   33 ( 4 )   412 - 420   2016.7

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  • 体力測定と心房細動発症の関連について

    加藤 公則, 小林 篤子, 小林 隆司, 田代 稔, 佐藤 幸示, 北川 寛, 笹川 力, 丸藤 祐子, 澤田 亨, 曽根 博仁

    人間ドック   31 ( 2 )   328 - 328   2016.7

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  • Is Carbohydrate Intake Associated with the Incidence of Diabetes Complications? Japan Diabetes Complication Study (JDCS)

    Chika Horikawa, Yukio Yoshimura, Chiemi Kamada, Shiro Tanaka, Sachiko Tanaka, Osamu Hanyu, Atsushi Araki, Hideki Ito, Akira Tanaka, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

    DIABETES   65   A198 - A198   2016.6

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  • Association of Physical Activity and Neighborhood Environment in Japanese Patients with Type 2 Diabetes: An Observational Study in Multiple Institutes across Japan (JDDM)

    Sakiko Yoshizawa, Kazuya Fujihara, Yoriko Heianza, Megumi Tsuruta, Kiminori Kato, Satoshi Matsunaga, Satoru Kodama, Osamu Hanyu, Koichi Kawai, Yoshio Kurihara, Satoshi Maekawa, Hirohito Sone

    DIABETES   65   A186 - A186   2016.6

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  • Impact of SGLT2 Inhibitor Tofogliflozin on Hyperinsulinemia and Fatty Liver (FL) through Hepatic Insulin Clearance (HIC) in Patients with Type 2 Diabetes Mellitus (T2DM)

    Yasuhiro Matsubayashi, Hideki Suganami, Kohei Kaku, Hirohito Sone

    DIABETES   65   A300 - A300   2016.6

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  • 【糖尿病治療における食事療法の課題と展望-新たなエビデンスに基づいた食事療法】 食事療法のエビデンス

    堀川 千嘉, 曽根 博仁

    カレントテラピー   34 ( 6 )   530 - 535   2016.6

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  • 包括的リスク管理とJASガイドライン 脳・心血管疾患高リスク者としての糖尿病患者への対応

    曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   48回   147 - 147   2016.6

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  • 副腎腫瘍におけるFDG-PET CTの有用性 当科での2症例をふまえて

    矢口 雄大, 川田 亮, 種村 聡, 佐藤 陽子, 松林 泰弘, 松永 佐登志, 藤原 和哉, 山田 貴穂, 鈴木 亜希子, 羽入 修, 曽根 博仁

    新潟医学会雑誌   130 ( 6 )   376 - 376   2016.6

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    Other Link: http://search.jamas.or.jp/link/ui/2017051751

  • 地域医療 オール新潟体制で作成した「糖尿病患者向けテキスト」のご紹介

    五十嵐 智雄, 阿部 孝洋, 北澤 勝, 曽根 博仁

    新潟県医師会報   ( 795 )   16 - 18   2016.6

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  • 抗CCR4抗体併用化学療法により寛解が得られた後に、臍帯血移植を行ったATLLの1例

    諏訪部 達也, 柴崎 康彦, 片桐 隆幸, 宮腰 淑子, 布施 香子, 小林 弘典, 牛木 隆志, 森山 雅人, 瀧澤 淳, 成田 美和子, 曽根 博仁, 増子 正義

    臨床血液   57 ( 6 )   776 - 776   2016.6

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  • 糖尿病合併症の疫学と最新の診断法について 大血管症の疫学と診断、リスク評価

    曽根 博仁

    糖尿病合併症   30 ( 1 )   51 - 57   2016.6

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  • 【糖尿病対策の先進的な取り組み】 地域包括糖尿病総合対策 新潟県魚沼地域Project8

    加藤 公則, 上村 伯人, 布施 克也, 高村 誠, 曽根 博仁

    内分泌・糖尿病・代謝内科   42 ( 6 )   431 - 437   2016.6

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    Other Link: http://search.jamas.or.jp/link/ui/2016291667

  • 経皮的中隔心筋焼灼術を施行した閉塞性肥大型心筋症の1例

    小林 紘子, 中坊 亜由美, 伊藤 正行, 水野 幸子, 加藤 靖彦, 高野 操, 松戸 隆之, 尾崎 和幸, 曽根 博仁, 南野 徹

    超音波検査技術   41 ( Suppl. )   S143 - S143   2016.6

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    DOI: 10.11272/jssabst.41.0_S143_1

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  • 脳心血管病予防に関する包括的リスク管理チャート

    羽入 修, 曽根 博仁

    内分泌・糖尿病・代謝内科   42 ( 6 )   480 - 484   2016.6

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  • 【スポーツ・運動療法は患者治療にどこまで有効か】 糖尿病、高血圧、脂質異常症と運動療法・スポーツ

    石黒 創, 曽根 博仁

    成人病と生活習慣病   46 ( 6 )   709 - 712   2016.6

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    糖尿病をはじめとした生活習慣病の患者は増大している。多くのガイドラインにて、運動療法は中程度の運動を1日30分以上、週3日以上が推奨されている。有酸素運動、無酸素運動ともに糖尿病患者において血糖値の改善効果が報告されており、両者を組み合わせるとより効果的である。有酸素運動および無酸素運動単独でも血糖改善効果は認められる。有酸素運動の方が無酸素運動よりも一般的に血糖改善効果は高い。一方で無酸素運動では、罹病期間が短い患者や過度の肥満がない患者において、よりHbA1cの改善率が高いことが報告されている。日本人糖尿病患者において、毎日30分以上の中程度の運動をすることは脳卒中や総死亡を減少させるエビデンスがある。高血圧症および脂質異常症に関しては、有酸素運動がより推奨される。高度の糖尿病合併症がある患者や重症高血圧患者、心肺機能に異常のある患者においては、運動療法は禁忌もしくは慎重に行う必要がある。(著者抄録)

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  • 食事療法のエビデンス

    堀川 千嘉, 曽根 博仁

    カレントテラピー   34 ( 6 )   20 - 25   2016.6

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  • THE PRE-TRANSPLANT BIOMARKER RISK INDEX BASED ON SERUM FERRITIN, ALBUMIN AND CRP CAN PREDICT OUTCOMES INDEPENDENTLY OF THE HCT-CI AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

    T. Suwabe, Y. Shibasaki, T. Katagiri, S. Miyakoshi, H. Kobayashi, K. Fuse, T. Ushiki, N. Sato, T. Yano, T. Kuroha, S. Hashimoto, M. Narita, H. Sone, T. Furukawa, M. Masuko

    HAEMATOLOGICA   101   289 - 290   2016.6

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  • Sedentary Behavior, Physical Activity and Kidney Stones: The Niigata Wellness Study

    Yuko Gando, Susumu S. Sawada, Ryoko Kawakami, Ryosuke Ando, Minoru Tashiro, Hirohito Sone, I-Min Lee, Steven N. Blair, Motohiko Miyachi, Kiminori Kato

    MEDICINE AND SCIENCE IN SPORTS AND EXERCISE   48 ( 5 )   226 - 226   2016.5

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    DOI: 10.1249/01.mss.0000485679.04195.cb

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  • Splenomegaly and thrombosis risk in essential thrombocythemia: the mayo clinic experience

    Yasuhiko Shibasaki, Takayuki Katagiri, Hironori Kobayashi, Takashi Ushiki, Miwako Narita, Hirohito Sone, Tatsuo Furukawa, Masayoshi Masuko

    AMERICAN JOURNAL OF HEMATOLOGY   91 ( 5 )   E296 - E296   2016.5

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    DOI: 10.1002/ajh.24334

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  • 【職域と糖尿病】 職域における糖尿病運動療法とその指導 大規模データ分析によるエビデンスを中心に

    曽根 博仁

    成人病と生活習慣病   46 ( 5 )   569 - 575   2016.5

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    職域における糖尿病の発症と重症化の予防は、退職者も含む国民全体の健康寿命延伸に大きな影響力を有する。運動とその指導は、代表的な生活習慣病である2型糖尿病の発症ならびに重症化抑制効果を有することが示されている。しかし、人材・施設不足や健康保険がカバーしていないことなどにより、保健指導や診療の現場では十分に指導・実施がなされていない。近年増加している大規模臨床研究のエビデンスに基づいた運動指導により、患者が運動を開始・継続できるようにサポートしていくことは、患者の健康寿命の延伸とともに、国民医療費抑制の観点からも重要である。(著者抄録)

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  • 【新時代の臨床糖尿病学(下)-より良い血糖管理をめざして-】 糖尿病合併症総論 日本人の糖尿病大血管症の特徴

    金子 正儀, 古川 和郎, 曽根 博仁

    日本臨床   74 ( 増刊2 新時代の臨床糖尿病学(下) )   22 - 26   2016.4

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  • 男女別にみた日本人の2型糖尿病発症予測のためのBMIおよびウエスト周囲径(WC)のカットポイントの検討

    五十嵐理沙, 藤原和哉, 平安座依子, 石澤正博, 鶴田恵, 治田麻理子, 治田麻理子, 由澤咲子, 堀川千嘉, 堀川千嘉, 松永佐澄志, 羽入修, 児玉暁, 佐藤幸示, 加藤公則, 加藤公則, 曽根博仁

    糖尿病(Web)   59 ( Suppl )   S.154(J‐STAGE) - 154   2016.4

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  • 耐糖能と骨密度の関連—健診データの縦断的解析

    石澤正博, 石澤正博, 藤原和哉, 田代稔, 松永佐澄志, 加藤公則, 鈴木亜希子, 山田貴穂, 羽入修, 曽根博仁

    糖尿病(Web)   59 ( Suppl )   S.340(J‐STAGE) - 340   2016.4

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  • わが国の糖尿病専門医の薬物療法における処方と患者背景の解析(第2報)

    藤原 和哉, 羽入 修, 松永 佐澄志, 松林 泰弘, 鈴木 亜希子, 山田 貴穂, 横山 宏樹, 島野 仁, 前川 聡, 山崎 勝也, 川井 紘一, 曽根 博仁, JDDMデータマネジメント研究会

    糖尿病   59 ( Suppl.1 )   S - 452   2016.4

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  • 日本人2型糖尿病における野菜・果物摂取量と糖尿病網膜症および心血管疾患発症の関連 Japan Diabetes Complications Study

    田中 司朗, 吉村 幸雄, 鎌田 智英美, 川崎 良, 堀川 千嘉, 田中 佐智子, 大橋 靖雄, 荒木 厚, 井藤 英喜, 赤沼 安夫, 山田 信博, 山下 英俊, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 443   2016.4

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  • 【肥満を伴う2型糖尿病のマネジメント】 日本における肥満2型糖尿病の疫学

    川田 亮, 曽根 博仁

    月刊糖尿病   8 ( 4 )   12 - 19   2016.4

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  • 糖尿病専門外来に通院する2型糖尿病患者の食事摂取状況の把握 JDDMからの報告

    鶴田 恵, 堀川 千嘉, 藤原 和哉, 平安座 依子, 由澤 咲子, 五十嵐 理沙, 治田 麻理子, 加藤 光敏, 加藤 則子, 横山 宏樹, 栗原 義夫, 岩崎 皓一, 宮澤 一裕, 朝長 修, 屋宜 宣治, 川井 紘一, 前川 聡, 曽根 博仁, 糖尿病データマネジメント研究会

    糖尿病   59 ( Suppl.1 )   S - 458   2016.4

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  • FDG-PET CTを施行された副腎腫瘍の2例

    矢口 雄大, 川田 亮, 種村 聡, 佐藤 陽子, 松林 泰弘, 松永 佐登志, 藤原 和哉, 山田 貴穂, 鈴木 亜希子, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   92 ( 1 )   324 - 324   2016.4

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  • インスリン自己免疫症候群にインスリン受容体異常症B型を合併した一例

    阿部 孝洋, 福武 嶺一, 吉岡 大志, 石澤 正博, 松林 泰弘, 鈴木 亜希子, 山田 貴穂, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   92 ( 1 )   308 - 308   2016.4

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  • 肝インスリンクリアランス(Hepatic C-peptide/Insulin比)の臨床的意義の検討 空腹時及び食後での評価と病態との関連

    松林 泰弘, 菅波 秀規, 加来 浩平, 曽根 博仁

    日本内分泌学会雑誌   92 ( 1 )   245 - 245   2016.4

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  • 三系統(PRL、ACTH、GH)のホルモン過剰分泌が疑われた微小下垂体腺腫の1例

    佐藤 陽子, 種村 聡, 松林 泰弘, 山田 貴穂, 鈴木 亜希子, 藤原 和哉, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   92 ( 1 )   233 - 233   2016.4

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  • 食品群からみた2型糖尿病患者の食事摂取状況と国際比較

    鶴田 恵, 堀川 千嘉, 藤原 和哉, 平安座 依子, 由澤 咲子, 五十嵐 理沙, 治田 麻理子, 伊部 陽子, 平澤 玲子, 前川 聡, 曽根 博仁, 糖尿病データマネジメント研究会

    日本栄養・食糧学会大会講演要旨集   70回   196 - 196   2016.4

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  • 糖尿病の有無で食事摂取状況や食行動は異なるか 平成22年国民健康・栄養調査の解析

    堀川 千嘉, 村山 伸子, 鶴田 恵, 押鐘 芳恵, 平澤 玲子, 谷内 洋子, 羽入 修, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   70回   210 - 210   2016.4

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  • リラグルチド中止例の特徴の探索 継続例との比較より

    中井 伸江, 畑中 麻梨恵, 高橋 直穂, 木村 祐之, 大内 基司, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   59 ( Suppl.1 )   S - 221   2016.4

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  • 癌の新規発見におけるスクリーニングと先行症状の比較

    加藤 昭二, 友重 栄美, 中村 公英, 曽根 博仁, 山田 大志郎, 首藤 龍人, 本庄 潤, 清水 平, 大内 基司, 木村 祐之, 横山 宏樹

    糖尿病   59 ( Suppl.1 )   S - 189   2016.4

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  • 糖尿病合併症発症に対する血糖、血圧、脂質の影響についての検討 JDCSサブ解析

    松永 佐澄志, 田中 司朗, 堀川 千嘉, 羽入 修, 荒木 厚, 守屋 達美, 大橋 靖雄, 赤沼 安夫, 山田 信博, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 151   2016.4

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  • 最新エビデンスに基づく大血管合併症の予防と今後 国内における糖尿病性微小血管障害の発症予測とリスク評価(Tackling diabetic macroangiopothy with the latest clinical evidences Prediction and risk assessment of diabetic macrovasucular complications in Japan)

    曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 73   2016.4

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  • 2型糖尿病患者における肥満の有無別CKD関連因子の検討

    平山 頌, 松永 佐澄志, 鶴田 恵, 五十嵐 理沙, 由澤 咲子, 石黒 創, 羽入 修, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 173   2016.4

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  • 男女別にみた日本人の2型糖尿病発症予測のためのBMIおよびウエスト周囲径(WC)のカットポイントの検討

    五十嵐 理沙, 藤原 和哉, 平安座 依子, 石澤 正博, 鶴田 恵, 治田 麻理子, 由澤 咲子, 堀川 千嘉, 松永 佐澄志, 羽入 修, 児玉 暁, 佐藤 幸示, 加藤 公則, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 154   2016.4

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  • 妊娠初期空腹時血糖値およびHbA1c値と妊娠糖尿病発症との関連の検討(TWC Study)

    谷内 洋子, 田中 康弘, 西端 泉, 菅原 歩美, 藤原 和哉, 児玉 暁, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   70回   211 - 211   2016.4

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  • 2型糖尿病患者の摂取エネルギー量及び身体活動量が過体重の有病率に与える影響の検討

    由澤 咲子, 藤原 和哉, 平安座 依子, 押鐘 芳恵, 鶴田 恵, 谷内 洋子, 広瀬 歩美, 堀川 千嘉, 五十嵐 理沙, 治田 麻理子, 前川 聡, 曽根 博仁, 糖尿病データマネジメント研究会

    日本栄養・食糧学会大会講演要旨集   70回   211 - 211   2016.4

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  • 食事療法の新たなエビデンスを求めて 日本人2型糖尿病患者における食品群・栄養成分・食習慣のエビデンス

    曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 66   2016.4

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  • 当院における外来糖尿病患者への栄養指導介入の現状と効果の検討

    治田 麻理子, 深澤 尚子, 桜井 健一, 津野 菜津美, 西山 陽子, 三ツ間 友里恵, 藤原 和哉, 曽根 博仁, 鈴木 克典

    糖尿病   59 ( Suppl.1 )   S - 414   2016.4

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  • 耐糖能と骨密度の関連 健診データの縦断的解析

    石澤 正博, 藤原 和哉, 田代 稔, 松永 佐澄志, 加藤 公則, 鈴木 亜希子, 山田 貴穂, 羽入 修, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 340   2016.4

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  • 2型糖尿病患者の臨床背景による食事療法及び運動療法の実施状況 JDDMからの報告

    由澤 咲子, 平安座 依子, 藤原 和哉, 鶴田 恵, 堀川 千嘉, 押鐘 芳恵, 治田 麻理子, 五十嵐 理沙, 山崎 勝也, 川井 紘一, 岩崎 皓一, 朝長 修, 宮澤 一裕, 栗原 義夫, 加藤 則子, 加藤 光敏, 横山 宏樹, 大石 まり子, 前川 聡, 曽根 博仁, 糖尿病データマネジメント研究会

    糖尿病   59 ( Suppl.1 )   S - 325   2016.4

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  • 2型糖尿病患者へのリラグルチド追加の効果 インスリン療法の有無による比較

    畑中 麻梨恵, 朝長 修, 高橋 直穂, 木村 裕之, 大内 基司, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   59 ( Suppl.1 )   S - 377   2016.4

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  • 「糖尿病標準診療マニュアル(一般診療所・クリニック向け)」(国立国際医療研究センター病院編)による診療の質の改善

    能登 洋, 谷澤 幸生, 相澤 徹, 曽根 博仁, 吉岡 成人, 寺内 康夫, 稲垣 暢也, 野田 光彦

    糖尿病   59 ( Suppl.1 )   S - 371   2016.4

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  • 糖尿病発症と握力の関係 新指標「握力体重比」について

    加藤 公則, 門間 陽樹, 小林 隆司, 丸藤 祐子, 児玉 暁, 小林 篤子, 田代 稔, 五十嵐 理沙, 山本 正彦, 石澤 正博, 藤原 和哉, 上村 伯人, 佐藤 幸示, 澤田 亨, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 288   2016.4

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  • トホグリフロジン(TOFO)の脂肪肝、肝インスリンクリアランス(Hepatic insulin clearance:HIC)に与える影響についての検討

    松林 泰弘, 菅波 秀規, 加来 浩平, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 282   2016.4

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  • わが国における糖尿病有無別の食事摂取状況 平成22年国民健康・栄養調査の解析

    堀川 千嘉, 村山 伸子, 鶴田 恵, 押鐘 芳恵, 平澤 玲子, 谷内 洋子, 藤原 和哉, 羽入 修, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 319   2016.4

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  • 最終糖化産物(AGE)はヒト血小板からSrc family kinaseの活性を介してBDNFの放出を促進させる

    古川 和郎, 武井 延之, 岩倉 百合子, 外山 英和, 羽入 修, 布施 一郎, 那波 宏之, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 309   2016.4

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  • SGLT2阻害薬の3-6ヵ月投与の評価

    樋詰 友香, 加藤 昭二, 木村 祐之, 大内 基司, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   59 ( Suppl.1 )   S - 230   2016.4

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  • 糖尿病発症と握力の関係—新指標「握力体重比」について

    加藤公則, 加藤公則, 門間陽樹, 小林隆司, 丸藤祐子, 児玉暁, 小林篤子, 田代稔, 五十嵐理沙, 山本正彦, 石澤正博, 藤原和哉, 上村伯人, 佐藤幸示, 澤田亨, 曽根博仁

    糖尿病(Web)   59 ( Suppl )   S.288(J‐STAGE) - 288   2016.4

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  • 血清脂質指標の2型糖尿病発症予測能の検討:The Niigata Wellness Study

    山本正彦, 山本正彦, 五十嵐理沙, 藤原和哉, 平安座依子, 石澤正博, 鶴田恵, 治田麻理子, 治田麻理子, 由澤咲子, 堀川千嘉, 堀川千嘉, 松永佐澄志, 羽入修, 児玉暁, 児玉暁, 佐藤幸示, 加藤公則, 加藤公則, 曽根博仁

    糖尿病(Web)   59 ( Suppl )   S.465(J‐STAGE) - 465   2016.4

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  • 血清脂質指標の2型糖尿病発症予測能の検討 The Niigata Wellness Study

    山本 正彦, 五十嵐 理沙, 藤原 和哉, 平安座 依子, 石澤 正博, 鶴田 恵, 治田 麻理子, 由澤 咲子, 堀川 千嘉, 松永 佐澄志, 羽入 修, 児玉 暁, 佐藤 幸示, 加藤 公則, 曽根 博仁

    糖尿病   59 ( Suppl.1 )   S - 465   2016.4

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  • 【体質から生活までを考える代謝内科学】 遺伝素因と環境を考える 生活習慣病を疫学・大規模臨床データから考える

    曽根 博仁

    日本内科学会雑誌   105 ( 3 )   383 - 390   2016.3

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    DOI: 10.2169/naika.105.383

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  • 日本人の大規模臨床エビデンスに基づく糖尿病の診療と予防

    曽根 博仁

    西宮市医師会医学雑誌   ( 21 )   85 - 86   2016.3

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  • 尿蛋白測定試験紙(±)症例におけるeGFR低値に関連する因子についての横断的検討

    番場 一成, 平安座 依子, 笠井 真由美, 大野 義将, 清水 不二雄, 上村 由紀, 山本 晃, 松浦 恵子, 曽根 博仁, 村山 実

    人間ドック   30 ( 5 )   847 - 850   2016.3

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    目的:尿蛋白(±)症例において、eGFR低値に関連する因子を横断的に検索することを目的とした。方法:2008年から2013年の6年間に、新潟縣健康管理協会を受診した20,340名(男性11,948名、女性8,392名、年齢52±11歳)を対象とした。尿蛋白(±)症例におけるeGFR低値と関連する可能性のある因子として、今回は生活習慣病に関わるBMI、腹囲、血圧を取りあ上げ、これら諸因子のeGFR低値との関連について、ロジスティック回帰分析により横断的に検討した。結果:すべての項目を含めた分析結果から、尿蛋白とBMIがeGFR低値に対して有意に関連する因子であることが明らかとなった。そこで尿蛋白(±)とBMI≧25とのeGFR低値に対する組み合わせ効果につき検討したところ、尿蛋白(-)かつBMI&lt;25の者に比し、尿蛋白(±)かつBMI≧25の者でeGFR低値に対する性・年齢調整オッズ比は2.04(95%CI1.44、2.90)であり、BMI高値例において尿蛋白(±)とeGFR低値との関連がより強く認められた。結論:尿蛋白(±)におけるBMI高値の共存はeGFR低値を呈する率をより高めた。(著者抄録)

    DOI: 10.11320/ningendock.30.847

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  • 急性期をエコーで観察し得た心サルコイドーシスの一例

    小林 ともよ, 中坊 亜由美, 小林 紘子, 伊藤 正行, 水野 幸子, 加藤 靖彦, 高野 操, 松戸 隆之, 曽根 博仁, 南野 徹

    超音波医学   43 ( 2 )   338 - 338   2016.3

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  • アルブミン,フェリチン,CRPを用いたBiomarker indexは,造血幹細胞移植前患者に対するHCT‐CIとは独立した予後予測因子である

    諏訪部達也, 柴崎康彦, 宮腰淑子, 布施香子, 小林弘典, 牛木隆志, 森山雅人, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   38th   221   2016.2

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  • 【新時代の臨床糖尿病学(上)-より良い血糖管理をめざして-】 日本人患者を対象とした糖尿病大規模臨床研究 JDCS(Japan Diabetes Complications Study)

    松永 佐澄志, 田中 司朗, 曽根 博仁

    日本臨床   74 ( 増刊1 新時代の臨床糖尿病学(上) )   645 - 649   2016.2

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  • 極端な偏食と紫外線遮断に起因したビタミンD欠乏症骨軟化症の1例

    橋本 浩平, 三ツ間 友里恵, 吉岡 大志, 松林 泰弘, 鈴木 亜希子, 羽入 修, 曽根 博仁

    新潟医学会雑誌   130 ( 2 )   140 - 141   2016.2

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  • 運動療法を科学する

    稲垣 暢也, 田村 好史, 曽根 博仁, 細井 雅之

    Diabetes Strategy   6 ( 1 )   5 - 19   2016.2

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  • 不安定な体重変動は、肥満と独立した2型糖尿病発症危険因子である メタ解析

    児玉 暁, 藤原 和哉, 石澤 正博, 石黒 創, 松林 泰弘, 松永 佐澄志, 山田 貴穂, 加藤 公則, 羽入 修, 曽根 博仁

    日本内科学会雑誌   105 ( Suppl. )   214 - 214   2016.2

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  • 妊娠初期における身体活動および栄養摂取状況と耐糖能異常との関連の検討

    田中 康弘, 谷内 洋子, 曽根 博仁

    日本産科婦人科学会雑誌   68 ( 2 )   968 - 968   2016.2

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  • 高血圧の詳細な家族歴が高血圧発症に及ぼす影響に関する前向き観察研究

    五十嵐理沙, 藤原和哉, 平安座依子, 児玉暁, 齋藤和美, 羽入修, 原茂子, 本田律子, 辻裕之, 荒瀬康司, 曽根博仁

    Journal of Epidemiology (Web)   26 ( Supplement 1 )   79   2016.1

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  • 高血圧の詳細な家族歴が高血圧発症に及ぼす影響に関する前向き観察研究

    五十嵐理沙, 藤原和哉, 平安座依子, 児玉暁, 齋藤和美, 羽入修, 原茂子, 本田律子, 辻裕之, 荒瀬康司, 曽根博仁

    Journal of Epidemiology (Web)   26 ( Supplement 1 )   79   2016.1

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  • 随時尿による推定塩分摂取量と推定カリウム摂取量について

    加藤 公則, 小林 篤子, 曽根 博仁

    生物試料分析   39 ( 1 )   118 - 118   2016.1

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  • 代謝 臨床分野での進歩 生活習慣と糖尿病合併症

    松永 佐澄志, 田中 司朗, 曽根 博仁

    Annual Review糖尿病・代謝・内分泌   2016   136 - 142   2016.1

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    食事,運動療法を含めた生活習慣介入は糖尿病をはじめとする生活習慣病治療の基本である.2型糖尿病の合併症予防におけるエビデンスとしてはUKPDS,Kumamoto Study以来多くの研究が発表されているが,生活習慣介入の効果をみた大規模臨床試験は少ない.本邦の2型糖尿病患者を対象としたJDCSでは生活習慣介入群で血圧やHbA1cは対象群と同等であったが,脳卒中の発症が有意に抑制された.一方で米国から報告されたLook AHEAD研究では肥満2型糖尿病患者に対する強化ライフスタイル介入で身体活動量の増加と体重やHbA1cの低下効果が得られたが,心血管イベントの抑制効果は示されなかった.しかしながら介入群で薬剤使用率と医療コストが抑えられており生活習慣介入の効果を否定するものではない.効率的な生活習慣介入の方法や介入効果が得られやすい患者の特徴などについてのエビデンス構築が望まれる.(著者抄録)

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  • 糖尿病 臨床分野での進歩 「日本人の食事摂取基準(2015年版)」の概要

    堀川 千嘉, 曽根 博仁

    Annual Review糖尿病・代謝・内分泌   2016   43 - 49   2016.1

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    食事摂取基準は,健康増進法に基づき,国民の健康の保持・増進を図る上で摂取することが望ましいエネルギー及び栄養素の量の基準を定めるものである.「日本人の食事摂取基準(2015年版)」の策定目的では,発症予防とともに『重症化予防』の概念が追加され,対象を健康な個人並びに集団および高血圧,脂質異常,高血糖,腎機能低下に関して保健指導レベルにある者までを含むものとし,食事摂取基準と疾病治療ガイドラインのギャップを埋める試みが行われた.本年の主な改定のポイントは,(1)エネルギー・栄養素と生活習慣病の発症予防・重症化予防の関連についてのレビューをもとにした新たな検討の実施,(2)エネルギーの摂取量及び消費量のバランスの維持を示す指標としてBMI(body mass index)の採用,(3)生活習慣病の予防を目的とした「目標量」の充実化,が挙げられる.本稿では,これらの主な改定箇所を重点的に概説する.(著者抄録)

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  • 糖尿病の療養指導Q&A 合併症のリスクエンジン 合併症のリスクエンジンとはなんでしょうか JDCS/J-EDITリスクエンジンについても教えてください

    田中 司朗, 曽根 博仁

    プラクティス   33 ( 1 )   89 - 92   2016.1

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  • 【目指せ!肥満症のトータルケア-減量に苦戦する患者について考える】 肥満のもたらす健康障害 高血圧・冠動脈疾患・脳梗塞

    松林 泰弘, 曽根 博仁

    内科   117 ( 1 )   35 - 40   2016.1

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    肥満関連高血圧は,交感神経活性の変化,インスリン抵抗性の増強など,さまざまな病態が複合して病態が形成されている.肥満症患者の高血圧は,心血管イベントとより強く関連するnon-dipperとなりやすくなることに留意が必要である.肥満は高血圧,脂質異常などのリスクの集積をもたらし,脳・心血管イベントを惹起するが,本邦においては,BMI増加が独立した危険因子として存在している可能性を示唆する報告もある.(著者抄録)

    DOI: 10.15106/J00974.2016089660

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  • 【中枢性自律神経障害-最近の話題-】 レプチンと視床下部 自律神経との関連

    小澤 鉄太郎, 曽根 博仁, 西澤 正豊

    神経内科   84 ( 1 )   83 - 87   2016.1

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  • 職域と糖尿病 職域における運動療法とその指導

    曽根 博仁

    日本成人病(生活習慣病)学会会誌   42   47 - 47   2016.1

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  • わが国の糖尿病専門医の薬物療法における処方と患者背景の解析(第2報)

    藤原和哉, 羽入修, 松永佐澄志, 松林泰弘, 鈴木亜希子, 山田貴穂, 横山宏樹, 島野仁, 前川聡, 山崎勝也, 川井紘一, 曽根博仁

    糖尿病(Web)   59 ( Suppl )   S.452(J‐STAGE)   2016

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  • 無症候性褐色細胞腫の一例

    横川かおり, 佐藤陽子, 金子正儀, 棚橋怜生, 山本正彦, 松林泰弘, 松永佐澄志, 岩永みどり, 山田貴穂, 藤原和哉, 羽生修, 曽根博仁, 山名一寿, 田崎正行

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   17th   80   2016

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  • 当院における外来糖尿病患者への栄養指導介入の現状と効果の検討

    治田麻理子, 治田麻理子, 深澤尚子, 桜井健一, 津野菜津美, 西山陽子, 三ツ間友里恵, 藤原和哉, 曽根博仁, 鈴木克典

    糖尿病(Web)   59 ( Suppl )   S.414(J‐STAGE)   2016

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  • わが国における糖尿病有無別の食事摂取状況:平成22年国民健康・栄養調査の解析

    堀川千嘉, 堀川千嘉, 村山伸子, 鶴田恵, 押鐘芳恵, 押鐘芳恵, 平澤玲子, 平澤玲子, 谷内洋子, 谷内洋子, 藤原和哉, 羽入修, 曽根博仁

    糖尿病(Web)   59 ( Suppl )   S.319(J‐STAGE)   2016

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  • 糖尿病専門外来に通院する2型糖尿病患者の食事摂取状況の把握:JDDMからの報告

    鶴田恵, 堀川千嘉, 堀川千嘉, 藤原和哉, 平安座依子, 由澤咲子, 五十嵐理沙, 治田麻理子, 治田麻理子, 加藤光敏, 加藤則子, 横山宏樹, 栗原義夫, 岩崎皓一, 宮澤一裕, 朝長修, 屋宜宣治, 川井紘一, 前川聡, 曽根博仁

    糖尿病(Web)   59 ( Suppl )   S.458(J‐STAGE)   2016

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  • 2型糖尿病患者の臨床背景による食事療法及び運動療法の実施状況:JDDMからの報告

    由澤咲子, 平安座依子, 藤原和哉, 鶴田恵, 堀川千嘉, 堀川千嘉, 押鐘芳恵, 治田麻理子, 五十嵐理沙, 山崎勝也, 川井紘一, 岩崎皓一, 朝長修, 宮澤一裕, 栗原義夫, 加藤則子, 加藤光敏, 横山宏樹, 大石まり子, 前川聡, 曽根博仁

    糖尿病(Web)   59 ( Suppl )   S.325(J‐STAGE)   2016

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  • 大規模臨床データ解析からみたメタボリックリスク 予防と治療の個別化への応用

    曽根 博仁

    メタボリックシンドローム   12 ( 1 )   51 - 63   2016

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  • The Sil Index Is a Useful Prognostic Indicator for Diffuse Large B-Cell Lymphoma

    Naoto Tomita, Taisei Suzuki, Kazuho Miyashita, Wataru Yamamoto, Kenji Motohashi, Takayoshi Tachibana, Hirotaka Takasaki, Rika Kawasaki, Maki Hagihara, Chizuko Hashimoto, Sachiya Takemura, Hideyuki Koharazawa, Etsuko Yamazaki, Jun Taguchi, Katsumichi Fujimaki, Hiroyuki Fujita, Rika Sakai, Shin Fujisawa, Shigeki Motomura, Keisuke Kawamoto, Hirohito Sone, Jun Takizawa

    BLOOD   126 ( 23 )   2015.12

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  • Combination of Low Rate of gamma delta T Cells and High Rate of Regulatory T Cells after Allogeneic Stem Cell Transplantation Is a Poor Prognostic Factor for Patients with Hematological Neoplasm

    Yasuhiko Shibasaki, Syukuko Miyakoshi, Takayuki Katagiri, Kyoko Fuse, Hironori Kobayashi, Takashi Ushiki, Masato Moriyama, Jun Takizawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko

    BLOOD   126 ( 23 )   2015.12

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  • 【糖尿病腎症の診断と治療Up To Date】 治療の実践 EBMを基盤とした血糖の管理目標と薬物療法

    松永 佐澄志, 曽根 博仁

    月刊糖尿病   7 ( 12 )   28 - 34   2015.12

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  • MRSAのVCMにおける薬剤感受性の検討

    草間 文子, 横山 和弘, 小林 めぐみ, 古川 久美子, 町田 良子, 吉田 彩, 近藤 千草, 高野 操, 茂呂 寛, 曽根 博仁

    日本臨床微生物学雑誌   26 ( Suppl. )   309 - 309   2015.12

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  • 【糖尿病治療新時代-糖尿病治療のupdate-】 日本人2型糖尿病患者の特徴と合併症の危険因子

    曽根 博仁

    日本臨床   73 ( 12 )   1979 - 1987   2015.12

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  • 【日本人糖尿病の大規模臨床・疫学研究】 JDCS

    松永 佐澄志, 田中 司朗, 曽根 博仁

    Diabetes Frontier   26 ( 6 )   699 - 704   2015.12

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  • 【日本人糖尿病の大規模臨床・疫学研究】 Tanaka Women's Clinic Study 若年女性のやせと妊娠糖尿病

    谷内 洋子, 田中 康弘, 曽根 博仁

    Diabetes Frontier   26 ( 6 )   752 - 756   2015.12

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  • 【日本人糖尿病の大規模臨床・疫学研究】 TOPICS Toranomon Hospital Health Management Center Study

    平安座 依子, 荒瀬 康司, 曽根 博仁

    Diabetes Frontier   26 ( 6 )   746 - 751   2015.12

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  • 流産に伴って発症した劇症1型糖尿病の一例

    白石 あかり, 市川 香也, 田中 憲一, 五十嵐 智雄, 福武 嶺一, 阿部 孝洋, 石澤 正博, 曽根 博仁

    新潟産科婦人科学会会誌   110 ( 2 )   91 - 91   2015.12

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  • 2015食事摂取基準 臨床における活用の是否 2015年食事摂取基準 糖尿病とその重症化予防の視点から

    曽根 博仁

    日本病態栄養学会誌   19 ( Suppl. )   S - 55   2015.12

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  • 極端な偏食と紫外線遮断に起因したビタミンD欠乏症骨軟化症の1例

    橋本 浩平, 三ツ間 友里恵, 吉岡 大志, 松林 泰弘, 二宮 悟, 福武 嶺一, 阿部 孝洋, 石澤 正博, 松永 佐澄志, 山田 貴穂, 小原 伸雅, 鈴木 亜希子, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   91 ( Suppl.Branch )   117 - 117   2015.12

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  • 【ドーンと図解で血糖変動のカラクリがわかる!高血糖・低血糖のメカニズムとコントロール】 血糖変動による影響のメカニズムとコントロール 高血糖と大血管症・そのほかの合併症

    北澤 勝, 曽根 博仁

    糖尿病ケア   12 ( 11 )   1049 - 1053   2015.11

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  • 大規模臨床研究、細小血管障害管理の面からの提案 JDCSからのメッセージ

    曽根 博仁

    糖尿病合併症   29 ( Suppl.1 )   229 - 229   2015.11

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  • 糖尿病合併症の疫学と最新の診断法について 大血管障害の疫学と診断、リスク評価

    曽根 博仁

    糖尿病合併症   29 ( Suppl.1 )   110 - 110   2015.11

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  • 睡眠とうつ 2型糖尿病患者におけるうつ病の予測因子についての検討 Japan Diabetes Complications Study

    松永 佐澄志, 田中 司朗, 堀川 千嘉, 羽入 修, 荒木 厚, 守屋 達美, 大橋 靖雄, 赤沼 安夫, 山田 信博, 曽根 博仁

    糖尿病合併症   29 ( Suppl.1 )   155 - 155   2015.11

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  • わが国における糖尿病運動療法の実施状況(第2報) 患者側への質問紙全国調査成績

    佐藤 祐造, 曽根 博仁, 小林 正, 河盛 隆造, 渥美 義仁, 押田 芳治, 田中 史朗, 鈴木 進, 牧田 茂, 大澤 功, 田村 好史, 渡邉 智之, 糖尿病運動療法, 運動処方確立のための学術調査研究委員会

    糖尿病   58 ( 11 )   850 - 859   2015.11

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    わが国における糖尿病運動療法の現状を把握することを目的に、糖尿病運動療法の実施状況に関して、患者側に質問紙調査を行った。全国各地の専門医に通院中の糖尿病外来患者5,100名に質問紙調査を行い、同意が得られた4,176名(81.9%)を解析対象とした。診察時に運動指導を受けている患者は食事療法とほぼ同率であったが、運動指導を「受けたことがない」が30%存在し、食事療法の10%より高率であった。医師から運動指導を受けている患者が52%と、コメディカル(理学療法士、健康運動指導士等)による指導は少なかった。一方、食事療法では、64%の患者が管理栄養士に指導を受けていた。運動療法を実施している患者は約半数であった。医師側(第1報)、患者側いずれの調査でも、糖尿病運動療法の指導体制は不十分であり、食事療法と比較して、「較差」が認められた。日本糖尿病学会編集による「糖尿病運動療法ガイドライン」作成を要望する。(著者抄録)

    DOI: 10.11213/tonyobyo.58.850

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  • 脳死両肺移植後の小腸DLBCL発症に対して化学療法施行後に気管支アスペルギローシスを発症した1例

    河本 啓介, 佐藤 征二郎, 根本 洋樹, 小林 弘典, 柴崎 康彦, 牛木 隆志, 森山 雅人, 瀧澤 淳, 成田 美和子, 土田 正則, 曽根 博仁, 増子 正義

    臨床血液   56 ( 11 )   2361 - 2361   2015.11

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  • 【糖尿病と機能性食品】 脂質摂取と糖尿病

    鈴木 浩史, 渡辺 賢一, 曽根 博仁

    機能性食品と薬理栄養   9 ( 3 )   131 - 134   2015.10

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    J-GLOBAL

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  • 妊娠初期の身体活動度および栄養摂取が糖代謝に与える影響の検討 TWC Study

    谷内 洋子, 田中 康弘, 西端 泉, 田島 諒子, 広瀬 歩美, 児玉 暁, 曽根 博仁

    糖尿病と妊娠   15 ( 2 )   S - 69   2015.10

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  • 遅発型カルニチン欠乏症が関与した低血糖症の一例

    種村 聡, 佐藤 陽子, 松林 泰弘, 矢口 雄大, 川田 亮, 石黒 創, 松永 佐澄志, 鈴木 亜希子, 山田 貴穂, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   91 ( 3 )   790 - 790   2015.10

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  • 【脳卒中と糖尿病】 糖尿病と脳卒中のただならぬ関係 疫学データを読み解く

    曽根 博仁

    Diabetes Contemporary   2 ( 3 )   6 - 11   2015.10

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    Other Link: http://search.jamas.or.jp/link/ui/2016071865

  • 60歳以上の高齢者では、閉眼片足立ちが心房細動発症を予知できる

    加藤 公則, 小林 篤子, 小林 隆司, 田代 稔, 上村 伯人, 丸藤 裕子, 澤田 亨, 曽根 博仁

    日本臨床スポーツ医学会誌   23 ( 4 )   S189 - S189   2015.10

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  • ROLE OF THE POLYCOMB GENE BCOR IN HEMATOPOIESIS

    Tomoyuki Tanakai, Yeako Nakajima-Takagi, Motohiko Oshima, Atsunori Saraya, Shiro Tara, Sha Si, Hirohito Sone, Haruhiko Koseki, Atsushi Iwama

    EXPERIMENTAL HEMATOLOGY   43 ( 9 )   S83 - S83   2015.9

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  • 体重変動と2型糖尿病発症との関連性に関するメタ解析

    児玉 暁, 羽入 修, 加藤 公則, 曽根 博仁

    肥満研究   21 ( Suppl. )   148 - 148   2015.9

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  • 【糖尿病の一次、二次、三次予防-エビデンスが導くもの-】 糖尿病の一次予防 健診コホート研究から見えてくるもの

    平安座 依子, 荒瀬 康司, 曽根 博仁

    プラクティス   32 ( 5 )   513 - 520   2015.9

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  • 糖尿病と非糖尿病におけるヘリコバクターピロリ感染の比較

    小川 真弓, 首藤 龍人, 安盛 織絵, 畑中 麻梨恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( 9 )   733 - 733   2015.9

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  • MMSEを用いたMCI(Mild Cognitive Impairment、軽度認知症)の特徴

    樋詰 友香, 小川 真弓, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( 9 )   731 - 731   2015.9

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  • インスリン療法へのDPP4阻害薬追加の効果

    畑中 麻梨恵, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( 9 )   723 - 723   2015.9

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  • 慢性疾患1854名における癌罹患率、癌検査施行数と癌検出率

    加藤 昭二, 友重 栄美, 沢崎 詩乃, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 首藤 龍人, 中村 公英, 横山 宏樹

    糖尿病   58 ( 9 )   722 - 722   2015.9

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  • 血中メトトレキサート測定における2試薬の基礎的検討

    菅井 貴裕, 藤巻 隼, 星山 良樹, 高野 操, 松戸 隆之, 曽根 博仁

    日本臨床検査自動化学会会誌   40 ( 4 )   507 - 507   2015.9

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  • SGLT2阻害剤トホグリフロジンの脂肪肝合併2型糖尿病患者への有効性 国内治験の部分集団解析

    松林 泰弘, 山田 貴穂, 鈴木 亜希子, 羽入 修, 菅波 秀規, 加来 浩平, 曽根 博仁

    肥満研究   21 ( Suppl. )   166 - 166   2015.9

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  • TAT改善を目的とした測定前作業プロセスの現状解析

    星山 良樹, 柿崎 隆紀, 高野 操, 松戸 隆之, 曽根 博仁

    日本臨床検査自動化学会会誌   40 ( 4 )   516 - 516   2015.9

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  • 治療抵抗性高血圧症患者の特徴 特に腎症病期に基づく糖尿病の解析

    渡邉 真恵, 佐藤 舞菜見, 畑中 麻梨恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( 9 )   734 - 734   2015.9

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  • SGLT2阻害薬の使用経験

    佐藤 舞菜見, 山田 大志郎, 小川 真弓, 渡邉 真恵, 脇原 規栄, 沖崎 進一郎, 清水 平, 本庄 潤, 曽根 博仁, 首藤 龍人, 横山 宏樹

    糖尿病   58 ( 9 )   737 - 737   2015.9

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  • 良好なA1c下でのシタグリプチン25mgへ減量の可能性

    水谷 有加利, 畑中 麻梨恵, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志朗, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( 9 )   736 - 736   2015.9

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  • WT1ペプチドワクチン施行したCML患者における抗原特異的細胞障害性T細胞のT細胞受容体β鎖可変領域レパトワの解析

    岩谷 俊平, 成田 美和子, 増子 正義, 西澤 幹則, 大岩 恵理, 柴崎 康彦, 内山 孝由, 瀧澤 淳, 曽根 博仁, 高橋 益廣

    新潟大学保健学雑誌   12 ( 1 )   83 - 89   2015.9

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    抗原特異的細胞傷害性T細胞(CTL)は抗腫瘍免疫療法において重要な役割を担っている。微量残存CML細胞を根絶するため、imatinib療法を4年間受けたCML症例にWT1ペプチドワクチンを投与した。混合リンパ球ペプチド培養(MLPC)を行い、WT1/MHC-tetramer+CD8+細胞の出現頻度の評価によって末梢血中のWT1特異的CTLの増幅効果の推移を確認した。その結果、WT1ペプチドワクチン投与を終了し6年経過した現在も、WT1特異的CTLはCD8陽性細胞中5-15×10^-6の頻度で検出され続けていることが確認された。CTLの検出の検討に加えて、長期間増幅されたWT1特異的CTLのT細胞受容体β鎖可変領域(TCRVβ)のレパトワを8回の解析を試みた。MLPC後、CD8+T細胞中のWT1特異的CTLの割合が高いwellについてレパトワ解析を行った。WT1ペプチドワクチンやMLPCには単一の9merのペプチドを使用したが、3種類のTCRVβの使用が見られた。imatinibとWT1ペプチドワクチン併用療法はCML症例においてWT1特異的CTLを長期間持続させる点で有効であることが確認された。さらに、本研究では、WT1特異的CTLにおいてはoligoclonalなTCRVβが使用されている可能性が示唆された。(著者抄録)

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    Other Link: http://hdl.handle.net/10191/38963

  • Possible involvement of lung cells harboring an abnormal karyotype in the pathogenesis of pulmonary alveolar proteinosis associated with myelodysplastic syndrome

    Masato Moriyama, Toshio Yano, Tatsuo Furukawa, Toshinori Takada, Takashi Ushiki, Masayoshi Masuko, Jun Takizawa, Hirohito Sone, Ryushi Tazawa, Yasuo Saijo, Haruyuki Ishii, Koh Nakata

    Annals of the American Thoracic Society   12 ( 8 )   1251 - 1253   2015.8

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    DOI: 10.1513/AnnalsATS.201503-175LE

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  • 妊娠中の母体血糖状態と低出生体重児出産

    谷内 洋子, 曽根 博仁

    糖尿病と妊娠   15 ( 1 )   12 - 16   2015.8

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    わが国では、少子化が国全体の社会問題となっている一方で、出生体重が2500g未満である低出生体重児出生率は、若年女性の「やせ」の割合に伴い上昇傾向にある。厚生労働省の人口動態統計によると、1980年に5%台であった低出生体重児の出生率は徐々に上昇し、2005年以降は停滞傾向ではあるものの依然10%弱を維持して推移、先進国の中でも極めて高いことが懸念されている。周産期医療の発達を背景にその要因はさまざまであるが、母体の飲酒や喫煙、出産年齢の上昇による影響に加えて、近年では母体の低栄養状態が指摘されている。低出生体重児は将来、糖尿病や高血圧といった生活習慣病発症リスクが高く、児の将来の健康に問題をきたしうる可能性が報告されていることから、低出生体重児出産の予防は将来の生活習慣病発症予防の観点から重要である。そこで本稿では、低出生体重児出生のメカニズムや将来の2型糖尿病発症との関連を中心に概説する。また近年顕著に減少傾向にある母体BMIと、胎児発育に影響を与えうる因子の1つと考えられる母体の血糖状態との組み合わせが、低出生体重児出産に与える影響について検討したわれわれの研究結果1]について、併せて紹介する。(著者抄録)

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    Other Link: http://search.jamas.or.jp/link/ui/2016006518

  • 当院通院中の糖尿病患者における皮膚AF(Autofluorescene)値測定の意義に関する検討

    川田 亮, 羽入 修, 古川 和郎, 石澤 正博, 山本 正彦, 大澤 妙子, 山田 貴穂, 皆川 真一, 鈴木 裕美, 山田 絢子, 鈴木 亜希子, 曽根 博仁

    新潟医学会雑誌   129 ( 8 )   482 - 482   2015.8

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  • わが国における糖尿病運動療法の実施状況(第1報) 医師側への質問紙全国調査成績

    佐藤 祐造, 曽根 博仁, 小林 正, 河盛 隆造, 渥美 義仁, 押田 芳治, 田中 史朗, 鈴木 進, 牧田 茂, 大澤 功, 田村 好史, 渡邉 智之, 糖尿病運動療法, 運動処方確立のための学術調査研究委員会

    糖尿病   58 ( 8 )   568 - 575   2015.8

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    わが国における糖尿病運動療法の現状を把握することを目的に、糖尿病運動療法の実施状況に関して、医師側に質問紙調査を行った。糖尿病専門医(以下、専門医)、専門医以外の内科医(以下、一般内科医)各600名を対象に、日本医師会との共同企画により、運動療法の実施状況に関して質問紙調査を行い、合計403名(33.6%)より回答を得た。その結果、専門医、一般内科医いずれも食事療法に関しては、ほとんど全ての初診患者に対し、指導を行っているが、運動療法に関しては40%前後にとどまっていた。また、専門医でも、運動指導専任スタッフは少なく、一般内科医では、実質的な指導がほとんど行われていないことが判明した。多くの専門医、一般内科医より糖尿病患者指導に用いるための適切な運動指導テキストのないことが指摘された。以上、糖尿病運動療法の指導体制は不十分であり、食事療法と比較して「較差」が認められることが判明した。(著者抄録)

    DOI: 10.11213/tonyobyo.58.568

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  • 尿蛋白測定試験紙(±)における腎機能低下に関連する因子についての検討

    番場 一成, 平安座 依子, 笠井 真由美, 清水 不二雄, 上村 由紀, 山本 晃, 松浦 恵子, 曽根 博仁, 村山 実

    人間ドック   30 ( 2 )   419 - 419   2015.7

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  • 随時尿から得られた推定カリウム摂取量と血圧の関係について Niigata Wellness Study

    加藤 公則, 小林 隆司, 松田 和博, 田代 稔, 小林 篤子, 佐藤 幸示, 北川 寛, 野沢 幸男, 平安座 依子, 曽根 博仁

    人間ドック   30 ( 2 )   382 - 382   2015.7

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  • EBMに立脚した生活習慣病の患者教育と医学教育

    曽根 博仁

    医学教育   46 ( Suppl. )   79 - 79   2015.7

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  • 健康的肥満(Metabolically Healthy Obesity)と慢性腎臓病(CKD)発症に関する大規模縦断的検討 Niigata Wellness Study

    平安座 依子, 加藤 公則, 児玉 暁, 田代 稔, 羽入 修, 佐藤 幸示, 曽根 博仁

    人間ドック   30 ( 2 )   260 - 260   2015.7

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  • 【糖尿病と合併症(後篇) 糖尿病合併症】 糖尿病血管合併症の疫学 我が国の糖尿病血管合併症とそのリスク因子の実態

    曽根 博仁

    最新医学   70 ( 7月増刊 )   1331 - 1339   2015.7

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    2型糖尿病の合併症には,人種差が見られるため,欧米の疫学データをそのまま使用するのは適切ではなく,我が国独自のエビデンス構築が必要である.近年我が国でも,Japan Diabetes Complications Study(JDCS)を始めとする前向き研究から,日本人患者の合併症や治療の実態に関するエビデンスが築かれつつある.さらに,個別患者における各合併症発症のリスク予測も可能になっており,臨床疫学が糖尿病診療の具体化や個別化に貢献できるようになった.(著者抄録)

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  • 魚沼地方で展開する健診Project 8の効果と新潟県全体への影響について Niigata Wellness Study

    加藤 公則, 上村 伯人, 布施 克也, 小林 隆司, 田村 かおり, 小宮山 仁美, 田代 稔, 小林 篤子, 佐藤 幸示, 曽根 博仁

    人間ドック   30 ( 2 )   260 - 260   2015.7

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  • 糖尿病合併症とEBM JDCS 食事・運動療法を中心とした最近の解析結果より

    曽根 博仁, 赤沼 安夫, 山田 信博

    糖尿病合併症   29 ( 2 )   189 - 194   2015.7

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  • 肥満と肝臓脂肪沈着がインスリン分泌動態とインスリン抵抗性・β細胞機能に与える影響の検討

    平安座 依子, 荒瀬 康司, 原 茂子, 児玉 暁, 齋藤 和美, 辻 裕之, 小林 哲郎, 曽根 博仁

    人間ドック   30 ( 2 )   300 - 300   2015.7

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  • 発症15年後に局在が判明した周期性異所性ACTH産生腫瘍の1例

    阿部 孝洋, 福武 嶺一, 吉岡 大志, 石澤 正博, 松林 泰弘, 山田 貴穂, 鈴木 亜希子, 羽入 修, 大橋 瑠子, 渡邉 佳緒里, 曽根 博仁

    新潟医学会雑誌   129 ( 7 )   424 - 424   2015.7

  • Curcumin Decreases Renal and Liver Triglyceride Accumulation through AMPK-SREBP Signaling Pathway in Streptozotocin-induced Type 1 Diabetic Rats

    Hiroshi Suzuki, Vigneshwaran Pitchaimani, Somasundaran Arumugam, Rajarajan A. Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreeedhar, Meilei Harima, Shizuka Miyashita, Mayumi Nomoto, Kenji Suzuki, Kenichi Watanabe, Hirohito Sone

    DIABETES   64   A146 - A146   2015.6

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  • Meat Intake and Incidence of Cardiovascular Disease in Japanese Patients with Type 2 Diabetes: Japan Diabetes Complication Study (JDCS)

    Chika Horikawa, Yukio Yoshimura, Shiro Tanaka, Sachiko Tanaka, Satoshi Matsunaga, Hideki Ito, Akira Tanaka, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

    DIABETES   64   A209 - A210   2015.6

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  • Brain Metabolic Alterations in Moderate and Severe Hypoglycemia of Mice

    Hiroshi Suzuki, Vigneshwaran Pitchaimani, Somasundaran Arumugam, Rajarajan A. Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreeedhar, Meilei Harima, Shizuka Miyashita, Mayumi Nomoto, Kenji Suzuki, Hirohito Sone, Kenichi Watanabe

    DIABETES   64   A107 - A107   2015.6

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  • 脳心血管病予防に関する包括的リスク管理 糖尿病診療の立場から

    曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   47回   150 - 150   2015.6

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  • 糖尿病と動脈硬化 わが国発の臨床研究と基礎研究 大規模データから見た日本人糖尿病患者の動脈硬化疾患とその対策

    曽根 博仁

    日本動脈硬化学会総会プログラム・抄録集   47回   123 - 123   2015.6

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  • EBV関連疾患寛解後の全血EBV-DNA定量の再発予測の有用性に関する検討

    河本 啓介, 根本 洋樹, 笠見 卓哉, 片桐 隆幸, 小林 弘典, 柴崎 康彦, 増子 正義, 成田 美和子, 曽根 博仁, 大島 孝一, 瀧澤 淳

    日本リンパ網内系学会会誌   55   107 - 107   2015.6

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  • MYC転座とBCL2転座を認めたCD20陰性EBV陽性胃原発B細胞リンパ腫の一例

    笠見 卓哉, 根本 洋樹, 片桐 隆幸, 河本 啓介, 小林 弘典, 柴崎 康彦, 増子 正義, 丸田 美和子, 曽根 博仁, 瀧澤 淳, 橋口 俊洋, 栗田 大輔, 大島 孝一

    日本リンパ網内系学会会誌   55   106 - 106   2015.6

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  • 再発時CCND1転座陽性となったCD5陽性MALTリンパ腫の1例

    根本 洋樹, 笠見 卓哉, 片桐 隆幸, 河本 啓介, 小林 弘典, 牛木 隆志, 柴崎 康彦, 森山 雅人, 増子 正義, 成田 美和子, 曽根 博仁, 瀧澤 淳, 大湊 絢, 張 大行, 尾山 徳秀, 福地 健郎, 竹内 賢吾, 中村 直哉, 栗田 大輔, 市川 理子, 大島 孝一

    日本リンパ網内系学会会誌   55   104 - 104   2015.6

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  • Type 2 Diabetic Patients with Rapid Renal Function Decline Had Increased Glomerular Filtration Rate: Japan Diabetes Complications Study (JDCS)

    Tatsumi Moriya, Shiro Tanaka, Hirohito Sone, Shun Ishibashi, Satoshi Matsunaga, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Masakazu Haneda, Shigehiro Katayama

    DIABETES   64   A157 - A157   2015.6

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  • Evaluation of Patient/Family Perception of Family Support for Medical Nutritional Therapy (MNT) in Japanese Patients with Type 2 Diabetes (T2DM)

    Megumi Tsuruta, Chika Horikawa, Risa Igarashi, Yoriko Heianza, Tamiko Watanabe, Yashuko Ono, Keiichi Yamatani, Naohito Tanabe, Yoshiko Kontai, Hirohito Sone

    DIABETES   64   A196 - A196   2015.6

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  • Family History of Diabetes, Presence or Absence of Metabolic Risk Factors, and 5-Year Incident Risk of Type 2 Diabetes in Japanese Men: Toranomon Hospital Health Management Center Study

    Igarashi Risa, Heianza Yoriko, Kodama Satoru, Hatta Mariko, Saito Kazumi, Hanyu Osamu, Hara Shigeko, Kobayashi Tetsuro, Arase Yasuji, Sone Hirohito

    DIABETES   64   A399 - A399   2015.6

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  • Longitudinal Trajectories of Glucose, Insulin Sensitivity, and Insulin Secretion during Development of Type 2 Diabetes in Japanese: Toranomon Hospital Health Management Center Study

    Yoriko Heianza, Kazuya Fujihara, Shigeko Hara, Osamu Hanyu, Kazumi Saito, Shiro Tanaka, Satoru Kodama, Tetsuro Kobayashi, Yasuji Arase, Hirohito Sone

    DIABETES   64   A399 - A399   2015.6

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  • Association between Patient/Family Perception of Family Support for Medical Nutritional Therapy (MNT) and Clinical Characteristics of Japanese Patients with Type 2 Diabetes (T2DM)

    Megumi Tsuruta, Chika Horikawa, Risa Igarashi, Yoriko Heianza, Tamiko Watanabe, Yashuko Ono, Keiichi Yamatani, Naohito Tanabe, Yoshiko Kontai, Hirohito Sone

    DIABETES   64   A192 - A192   2015.6

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  • Assessment of Kidney Dysfunction with Cystatin C- and Creatinine-based Estimated Glomerular Filtration Rate and Predicting Future Type 2 Diabetes among Japanese: Toranomon Hospital Health Management Center Study

    Yoriko Heianza, Shigeko Hara, Satoru Kodama, Kazumi Saito, Shiro Tanaka, Osamu Hanyu, Tetsuro Kobayashi, Yasuji Arase, Hirohito Sone

    DIABETES   64   A433 - A433   2015.6

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  • Relationship between Heart Rate (HR) at the Anaerobic Threshold (AT) Determined by Cardiopulmonary Exercise Test (CPX) and HRs Calculated by Different Karvonen's Coefficients Considering the HR Reserve (HRR) in Patients with Diabetes

    Kazuya Fujihara, Yoshitsugu Nakagawa, Yoriko Heianza, Shoko Furukawa, Momoko Isono, Ryo Kumagai, Yoko Sugano, Hiroaki Suzuki, Hiroyuki Kobayashi, Shigeyuki Watanabe, Hirohito Sone, Hitoshi Shimano, Hiroaki Yagyu

    DIABETES   64   A608 - A608   2015.6

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  • Impact of Combinations of Short Sleep Duration or Physical Inactivity and Overweight on Glycemic Control in Japanese Patients with Type 2 Diabetes

    Hatta Mariko, Igarashi Risa, Heianza Yoriko, Horikawa Chika, Saito Aki, Yachi Yoko, Hirose Ayumi, Hirasawa Reiko, Fujihara Kazuya, Sone Hirohito

    DIABETES   64   A216 - A216   2015.6

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  • 【糖尿病と腎疾患2015】 糖尿病総論 糖尿病の疫学

    石澤 正博, 曽根 博仁

    腎と透析   78 ( 増刊 )   10 - 13   2015.6

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  • 糖尿病患者に特徴的な食事パターン、および、その食事パターンとHbA1cとの関連について 佐渡コホートのベースラインデータから

    辻 友美, 田邊 直仁, 百都 健, 三瓶 一弘, 鈴木 啓介, 堀川 千嘉, 曽根 博仁

    日本循環器病予防学会誌   50 ( 2 )   126 - 126   2015.6

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  • USEFULNESS OF DUAL-ENERGY CT FOR DETECTION OF LIVER IRON DEPOSITION IN TRANSFUSION-DEPENDENT PATIENTS

    H. Kobayashi, N. Yoshimura, T. Kasami, T. Katagiri, H. Nemoto, K. Kawamoto, T. Ushiki, Y. Shibasaki, M. Moriyama, J. Takizawa, M. Narita, H. Sone, M. Masuko

    HAEMATOLOGICA   100   789 - 789   2015.6

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  • PERIPHERAL BLOOD EOSINOPHIL COUNT AT DAY 28 AS A PROGNOSTIC INDICATOR IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

    K. Kawamoto, Y. Shibasaki, H. Kobayashi, T. Ushiki, N. Sato, T. Yano, M. Moriyama, T. Kuroha, J. Takizawa, S. Hashimoto, M. Narita, T. Furukawa, H. Sone, M. Masuko

    HAEMATOLOGICA   100   280 - 280   2015.6

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  • Hodgkin-like ATLLの1症例

    鈴木 隆晴, 河本 啓介, 宮腰 淑子, 柴崎 康彦, 増子 正義, 曽根 博仁, 瀧澤 淳, 野本 信彦, 大島 孝一

    新潟医学会雑誌   129 ( 5 )   289 - 289   2015.5

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  • 日本語版Audit of Diabetes-Dependent Quality of Life(ADDQoL)尺度の開発

    広瀬 歩美, 藤原 和哉, 平安座 依子, 堀川 千嘉, 谷内 洋子, 曽根 博仁, 宮増 フラミニア, 岩壁 茂, 新保 みさ

    成人病と生活習慣病   45 ( 5 )   651 - 652   2015.5

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  • 「日本人の食事摂取基準(2015年版)」は健康長寿社会の基盤となるか 糖尿病とその重症化予防の観点から

    曽根 博仁

    日本抗加齢医学会総会プログラム・抄録集   15回   123 - 123   2015.5

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  • PNH型赤血球の出現を合併したEvans症候群の1例

    小林 弘典, 笠見 卓哉, 片桐 隆幸, 根本 洋樹, 河本 啓介, 牛木 隆志, 柴崎 康彦, 森山 雅人, 瀧澤 淳, 成田 美和子, 曽根 博仁, 亀崎 豊実, 増子 正義

    臨床血液   56 ( 5 )   550 - 551   2015.5

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  • 内科医の考える予防医療

    曽根 博仁

    ACP(米国内科学会)日本支部年次総会プログラム集   2015   52 - 53   2015.5

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  • 【診断から治療へのシームレスなフォロー・アップ-診断と病状把握のマーカーとその活用-】 糖尿病性合併症および併発症の現今 糖尿病と癌

    曽根 博仁

    糖尿病UP-DATE   ( 31 )   192 - 199   2015.5

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  • TSH/GH産生下垂体腺腫の2例

    吉岡 大志, 松林 泰弘, 山田 貴穂, 福武 嶺一, 阿部 孝洋, 石澤 正博, 小原 伸雅, 鈴木 亜希子, 羽入 修, 曽根 博仁

    新潟医学会雑誌   129 ( 4 )   221 - 221   2015.4

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  • BMI層別化による2型糖尿病の肥満と臨床像との関わり

    樋詰 友香, 佐藤 舞菜見, 畑中 麻梨恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( Suppl.1 )   S - 332   2015.4

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  • 【日本人肥満メタボ型糖尿病の実相、病態、治療】 肥満2型糖尿病の治療とその新展開 大規模臨床研究からみた肥満と2型糖尿病の関係

    松永 佐澄志, 曽根 博仁

    The Lipid   26 ( 2 )   143 - 148   2015.4

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    日本人2型糖尿病患者の平均BMIは増加の一途をたどっている。肥満は2型糖尿病の発症リスクとなるだけでなく、細小血管症や大血管症、死亡のリスクも上昇させることがわかっている。肥満の評価にはBMIが用いられているが、BMIは身長と体重のみから計算されるため、筋量や体内の脂肪分布を表しているわけではなく、臨床研究においては解釈に注意を要する。また、日本人を含むアジア人はBMIが低い段階で糖尿病を発症することが知られており、人種による病態の違いも考慮しなければならない。適切に病的意義のある肥満を抽出し、治療することが重要であり、わが国においても2型糖尿病患者に対する肥満治療のエビデンスが構築されることが望まれる。(著者抄録)

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  • 【糖尿病治療 通説への挑戦 進化する科学知識は既存の糖尿病治療学に何を伝えたいのか】 合併症 糖尿病三大合併症

    金子 正儀, 羽入 修, 曽根 博仁

    内科   115 ( 4 )   621 - 626   2015.4

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    細小血管合併症である神経障害,網膜症,腎症の進展予防にはHbA1c(NGSP)7.0%未満が目標とされている.神経障害の診断には糖尿病性神経障害を考える会の「糖尿病多発神経障害の簡易診断基準案」がよく使用されている.網膜症の治療初期の増悪を防ぐためには,HbA1cの低下幅は月に1〜1.5%以下に留めたほうがよいといわれている.糖尿病腎症の治療は血糖・血圧コントロールが中心となる.糖尿病の予防・啓発は,糖尿病がもたらす合併症の医療費の削減の観点からも重要である.(著者抄録)

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  • 発症15年後に局在が判明した周期性異所性ACTH産生腫瘍の1例

    阿部 孝洋, 福武 嶺一, 吉岡 大志, 石澤 正博, 松林 泰弘, 山田 貴穂, 鈴木 亜希子, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   91 ( 1 )   375 - 375   2015.4

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  • 糖尿病診療における食事療法・運動療法の現状 糖尿病患者の全国調査集計成績

    荒川 聡美, 渡邉 智之, 曽根 博仁, 小林 正, 河盛 隆造, 渥美 義仁, 押田 芳治, 田中 史朗, 鈴木 進, 牧田 茂, 大澤 功, 田村 好史, 佐藤 祐造

    糖尿病   58 ( 4 )   265 - 278   2015.4

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    わが国の糖尿病診療における食事療法・運動療法の現状を調査した。協力が得られた全国各地の医療施設糖尿病外来通院中の糖尿病患者5,100名に対し、質問紙調査を実施した。そのうち、同意が得られた4,176名を解析対象とした。日常診療における食事療法・運動療法の指導状況に関して、指導頻度は食事療法と比較し運動療法が有意に低かった。運動療法継続のために必要なもの、運動療法を実施していない理由は「時間」が最も多い回答であった。また、日常生活における身体活動量とHbA1cの関係について検討を加え、身体活動量が多い群でHbA1c低値が多かった。以上、今回の調査成績から、糖尿病患者からみた現在の運動療法指導体制は不十分であり、食事療法と比較して「較差」が認められることが判明した。運動療法の実施に必要なものは「時間」であり、個々の症例に応じた運動療法指導や身体活動量を増加させる必要性があると考えられた。(著者抄録)

    DOI: 10.11213/tonyobyo.58.265

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  • 脳心血管病予防に関する包括的リスク管理チャートについて

    寺本 民生, 横出 正之, 磯 博康, 北村 明彦, 塩見 紘樹, 木村 剛, 松本 昌泰, 飯田 真美, 佐々木 淳, 井上 茂, 永富 良一, 庄司 哲雄, 荒井 秀典, 楽木 宏実, 曽根 博仁, 山下 静也, 宮崎 滋, 脳心血管病予防に関する包括的リスク管理合同会議

    日本内科学会雑誌   104 ( 4 )   824 - 864   2015.4

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    DOI: 10.2169/naika.104.824

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  • 糖尿病入門 日本人2型糖尿病のエビデンスに基づく今後の食事療法 「日本人の食事摂取基準2015年版」を踏まえて

    堀川 千嘉, 曽根 博仁

    Diabetes Update   4 ( 2 )   74 - 78   2015.4

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  • 日本人2型糖尿病患者における、肉摂取量と心血管疾患発症との関係:JDCSによる報告

    堀川 千嘉, 鎌田 智恵実, 田中 司朗, 田中 佐智子, 松永 佐澄志, 井藤 英喜, 赤沼 安夫, 山田 信博, 吉村 幸雄, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 134   2015.4

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  • 大規模スタディから学ぶ 医療ビッグデータを活用した糖尿病予防研究

    曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 83   2015.4

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  • 糖尿病患者における抑うつ症状と総死亡の関係 JDCS

    松永 佐澄志, 田中 司朗, 田中 佐智子, 荒木 厚, 井藤 英喜, 大橋 靖雄, 赤沼 安夫, 山田 信博, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 134   2015.4

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  • 妊娠を契機に診断されたUpshaw-Schulman症候群症例における第二子妊娠の周産期管理

    森山 雅人, 玉木 悦子, 松本 雅則, 石西 綾美, 松本 吉史, 冨永 麻理恵, 工藤 理沙, 安達 聡介, 生野 寿史, 高桑 好一, 宮腰 淑子, 小堺 貴司, 小林 弘典, 牛木 隆志, 柴崎 康彦, 増子 正義, 瀧澤 淳, 成田 美和子, 曽根 博仁, 西條 康夫

    日本血栓止血学会誌   26 ( 2 )   193 - 193   2015.4

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  • 血糖降下薬多剤併用で治療中の2型糖尿病患者へのリラグルチド追加の効果

    畑中 麻梨恵, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( Suppl.1 )   S - 307   2015.4

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  • SGLT2阻害薬の4ヵ月投与の評価 通常量と半量の比較

    佐藤 舞菜見, 山田 大志郎, 前田 修一, 首藤 龍人, 佐藤 未希, 沖崎 進一郎, 清水 平, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( Suppl.1 )   S - 295   2015.4

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  • DPP4阻害薬の通常量から半量へ 血糖コントロール良好者に対して

    水谷 有加利, 畑中 麻梨恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( Suppl.1 )   S - 243   2015.4

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  • 糖尿病家族歴とメタボリックリスクファクターの重なりの有無の組み合わせが2型糖尿病発症に与える影響の大規模前向き検討

    五十嵐 理沙, 平安座 依子, 原 茂子, 児玉 暁, 斉藤 和美, 辻 裕之, 小林 哲郎, 荒瀬 康司, 田中 司朗, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 191   2015.4

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  • 癌の新規発見へ向けて 先行症状かスクリーニングか 既往歴も含めた癌調査

    加藤 昭二, 友重 栄美, 沢崎 詩乃, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 首藤 龍人, 中村 公英, 横山 弘樹

    糖尿病   58 ( Suppl.1 )   S - 278   2015.4

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  • 日本人2型糖尿病における腎機能低下には観察開始時のGFRの影響が大きい JDCSサブ解析

    守屋 達美, 田中 司朗, 曽根 博仁, 赤沼 安夫, 山田 信博, 大橋 靖雄, 片山 茂裕

    糖尿病   58 ( Suppl.1 )   S - 252   2015.4

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  • MMSEを用いたMCI(Mild Cognitive Impaiment、軽度認知症)の特徴

    佐藤 未希, 樋詰 友香, 小川 真弓, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( Suppl.1 )   S - 156   2015.4

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  • Project 8(全ての人がHbA1c 8%以下に)と新潟県職域健診の推移

    加藤 公則, 上村 伯人, 布施 克也, 平安座 依子, 小原 伸雅, 児玉 暁, 田代 稔, 小林 篤子, 小林 隆司, 佐藤 幸示, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 154   2015.4

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  • トホグリフロジンのHbA1c投与前値別にみる血糖低下・体重減少に関する検討 国内治験の併合データを用いたサブグループ解析

    阿部 孝洋, 松林 泰弘, 小原 伸雅, 山田 貴穂, 鈴木 亜希子, 羽入 修, 菅波 秀規, 加来 浩平, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 174   2015.4

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  • 血中シスタチンC、クレアチニンを用いた腎機能評価と2型糖尿病発症リスク Toranomon Hospital Health Management Center Study

    平安座 依子, 原 茂子, 児玉 暁, 齋藤 和美, 辻 裕之, 五十嵐 理沙, 森 保道, 藤原 和哉, 田中 司朗, 小林 哲郎, 荒瀬 康司, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 160   2015.4

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  • 糖尿病と非糖尿病におけるヘリコバクターピロリ感染の比較

    小川 真弓, 首藤 龍人, 安盛 織絵, 佐藤 洋子, 畑中 麻梨恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   58 ( Suppl.1 )   S - 395   2015.4

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  • 糖尿病患者の心肺運動負荷試験での嫌気性代謝閾値心拍数と心拍予備能を考慮したKarvonenの様々な計数で算出した運動強度の関係

    藤原 和哉, 中川 義嗣, 平安座 依子, 古川 祥子, 熊谷 亮, 五十野 桃子, 柏 俊一, 吉田 怜, 小島 栄治, 菅野 洋子, 鈴木 浩明, 外山 昌弘, 黒田 裕久, 小林 裕幸, 渡辺 重行, 曽根 博仁, 島野 仁, 野牛 宏晃

    糖尿病   58 ( Suppl.1 )   S - 390   2015.4

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  • 2型糖尿病患者の食事療法に関する家族支援と血糖コントロールの関連

    鶴田 恵, 木田 早紀, 小野 康子, 堀川 千嘉, 金胎 芳子, 渡辺 田美子, 山谷 恵一, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 438   2015.4

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  • 2型糖尿病患者における経口血糖降下薬の服薬アドヒアランス調査

    渡邉 真恵, 横山 宏樹, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 本庄 潤, 首藤 龍人, 山田 大志郎, 曽根 博仁, 山下 りさ, 中村 公英

    糖尿病   58 ( Suppl.1 )   S - 397   2015.4

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  • 小児1型糖尿病キャンプにおける若手栄養スタッフの専門的知識とその活用の評価 事前学習会を通して

    村山 稔子, 堀川 千嘉, 細田 耕平, 太田 優子, 山口 朝子, 伊藤 知子, 曽根 博仁, 佐藤 英利, 小川 洋平, 長崎 啓祐

    糖尿病   58 ( Suppl.1 )   S - 335   2015.4

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  • 認知機能低下合併糖尿病患者の臨床的・社会的特徴についての検討

    山本 正彦, 百都 健, 田邊 直仁, 山田 貴穂, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 317   2015.4

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  • 既存の経口血糖降下剤に、選択的SGLT2阻害剤トホグリフロジンを長期併用した場合の各種パラメータに与える影響と安全性の検討 国内治験データを用いたサブグループ解析

    松林 泰弘, 小原 伸雅, 山田 貴穂, 鈴木 亜希子, 羽入 修, 菅波 秀規, 加来 浩平, 曽根 博仁

    糖尿病   58 ( Suppl.1 )   S - 357   2015.4

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  • 2型糖尿病の治療抵抗性高血圧症 その頻度と特徴 JSH130/80mmHg、8th JNC140/90mmHgの異なる降圧目標から見た解析

    脇原 規栄, 渡邉 真恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 本庄 潤, 首藤 龍人, 山田 大志朗, 曽根 博仁, 中村 公英, 横山 宏樹

    糖尿病   58 ( Suppl.1 )   S - 356   2015.4

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  • メタアナリシスと日本人大規模臨床研究の融合による実地診療に役立つエビデンスの創生

    曽根 博仁

    日本医学会総会会誌   29回 ( 学術講演要旨 )   128 - 128   2015.4

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  • 白血病性形質細胞様樹状細胞株(PMDC11)およびPMDC11由来エクソソームを用いた抗原特異的細胞傷害性T細胞(CTL)の誘導

    内山 孝由, 成田 美和子, 岩谷 俊平, 大岩 恵理, 西澤 幹則, 高橋 益廣, 橋本 誠雄, 瀧澤 淳, 曽根 博仁, Kasahara Noriyuki

    新潟医学会雑誌   129 ( 3 )   125 - 139   2015.3

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    私たちは白血病性形質細胞様樹状細胞株(PMDC05)を樹立し、この細胞株が抗原特異的細胞傷害性T細胞(CTL)誘導能を有することを報告してきた。さらに、CD80遺伝子を導入したPMDC05であるPMDC11の抗原提示能がさらに増強することも報告した。エクソソームは、多くの細胞により分泌される30〜100nmの大きさの小粒子であり、抗原提示細胞(APC)由来エクソソームは主要組織適合抗原(MHC)や抗原提示関連分子などを多く含んでいることが知られており、単球由来樹状細胞(moDC)の分泌するエクソソーム(dexosome)が抗原提示能を有することが示され、これを用いた臨床研究も行われている。本研究では、PMDC11細胞由来エクソソームを同定するとともに、PMDC11細胞とそのエクソソームによるCTL誘導について検討した。抗原ペプチドをパルスしたPMDC11細胞またはmoDCの培養上清からExoQuick-TCを用いてエクソソームを抽出した。この抽出物がエクソソームであることを、磁気ビーズとフローサイトメトリーを用いて確認した。磁気ビーズで捕捉した抽出物は、HLA-DR、CD54、CD86、CD80、CD123陽性であり、さらにエクソソームマーカーであるCD63(LAMP3)が陽性であることから、PMDC11細胞はエクソソーム(PMDC11-dex)を放出することが確認された。次に、サイトメガロウイルス(CMV)pp65ペプチドまたは改変型ウィルムス腫瘍遺伝子(mWT1)ペプチドをパルスしたPMDC11細胞を用いてHLA-A*24:02健常人末梢血CD8+T細胞を刺激培養し、抗原特異的CTL誘導についてテトラマー解析を行った。PMDC11細胞刺激培養において、抗原特異的CTLの増幅が確認された。CMV pp65ペプチドまたはmWT1ペプチドをパルスしたPMDC11細胞培養上清より抽出したPMDC11-dexによる刺激培養では、PMDC11-dex添加培養系において抗原特異的CTLの増幅が確認された。これらの結果よりPMDC細胞株はエクソソーム分泌能有し、PMDC11-dexは抗原特異的CTL誘導能を有することが示唆された。PMDC11細胞は、細胞自体がCTL養子免疫療法に応用できるのみならず、エクソソームを用いた無細胞系ワクチンの開発にも有用であると思われた。(著者抄録)

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  • 【糖尿病網膜症2015年】 糖尿病と糖尿病網膜症の疫学

    曽根 博仁, 川崎 良, 山下 英俊

    あたらしい眼科   32 ( 3 )   313 - 319   2015.3

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  • 臍帯血移植後,血漿HHV‐6DNA量が比較的低値でありながらHHV‐6脳炎を発症したEBウイルス関連リンパ増殖症(EBV‐LPD)の一例

    根本洋樹, 小林弘典, 笠見卓哉, 片桐隆幸, 河本啓介, 牛木隆志, 柴崎康彦, 森山雅人, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義, 石原智彦, 西澤正豊

    日本造血細胞移植学会総会プログラム・抄録集   37th   306   2015.2

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  • 造血幹細胞移植後28日目の末梢血好酸球数50/μl未満は予後不良因子である

    河本啓介, 柴崎康彦, 小林弘典, 牛木隆志, 森山雅人, 瀧澤淳, 成田美和子, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   37th   230   2015.2

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  • 同種造血幹細胞移植における血清蛋白と発熱・炎症反応との関連性の検討

    森山雅人, 柴崎康彦, 増子正義, 根本洋樹, 片桐隆幸, 笠見卓哉, 河本啓介, 田中智之, 宮腰淑子, 小堺貴司, 小林弘典, 布施香子, 牛木隆志, 瀧澤淳, 曽根博仁, 西條康夫

    日本造血細胞移植学会総会プログラム・抄録集   37th   309   2015.2

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  • MDSに対する同種移植によるMDS transplant risk indexの有用性

    片桐隆幸, 柴崎康彦, 小林弘典, 牛木隆志, 佐藤直子, 矢野敏雄, 森山雅人, 黒羽高志, 瀧澤淳, 橋本誠雄, 小池正, 曽根博仁, 古川達雄, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   37th   237   2015.2

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  • 【動脈硬化症の最先端】 動脈硬化症のリスク管理と指導

    金子 正儀, 羽入 修, 曽根 博仁

    臨床検査   59 ( 2 )   143 - 149   2015.2

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    <Point>脂質異常症・高血圧症・糖尿病・喫煙は動脈硬化に起因する心・血管イベントを引き起こす.各症例ごとにリスク因子を評価し,個々の目標値を設定する.生活習慣の改善を基本として,目標に満たない場合に薬物療法を開始する.患者に治療の必要性を説明,理解してもらうことが治療継続には重要である.(著者抄録)

    DOI: 10.11477/mf.1542200232

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  • Propranolol投与にて心不全を来たしたBasedow病の1例

    鈴木 達郎, 植村 靖之, 鈴木 亜希子, 北澤 勝, 鈴木 浩史, 皆川 真一, 山田 貴穂, 羽入 修, 曽根 博仁

    新潟医学会雑誌   129 ( 2 )   95 - 96   2015.2

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  • 【肥満2型糖尿病の実践的管理】 肥満と2型糖尿病 わが国における動向

    植村 靖行, 平安座 依子, 児玉 暁, 曽根 博仁

    Diabetes Frontier   26 ( 1 )   20 - 26   2015.2

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  • 【糖尿病診療でみんなが困る疑問を集めました。血糖コントロールがうまくいくコツ】 (第2章)外来診療の疑問 欧米とのガイドラインの違いは?

    松林 泰弘, 曽根 博仁

    レジデントノート   16 ( 17 )   3236 - 3244   2015.2

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    <Point>・2型糖尿病は「インスリン分泌低下を主体とするものと、インスリン抵抗性が主体で、それにインスリンの相対的不足を伴うものなどがある」と定義される。インスリン分泌不全とインスリン抵抗性それぞれの関与の程度は症例により異なる(これには人種差を含めた遺伝的背景も大きく関与する)・併存疾患や、患者さんがおかれている社会環境、治療介入に伴う副作用リスク等を包括的に判断し、治療目標を立てる必要がある・したがって、目標とする血糖管理値や治療方法は、個々の症例の病態を考慮し、個別化する必要がある(これは血圧、脂質にも共通するところがある)・日常診療における、欧米とわが国のおかれている状況との相違や、人種差、文化(食生活を含む)の相違、また、それらを背景とした疾病構造の相違等から、欧米のガイドラインをそのまま適用するのは決して望ましいとは言えない。ガイドラインを参照する際も、以上を踏まえたうえで解釈する必要がある(著者抄録)

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  • 2型糖尿病患者におけるレジスタンストレーニングのメタ解析 どのような患者にどのように指導すべきか?

    石黒 創, 児玉 暁, 小原 伸雅, 山田 貴穂, 鈴木 亜希子, 羽入 修, 曽根 博仁

    日本内科学会雑誌   104 ( Suppl. )   159 - 159   2015.2

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  • 体幹の柔軟性と高血圧罹患の関係 人間ドック受診者を対象としたコホート研究(the Niigata Wellness Study)

    加藤 公則, 丸藤 祐子, 澤田 亨, 田代 稔, 平安座 依子, 小原 伸雅, 児玉 暁, 鈴木 亜希子, 羽入 修, 曽根 博仁

    日本内科学会雑誌   104 ( Suppl. )   154 - 154   2015.2

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  • わが国の糖尿病専門医の薬物療法における処方パターンと患者背景の解析

    藤原 和哉, 羽入 修, 鈴木 亜希子, 野牛 宏晃, 横山 宏樹, 島野 仁, 柏木 厚典, 山崎 勝也, 川井 紘一, 曽根 博仁

    日本内科学会雑誌   104 ( Suppl. )   213 - 213   2015.2

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  • ゲノムワイド関連解析(GWAS)で検出された一塩基多型(SNP)を用いた2型糖尿病のスクリーニング・予測能の定量メタ分析

    児玉 暁, 藤原 和哉, 小原 伸雅, 加藤 公則, 羽入 修, 曽根 博仁

    日本内科学会雑誌   104 ( Suppl. )   209 - 209   2015.2

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  • 妊娠中の身体活動と耐糖能異常発症リスクとの関連の検討(TWC Study)

    田中 康弘, 谷内 洋子, 曽根 博仁

    日本産科婦人科学会雑誌   67 ( 2 )   595 - 595   2015.2

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  • 【最新の糖尿病の実地日常診療 第一線の実地医家が実践すべき最新の診療の実際】 治療 第一線の実地医家による有効な最新の実践的治療の実際 運動療法の効果と実践的運動療法のありかたと実際

    古川 和郎, 曽根 博仁

    Medical Practice   32 ( 1 )   122 - 128   2015.1

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  • Reply to: Relationship between leptin and blood pressure in patients with multiple system atrophy

    Tetsutaro Ozawa, Hirohito Sone, Masatoyo Nishizawa

    JOURNAL OF THE NEUROLOGICAL SCIENCES   348 ( 1-2 )   285 - 285   2015.1

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    DOI: 10.1016/j.jns.2014.11.029

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  • 【糖尿病のすべて】 疫学・診断・病態update 糖尿病合併症の疫学 わが国の2型糖尿病患者データを中心に

    曽根 博仁

    医学のあゆみ   252 ( 5 )   355 - 361   2015.1

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    多因子遺伝と生活習慣の両者が深く関与する2型糖尿病の合併症は、人種の影響を強く受けるため欧米の疫学データを流用することはできず、わが国独自のエビデンス構築が必要である。近年わが国でも、Japan Diabetes Complications Study(JDCS)をはじめとする前向き研究から、日本人患者の合併症や治療の実態に関するエビデンスが築かれつつある。それらの結果、糖尿病合併症と血糖、血圧、脂質コントロールとの強い関連が認められたほか、腎症における喫煙や、網膜症における果物、動脈硬化合併症における食物繊維や食塩など食事関連因子の関与や、運動療法を十分行っていた患者において脳卒中や死亡率が半減していたことなど、生活習慣の重要性が明らかにされている。さらに個別患者における合併症発症率の予測も可能になっており、疫学データが糖尿病診療の具体化や個別化に貢献できる時代になってきた。(著者抄録)

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  • 日本語版Audit of Diabetes-Dependent Quality of Life(ADDQoL)尺度の開発

    広瀬 歩美, 藤原 和哉, 宮増 フラミニア, 岩壁 茂, 新保 みさ, 平安座 依子, 堀川 千嘉, 谷内 洋子, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   41   68 - 68   2015.1

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  • 【新薬展望2015】 (第III部)治療における最近の新薬の位置付け<薬効別> 新薬の広場 糖尿病治療薬

    阿部 孝洋, 曽根 博仁

    医薬ジャーナル   51 ( 増刊 )   451 - 460   2015.1

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    糖尿病治療薬は、2009年以降にインクレチン関連薬であるDPP-4(ジペプチジルペプチダーゼ4)阻害薬、GLP-1(glucagon-like peptide 1)受容体作動薬が登場した。これらは体重増加をきたしにくく、血糖依存性に血糖降下をもたらし、単独では低血糖をきたしにくいという特徴から広く使用されるようになり、治療の主役を担うようになった。2014年には新たにSGLT2(sodium-dependent glucose co-transporter 2)阻害薬が登場した。これは腎近位尿細管からのグルコース再吸収を抑制し、尿糖排泄促進による血糖降下作用を起こす、全く新しい機序の薬剤である。GPR40(G protein-coupled receptor 40)作動薬は、血糖依存性にインスリン分泌を促進する薬剤として登場が期待されていたが、肝臓における安全性の懸念からfasiglifam(開発コードTAK-875)の開発が中止された。DPP-4阻害薬では、週1回投与型のtrelagliptin(開発コードSYR-472)の国内承認が申請中である。インスリンでは、インスリンデグルデクとインスリンアスパルトの混合製剤であるライゾデグ配合注が認可を受け、現在承認申請中である。(著者抄録)

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  • 体重(数字)にとらわれるのではなく、適切な食事と運動で健康な身体づくりを

    広瀬歩美, 曽根博仁

    すこやかファミリー   2015 ( 11 )   31   2015

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  • 生活習慣病 糖尿病治療最前線 糖尿病運動療法の実行・継続率を高めるには メッツ表を活用した運動処方の提案

    曽根 博仁

    Astellas Square: 明日の医療を考える   10 ( 6 )   18 - 20   2014.12

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  • 加齢による睡眠時間の影響と将来の2型糖尿病発症リスク Niigata Wellness Study

    平安座 依子, 加藤 公則, 児玉 暁, 田代 稔, 佐藤 幸示, 曽根 博仁

    日本病態栄養学会誌   18 ( Suppl. )   S - 79   2014.12

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  • 体格的肥満・腹部肥満と代謝異常の程度の組み合わせが2型糖尿病発症リスクに与える影響

    平安座 依子, 加藤 公則, 児玉 暁, 田代 稔, 五十嵐 理沙, 由澤 咲子, 小原 伸雅, 羽入 修, 佐藤 幸示, 曽根 博仁

    日本病態栄養学会誌   18 ( Suppl. )   S - 86   2014.12

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  • Role of the Polycomb Gene Bcor in Hematopoiesis

    Tomoyuki Tanaka, Yaeko Nakajima-Takagi, Sha Si, Atsunori Saraya, Sone Hirohito, Haruhiko Koseki, Atsushi Iwama

    BLOOD   124 ( 21 )   2014.12

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  • 【新たな「日本人の食事摂取基準(2015年版)」を理解し、活用する【2】】 糖尿病とエネルギー・栄養素との関係

    広瀬 歩美, 曽根 博仁

    日本栄養士会雑誌   57 ( 11 )   801 - 804   2014.11

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  • Combination effect of hypertension and diabetes mellitus on urinary protein excretion Reply

    Nobumasa Ohara, Osamu Hanyu, Hirohito Sone

    JOURNAL OF HYPERTENSION   32 ( 11 )   2278 - 2278   2014.11

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    DOI: 10.1097/HJH.0000000000000353

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  • 視床下部性副腎機能低下を合併したインスリノーマの1例

    福武 嶺一, 阿部 孝洋, 吉岡 大志, 石澤 正博, 松林 康弘, 松永 佐澄志, 小原 伸雅, 鈴木 亜希子, 山田 貴穂, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   90 ( 3 )   942 - 942   2014.10

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  • 【高齢者糖尿病のマネジメント】 高齢者糖尿病の合併症の疫学

    鈴木 浩史, 曽根 博仁

    Aging & Health   23 ( 3 )   15 - 18   2014.10

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  • 生活習慣病の予防と治療における生活習慣の意義 運動の生活習慣病予防・治療における効果と意義

    曽根 博仁

    日本未病システム学会学術総会抄録集   21回   56 - 56   2014.10

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  • 妊娠中期における身体活動が糖代謝に与える影響の検討 TWC Study

    谷内 洋子, 田中 康弘, 西端 泉, 広瀬 歩美, 藤原 和哉, 児玉 暁, 曽根 博仁

    糖尿病と妊娠   14 ( 2 )   S - 97   2014.10

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  • 【糖尿病治療薬の心血管アウトカム】 糖尿病治療薬の心血管アウトカム抑制効果 糖尿病患者の心血管アウトカムから学んだ基本的な治療の考え方

    藤原 和哉, 曽根 博仁

    ホルモンと臨床   62 ( 10 )   763 - 770   2014.10

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  • 【境界型糖尿病の診断と治療管理】 健診データを活かした糖尿病早期診断と発症予測

    平安座 依子, 曽根 博仁

    月刊糖尿病   6 ( 8 )   30 - 37   2014.9

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  • 2型糖尿病患者における、血糖変動と神経障害発症との関連性の検討

    堀川 千嘉, 広瀬 歩美, 川井 紘一, 本橋 しのぶ, 齋藤 和美, 児玉 暁, 羽入 修, 山崎 勝也, 島野 仁, 曽根 博仁

    糖尿病合併症   28 ( Suppl.1 )   178 - 178   2014.9

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  • 日本人妊婦325名における、妊娠早期の炭水化物摂取量と50g糖負荷試験陽性リスクの関連

    田島 諒子, 飯田 薫子, 穴迫 唯衣, 田中 康弘, 曽根 博仁, 谷内 洋子

    New Diet Therapy   30 ( 2 )   117 - 117   2014.9

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  • 【糖尿病診療2014】 日本人2型糖尿病患者の病態と実態 JDCSの結果を中心に

    曽根 博仁

    診断と治療   102 ( 9 )   1279 - 1288   2014.9

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    1. 生活習慣と多因子遺伝の両方が関与する2型糖尿病の病態や合併症には、大きな人種/民族差(ethnic differences)がみられる。日本人患者の診療には、できるだけ日本人のエビデンスを用いることが望ましい。2. JDCSはアジアの代表的な糖尿病大規模臨床研究の一つで、日本人2型糖尿病患者の特徴や合併症のリスク因子を多数明らかにしてきた。3. 糖尿病の各合併症を抑制するためには、血糖だけでなく、血圧や血清脂質、禁煙や運動・食事も含めた総合的コントロールが必要である。4. 日本人2型糖尿病患者における各合併症の発症リスク計算器が実用化され、実地診療で使用可能となっている。(著者抄録)

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  • 2型糖尿病患者の塩分摂取量と合併症発症リスクの関係 JDCSにおける報告

    堀川 千嘉, 鎌田 智恵実, 田中 司朗, 田中 佐智子, 井藤 秀喜, 赤沼 安夫, 山田 信博, 吉村 幸雄, 曽根 博仁

    糖尿病合併症   28 ( Suppl.1 )   176 - 176   2014.9

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  • 糖尿病合併症とEBM JDCS 食事・運動療法を中心にした最近の解析結果より

    曽根 博仁, 赤沼 安夫, 山田 信博

    糖尿病合併症   28 ( Suppl.1 )   94 - 94   2014.9

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  • 糖尿病患者におけるうつ病と死亡の関係

    松永 佐澄志, 田中 司朗, 田中 佐智子, 羽入 修, 荒木 厚, 井藤 英喜, 大橋 靖雄, 赤沼 安夫, 山田 信博, 曽根 博仁

    糖尿病合併症   28 ( Suppl.1 )   178 - 178   2014.9

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  • 潜在性甲状腺機能亢進症から甲状腺中毒症に移行した機能性甲状腺結節の1例

    山田 貴穂, 白石 友信, 植村 靖行, 阿部 孝洋, 小原 伸雅, 鈴木 亜希子, 羽入 修, 佐藤 浩史, 石岡 孝二郎, 大橋 瑠子, 曽根 博仁

    日本内分泌学会雑誌   90 ( 2 )   541 - 541   2014.9

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  • Metabolically healthy obesity, presence or absence of fatty liver, and risk of type 2 diabetes in Japanese individuals

    Y. Heianza, Y. Arase, K. Fujihara, S. Hsieh, K. Saito, O. Hanyu, S. Kodama, S. Hara, H. Sone

    DIABETOLOGIA   57   S130 - S130   2014.9

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  • Characteristics of patients with type 2 diabetes who achieved better glycaemic control through resistance training: a meta-analysis

    H. Ishiguro, S. Kodama, S. Matsunaga, C. Horikawa, Y. Heianza, N. Ohara, T. Yamada, A. Suzuki, O. Hanyu, H. Sone

    DIABETOLOGIA   57   S259 - S259   2014.9

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  • 糖尿病食事療法関連ウェブサイトの質と学習効果の関連

    平澤玲子, 堀川千嘉, 伊部陽子, 平安座依子, 菅原歩美, 谷内洋子, 飯田薫子, 近藤和雄, 曽根博仁

    栄養学雑誌   72 ( 5 Supplement )   218   2014.8

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    J-GLOBAL

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  • 大規模臨床研究のエビデンスに基づく糖尿病療養指導と将来

    由澤 咲子, 長谷川 美代, 曽根 博仁

    臨床栄養   125 ( 2 )   195 - 200   2014.8

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  • 特集:難聴と糖尿病

    堀川 千嘉, 曽根 博仁

    月刊糖尿病ライフさかえ   8   7 - 12   2014.8

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  • 【糖尿病強化療法-低血糖を巡る諸問題】 低血糖と慢性合併症 大血管障害のリスクファクターとしての低血糖

    松林 泰弘, 曽根 博仁

    Diabetes Frontier   25 ( 4 )   421 - 427   2014.8

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  • 重症再生不良性貧血に対する免疫抑制療法中に長期の潜伏期を経て発症したレジオネラ肺炎の1例

    小林 弘典, 宮腰 淑子, 小堺 貴司, 柴崎 康彦, 森山 雅人, 増子 正義, 瀧澤 淳, 曽根 博仁, 田邊 嘉也

    臨床血液   55 ( 7 )   827 - 827   2014.7

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  • 尿蛋白測定試験紙(±)症例における腎機能低下に関連する因子についての検討

    番場 一成, 平安座 依子, 笠井 真由美, 大野 義将, 清水 不二雄, 上村 由紀, 山本 晃, 松浦 恵子, 曽根 博仁, 村山 実

    人間ドック   29 ( 2 )   210 - 210   2014.7

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  • 脂肪肝の臨床背景におよぼすアルコールのインパクト

    荒瀬 康司, 陣内 由紀, 児玉 暁, 岩男 暁子, 四倉 淑江, 田邉 真帆, 尾形 知英, 辻 裕之, 原 茂子, 曽根 博仁

    人間ドック   29 ( 2 )   312 - 312   2014.7

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  • RESPONSE TO COMMENT ON HEIANZA ET AL. Effect of Postmenopausal Status and Age at Menopause on Type 2 Diabetes and Prediabetes in Japanese Individuals: Toranomon Hospital Health Management Center Study 17 (TOPICS 17). Diabetes Care 2013; 36: 4007-4014

    Yoriko Heianza, Hirohito Sone

    DIABETES CARE   37 ( 7 )   E165 - E166   2014.7

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    DOI: 10.2337/dc14-0745

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  • 随時尿より測定した推定塩分摂取量と血圧の関連について 経年変化に着目して

    加藤 公則, 松田 和博, 小林 篤子, 田代 稔, 小林 隆司, 佐藤 幸示, 北川 寛, 野沢 幸男, 笹川 力, 曽根 博仁

    人間ドック   29 ( 2 )   306 - 306   2014.7

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  • ブルガダ型心電図診断に対する取り組みについて

    加藤 公則, 松田 和博, 池主 雅臣, 南野 徹, 小林 隆司, 佐藤 幸示, 北川 寛, 笹川 力, 上村 伯人, 曽根 博仁

    人間ドック   29 ( 2 )   356 - 356   2014.7

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  • ボルテゾミブが奏効した消化管出血を主症状とする全身性・原発性ALアミロイドーシス

    井田 桃里, 林 和直, 井田 徹, 平野 聡子, 中村 文枝, 曽根 博仁, 藤原 正博

    臨床血液   55 ( 7 )   808 - 814   2014.7

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    消化管出血症状が著明な全身性ALアミロイドーシスに対してボルテゾミブが著効した貴重な症例を報告する。83歳女性。食欲不振を主訴に受診し,上部消化管内視鏡検査で多発胃潰瘍と診断された。病理組織学的検査でALアミロイドの沈着が証明され,精査加療目的に入院した。皮膚生検でもアミロイドの沈着が証明され,またIgG-λ型Mタンパク血症を有し,全身性・原発性ALアミロイドーシスと診断された。心筋,膀胱,下部消化管へのアミロイドの沈着も疑われたが,止血困難な胃粘膜出血,皮下出血斑,血尿と出血症状が著しく,侵襲的な全身検索は施行できなかった。ボルテゾミブ・デキサメタゾンを用いた治療を開始し,全身の出血症状は軽快した。治療継続1年後には明らかな出血症状は認めないものの,病理組織学的検査で胃粘膜と皮下に依然としてアミロイドの沈着を認めた。(著者抄録)

    DOI: 10.11406/rinketsu.55.808

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01540&link_issn=&doc_id=20140807410013&doc_link_id=130004678959&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130004678959&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • αGlの内服によって食事性低血圧による失神を予防できた2型糖尿病の1例

    古川 和郎, 鈴木 達郎, 石黒 創, 皆川 真一, 松永 佐澄志, 山田 貴穂, 森川 洋, 鈴木 亜希子, 羽入 修, 村山 稔子, 曽根 博仁

    糖尿病   57 ( 6 )   467 - 467   2014.6

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  • 多発性内分泌腫瘍症(MEN)I型が疑われた前縦隔神経内分泌腫瘍の1例

    坪谷 隆介, 鈴木 浩史, 植村 靖行, 山田 貴穂, 鈴木 達郎, 北澤 勝, 阿部 孝洋, 古川 和郎, 松永 佐澄志, 皆川 真一, 鈴木 亜希子, 羽入 修, 曽根 博仁, 土田 正則

    新潟医学会雑誌   128 ( 6 )   277 - 277   2014.6

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    Other Link: http://search.jamas.or.jp/link/ui/2015006251

  • Risk of Development of Type 2 Diabetes by Overall Obesity, Abdominal Obesity, and Metabolic Abnormalities-Does Metabolically Healthy Obesity Really Exist?

    Yoriko Heianza, Kiminori Kato, Akiko Suzuki, Chika Horikawa, Satoshi Matsunaga, Sakiko Yoshizawa, Osamu Hanyu, Satoru Kodama, Koji Sato, Hirohito Sone

    DIABETES   63   A519 - A519   2014.6

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  • Metabolic Predictors of Ischemic Heart Disease and Cerebrovascular Attack in Late Elderly Diabetic Individuals: Lessons from 9 Years Observation of 4014 Diabetic Patients

    Toshio Hayashi, Koutaro Yokote, Minoru Takemoto, Mitsuhiko Noda, Hiroshi Noto, Atsushi Araki, Hirohito Sone, Koichiro Ina, Hideki Nomura

    DIABETES   63   A352 - A352   2014.6

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  • Stability and Changes in the Metabolically Healthy Overweight or Obese State and the Risk of Development of Future Type 2 Diabetes

    Yoriko Heianza, Akiko Suzuki, Kiminori Kato, Kazuya Fujihara, Takaho Yamada, Osamu Hanyu, Satoru Kodama, Koji Sato, Hirohito Sone

    DIABETES   63   A21 - A21   2014.6

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  • 抗精神病薬が原因と考えられる低血糖を呈した1例

    羽入 修, 石黒 創, 保谷 智史, 諸橋 数昭, 黒岩 巌志, 桑原 治, 仲丸 司, 布施 克也, 佐藤 幸示, 曽根 博仁

    糖尿病   57 ( 6 )   458 - 458   2014.6

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  • 新医学へと展開する疫学・統計学 抗加齢医学における実例と今後 運動による健康長寿の可能性 臨床疫学の視点から

    曽根 博仁, 田中 司朗, 児玉 暁

    日本抗加齢医学会総会プログラム・抄録集   14回   285 - 285   2014.6

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  • MALTリンパ腫65例の臨床病理学的検討

    瀧澤 淳, 小林 弘典, 柴崎 康彦, 森山 雅人, 増子 正義, 曽根 博仁, 成田 美和子, 大湊 絢, 張 大行, 尾山 徳秀, 福地 健郎, 青木 定夫, 中村 直哉, 大島 孝一

    日本リンパ網内系学会会誌   54   101 - 101   2014.6

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  • MALTリンパ腫65例の臨床病理学的検討

    瀧澤 淳, 小林 弘典, 柴崎 康彦, 森山 雅人, 増子 正義, 曽根 博仁, 成田 美和子, 大湊 絢, 張 大行, 尾山 徳秀, 福地 健郎, 青木 定夫, 中村 直哉, 大島 孝一

    日本リンパ網内系学会会誌   54   91 - 91   2014.6

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  • Relationship between Clinical Characteristics and Vegetable Intake in Japanese Patients with Type 2 Diabetes: Analysis from Japan Diabetes Complications Study

    Chika Horikawa, Chiemi Kamada, Ryota Okumura, Shiro Tanaka, Sachiko Tanaka, Yasuo Ohashi, Atsushi Araki, Hideki Ito, Yukio Yoshimura, Hirohito Sone

    DIABETES   63   A385 - A385   2014.6

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  • Magnitude of Risk of Diabetes Mellitus in Relation to Carrying Risk Alleles of Diabetes-Susceptible Genes Was Not Influenced by Covariates: A Meta-analysis

    Hajime Ishiguro, Satoru Kodama, Chika Horikawa, Kazuo Furukawa, Hiromi Suzuki, Kazuya Fujiwara, Yoriko Heianza, Akiko Suzuki, Osamu Hanyu, Hirohito Sone

    DIABETES   63   A360 - A360   2014.6

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  • Predictive Value of Combined Single Nucleotide Polymorphisms for Diabetes Mellitus-A Meta-analysis

    Satoru Kodama, Chika Horikawa, Satoshi Matsunaga, Kazuya Fujihara, Yoriko Heianza, Ayumi Hirose, Takaho Yamada, Akiko Suzuki, Osamu Hanyu, Hirohito Sone

    DIABETES   63   A360 - A360   2014.6

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  • High Serum Uric Acid Level Is More Predictive of Risk of Future Type 2 Diabetes in Nonobese Than in Overweight/Obese People: The Niigata Wellness Study

    Satoshi Matsunaga, Yoriko Heianza, Tatsuro Suzuki, Masaru Kitazawa, Shinichi Minagawa, Takaho Yamada, Akiko Suzuki, Osamu Hanyu, Kiminori Kato, Koji Sato, Hirohito Sone

    DIABETES   63   A367 - A367   2014.6

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  • Nonfasting Plasma Glucose Concentration and Prediction of Future Risk of Diabetes Mellitus: The Sado Cohort Study

    Naohito Tanabe, Masahiko Yamamoto, Takeshi Momotsu, Keisuke Suzuki, Kazuhiro Sanpei, Tomomi Tsuji, Hirohito Sone

    DIABETES   63   A361 - A361   2014.6

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  • Resistance Exercise Was Effective in Improving Glycemic Control but Inferior to Aerobic Exercise for Patients with Type 2 Diabetes Mellitus-A Meta-analysis

    Hajime Ishiguro, Satoru Kodama, Chika Horikawa, Hiroshi Suzuki, Satoshi Matsunaga, Yoriko Heianza, Takaho Yamada, Akiko Suzuki, Osamu Hanyu, Hirohito Sone

    DIABETES   63   A185 - A185   2014.6

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  • HMG-CoA Reductase Inhibitors Prevent Cerebrovascular Attack via a Direct Effect in Type 2 Diabetic Patients, Including Late Elderly

    Toshio Hayashi, Kiyoshi Kubota, Koutaro Yokote, Minoru Takemoto, Mitsuhiko Noda, Hiroshi Noto, Hirohito Sone, Atsushi Araki, Koichiro Ina, Hideki Nomura

    DIABETES   63   A124 - A124   2014.6

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  • Diabetes Risk Related to Carrying 1 Risk Allele of a Diabetes-Susceptible Gene Is Comparable to That Related to 1 Unit of Increased Body Mass Index: A Meta-analysis

    Chika Horikawa, Satoru Kodama, Satoshi Matsunaga, Sakiko Yoshizawa, Yoriko Heianza, Yoko Yachi, Nobumasa Ohara, Akiko Suzuki, Osamu Hanyu, Hirohito Sone

    DIABETES   63   A360 - A360   2014.6

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  • Comprehensive Analysis of Patterns of First-Line Medication for Patients with Diabetes in Japan: Nationwide Claims Database Study

    Akiko Suzuki, Yoriko Heianza, Tatsurou Suzuki, Masaru Kitazawa, Takahiro Abe, Yasuyuki Uemura, Satoshi Matsunaga, Shinichi Minagawa, Takaho Yamada, Osamu Hanyu, Hirohito Sone

    DIABETES   63   A609 - A610   2014.6

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  • THE ASSOCIATION OF REDUCTION OF WT1 TRANSCRIPTS IN BONE MARROW AND OUTCOMES IN ACUTE MYELOID LEUKEMIA PATIENTS

    Y. Shibasaki, T. Tanaka, S. Miyakoshi, K. Fuse, T. Kozakai, H. Kobayashi, T. Ushiki, M. Moriyama, J. Takizawa, M. Narita, M. Takahashi, H. Sone, M. Masuko

    HAEMATOLOGICA   99   565 - 566   2014.6

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  • 高血圧を合併したサブクリニカルクッシング症候群の1例

    山本 正彦, 山田 貴穂, 鈴木 亜希子, 曽根 博仁, 滝澤 逸大, 小松 集一, 笠原 隆

    新潟医学会雑誌   128 ( 5 )   233 - 233   2014.5

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  • 【最新肥満症学-基礎・臨床研究の最前線-】 Metabolically obese normal-weight(MONW)とmetabolically healthy obese(MHO)の概念と臨床的意義

    小原 伸雅, 平安座 依子, 曽根 博仁

    日本臨床   72 ( 増刊4 最新肥満症学 )   697 - 702   2014.5

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  • 糖尿病大血管症の予防・治療を目指した新しい治療戦略 糖尿病と脳・心血管イベント Japan Diabetes Complications Study(JDCS)からのメッセージ

    曽根 博仁, 田中 司朗, 片山 茂裕, 山下 英俊, 赤沼 安夫, 山田 信博

    糖尿病合併症   28 ( 1 )   59 - 65   2014.5

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  • 2型糖尿病患者における食塩摂取量と合併症発症リスクの関連性 JDCS

    堀川 千嘉, 羽入 修, 曽根 博仁, 田中 司朗, 井藤 秀喜, 大橋 靖雄, 吉村 幸雄

    成人病と生活習慣病   44 ( 5 )   592 - 592   2014.5

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  • 糖尿病患者におけるヘリコバクター・ピロリ菌感染と血糖コントロールの関係 メタ解析

    堀川 千嘉, 児玉 暁, 藤原 和哉, 谷内 洋子, 羽入 修, 曽根 博仁, 島野 仁

    成人病と生活習慣病   44 ( 5 )   583 - 583   2014.5

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  • 糖尿病患者は非糖尿病患者よりもヘリコバクター・ピロリ菌除菌成功率が低い メタ解析

    堀川 千嘉, 児玉 暁, 藤原 和哉, 谷内 洋子, 羽入 修, 曽根 博仁, 島野 仁

    成人病と生活習慣病   44 ( 5 )   603 - 603   2014.5

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  • 糖尿病患者における、ヘリコバクター・ピロリ菌感染とその除菌成功率 メタアナリシスによる報告

    堀川 千嘉, 児玉 暁, 藤原 和哉, 谷内 洋子, 羽入 修, 島野 仁, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 451   2014.4

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  • 2型糖尿病患者における、野菜摂取量と臨床検査指標との関連性 JDCS

    鎌田 智恵美, 堀川 千嘉, 奥村 亮太, 田中 司朗, 田中 佐智子, 荒木 厚, 井藤 英喜, 赤沼 安夫, 山田 信博, 曽根 博仁, 吉村 幸雄

    糖尿病   57 ( Suppl.1 )   S - 444   2014.4

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  • インスリン療法へDPP4阻害薬追加の効果

    畑中 麻梨恵, 水谷 有加利, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   57 ( Suppl.1 )   S - 401   2014.4

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  • わが国の糖尿病専門医の薬物療法における処方パターンと意図の解析

    藤原 和哉, 羽入 修, 鈴木 亜希子, 山田 貴穂, 横山 宏樹, 田中 司朗, 野牛 宏晃, 島野 仁, 柏木 厚典, 山崎 勝也, 川井 紘一, 曽根 博仁, 糖尿病データマネージメント研究会

    糖尿病   57 ( Suppl.1 )   S - 387   2014.4

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  • 妊娠中期の身体活動量が糖代謝に及ぼす影響の検討(TWC Study)

    谷内 洋子, 田中 康弘, 西端 泉, 由澤 咲子, 藤原 和哉, 児玉 暁, 鈴木 亜希子, 羽入 修, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 377   2014.4

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  • 治療抵抗性高血圧症患者の特徴

    渡邉 真恵, 佐藤 舞菜見, 畑中 麻里恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 本庄 潤, 首藤 龍人, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   57 ( Suppl.1 )   S - 394   2014.4

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  • レセプトデータを利用した新規糖尿病治療薬処方状況の検討

    鈴木 亜希子, 平安座 依子, 羽入 修, 鈴木 達郎, 北澤 勝, 阿部 孝洋, 植村 靖行, 皆川 真一, 山田 貴穂, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 387   2014.4

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  • グラルギン、デテミルからデグルデクへ変更後の作用効果

    水谷 有加利, 畑中 麻梨恵, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   57 ( Suppl.1 )   S - 275   2014.4

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  • 尿酸の糖尿病発症への影響は非肥満者で強い

    松永 佐澄志, 平安座 依子, 皆川 真一, 鈴木 亜希子, 山田 貴穂, 羽入 修, 田代 稔, 大塚 政人, 佐藤 幸示, 加藤 公則, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 274   2014.4

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  • ビルダグリプチンのシタグリプチンとの比較

    佐藤 舞菜見, 小川 真弓, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志朗, 本庄 潤, 曽根 博仁, 首藤 龍人, 横山 宏樹

    糖尿病   57 ( Suppl.1 )   S - 299   2014.4

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  • 健康的肥満(Metabolically Healthy Obesity)と2型糖尿病発症に関する大規模前向き研究 TOPICS

    平安座 依子, 児玉 暁, 原 茂子, 謝 勲東, 森 保道, 辻 裕之, 齋藤 和美, 藤原 和哉, 島野 仁, 羽入 修, 鈴木 亜希子, 荒瀬 康司, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 286   2014.4

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  • 住民検診と人間ドックで把握された糖尿病患者の死亡リスク

    山本 正彦, 三瓶 一弘, 鈴木 啓介, 百都 健, 田邊 直仁, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 461   2014.4

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  • SOCS3ノックアウトはSOCS1ノックアウトによる慢性炎症を重症化する

    牛木 隆志, 曽根 博仁, 中田 光, Andrew Roberts, Warren Alexander

    日本臨床分子医学会学術総会プログラム・抄録集   51回   99 - 99   2014.4

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  • 巣症状を来したインスリノーマによる低血糖性脳症2例

    鈴木 達郎, 阿部 孝洋, 鈴木 亜希子, 北澤 勝, 皆川 真一, 山田 貴穂, 羽入 修, 曽根 博仁, 石澤 正博, 大澤 妙子

    日本内分泌学会雑誌   90 ( 1 )   319 - 319   2014.4

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  • 【心血管系疾患と糖尿病-どう対応していくか-】 識る 日本人の心血管疾患に糖尿病はどの程度影響しているのか?

    阿部 孝洋, 曽根 博仁

    Heart View   18 ( 4 )   358 - 367   2014.4

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  • 日本発臨床研究の紹介と反省点を語る 日本人2型糖尿病における顕性アルブミン尿発症と腎機能低下に対する糖尿病網膜症および微量アルブミン尿の影響 JDCSサブ解析から

    守屋 達美, 川崎 良, 曽根 博仁, 山下 英俊, 片山 茂裕

    日本内科学会雑誌   103 ( 4 )   987 - 993   2014.4

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    DOI: 10.2169/naika.103.987

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  • 【Brush Up! CDE 糖尿病合併症事典】 慢性合併症【大血管障害】 狭心症,心筋梗塞,無痛性心筋梗塞

    鈴木 裕美, 曽根 博仁

    糖尿病診療マスター   12 ( 3 )   282 - 285   2014.4

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    DOI: 10.11477/mf.1415101708

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  • 【糖尿病の最新食事療法のなぜに答える 基礎編】導入部 HbA1cの目標値が最近変わりました。なぜ変わったのですか?療養指導にどのように影響するのでしょうか?

    北澤 勝, 曽根 博仁

    臨床栄養   別冊 ( 栄養指導・管理のためのスキルアップシリーズ1 )   10 - 13   2014.4

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  • 【糖尿病の最新食事療法のなぜに答える 基礎編】導入部 糖尿病の診断は何を基準に行い、どのように治療方針をたてるのでしょうか?

    鈴木 浩史, 曽根 博仁

    臨床栄養   別冊 ( 栄養指導・管理のためのスキルアップシリーズ1 )   6 - 9   2014.4

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  • 詳細な食事調査で見る2型糖尿病通院者における各栄養摂取量と臨床値の関わり

    樋詰 友香, 畑中 麻梨恵, 水谷 有加利, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   57 ( Suppl.1 )   S - 204   2014.4

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  • シスタチンCとクレアチニンによる推算GFRの比較

    小川 真弓, 佐藤 舞菜見, 畑中 麻梨恵, 水谷 有加利, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹, 羽田 勝計

    糖尿病   57 ( Suppl.1 )   S - 187   2014.4

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  • 問診による2型糖尿病予測能のメタ分析

    由澤 咲子, 児玉 暁, 藤原 和哉, 堀川 千嘉, 菅原 歩美, 谷内 洋子, 山田 貴穂, 鈴木 亜希子, 羽入 修, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 205   2014.4

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  • 糖尿病スクリーニング後の早期治療と未治療放置が短期間の血糖コントロールに与える影響の大規模疫学的検討

    五十嵐 理沙, 平安座 依子, 児玉 暁, 由澤 咲子, 山田 貴穂, 藤原 和哉, 鈴木 亜希子, 羽入 修, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 144   2014.4

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  • 日本人糖尿病大規模臨床研究からのメッセージ これまでのまとめと将来展望 JDCS

    曽根 博仁, 赤沼 安夫, 山田 信博

    糖尿病   57 ( Suppl.1 )   S - 84   2014.4

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  • 肥満と臨床代謝指標の変化がその後の糖尿病発症に与える影響についての大規模縦断的検討 the Niigata Wellness Study

    羽入 修, 平安座 依子, 加藤 公則, 松永 佐澄志, 田代 稔, 児玉 暁, 藤原 和哉, 鈴木 亜希子, 佐藤 幸示, 曽根 博仁

    糖尿病   57 ( Suppl.1 )   S - 176   2014.4

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  • インスリンアスパルト・リスプロをグルリジンへ変更したときの影響

    柴野 淑子, 佐藤 舞菜見, 畑中 麻梨恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 首藤 龍人, 横山 宏樹

    糖尿病   57 ( Suppl.1 )   S - 160   2014.4

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  • CMLに対するWT1ペプチドワクチン療法によるWT1特異的CTLの長期間の増幅

    岩谷 俊平, 成田 美和子, 増子 正義, 西澤 幹則, 大岩 恵理, 井田 桃里, 岩渕 南, 内山 孝由, 柴崎 康彦, 瀧澤 淳, 曽根 博仁, 高橋 益廣

    新潟大学保健学雑誌   11 ( 1 )   83 - 91   2014.3

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    imatinibと改変型WT1ペプチドワクチンの併用療法を行ったHLA-A*24:02陽性の慢性骨髄性白血病慢性期(chronic myeloid leukemia-chronic phase;CML-CP)の症例に対し、ワクチン接種前から4週間毎に14日の末梢血単核球を混合リンパ球ペプチド培養(mixed lymphocyte peptide culture;MLPC)行い、WT1/MHC-tetramer+CD8+細胞の末梢血CD8陽性細胞中の頻度の変動を6年間継続して解析した。ペプチドを添加した自己B細胞株を標的細胞として細胞傷害活性試験を行い、今回検出されたWT1/MHC-tetramer+CD8+細胞は確実に細胞傷害活性を有することを確認した。WT1ペプチドワクチンの臨床効果も確認された。すなわち、ワクチン投与終了7ヵ月後には、bcr/ablコピー数が次第に減少しMMR(major molecular response;MMR)に入り、その後、CMR(complete molecular response;CMR)に到達し、WT1ペプチドワクチン投与終了後5年経過した現在もCMRは維持されている。WT1ペプチドワクチンとimatinib併用療法は、TKI(tyrosine kinase inhibitor;TKI)が十分に作用できないCML幹細胞に対し有効である可能性が示された。(著者抄録)

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    Other Link: http://hdl.handle.net/10191/38944

  • 詳細な食事摂取調査で見る2型糖尿病通院者における各栄養摂取と臨床値の関わり

    樋詰 友香, 柴野 淑子, 畑中 麻梨恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   57 ( 3 )   205 - 205   2014.3

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  • 【糖尿病の臨床研究をどう紐解くか-批判的吟味を実臨床へつなぐ-】 システマティックレビュー・メタアナリシスを紐解く(2)"The association between dietary patterns and type 2 diabetes:a systematic review and meta-analysis of cohort studies"を題材に

    児玉 暁, 曽根 博仁

    プラクティス   31 ( 2 )   205 - 209   2014.3

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  • 糖尿病患者における運動療法のエビデンス

    曽根 博仁

    Diabetes Journal: 糖尿病と代謝   42 ( 1 )   7 - 13   2014.3

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    運動は糖尿病予防効果を有することが知られている。しかし糖尿病患者に対する運動療法は、臨床現場における療養指導も、臨床エビデンスの充実度(とくに介入研究)も十分とはいえない。わが国の2型糖尿病患者を対象にしたJapan Diabetes Complications Study(JDCS)では、最も運動量が多い3分位の患者の脳卒中発症率や死亡率が、最も運動量が少ない3分位の患者と比較して半減していた。その最も運動量が多い3分位の境界値は速足歩き換算で1日30分以上であったが、その群に属する患者の平均量は1日70分に達していた。一方、最も運動量が少ない3分位の患者は、仕事と家事以外に、運動療法としての運動をほとんど実施していなかった。患者が運動を開始・継続できるようにサポートし、運動療法に関するさまざまな臨床エビデンスを充実させることは、患者の健康寿命の延伸とともに国民医療費の抑制の観点からも大きな効果が期待される。(著者抄録)

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  • 2型糖尿病患者における糖尿病網膜症の発症と進展及びその危険因子 The Japan Diabetes Complications Study(JDCS)8年追跡調査

    川崎 良, 田中 司朗, 田中 佐智子, 山本 禎子, 曽根 博仁, 大橋 靖雄, 赤沼 安夫, 山田 信博, 山下 英俊

    日本糖尿病眼学会誌   18   11 - 11   2014.3

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  • 県医よろずQ&A 新しい糖尿病治療薬の使い分けについて

    曽根 博仁

    新潟県医師会報   ( 768 )   57 - 57   2014.3

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  • 難治性高血圧症患者の特徴

    菅野 咲子, 佐藤 舞菜見, 畑中 麻梨恵, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   57 ( 3 )   216 - 216   2014.3

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  • ABI異常者の死亡、心血管イベントへ及ぼす影響 3,300名の観察コホート研究

    畑中 麻梨恵, 菅野 咲子, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   57 ( 3 )   215 - 215   2014.3

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  • MMSEを用いた1,400例への認知機能の評価

    小川 真弓, 菅野 咲子, 友重 栄美, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 首藤 龍人, 曽根 博仁, 横山 宏樹

    糖尿病   57 ( 3 )   222 - 222   2014.3

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  • ビルダグリプチンのシタグリプチンとの比較

    佐藤 舞菜見, 菅野 咲子, 小川 真弓, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 首藤 龍人, 横山 宏樹

    糖尿病   57 ( 3 )   219 - 219   2014.3

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  • 再発後の再移植後の汎血球減少期にgrade4の重症心不全を併発するも救命しえた急性骨髄性白血病

    宮腰淑子, 柴崎康彦, 布施香子, 森山雅人, 古川達雄, 勝海悟郎, 小田雅人, 渡部裕, 柏村健, 南野徹, 曽根博仁, 増子正義

    日本造血細胞移植学会総会プログラム・抄録集   36th   341   2014.2

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  • 同種造血幹細胞移植における血清蛋白と発熱・炎症所見との関連性の検討

    松本瑛生, 森山雅人, 平安座依子, 田中智之, 宮腰淑子, 小堺貴司, 小林弘典, 布施香子, 柴崎康彦, 増子正義, 瀧澤淳, 古川達雄, 曽根博仁, 西條康夫

    日本造血細胞移植学会総会プログラム・抄録集   36th   360   2014.2

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  • 急性骨髄性白血病及び骨髄異形成症候群に対する同種造血幹細胞移植成績に移植前骨髄の芽球率が与える影響

    柴崎康彦, 宮越淑子, 小堺貴司, 小林弘典, 森山雅人, 古川達雄, 増子正義, 曽根博仁

    日本造血細胞移植学会総会プログラム・抄録集   36th   331   2014.2

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  • メタ分析によるゲノムワイド関連解析(GWAS)における糖尿病関連複数遺伝子と糖尿病との定量的相関性の検討

    児玉 暁, 藤原 和哉, 松永 佐澄志, 古川 和郎, 山田 貴穂, 鈴木 亜希子, 島野 仁, 羽入 修, 曽根 博仁

    日本内科学会雑誌   103 ( Suppl. )   152 - 152   2014.2

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  • 【2型糖尿病の新しい処方戦略】 食後高血糖の改善を目指して α-グルコシダーゼ阻害薬

    藤原 和哉, 曽根 博仁

    Pharma Medica   32 ( 2 )   27 - 32   2014.2

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  • 妊娠中期糖負荷後血糖値は低出生体重児出産を予測する指標として有用である

    田中 康弘, 谷内 洋子, 曽根 博仁

    日本産科婦人科学会雑誌   66 ( 2 )   757 - 757   2014.2

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  • 原発性アルドステロン症 新潟プロトコールについての提案

    鈴木 裕美, 鈴木 達郎, 北澤 勝, 植村 靖行, 鈴木 浩史, 古川 和郎, 山田 貴穂, 松永 佐澄志, 皆川 真一, 鈴木 亜希子, 羽入 修, 曽根 博仁

    新潟医学会雑誌   128 ( 2 )   92 - 93   2014.2

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  • 糖尿病・脂質異常症・高血圧に対する運動療法の効果と意義

    曽根 博仁

    体力科学   63 ( 1 )   38 - 38   2014.2

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    DOI: 10.7600/jspfsm.63.38

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    Other Link: http://search.jamas.or.jp/link/ui/2014173214

  • MYC転座陽性アグレッシブB細胞リンパ腫15例の後方視的解析

    瀧澤 淳, 宮腰 淑子, 田中 智之, 小堺 貴司, 小林 弘典, 柴崎 康彦, 森山 雅人, 増子 正義, 曽根 博仁

    日本内科学会雑誌   103 ( Suppl. )   174 - 174   2014.2

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  • 現在BMIと20歳時や生涯最大BMIを組み合わせた高血圧発症予測の縦断的検討

    平安座依子, 児玉暁, 齋藤和美, 島野仁, 田中司朗, 荒瀬康司, 原茂子, 曽根博仁

    J Epidemiol   24 ( Supplement 1 )   72   2014.1

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  • 糖尿病患者のヘリコバクター・ピロリ菌感染における血糖コントロール及び除菌成功率との関連性:メタ解析

    堀川千嘉, 児玉暁, 藤原和哉, 谷内洋子, 羽入修, 島野仁, 曽根博仁

    J Epidemiol   24 ( Supplement 1 )   102   2014.1

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  • 妊娠中の母体の血糖状態と低出生体重児出産との関連(TWC Study)

    谷内洋子, 田中康弘, 西端泉, 由澤咲子, 藤原和哉, 児玉暁, 鈴木亜希子, 羽入修, 曽根博仁

    J Epidemiol   24 ( Supplement 1 )   114   2014.1

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  • ヘモグロビンA1c検査による糖尿病スクリーニングとその後の通院治療開始が血糖コントロールに与える影響

    平安座依子, 羽入修, 鈴木亜希子, 児玉暁, 島野仁, 曽根博仁

    J Epidemiol   24 ( Supplement 1 )   72   2014.1

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  • 2型糖尿病患者における食塩摂取量と合併症発症リスクの関連性 JDCS

    堀川 千嘉, 田中 司朗, 羽入 修, 井藤 秀喜, 大橋 靖雄, 吉村 幸雄, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   40   64 - 64   2014.1

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  • 【糖尿病と脳卒中】 DPP-4阻害薬による脳卒中予防効果

    小原 伸雅, 曽根 博仁

    分子脳血管病   13 ( 1 )   27 - 32   2014.1

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    新しい経口2型糖尿病治療薬であるdipeptidyl peptidase-4(DPP-4)阻害薬は、おもに食後高血糖の改善効果に優れ、体重増加や低血糖を起こしにくいことを特徴とする。糖尿病患者に対する血糖管理の脳卒中(脳梗塞)を予防する効果が今まで必ずしも明確となっていないなかで、欧米人においてDPP-4阻害薬を用いた血糖管理による脳梗塞発症予防効果が示されている。日本人2型糖尿病患者と欧米患者とのあいだでは、肥満度の明らかな違いに加えてDPP-4阻害薬の効果にも差がある可能性が示唆されており、DPP-4阻害薬による脳梗塞予防効果について日本人患者での検討も必要である。(著者抄録)

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  • 糖尿病患者におけるヘリコバクター・ピロリ菌感染と血糖コントロールの関係 メタ解析

    堀川 千嘉, 児玉 暁, 藤原 和哉, 谷内 洋子, 羽入 修, 島野 仁, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   40   55 - 55   2014.1

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  • 糖尿病患者は非糖尿病患者よりもヘリコバクター・ピロリ菌除菌成功率が低い メタ解析

    堀川 千嘉, 児玉 暁, 藤原 和哉, 谷内 洋子, 羽入 修, 島野 仁, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   40   75 - 75   2014.1

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  • 日本人の食事摂取基準の策定に資する代謝性疾患の栄養評価に関する研究「糖尿病合併症と食事に関する最近の研究のレビュー」

    曽根博仁, 児玉暁

    日本人の食事摂取基準の策定に資する代謝性疾患の栄養評価に関する研究 平成25年度 総括・分担研究報告書   367 - 410   2014

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  • 妊娠初期HbA1c値および空腹時血糖値と妊娠糖尿病発症との関連の検討(TWC Study)

    谷内 洋子, 田中 康弘, 西端 泉, 広瀬 歩美, 児玉 暁, 曽根 博仁

    DOHaD研究   3 ( 1 )   44 - 44   2014

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    第3回日本DOHaD研究会学術集会 抄録集 【ポスター発表】

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    Nobumasa Ohara, Osamu Hanyu, Hirohito Sone

    Journal of Hypertension   32 ( 11 )   2278   2014

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    DOI: 10.1097/HJH.0000000000000353

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  • 日本人妊婦325名における,妊娠早期の炭水化物摂取量と50g糖負荷試験陽性リスクの関連

    田島諒子, 飯田薫子, 穴迫唯衣, 田中康弘, 曽根博仁, 谷内洋子

    New Diet Therapy   30 ( 2 )   2014

  • 診断に難渋した妊娠時発症甲状腺クリーゼの1例

    鈴木 浩史, 周 啓亮, 山田 貴穂, 鈴木 達郎, 北澤 勝, 植村 靖行, 皆川 慎一, 鈴木 亜希子, 羽入 修, 曽根 博仁, 山口 雅幸, 本多 忠幸, 山谷 恵一

    日本内分泌学会雑誌   89 ( 3 )   955 - 955   2013.12

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  • メタボリックシンドロームに取り組む機能性食品 糖尿病、糖代謝異常と機能性食品

    曽根 博仁

    機能性食品と薬理栄養   8 ( 1 )   64 - 64   2013.12

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  • Early Responses At 3 Months and 12 Months After Starting Imatinib As Predictive Factors For The Achievement Of Deep MR In Japanese CML Patients

    Masayoshi Masuko, Tatsuo Furukawa, Tadashi Koike, Kazue Takai, Koichi Nagai, Kenji Kishi, Yoshinobu Seki, Hoyu Takahashi, Sadao Aoki, Takashi Kozakai, Yasuhiko Shibasaki, Takashi Ushiki, Ken Toba, Miwako Narita, Masuhiro Takahashi, Hirohito Sone, Akira Shibata

    BLOOD   122 ( 21 )   2013.11

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    DOI: 10.1182/blood.V122.21.2744.2744

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  • HbA(1c) variability and the development of microalbuminuria in type 2 diabetes: Tsukuba Kawai Diabetes Registry 2 (vol 55, pg 2128, 2012)

    A. Sugawara, K. Kawai, S. Motohashi, K. Saito, S. Kodama, Y. Yachi, R. Hirasawa, H. Shimano, K. Yamazaki, H. Sone

    DIABETOLOGIA   56 ( 11 )   2548 - 2548   2013.11

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    DOI: 10.1007/s00125-013-3042-6

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  • 東アジア発の臨床エビデンスを創る

    曽根 博仁

    新潟医学会雑誌   127 ( 11 )   585 - 591   2013.11

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    わが国でもEvidence-based medicine(科学的根拠に基づく医療)は一般的になって久しいが、診療ガイドラインの記載内容を含め、今のところこれを支えているのは、残念ながら大部分が欧米の大規模臨床研究の臨床エビデンスである。特に2型糖尿病を代表とする代謝疾患や動脈硬化疾患(いわゆる生活習慣病)では、その発症と進行に遺伝的背景や生活環境が強く関連するため、欧米人を対象にした研究から得られた臨床エビデンスが、わが国の患者にはそのまま当てはまらないことも多い。したがって日本における生活習慣病の診療ならびにその施策立案には、大人数の日本人対象者を擁する大規模臨床研究を実施する必要がある。本稿では糖尿病を例に、日本と欧米との臨床像や臨床エビデンスの違いを述べ、さらにこれまでの大規模臨床研究の歴史を概説した上、今後、我々が進むべき方向性について考察する。(著者抄録)

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  • 【高齢者の糖尿病】 高齢者糖尿病の予後増悪因子とその予防・管理 脳卒中

    皆川 真一, 羽入 修, 曽根 博仁

    日本臨床   71 ( 11 )   1948 - 1953   2013.11

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  • 【糖尿病運動療法:運動指導成功のためのノウハウ-ホップ・ステップ・ジャンプ-】 糖尿病運動療法のエビデンス

    曽根 博仁

    臨床スポーツ医学   30 ( 10 )   939 - 946   2013.10

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  • 糖尿病合併症予防のための血糖管理の重要性

    西尾 善彦, King George L, 曽根 博仁

    Diabetes Frontier   24 ( 5 )   576 - 579   2013.10

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  • 遅延性に輸血後E型肝炎を発症した急性前骨髄球性白血病の1例

    高橋 祥史, 上村 顕也, 阿部 寛幸, 水野 研一, 竹内 学, 須田 剛士, 野本 実, 青柳 豊, 布施 香子, 森山 雅人, 増子 正義, 曽根 博仁

    新潟医学会雑誌   127 ( 10 )   568 - 568   2013.10

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  • 妊娠初期空腹時血糖およびHbA1c値両者の同時測定は妊娠糖尿病発症を予測する指標として有用である(TWC Study)

    谷内 洋子, 田中 康弘, 西端 泉, 由澤 咲子, 藤原 和哉, 児玉 暁, 鈴木 亜希子, 羽入 修, 曽根 博仁

    糖尿病と妊娠   13 ( 2 )   S - 80   2013.10

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  • 医学と医療の最前線 日本人2型糖尿病患者の特徴と病態についての臨床疫学

    曽根 博仁, 赤沼 安夫, 山田 信博

    日本内科学会雑誌   102 ( 10 )   2714 - 2722   2013.10

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    DOI: 10.2169/naika.102.2714

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  • 【糖尿病治療薬の最前線〜臨床試験・臨床疫学的観点も含めて〜】 糖尿病における脂質異常症治療とその成績

    皆川 真一, 曽根 博仁

    医薬ジャーナル   49 ( 10 )   2401 - 2406   2013.10

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    糖尿病治療の目的は、合併症の発症、進展の予防である。特に大血管合併症は、生命予後と深く関連している。日本人を対象としたJapan Diabetes Complication Study(JDCS)では、冠動脈疾患の発症リスク因子として、LDL(低比重リポ蛋白)コレステロール、中性脂肪がHbA1cより上位であることが示され、脂質管理の重要性が改めて認識されている。本稿では大血管合併症予防における脂質管理について述べるとともに、フィブラートでの細小血管合併症予防効果についてもまとめた。(著者抄録)

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  • 【糖尿病治療薬の最前線〜臨床試験・臨床疫学的観点も含めて〜】 αグルコシダーゼ阻害薬と治療成績

    藤原 和哉, 曽根 博仁

    医薬ジャーナル   49 ( 10 )   2353 - 2359   2013.10

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    αグルコシダーゼ阻害薬は、上部小腸からの炭水化物の吸収を遅らせ、食後血糖値の上昇を抑制する薬物である。単独投与において低血糖の頻度が低く、体重増加をきたしにくいという特性を持ち、他の糖尿病治療薬との併用効果もあり、幅広い使い方が可能である。さらに、食後高血糖を是正することにより2型糖尿病発症抑制や、心血管疾患を抑制することも報告されている。以前より食後高血糖が心血管疾患の危険因子である可能性が指摘されてきたが、24時間持続血糖モニタリングの普及にて食後血糖を含めた1日の血糖変動の測定が可能となり、今後は低血糖を回避するとともに、食後高血糖を意識したきめ細かい血糖コントロールを行うことが重要となる。本稿では、αグルコシダーゼ阻害薬の種類と特徴、食後血糖のエビデンスについて述べる。(著者抄録)

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  • 健常妊婦における栄養と妊娠経過に関する中間解析

    谷内 洋子, 曽根 博仁

    栄養学雑誌   71 ( 5 )   242 - 252   2013.10

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    【目的】健常妊婦を対象に、妊娠末期に3日間の食事調査を実施し、妊娠中の栄養摂取状況を明らかにするとともに、初診時および出産時のBMIと低出生体重児(LBWI)出産との関連について前向きに検討する。【方法】妊娠13週までに都内産科医院を初診した、単胎妊娠かつ正常血圧で糖尿病の既往がない妊婦199名を対象に、妊娠末期(28〜32週)において3日間の食事調査を実施、栄養素別摂取量を算出した。また、初診時および出産時BMIとLBWI出産との関係をロジスティック回帰分析により検討した。【結果】平均総摂取エネルギー量は1,768±286kcalで、日本人の食事摂取基準における妊娠末期推定エネルギー必要量を下回っていた。ロジスティック回帰分析の結果、初診時BMIのオッズ比は0.54:(95%Cl:0.33〜0.91)で、母体年齢や妊娠週数などとは独立してLBWI出産と関連を認め(p&lt;0.05)、同様に出産時BMIについても0.54:(95%Cl:0.33〜0.88)とLBWI出産と関連を認めた(p&lt;0.05)。すなわち、BMIが高いほどLBWI出産リスクが低下した。【結論】対象妊婦において、妊娠末期のエネルギー摂取不足の現状が明らかとなった。また初診時および出産時の低いBMIとLBWI出産に関連があったことから、妊娠前・妊娠中を通して継続的な健康栄養教育の促進が急務と考えられた。(著者抄録)

    DOI: 10.5264/eiyogakuzashi.71.242

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  • 多彩な画像所見を呈し肝生検で確診した血管内リンパ腫の1例

    眞水 麻以子, 西山 佑樹, 畠野 雄也, 阿部 寛幸, 上村 顕也, 高橋 祥史, 水野 研一, 竹内 学, 川合 弘一, 野本 実, 青柳 豊, 柴崎 康彦, 瀧澤 淳, 曽根 博仁, 石黒 敬信, 堅田 慎一, 西澤 正豊, 高野 徹

    新潟医学会雑誌   127 ( 10 )   581 - 582   2013.10

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  • αグルコシダーゼ阻害薬と治療成績 (特集 糖尿病治療薬の最前線 : 臨床試験・臨床疫学的観点も含めて)

    藤原 和哉, 曽根 博仁

    医薬ジャーナル   49 ( 10 )   65 - 71   2013.10

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  • 糖尿病における脂質異常症治療とその成績 (特集 糖尿病治療薬の最前線 : 臨床試験・臨床疫学的観点も含めて)

    皆川 真一, 曽根 博仁

    医薬ジャーナル   49 ( 10 )   113 - 118   2013.10

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  • Dietary sodium intake and incidence of diabetic complications in Japanese patients with type 2 diabetes: analysis of the Japan Diabetes Complications Study (JDCS)

    C. Horikawa, Y. Yoshimura, C. Kamada, S. Tanaka, S. Tanaka, T. Yamada, A. Suzuki, O. Hanyu, A. Araki, A. Tanaka, Y. Ohashi, Y. Akanuma, N. Yamada, H. Sone

    DIABETOLOGIA   56   S104 - S104   2013.9

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  • 【臓器脂質の視点からみた糖尿病病態-リポトキシシティアップデート-】 食後脂質異常症と大血管合併症

    植村 靖行, 曽根 博仁

    月刊糖尿病   5 ( 9 )   66 - 73   2013.9

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  • 【どこが違う?どう違う? 図解でくらべる→わかる! 糖尿病の病態・治療・ケア】 (第3章)糖尿病合併症〜慢性合併症 脳梗塞と心筋梗塞

    松永 佐澄志, 曽根 博仁

    糖尿病ケア   ( 2013秋季増刊 )   140 - 147   2013.9

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  • 【糖尿病運動療法-今すぐできる工夫と今後の課題-】 糖尿病治療における運動のエビデンスと今後の課題

    曽根 博仁

    プラクティス   30 ( 5 )   569 - 576   2013.9

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  • 術後に微小癌の合併が判明した甲状腺機能性結節の1例

    山田 貴穂, 阿部 孝洋, 松林 泰弘, 横山 侑輔, 渡辺 順, 橋本 茂久, 渋谷 宏行, 百都 健, 曽根 博仁

    日本内分泌学会雑誌   89 ( 2 )   506 - 506   2013.9

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  • Predicting macro- and microvascular complications in type 2 diabetes: the Japan diabetes complications study / the Japanese elderly diabetes intervention trial risk engine

    S. Tanaka, S. Tanaka, S. Iimuro, H. Yamashita, S. Katayama, Y. Akanuma, N. Yamada, A. Araki, H. Ito, H. Sone, Y. Ohashi

    DIABETOLOGIA   56   S188 - S188   2013.9

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  • Predictive ability of simple clinical information without blood tests for future incident diabetes: a meta-analysis

    S. Yoshizawa, S. Kodama, K. Fujihara, C. Horikawa, A. Sugawara, Y. Heianza, Y. Yachi, S. Tanaka, S. Minakawa, T. Yamada, A. Suzuki, O. Hanyu, H. Sone

    DIABETOLOGIA   56   S137 - S137   2013.9

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  • 糖尿病の運動療法(第7回) 運動療法の意義 身体運動と糖尿病 疫学的研究成績

    曽根 博仁

    月刊糖尿病   5 ( 8 )   102 - 108   2013.8

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  • 糖尿病治療における脂質管理の効果と意義

    横手 幸太郎, 古家 大祐, 曽根 博仁, 宮内 克己

    Cardio-Renal Diabetes   2 ( 3 )   104 - 112   2013.8

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  • 当院における副腎静脈サンプリングの実績

    鈴木 裕美, 金子 正儀, 川田 亮, 大澤 妙子, 古川 和郎, 山田 貴穂, 山田 絢子, 伊藤 崇子, 鈴木 亜希子, 羽入 修, 曽根 博仁, 吉村 宣彦, 青山 英史

    新潟医学会雑誌   127 ( 8 )   446 - 446   2013.8

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  • 地域において未病を考える 地域医療における糖尿病の予防と治療 未病システム学における糖尿病の意義

    曽根 博仁

    日本未病システム学会雑誌   19 ( 2 )   73 - 78   2013.8

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  • 2型糖尿病網膜症患者における糖尿病網膜症の発症と進展およびその危険因子 Japan Diabetes Complications Study(JDCS)の結果を中心に

    川崎 良, 田中 司朗, 田中 佐智子, 山本 禎子, 曽根 博仁, 大橋 靖雄, 赤沼 安夫, 山田 信博, 山下 英俊

    糖尿病合併症   27 ( 2 )   147 - 154   2013.8

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    成人2型糖尿病患者における糖尿病網膜症の発症と進展およびその危険因子をJapan Diabetes Complications Study(JDCS)の8年間追跡調査を元に調査した。JDCSは全国59糖尿病専門施設が参加する大規模多施設共同研究で、40-70歳の2型糖尿病患者を対象とし、研究開始時に糖尿病網膜症を有しない症例1,221名の糖尿病網膜症の発症率は38.3/1,000人年、研究開始時に軽症非増殖糖尿病網膜症を有する症例410名における重症非増殖網膜症あるいは増殖網膜症への進展率は21.1/1,000人年であった。網膜症発症の危険因子として、高ヘモグロビンA1c(HbA1c)[+1%あたり1.36倍糖尿病罹病期間(5年あたり1.26倍)]、高収縮期血圧(+10mmHgあたり1.01倍)、そして高BMI(+1kg/m2あたり1.05倍)が挙げられた。高HbA1cは糖尿病網膜症の進展率とも関連していた(+1%あたり1.66倍)。HbA1cと糖尿病網膜症の発症は直線的な線形回帰で説明されたが、糖尿病罹病期間と網膜症発症の間には閾値が存在し、特に罹病期間5年から10年の間に網膜症発症の危険が急峻に高まることが示唆された。(著者抄録)

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  • 【糖尿病における性差医療】 細小血管障害

    山田 貴穂, 鈴木 亜希子, 曽根 博仁

    糖尿病   56 ( 8 )   535 - 538   2013.8

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    DOI: 10.11213/tonyobyo.56.535

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  • 糖尿病大血管症の予防・治療を目指した新しい治療戦略 糖尿病と脳・心血管イベント JDCSからのメッセージ

    曽根 博仁, 赤沼 安夫, 山田 信博

    糖尿病合併症   27 ( Suppl.1 )   78 - 78   2013.8

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  • High-Dose Metformin vs. Sitagliptin in Addition to Metformin 750mg in Insufficiently Controlled Japanese Type 2 Diabetes Patients With Metformin 750mg

    Kazuo Furukawa, Osamu Hanyu, Yoriko Heianza, Yasuyuki Uemura, Ryo Kawada, Masahiko Yamamoto, Taeko Osawa, Masanori Kaneko, Takaho Yamada, Hiromi Suzuki, Shinichi Minagawa, Ayako Yamada, Akiko Suzuki, Hirohito Sone

    DIABETES   62   A671 - A671   2013.7

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  • Intakes of Dietary Fiber, Vegetables, and Fruits and Incidence of Cardiovascular Disease in Japanese Patients With Type 2 Diabetes

    Shiro Tanaka, Yukio Yoshimura, Chiemi Kamada, Sachiko Tanaka, Chika Horikawa, Ryota Okumura, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

    DIABETES   62   A398 - A398   2013.7

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  • Utility of Elevated 1-h Glucose Values for Assessment of Pathogenesis of Type 2 Diabetes in Japanese Individuals

    Yoriko Heianza, Yasuji Arase, Satoru Kodama, Shiun Dong Hsieh, Kazuya Fujihara, Shiro Tanaka, Akiko Suzuki, Osamu Hanyu, Kazumi Saito, Hitoshi Shimano, Shigeko Hara, Hirohito Sone

    DIABETES   62   A380 - A380   2013.7

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  • Relationship between Body Weight (BW) Gain from Early Adulthood and Incident Type 2 Diabetes (T2DM): A Meta-Analysis

    Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Ryoko Tajima, Yoriko Heianza, Yoko Yachi, Kaoruko T. Iida, Hitoshi Shimano, Osamu Hanyu, Hirohito Sone

    DIABETES   62   A389 - A389   2013.7

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  • Relationship of Living Alone With Undiagnosed Diabetes in Japan: Toranomon Hospital Health Management Center Study

    Yoriko Heianza, Yasuji Arase, Satoru Kodama, Shiun Dong Hsieh, Ayumi Sugawara, Shiro Tanaka, Akiko Suzuki, Osamu Hanyu, Kazumi Saito, Hitoshi Shimano, Shigeko Hara, Hirohito Sone

    DIABETES   62   A209 - A209   2013.7

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  • Low Eradication Rate of Helicobacter Pylori (HP) in Patients With Diabetes: A Meta-Analysis

    Chika Horikawa, Satoru Kodama, Sakiko Yoshizawa, Kazuya Fujihara, Ryoko Tajima, Yoko Yachi, Akiko Suzuki, Osamu Hanyu, Hitoshi Shimano, Hirohito Sone

    DIABETES   62   A408 - A408   2013.7

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  • Comparison of Significance of Body Weight (BW) Change Associated With Subsequent Type 2 Diabetes (T2DM) Risk in Different Periods of Adulthood-A Meta-Analysis

    Satoru Kodama, Kazuya Fujihara, Chika Horikawa, Ryoko Tajima, Sakiko Yoshizawa, Kazumi Saito, Shiro Tanaka, Osamu Hanyu, Hitoshi Shimano, Hirohito Sone

    DIABETES   62   A20 - A21   2013.7

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  • Skin Accumulation of Advanced Glycation End-Products (AGEs) Highly Correlates With Severity of Renal Complications in Patients With Diabetes

    Ryo Kawada, Osamu Hanyu, Kazuo Furukawa, Masahiro Ishizawa, Masahiko Yamamoto, Taeko Osawa, Takaho Yamada, Shiniti Minagawa, Hiromi Suzuki, Ayako Yamada, Yoriko Heiznza, Akiko Suzuki, Hirohito Sone

    DIABETES   62   A396 - A396   2013.7

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  • Effect of Helicobacter Pylori (HP) Infection on Glycemic Control in Patients With Diabetes: A Meta-Analysis

    Sakiko Yoshizawa, Satoru Kodama, Ryoko Tajima, Kazuya Fujihara, Chika Horikawa, Yoko Yachi, Akiko Suzuki, Osamu Hanyu, Hitoshi Shimano, Hirohito Sone

    DIABETES   62   A412 - A412   2013.7

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  • 発症8年後に悪性貧血を併発した特発性1型糖尿病の1例

    小原 伸雅, 金子 正儀, 皆川 真一, 矢野 敏雄, 佐藤 直子, 曽根 博仁, 鴨井 久司, 金子 兼三

    糖尿病   56 ( 7 )   451 - 451   2013.7

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  • Basic & Clinical TOPICS (臨床1)2型糖尿病におけるスルホニル尿素薬、メトホルミンの初期単剤療法が心血管リスクに与える影響

    鈴木 亜希子, 曽根 博仁

    Diabetes Update   2 ( 3 )   158 - 159   2013.7

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  • Aspergillus fumigatusによる頭蓋底骨髄炎を発症した2型糖尿病の1例

    金子 正儀, 大澤 妙子, 鈴木 亜希子, 川田 亮, 古川 和郎, 山田 絢子, 山田 貴穂, 鈴木 裕美, 伊藤 崇子, 羽入 修, 曽根 博仁

    糖尿病   56 ( 7 )   462 - 462   2013.7

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  • 多彩な画像所見を呈し肝生検で診断しえた血管内リンパ腫の1例

    岩瀬 麻以子, 阿部 寛幸, 上村 顕也, 高橋 祥史, 水野 研一, 竹内 学, 川合 弘一, 野本 実, 青柳 豊, 畠野 雄也, 石黒 敬信, 堅田 慎一, 西澤 正豊, 岡塚 貴世志, 瀧澤 淳, 曽根 博仁, 高野 徹

    新潟医学会雑誌   127 ( 7 )   389 - 390   2013.7

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  • 腹水を契機に発見されたTPLLの1例

    棚橋 怜生, 布施 香子, 田中 智之, 小堺 貴司, 森山 雅人, 増子 正義, 瀧澤 淳, 古川 達雄, 曽根 博仁

    新潟医学会雑誌   127 ( 7 )   386 - 386   2013.7

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  • 右片麻痺をきたしたインスリノーマの1例

    大澤 妙子, 金子 正儀, 鈴木 亜希子, 山本 正彦, 川田 亮, 古川 和郎, 山田 貴穂, 皆川 真一, 鈴木 裕美, 山田 絢子, 伊藤 崇子, 羽入 修, 曽根 博仁

    新潟医学会雑誌   127 ( 7 )   386 - 386   2013.7

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  • HbA1C in the First Trimester Predicts Gestational Diabetes Independent of Fasting Glucose in Japanese Pregnant Women: TWC Study

    Yoko Yachi, Yasuhiro Tanaka, Ayumi Sugawara, Izumi Nishibata, Chika Horikawa, Yoriko Heianza, Kazuya Fujihara, Osamu Hanyu, Satoru Kodama, Hirohito Sone

    DIABETES   62   A358 - A358   2013.7

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  • Relationship between Diabetic Neuropathy and Sleep Apnea Syndrome-A Meta-Analysis

    Kazuya Fujihara, Satoru Kodama, Chika Horikawa, Ayumi Sugawara, Yoriko Heianza, Hitoshi Shimano, Yoko Yachi, Kazumi Saito, Osamu Hanyu, Hirohito Sone

    DIABETES   62   A397 - A397   2013.7

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  • メトホルミンの血中濃度を追跡し救命した乳酸アシドーシスの1例

    尾本 美代子, 五十野 桃子, 藤原 和哉, 錦 健太, 高橋 昭光, 小林 和人, 矢藤 繁, 鈴木 浩明, 島野 仁, 山田 信博, 野牛 宏晃, 曽根 博仁

    日本内分泌学会雑誌   89 ( Suppl.Update )   90 - 91   2013.6

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    インスリン不足の糖尿病では、ミトコンドリアでのピルビン酸脱水素酵素活性の低下によりピルビン酸・乳酸が蓄積しやすい状態にある。今回著者等は、高齢の1型糖尿病患者でメトホルミンによる乳酸アシドーシスを引き起こし、早期の血液透析により救命しえた症例を経験した。患者は81歳女性、メトホルミンの血中濃度を第8病日まで追跡し、経時的に低下していることを確認した。

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  • 2型糖尿病患者におけるMDA-LDLを用いた脂質指標の冠動脈狭窄病変予測能の検討

    藤原 和哉, 鈴木 浩明, 佐藤 明, 石津 智子, 平安座 依子, 児玉 暁, 高橋 昭光, 小林 和人, 矢藤 繁, 矢作 直也, 野牛 宏晃, 曽根 博仁, 島野 仁

    日本動脈硬化学会総会プログラム・抄録集   45回   312 - 312   2013.6

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  • INHIBITION OF ERYTHROPOIESIS THROUGH HEPCIDIN AND ROS IN TRANSFUSION-RELATED IRON OVERLOAD MICE

    M. Masuko, H. Kobayashi, T. Ushiki, T. Kozakai, G. Hasegawa, H. Hanawa, T. Furukawa, H. Sone, M. Naito

    HAEMATOLOGICA   98   417 - 418   2013.6

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  • メタ解析 成人においてどの時期の体重増加が2型糖尿病発症に大きく関わるか?

    児玉 暁, 堀川 千嘉, 藤原 和哉, 由澤 咲子, 伊部 陽子, 平安座 依子, 谷内 洋子, 鈴木 亜紀子, 羽入 修, 曽根 博仁

    成人病と生活習慣病   43 ( 5 )   629 - 629   2013.5

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  • 【2型糖尿病診療における15のコントロバシー】 糖尿病の代謝管理 糖尿病患者における脂質管理はどこまで厳格であるべきか 異論/争論,私の意見

    羽入 修, 曽根 博仁

    糖尿病診療マスター   11 ( 4 )   391 - 396   2013.5

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    DOI: 10.11477/mf.1415101523

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  • RE: "COMPARISONS OF THE STRENGTH OF ASSOCIATIONS WITH FUTURE TYPE 2 DIABETES RISK AMONG ANTHROPOMETRIC OBESITY INDICATORS, INCLUDING WAIST-TO-HEIGHT RATIO: A META-ANALYSIS" REPLY

    Satoru Kodama, Hirohito Sone

    AMERICAN JOURNAL OF EPIDEMIOLOGY   177 ( 8 )   863 - 863   2013.4

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    DOI: 10.1093/aje/kwt036

    Web of Science

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  • 肥満度指数(BMI)別にみた血清中性脂肪(TG)と糖尿病発症の関連の検討 茨城県健康研究

    藤原 和哉, 菅原 歩美, 西連地 利己, 入江 ふじこ, 渡辺 宏, 曽根 博仁, 大田 仁史

    糖尿病   56 ( Suppl.1 )   S - 117   2013.4

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  • 当科における悪性リンパ腫と合併する悪性腫瘍の後方視的検討

    宮腰 淑子, 瀧澤 淳, 田中 智之, 布施 香子, 小堺 貴司, 柴崎 康彦, 森山 雅人, 増子 正義, 曽根 博仁, 尾山 徳秀, 大島 孝一

    日本リンパ網内系学会会誌   53   113 - 113   2013.4

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  • 妊娠を契機に診断された新規の遺伝子変異を伴うUpshaw-Schulman症候群(USS)の一例

    小堺 貴司, 森山 雅人, 布施 一郎, 柴崎 康彦, 増子 正義, 瀧澤 淳, 鳥羽 健, 吉田 邦彦, 小亀 浩市, 宮田 敏行, 松本 雅則, 藤村 吉博, 曽根 博仁

    日本血栓止血学会誌   24 ( 2 )   213 - 213   2013.4

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  • Nelarabine/Fludarabine併用療法により寛解を得たT-PLLの一例

    布施 香子, 瀧澤 淳, 宮腰 淑子, 田中 智之, 小堺 貴司, 柴崎 康彦, 森山 雅人, 増子 正義, 曽根 博仁, 三好 寛明, 大島 孝一, 横濱 章彦

    日本リンパ網内系学会会誌   53   151 - 151   2013.4

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  • 尿路結石による水腎症、無機能腎を呈し、同側腎からの高レニン血症により二次性高血圧を来たした1例

    古川 祥子, 藤原 和哉, 五十野 桃子, 五十野 博基, 志鎌 明人, 宜保 英彦, 尾本 美代子, 曽根 博仁

    日本内分泌学会雑誌   89 ( 1 )   341 - 341   2013.4

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  • 当院における原発性アルドステロン症に対する副腎静脈サンプリングの検討

    鈴木 裕美, 金子 正義, 川田 亮, 山本 正彦, 大澤 妙子, 古川 和郎, 山田 貴穂, 皆川 真一, 鈴木 亜希子, 羽入 修, 吉村 宣彦, 青山 英史, 曽根 博仁

    日本内分泌学会雑誌   89 ( 1 )   282 - 282   2013.4

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  • 治療後3ヵ月の血清IL-2R値はびまん性大細胞型B細胞性リンパ腫の長期予後を反映する

    田中 智之, 瀧澤 淳, 宮腰 淑子, 小堺 貴司, 布施 香子, 柴崎 康彦, 森山 雅人, 増子 正義, 曽根 博仁, 尾山 徳秀, 大島 孝一

    日本リンパ網内系学会会誌   53   120 - 120   2013.4

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  • 細小・大血管合併症の両方を視野に入れた日本人患者に適した血糖コントロールを

    曽根 博仁

    糖尿病   56 ( Suppl.1 )   S - 103   2013.4

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  • 非アルコール性脂肪性肝炎における脂肪酸伸長酵素Elovl6の役割

    松坂 賢, 渥美 綾香, 唐 ネ, 煙山 紀子, 久芳 素子, 中川 嘉, 嶋田 昌子, 小林 和人, 矢藤 潔, 高橋 昭光, 曽根 博仁, 矢作 直也, 鈴木 浩明, 中牟田 誠, 山田 信博, 島野 仁

    糖尿病   56 ( Suppl.1 )   S - 128   2013.4

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  • 蛋白質摂取量、塩分摂取量による腎機能、インスリン分泌能への負担に関する検討

    菅野 咲子, 山下 りさ, 佐藤 舞菜見, 清水 平, 沖崎 進一郎, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( Suppl.1 )   S - 330   2013.4

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  • 糖尿病患者における経皮的AF値(Autofluorescence)の規定因子および合併症との関連についての検討

    川田 亮, 羽入 修, 古川 和郎, 石澤 正博, 山本 正彦, 大澤 妙子, 山田 貴穂, 皆川 真一, 鈴木 裕美, 山田 絢子, 鈴木 亜希子, 曽根 博仁

    糖尿病   56 ( Suppl.1 )   S - 132   2013.4

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  • ABI異常者の死亡、心血管イベントへ及ぼす影響 3300名の観察コホート研究

    畑中 麻梨恵, 山下 りさ, 菅野 咲子, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( Suppl.1 )   S - 228   2013.4

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  • 2型糖尿病患者における食塩摂取量増加は脳卒中発症リスクに関連しないが、心血管疾患発症リスク上昇と関連する JDCS

    堀川 千嘉, 奥村 亮太, 鎌田 智恵実, 田中 司朗, 田中 佐智子, 井藤 英喜, 赤沼 安夫, 山田 信博, 吉村 幸雄, 曽根 博仁

    糖尿病   56 ( Suppl.1 )   S - 209   2013.4

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  • 医学における栄養学の最新研究 医学で栄養学はどの程度の役割を果たしているか 生活習慣病の食事療法に関する大規模臨床エビデンス

    曽根 博仁

    日本栄養・食糧学会大会講演要旨集   67回   59 - 59   2013.4

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  • 単身生活と未診断2型糖尿病に関する大規模検討 Toranomon Hospital Health Management Center Study(TOP-ICS)

    平安座 依子, 原 茂子, 児玉 暁, 謝 勲東, 羽入 修, 齋藤 和美, 山田 信博, 島野 仁, 荒瀬 康司, 曽根 博仁

    糖尿病   56 ( Suppl.1 )   S - 423   2013.4

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  • 単身生活や他の生活習慣と2型糖尿病に関する大規模検討 The Toranomon Hospital Health Management Center Study

    平安座 依子, 原 茂子, 藤原 和哉, 謝 勲東, 齋藤 和美, 辻 裕之, 児玉 暁, 島野 仁, 荒瀬 康司, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   67回   169 - 169   2013.4

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  • 脂質摂取と2型糖尿病リスクとの関連性についてのメタ解析

    田島 諒子, 児玉 暁, 堀川 千嘉, 藤原 和哉, 吉澤 咲子, 平安座 依子, 菅原 歩美, 谷内 洋子, 齋藤 あき, 飯田 薫子, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   67回   153 - 153   2013.4

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  • Project8 高齢者に対しリラグルチドを導入した際の有用性と副作用についての検討

    石黒 創, 布施 克也, 佐藤 幸示, 上原 喜美子, 大橋 麻紀, 高野 久美子, 長島 会吏子, 吉崎 麗美, 高村 誠, 曽根 博仁

    糖尿病   56 ( Suppl.1 )   S - 342   2013.4

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  • 特定健診による要受診判定後の医療機関受診率とその推移

    羽入 修, 平安座 依子, 古川 和郎, 川田 亮, 大澤 妙子, 山本 正彦, 皆川 真一, 鈴木 裕美, 山田 絢子, 山田 貴穂, 鈴木 亜希子, 曽根 博仁

    糖尿病   56 ( Suppl.1 )   S - 339   2013.4

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  • メトホルミン750mgでコントロール不十分の2型糖尿病患者におけるメトホルミン増量とシタグリプチン追加との有用性の比較検討

    古川 和郎, 羽入 修, 平安座 依子, 植村 靖行, 川田 亮, 大澤 妙子, 金子 正儀, 山田 貴穂, 鈴木 裕美, 皆川 真一, 森川 洋, 鈴木 亜希子, 曽根 博仁

    糖尿病   56 ( Suppl.1 )   S - 386   2013.4

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  • 妊娠初期HbA1c値と妊娠糖尿病発症との関連の検討(TWC Study)

    谷内 洋子, 田中 康弘, 西端 泉, 児玉 暁, 鈴木 亜希子, 羽生 修, 曽根 博仁

    糖尿病   56 ( Suppl.1 )   S - 351   2013.4

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  • 糖尿病患者の感情負担度に関わる因子 初診時解析からPAIDを用いて

    佐藤 舞菜見, 山下 りさ, 菅野 咲子, 小川 真弓, 友重 栄美, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( Suppl.1 )   S - 139   2013.4

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  • わが国における糖尿病運動療法の実施状況に関する調査研究(第三報) 糖尿病患者の運動療法実施に影響を与える因子について

    荒川 聡美, 渡邉 智之, 曽根 博仁, 小林 正, 河盛 隆造, 渥美 義仁, 押田 芳治, 田中 史朗, 鈴木 進, 牧田 茂, 大澤 功, 田村 好史, 佐藤 祐造

    糖尿病   56 ( Suppl.1 )   S - 282   2013.4

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  • 飲酒と喫煙の掛け合わせが糖尿病発症に及ぼす影響の検討 茨城県健康研究

    菅原 歩美, 西連地 利己, 藤原 和哉, 入江 ふじこ, 渡辺 宏, 曽根 博仁, 大田 仁史

    糖尿病   56 ( Suppl.1 )   S - 277   2013.4

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  • 血糖コントロール不良例では、初期治療はインスリン療法であるべきか

    小川 真弓, 菅野 咲子, 山下 りさ, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( Suppl.1 )   S - 237   2013.4

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  • ABI異常に関する因子の探求 非糖尿病600名を含む3500名の横断調査

    沢崎 詩乃, 畑中 麻梨恵, 山下 りさ, 菅野 咲子, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( Suppl.1 )   S - 228   2013.4

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  • MMSEを用いた1300例への認知機能の評価

    友重 栄美, 鈴木 美佑希, 菅野 咲子, 山下 りさ, 畑中 麻梨恵, 水谷 有加利, 小川 真弓, 佐藤 舞菜見, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志朗, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( Suppl.1 )   S - 269   2013.4

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  • グリメピリド0.25mgの血糖改善および低血糖減少への効果

    水谷 有加利, 畑中 麻梨恵, 山下 りさ, 菅野 咲子, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( Suppl.1 )   S - 265   2013.4

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  • 糖尿病・生活習慣病の大規模臨床研究とその可能性

    曽根 博仁

    新潟県医師会報   ( 756 )   2 - 11   2013.3

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  • 【喫煙と健康障害-禁煙支援の理解・普及から「脱タバコ社会」を目指して-】 喫煙と疾患のかかわり 喫煙と糖尿病・代謝疾患

    齋藤 和美, 曽根 博仁

    日本臨床   71 ( 3 )   443 - 448   2013.3

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    Other Link: http://search.jamas.or.jp/link/ui/2013135866

  • 大学生に対する多角的栄養教育プログラムの構築

    伊部 陽子, 平安座 依子, 飯島 和子, 宮川 八平, 布施 泰子, 堀口 祐子, 水庭 真紀子, 三橋 典代, 深谷 美架, 児玉 暁, 曽根 博仁

    CAMPUS HEALTH   50 ( 1 )   264 - 266   2013.3

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    大学生の栄養教育プログラム作成の検討に資することを目的に、本学(大学)農学部1年生80名(男子35名、女子45名)へ食物摂取状況および食物摂取の知識・態度・行動などについてアンケート調査を行った。その結果、国民健康栄養調査(18〜29歳)との比較では、男女とも食物繊維・鉄分・カルシウムが不足傾向、野菜、魚介類の摂取が不足傾向であった。また、食物摂取に対する知識・態度・行動レベルでは、男子学生より女子学生の方が高値を示す項目が多かった。

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  • 腎移植後の腎障害合併MDS患者に対して減量フルダラビン,ブスルファンによる前処置による骨髄非破壊的造血幹細胞移植を行った一例

    西脇邦恵, 岡塚貴世志, 宮腰淑子, 柴崎康彦, 増子正義, 森山雅人, 瀧澤淳, 中川由紀, 斎藤和英, 鳴海福星, 高橋公太, 曽根博仁, 古川達雄

    日本造血細胞移植学会総会プログラム・抄録集   35th   265   2013.2

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  • Disease Risk Index(DRI)が造血器腫瘍に対する同種造血幹細胞移植成績に与える影響

    田中智之, 増子正義, 小堺貴司, 布施香子, 柴崎康彦, 岡塚貴世志, 森山雅人, 宮腰淑子, 瀧澤淳, 鳥羽健, 曽根博仁, 古川達雄

    日本造血細胞移植学会総会プログラム・抄録集   35th   212   2013.2

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  • 骨髄破壊的前処置による同種造血幹細胞移植後早期の末梢血リンパ球数が予後に与える影響

    柴崎康彦, 増子正義, 森山雅人, 岡塚貴世志, 布施香子, 小堺貴司, 宮越淑子, 田中智之, 鳥羽健, 曽根博仁, 古川達雄

    日本造血細胞移植学会総会プログラム・抄録集   35th   218   2013.2

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  • 定量的メタ解析 糖尿病患者における脈圧(PP)、平均血圧(MAP)と将来の心血管疾患(CVD)発症リスクとの関連性

    児玉 暁, 藤原 和哉, 齋藤 和美, 羽入 修, 曽根 博仁

    日本内科学会雑誌   102 ( Suppl. )   211 - 211   2013.2

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  • 2型糖尿病発症に至るまでのBMIの長期変化に関する大規模縦断的検討:TOPICS

    平安座依子, 原茂子, 謝勲東, 齋藤和美, 辻裕之, 羽入修, 児玉暁, 島野仁, 山田信博, 荒瀬康司, 曽根博仁

    J Epidemiol   23 ( Supplement 1 )   97   2013.1

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  • ウエスト周囲長・身長比による2型糖尿病予測スクリーニング精度の検討:TOPICS

    平安座依子, 謝勲東, 児玉暁, 辻裕之, 齋藤和美, 島野仁, 荒瀬康司, 原茂子, 曽根博仁

    J Epidemiol   23 ( Supplement 1 )   96   2013.1

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  • 糖尿病と閉塞性睡眠時無呼吸症候群の関連性及び方向性のメタ解析

    藤原和哉, 児玉暁, 堀川千嘉, 平安座依子, 由澤咲子, 菅原歩美, 平澤玲子, 谷地洋子, 斎藤和美, 島野仁, 山田信博, 曽根博仁

    J Epidemiol   23 ( Supplement 1 )   130   2013.1

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  • 喫煙と飲酒の組み合わせによる糖尿病発症リスクの検討:茨城県健康研究

    菅原歩美, 西連地利己, 藤原和哉, 入江ふじこ, 渡辺宏, 曽根博仁, 大田仁史

    J Epidemiol   23 ( Supplement 1 )   90   2013.1

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  • 食後血糖の管理

    綿田 裕孝, 曽根 博仁, 西村 理明, 山田 悟

    Diabetes Update   2 ( 1 )   4 - 14   2013.1

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  • グリメピリド使用量0.25mgの血糖改善および低血糖頻度への影響

    水谷 有加利, 山下 りさ, 大場 昌恵, 菅野 咲子, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( 1 )   47 - 47   2013.1

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  • 観察コホート研究によるDPP4阻害薬登場がSU二次無効発現率へ及ぼす効果の検討

    遠藤 こずか, 山下 りさ, 菅野 咲子, 高橋 直穂, 清水 平, 沖崎 進一郎, 山田 大志郎, 本庄 剛, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( 1 )   44 - 44   2013.1

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  • DPP-4阻害薬併用例におけるグリメピリド中止後のHbA1cの推移

    吉村 真由, 菅野 咲子, 大場 昌恵, 山下 りさ, 高橋 直穂, 清水 平, 沖崎 進一郎, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( 1 )   55 - 55   2013.1

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  • メタ解析 成人においてどの時期の体重増加が2型糖尿病発症に大きく関わるか?

    児玉 暁, 堀川 千嘉, 藤原 和哉, 由澤 咲子, 平安座 依子, 伊部 陽子, 谷内 洋子, 鈴木 亜希子, 羽入 修, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   39   65 - 65   2013.1

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  • ABIの異常頻度と臨床的特徴

    畑中 麻梨恵, 大場 昌恵, 山下 りさ, 菅野 咲子, 高橋 直穂, 沖崎 進一郎, 清水 平, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   56 ( 1 )   38 - 38   2013.1

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  • <編集アドバイザー>Cardio-Renal Diabetes

    糖尿病分野, 山田祐一郎, 石原寿光, 植木浩二郎, 山内敏正, 綿田裕孝, 小田原雅人, 宇都宮一典, 柴輝男, 寺内康夫, 曽根博仁, 戸邉一之, 篁俊成, 古家大祐, 中村二郎, 前川聡, 長嶋一昭, 下村伊一郎, 池上博司, 古田浩人, 藤本新平, 荒木栄一

    Cardio-Renal Diabetes   2 ( 1~4 )   2013

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  • Comparisons of the Strength of Associations With Future Type 2 Diabetes Risk Among Anthropometric Obesity Indicators, Including Waist-to-Height Ratio: A Meta-Analysis

    Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Yoriko Heianza, Reiko Hirasawa, Yoko Yachi, Ayumi Sugawara, Shiro Tanaka, Hitoshi Shimano, Kaoruko Tada Iida, Kazumi Saito, Hirohito Sone

    AMERICAN JOURNAL OF EPIDEMIOLOGY   176 ( 11 )   959 - 969   2012.12

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    The aim of this meta-analysis was to compare the association of waist-to-height ratio (WHtR) with risk of incident diabetes with the associations of 3 other conventional obesity indicators (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) with risk of incident diabetes. Literature searches in MEDLINE (January 1950 to April 27, 2011) and EMBASE (January 1974 to April 27, 2011) were conducted for prospective studies that made it possible to estimate the relative risk of diabetes per 1-standard deviation increase in WHtR, in addition to the RR of BMI, WC, or WHR. Strength of the estimated pooled relative risk for a 1-standard deviation increase of each indicator (expressed as RRWHtR, RRBMI, RRWC, and RRWHR) was compared with a bivariate random-effects model. Pooled relative risks of the 15 eligible studies with 6,472 diabetes cases were 1.62 (95 CI: 1.48, 1.78) for RRWHtR, 1.55 (95 CI: 1.43, 1.69) for RRBMI, 1.63 (95 CI: 1.49, 1.79) for RRWC, and 1.52 (95 CI: 1.40, 1.66) for RRWHR. WHtR had an association stronger than that of BMI (P0.001) or WHR (P0.001). The present meta-analysis showed that WHtR has a modestly but statistically greater importance than BMI and WHR in prediction of diabetes. Nevertheless, measuring height in addition to WC appeared to have no additional benefit.

    DOI: 10.1093/aje/kws172

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  • Comparisons of the Strength of Associations With Future Type 2 Diabetes Risk Among Anthropometric Obesity Indicators, Including Waist-to-Height Ratio: A Meta-Analysis

    Satoru Kodama, Chika Horikawa, Kazuya Fujihara, Yoriko Heianza, Reiko Hirasawa, Yoko Yachi, Ayumi Sugawara, Shiro Tanaka, Hitoshi Shimano, Kaoruko Tada Iida, Kazumi Saito, Hirohito Sone

    AMERICAN JOURNAL OF EPIDEMIOLOGY   176 ( 11 )   959 - 969   2012.12

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    The aim of this meta-analysis was to compare the association of waist-to-height ratio (WHtR) with risk of incident diabetes with the associations of 3 other conventional obesity indicators (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) with risk of incident diabetes. Literature searches in MEDLINE (January 1950 to April 27, 2011) and EMBASE (January 1974 to April 27, 2011) were conducted for prospective studies that made it possible to estimate the relative risk of diabetes per 1-standard deviation increase in WHtR, in addition to the RR of BMI, WC, or WHR. Strength of the estimated pooled relative risk for a 1-standard deviation increase of each indicator (expressed as RRWHtR, RRBMI, RRWC, and RRWHR) was compared with a bivariate random-effects model. Pooled relative risks of the 15 eligible studies with 6,472 diabetes cases were 1.62 (95 CI: 1.48, 1.78) for RRWHtR, 1.55 (95 CI: 1.43, 1.69) for RRBMI, 1.63 (95 CI: 1.49, 1.79) for RRWC, and 1.52 (95 CI: 1.40, 1.66) for RRWHR. WHtR had an association stronger than that of BMI (P0.001) or WHR (P0.001). The present meta-analysis showed that WHtR has a modestly but statistically greater importance than BMI and WHR in prediction of diabetes. Nevertheless, measuring height in addition to WC appeared to have no additional benefit.

    DOI: 10.1093/aje/kws172

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  • 【脂質異常症 動脈硬化性疾患を予防する実践的治療戦略】 セミナー/脂質異常症の実地診療の基礎と応用 動脈硬化症のハイリスクグループにおける脂質管理の意義と実際 糖尿病における動脈硬化症の予防

    曽根 博仁

    Medical Practice   29 ( 12 )   2085 - 2090   2012.12

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  • 意識障害を繰り返した潜在性続発性副腎皮質機能低下症の1例

    大澤 妙子, 金子 正儀, 鈴木 亜希子, 川田 亮, 古川 和郎, 山田 貴穂, 鈴木 裕美, 伊藤 崇子, 羽入 修, 曽根 博仁

    日本内分泌学会雑誌   88 ( 3 )   1017 - 1017   2012.12

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  • 【性差の運動生理学】 疫学的研究からみた健康と運動の性差

    堀川 千嘉, 羽入 修, 曽根 博仁

    体育の科学   62 ( 12 )   934 - 941   2012.12

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    生活習慣病に対する運動の効果としては、運動は心血管疾患リスクを低下させる血中HDL-コレステロール値を上昇させ、更に冠動脈疾患・脳卒中リスクを低下させ、寿命延伸に有効であることが知られており、運動の習慣的な実践をより身近なものとするための効果的な実践方法の探求が求められている。同時に、運動効果に関連する体格や体質、生活習慣や社会環境などの影響には性差があることが認められている。このことから、運動についての疫学的研究を実施するに当たり、性差を考慮することは重要であるといえる。疫学的研究からみた運動効果と性差、運動に関連する要因と性差について概説した。

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  • 閉塞性睡眠時無呼吸症候群(OSA)は、糖尿病発症関連因子である

    藤原 和哉, 児玉 暁, 堀川 千嘉, 平安座 依子, 由澤 咲子, 菅原 歩, 平澤 玲子, 谷地 洋子, 斎藤 和美, 島野 仁, 山田 信博, 曽根 博仁

    日本内分泌学会雑誌   88 ( 3 )   1073 - 1073   2012.12

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  • メトホルミンの血中濃度を追跡し救命した乳酸アシドーシスの1例

    尾本 美代子, 五十野 桃子, 藤原 和哉, 錦 健太, 曽根 博仁

    日本内分泌学会雑誌   88 ( 3 )   1071 - 1071   2012.12

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  • マタニティビクスの運動強度に及ぼす妊娠週数の影響

    西端 泉, 穴迫 唯衣, 小林 香織, 谷内 洋子, 田中 康弘, 曽根 博仁

    体力科学   61 ( 6 )   675 - 675   2012.12

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  • 傍神経節細胞腫との鑑別に極めて難渋した偽性褐色細胞腫の1例

    五十野 桃子, 藤原 和哉, 片山 皓太, 御子柴 卓弥, 鎌田 一宏, 五十野 博基, 秋根 大, 尾本 美代子, 曽根 博仁

    日本内分泌学会雑誌   88 ( 3 )   1065 - 1065   2012.12

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  • 【メタボリックシンドロームと糖尿病-日本人の健康増進のために-】 海外のエビデンス 生活習慣介入試験より アウトカム別にみた効果

    曽根 博仁

    月刊糖尿病   4 ( 12 )   27 - 32   2012.11

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    Other Link: http://search.jamas.or.jp/link/ui/2012373745

  • Comparison of Framingham risk score, UKPDS risk engine, maximum-IMT, and LDL-C/HDL-C ratio for predicting coronary plaque in asymptomatic patients with type 2 diabetes

    K. Fujihara, H. Suzuki, A. Sato, S. Kodama, Y. Heianza, T. Ishizu, K. Saito, H. Iwasaki, K. Kobayashi, S. Yatoh, A. Takahashi, N. Yamada, H. Sone, H. Shimano

    DIABETOLOGIA   55   S494 - S494   2012.10

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  • Comparison of current BMI and BMI histories to screen for undiagnosed diabetes in Japanese men: Toranomon Hospital Health Management Center Study

    S. Yoshizawa, Y. Heianza, C. Horikawa, S. Hara, K. Saito, S. Kodama, S. D. Hsieh, H. Tsuji, N. Yamada, Y. Arase, H. Sone

    DIABETOLOGIA   55   S136 - S137   2012.10

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  • Development and evaluation of screening score for detecting undiagnosed diabetes and estimating absolute risk of future type 2 diabetes: TOPICS

    Y. Heianza, S. Hara, S. Yoshizawa, S. Kodama, K. Saito, S. D. Hsieh, C. Horikawa, H. Tsuji, N. Yamada, Y. Arase, H. Sone

    DIABETOLOGIA   55   S358 - S358   2012.10

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  • High normal HbA1c levels were associated with impaired insulin secretion without escalating insulin resistance in Japanese individuals: the Toranomon Hospital Health Management Center Study 8 (TOPICS 8)

    Y. Heianza, Y. Arase, K. Fujihara, H. Tsuji, K. Saito, S. D. Hsieh, S. Kodama, H. Shimano, N. Yamada, S. Hara, H. Sone

    DIABETIC MEDICINE   29 ( 10 )   1285 - 1290   2012.10

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    Diabet. Med. 29, 12851290 (2012) Abstract Aims We aimed to characterize the association of insulin resistance, impaired insulin secretion and beta-cell dysfunction in relation to HbA1c levels in a non-diabetic range in Japanese individuals without clinically diagnosed diabetes. Methods This cross-sectional study included 1444 individuals without a history of outpatient treatment of diabetes or use of insulin or oral hypoglycaemic agents. The homeostasis model assessment of insulin resistance and beta-cell function, insulinogenic index, Matsuda index and disposition index were calculated using data from 75-g oral glucose tolerance tests and compared across quintile (Q) categories of HbA1c levels. Results Fasting plasma glucose and 30-min and 60-min plasma glucose (PG) levels were significantly higher when HbA1c exceeded 36 mmol/mol (5.4%). A HbA1c concentration of 3637 mmol/mol (5.45.5%) (Q3) was significantly associated with a 15% lower homeostasis model assessment of beta-cell function value and 31% lower insulinogenic index value compared with HbA1c = 32 mmol/mol (= 5.1%) (Q1) (P &lt;0.01). Further, a HbA1c concentration of 3840 mmol/mol (5.65.8%) (Q4) was associated with 17% (P &lt;0.01) and 24% (P &lt;0.05) reductions in those indexes, respectively. However, the homeostasis model assessment of insulin resistance was not significantly elevated and the Matsuda index was not significantly lower unless HbA1c exceeded 41 mmol/mol (5.9%). Individuals with HbA1c = 41 mmol/mol (= 5.9%) (Q5) had a 69% lower disposition index than those with a HbA1c concentration of = 32 mmol/mol (= 5.1%) (Q1). Conclusions Elevated HbA1c levels = 41 mmol/mol (= 5.9%) were associated with substantial reductions in insulin secretion, insulin sensitivity and beta-cell dysfunction in Japanese individuals not treated for diabetes. High normal HbA1c levels of 3640 mmol/mol (5.45.8%) were also associated with impaired insulin secretion without marked insulin resistance in Japanese individuals.

    DOI: 10.1111/j.1464-5491.2012.03667.x

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  • High normal HbA1c levels were associated with impaired insulin secretion without escalating insulin resistance in Japanese individuals: the Toranomon Hospital Health Management Center Study 8 (TOPICS 8)

    Y. Heianza, Y. Arase, K. Fujihara, H. Tsuji, K. Saito, S. D. Hsieh, S. Kodama, H. Shimano, N. Yamada, S. Hara, H. Sone

    DIABETIC MEDICINE   29 ( 10 )   1285 - 1290   2012.10

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    Diabet. Med. 29, 12851290 (2012) Abstract Aims We aimed to characterize the association of insulin resistance, impaired insulin secretion and beta-cell dysfunction in relation to HbA1c levels in a non-diabetic range in Japanese individuals without clinically diagnosed diabetes. Methods This cross-sectional study included 1444 individuals without a history of outpatient treatment of diabetes or use of insulin or oral hypoglycaemic agents. The homeostasis model assessment of insulin resistance and beta-cell function, insulinogenic index, Matsuda index and disposition index were calculated using data from 75-g oral glucose tolerance tests and compared across quintile (Q) categories of HbA1c levels. Results Fasting plasma glucose and 30-min and 60-min plasma glucose (PG) levels were significantly higher when HbA1c exceeded 36 mmol/mol (5.4%). A HbA1c concentration of 3637 mmol/mol (5.45.5%) (Q3) was significantly associated with a 15% lower homeostasis model assessment of beta-cell function value and 31% lower insulinogenic index value compared with HbA1c = 32 mmol/mol (= 5.1%) (Q1) (P &lt;0.01). Further, a HbA1c concentration of 3840 mmol/mol (5.65.8%) (Q4) was associated with 17% (P &lt;0.01) and 24% (P &lt;0.05) reductions in those indexes, respectively. However, the homeostasis model assessment of insulin resistance was not significantly elevated and the Matsuda index was not significantly lower unless HbA1c exceeded 41 mmol/mol (5.9%). Individuals with HbA1c = 41 mmol/mol (= 5.9%) (Q5) had a 69% lower disposition index than those with a HbA1c concentration of = 32 mmol/mol (= 5.1%) (Q1). Conclusions Elevated HbA1c levels = 41 mmol/mol (= 5.9%) were associated with substantial reductions in insulin secretion, insulin sensitivity and beta-cell dysfunction in Japanese individuals not treated for diabetes. High normal HbA1c levels of 3640 mmol/mol (5.45.8%) were also associated with impaired insulin secretion without marked insulin resistance in Japanese individuals.

    DOI: 10.1111/j.1464-5491.2012.03667.x

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  • 2型糖尿病患者における糖尿病網膜症の発症と進展及びその危険因子 The Japan Diabetes Complications Study(JDCS)8年追跡調査

    川崎 良, 田中 司朗, 田中 佐智子, 山本 禎子, 曽根 博仁, 大橋 靖雄, 赤沼 安夫, 山田 信博, 山下 英俊

    糖尿病合併症   26 ( Suppl.1 )   74 - 74   2012.10

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  • 妊娠中の母体の血糖状態と低出生体重児出産との関連の検討

    谷内 洋子, 田中 康弘, 西端 泉, 菅原 歩美, 児玉 暁, 斎藤 和美, 曽根 博仁

    糖尿病と妊娠   12 ( 2 )   S - 80   2012.10

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  • 糖尿病患者における心血管合併症の疫学

    曽根 博仁

    循環器内科   72 ( 4 )   438 - 447   2012.10

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  • 【糖尿病の今】 糖尿病と合併症を防ぐための初期対応

    曽根 博仁

    公衆衛生   76 ( 10 )   766 - 772   2012.10

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  • 腎症3期の経過観察

    奥田 昌恵, 菅野 咲子, 高橋 直穂, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   55 ( 10 )   833 - 833   2012.10

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  • リラグルチドの多数例での有効無効の検討

    今田 敦子, 菅野 咲子, 奥田 昌恵, 曽根 博仁, 本庄 潤, 山田 大志郎, 横山 宏樹

    糖尿病   55 ( 10 )   829 - 829   2012.10

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  • 【Helicobacter pyloriとその関連疾患】 Helicobacter pyloriと糖尿病

    藤原 和哉, 羽入 修, 曽根 博仁

    成人病と生活習慣病   42 ( 10 )   1241 - 1245   2012.10

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    ・Helicobacter pyloriは、らせん状またはS字状の形状を呈するグラム陰性桿菌であり、本邦においても約6,000万人の感染者がいると推測されている。近年H.pylori感染は、急性胃炎・慢性胃炎、消化性潰瘍、胃癌などの消化器疾患のみならず、血液疾患やアレルギー疾患、さらには心血管疾患や関節リウマチなど、さまざまな疾患と関連することが明らかとなり注目される慢性感染症となった。・糖尿病患者の急増もまた深刻な問題であり、今後さらなる増加が予測されることから、糖尿病発症の予防を含め重要な検討課題である。糖尿病患者では、非糖尿病患者と比較して、感染症の罹患率が高く、その重症度も高いことが知られている。また以前よりH.pylori感染と糖尿病の関連性に関する議論は続いているが、一定の見解には至っていない。本稿では、疫学的な側面を中心にH.pylori感染と糖尿病の関連について言及する。(著者抄録)

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  • DPP4阻害薬開始に伴う効果 SU剤併用の有無、他剤(Met、αGI、TZD)からの切り替え

    鈴木 美佑希, 高橋 直穂, 菅野 咲子, 奥田 昌恵, 山下 りさ, 山田 大志朗, 本庄 潤, 曽根 博仁, 清水 平, 横山 宏樹

    糖尿病   55 ( 10 )   833 - 833   2012.10

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  • Association between pulse pressure and cardiovascular risk in diabetes mellitus: a meta-analysis

    C. Horikawa, S. Kodama, Y. Heianza, S. Yoshizawa, K. Fujihara, S. Tanaka, K. T. Iida, Y. Yachi, Y. Ohashi, H. Sone

    DIABETOLOGIA   55   S504 - S504   2012.10

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  • Predictors of ischaemic heart disease and cerebrovascular attack in late elderly diabetic individuals: the roles of HDL-cholesterol and the LDL-C/HDL-C ratio

    T. Hayashi, H. Itoh, A. Araki, H. Sone, H. Watanabe, T. Ohrui, K. Yokote, M. Takemoto, M. Noda, K. Ina, H. Nomura

    DIABETOLOGIA   55   S487 - S487   2012.10

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  • Leisure-time physical activity is a significant predictor for total mortality and stroke among Japanese patients with type 2 diabetes: the Japan Diabetes Complications Study

    H. Sone, S. Tanaka, S. Tanaka, S. Suzuki, H. Seino, A. Sato, A. Araki, S. Ishibashi, Y. Ohashi, Y. Akanuma, N. Yamada

    DIABETOLOGIA   55   S139 - S139   2012.10

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  • 2型糖尿病患者におけるヘモグロビンA1cの長期変動が微量アルブミン尿の発症に及ぼす影響の検討

    菅原歩美, 曽根博仁

    栄養学雑誌   70 ( 5 Supplement )   239   2012.9

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  • 2型糖尿病患者における,罹病期間と糖尿病に特化した心理的負担の変化の検討

    菅原歩美, 川井紘一, 平澤玲子, 堀川千嘉, 谷内洋子, 飯田薫子, 曽根博仁

    日本臨床栄養学会雑誌   34 ( 3 )   133   2012.9

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  • “Healthy diet”に関するインターネット情報のクオリティ評価

    平澤玲子, 谷内洋子, 菅原歩美, 堀川千嘉, 飯田薫子, 近藤和雄, 曽根博仁

    日本臨床栄養学会雑誌   34 ( 3 )   162   2012.9

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  • 乳製品摂取とメタボリックシンドロームの関連性についてのメタ解析

    堀川千嘉, 谷内洋子, 菅原歩美, 平澤玲子, 飯田薫子, 曽根博仁

    日本臨床栄養学会雑誌   34 ( 3 )   128   2012.9

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  • Fasting Insulin Levels and Metabolic Risk Factors in Type 2 Diabetic Patients at the First Visit in Japan

    Ikuro Matsuba, Kazumi Saito, Masahiko Takai, Koichi Hirao, Hirohito Sone

    DIABETES CARE   35 ( 9 )   1853 - 1857   2012.9

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    OBJECTIVE-To investigate the relationship between fasting insulin levels and metabolic risk factors (MRFs) in type 2 diabetic patients at the first clinic/hospital visit in Japan over the years 2000 to 2009.
    RESEARCH DESIGN AND METHODS-In total, 4,798 drug-naive Japanese patients with type 2 diabetes were registered on their first clinic/hospital visits. Conventional clinical factors and fasting insulin levels were observed at baseline within the Japan Diabetes Clinical Data Management (JDDM) study between consecutive 2-year groups. Multiple linear regression analysis was performed using a model in which the dependent variable was fasting insulin values using various clinical explanatory variables.
    RESULTS-Fasting insulin levels were found to be decreasing from 2000 to 2009. Multiple linear regression analysis with the fasting insulin levels as the dependent variable showed that waist circumference (WC), BMI, mean blood pressure, triglycerides, and HDL cholesterol were significant, with WC and BMI as the main factors. ANCOVA after adjustment for age and fasting plasma glucose clearly shows the decreasing trend in fasting insulin levels and the increasing trend in BMI.
    CONCLUSIONS-During the 10-year observation period, the decreasing trend in fasting insulin was related to the slight increase in WC/BMI in type 2 diabetes. Low pancreatic beta-cell reserve on top of a lifestyle background might be dependent on an increase in MRFs.

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  • Fasting Insulin Levels and Metabolic Risk Factors in Type 2 Diabetic Patients at the First Visit in Japan

    Ikuro Matsuba, Kazumi Saito, Masahiko Takai, Koichi Hirao, Hirohito Sone

    DIABETES CARE   35 ( 9 )   1853 - 1857   2012.9

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    OBJECTIVE-To investigate the relationship between fasting insulin levels and metabolic risk factors (MRFs) in type 2 diabetic patients at the first clinic/hospital visit in Japan over the years 2000 to 2009.
    RESEARCH DESIGN AND METHODS-In total, 4,798 drug-naive Japanese patients with type 2 diabetes were registered on their first clinic/hospital visits. Conventional clinical factors and fasting insulin levels were observed at baseline within the Japan Diabetes Clinical Data Management (JDDM) study between consecutive 2-year groups. Multiple linear regression analysis was performed using a model in which the dependent variable was fasting insulin values using various clinical explanatory variables.
    RESULTS-Fasting insulin levels were found to be decreasing from 2000 to 2009. Multiple linear regression analysis with the fasting insulin levels as the dependent variable showed that waist circumference (WC), BMI, mean blood pressure, triglycerides, and HDL cholesterol were significant, with WC and BMI as the main factors. ANCOVA after adjustment for age and fasting plasma glucose clearly shows the decreasing trend in fasting insulin levels and the increasing trend in BMI.
    CONCLUSIONS-During the 10-year observation period, the decreasing trend in fasting insulin was related to the slight increase in WC/BMI in type 2 diabetes. Low pancreatic beta-cell reserve on top of a lifestyle background might be dependent on an increase in MRFs.

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  • 大学生に対する多角的栄養教育プログラムの構築

    伊部 陽子, 平安座 依子, 飯島 和子, 宮川 八平, 堀口 祐子, 水庭 真紀子, 三橋 典代, 深谷 美架, 児玉 暁, 曽根 博仁

    CAMPUS HEALTH   49 ( 4 )   83 - 83   2012.9

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  • 世界と日本の大規模研究からわかったこと Japan Diabetes Complications Study(JDCS)

    曽根 博仁, 田中 司朗, 片山 茂裕, 山下 英俊, 赤沼 安夫, 山田 信博

    糖尿病学の進歩   ( 46 )   237 - 246   2012.9

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  • "Healthy diet"に関するインターネット情報のクオリティ評価

    平澤 玲子, 谷内 洋子, 菅原 歩美, 堀川 千嘉, 飯田 薫子, 近藤 和雄, 曽根 博仁

    New Diet Therapy   28 ( 2 )   162 - 162   2012.9

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  • 2型糖尿病患者における、罹病期間と糖尿病に特化した心理的負担の変化の検討

    菅原 歩美, 川井 紘一, 平澤 玲子, 堀川 千嘉, 谷内 洋子, 飯田 薫子, 曽根 博仁, 糖尿病データマネジメント研究会(JDDM

    New Diet Therapy   28 ( 2 )   133 - 133   2012.9

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  • 成人期の体重増加と2型糖尿病発症(T2DM)との関連性のメタ解析

    児玉 暁, 堀川 千嘉, 田中 司朗, 藤原 和哉, 由澤 咲子, 平澤 玲子, 伊部 陽子, 大橋 靖雄, 曽根 博仁

    肥満研究   18 ( Suppl. )   170 - 170   2012.9

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  • 乳製品摂取とメタボリックシンドロームの関連性についてのメタ解析

    堀川 千嘉, 谷内 洋子, 菅原 歩美, 平澤 玲子, 飯田 薫子, 曽根 博仁

    New Diet Therapy   28 ( 2 )   128 - 128   2012.9

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  • 大規模臨床研究から見える日本人2型糖尿病患者の合併症 : JDCSから (特集 糖尿病最新事情(前編)日本発の大規模研究)

    曽根 博仁

    メディカル朝日   41 ( 9 )   21 - 23   2012.9

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  • 若年期の低BMIと妊娠糖尿病発症

    谷内 洋子, 田中 康弘, 菅原 歩美, 曽根 博仁

    糖尿病と妊娠   12 ( 1 )   40 - 44   2012.8

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    わが国では、中高齢者や男性における肥満が社会問題化している一方で、若年女性においてはやせ過ぎが深刻で、生理的に体重増加が求められる妊婦をも巻き込んで若年女性の痩身化が進んでいる。「体重を減らしたい、やせたい」というやせ願望は、世界中の若年女性にみられる現象で日本人特有のものではないが、国レベルでこれほど顕著に若年女性のBMIが実際に低下しているのは世界的にもまれであり、妊娠・出産年齢にある日本人若年女性の栄養不良傾向が懸念されている。肥満は妊娠糖尿病(以下GDMと略す)発症の主要なリスク因子であることが知られているが、日本人を含むアジア系民族では、標準BMI(25.0kg/m2未満)であってもGDM有病率が高いことが報告されており、GDM発症リスクが上昇するBMIの閾値は、他の人種に比べ低いと考えられている。また近年の欧米の研究では、妊娠前の体重増加もGDMの独立したリスク因子となることが報告されており、妊娠前の体型および体重歴がGDM発症において重要な因子であることが示唆されているが、欧米人に比べ若年女性の平均BMIが低い日本人女性においても同様であるかどうかは不明である。そこで本稿では、近年の日本人若年女性のBMIおよびやせの現状を概説するとともに、妊娠前の体重歴とGDM発症との関連について、日本人健常妊婦を対象に前向きに検討したわれわれの研究結果を紹介する。(著者抄録)

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  • Basic & Clinical TOPICS : HbA1c 5.7-6.4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan : a longitudinal cohort study

    1 ( 1 )   18 - 20   2012.8

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  • Chronic kidney disease categories and renal-cardiovascular outcomes in type 2 diabetes without prevalent cardiovascular disease: a prospective cohort study (JDDM25)

    H. Yokoyama, S. Araki, M. Haneda, M. Matsushima, K. Kawai, K. Hirao, M. Oishi, K. Sugimoto, H. Sone, H. Maegawa, A. Kashiwagi

    DIABETOLOGIA   55 ( 7 )   1911 - 1918   2012.7

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    Aims/hypothesis In type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low- and high-risk diabetic patients.
    Methods This 4 year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine &lt; 176.8 mu mol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; ml min(-1) 1.73 m(-2)). Association of progression from 'no CKD' stage (ACR &lt; 3.5 mg/mmol and eGFR &gt;= 90 ml min(-1) 1.73 m(-2)) with risk for CVD onset was also evaluated.
    Results During follow-up (median 3.8 years), 89 CVD events occurred. Compared with patients with 'no CKD' as reference, those with ACR &gt;= 35.0 mg/mmol with co-existing eGFR 60-89 ml min(-1) 1.73 m(-2) or &lt; 60 ml min(-1) 1.73 m(-2) showed increased risk for CVD onset, whereas those with eGFR &gt;= 90 ml min(-1) 1.73 m(-2) did not. Those with ACR &lt; 3.5 mg/mmol and eGFR &lt; 60 ml min(-1) 1.73 m(-2) did not show any increased risk. Among patients with 'no CKD' stage at baseline, those who progressed to ACR &gt;= 3.5 mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR &lt; 90 ml min(-1) 1.73 m(-2) did not have increased risk.
    Conclusions/interpretation The risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD.

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  • Chronic kidney disease categories and renal-cardiovascular outcomes in type 2 diabetes without prevalent cardiovascular disease: a prospective cohort study (JDDM25)

    H. Yokoyama, S. Araki, M. Haneda, M. Matsushima, K. Kawai, K. Hirao, M. Oishi, K. Sugimoto, H. Sone, H. Maegawa, A. Kashiwagi

    DIABETOLOGIA   55 ( 7 )   1911 - 1918   2012.7

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    Aims/hypothesis In type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low- and high-risk diabetic patients.
    Methods This 4 year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine &lt; 176.8 mu mol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; ml min(-1) 1.73 m(-2)). Association of progression from 'no CKD' stage (ACR &lt; 3.5 mg/mmol and eGFR &gt;= 90 ml min(-1) 1.73 m(-2)) with risk for CVD onset was also evaluated.
    Results During follow-up (median 3.8 years), 89 CVD events occurred. Compared with patients with 'no CKD' as reference, those with ACR &gt;= 35.0 mg/mmol with co-existing eGFR 60-89 ml min(-1) 1.73 m(-2) or &lt; 60 ml min(-1) 1.73 m(-2) showed increased risk for CVD onset, whereas those with eGFR &gt;= 90 ml min(-1) 1.73 m(-2) did not. Those with ACR &lt; 3.5 mg/mmol and eGFR &lt; 60 ml min(-1) 1.73 m(-2) did not show any increased risk. Among patients with 'no CKD' stage at baseline, those who progressed to ACR &gt;= 3.5 mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR &lt; 90 ml min(-1) 1.73 m(-2) did not have increased risk.
    Conclusions/interpretation The risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD.

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  • 未診断糖尿病の検出には現在の体重より過去の最大体重の方が有効である

    児玉 暁, 由澤 咲子, 平安座 依子, 齋藤 和美, 辻 裕之, 謝 勲東, 荒瀬 康司, 原 茂子, 曽根 博仁

    人間ドック   27 ( 2 )   338 - 338   2012.7

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  • 若年女性のやせすぎの現状とリスク

    菅原 歩美, 谷内 洋子, 曽根 博仁

    日本医事新報   ( 4604 )   80 - 85   2012.7

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  • 【糖尿病合併症の成因と薬物療法】 糖尿病合併症予防の薬物療法の現状と限界 大血管障害

    藤原 和哉, 曽根 博仁

    月刊糖尿病   4 ( 8 )   34 - 44   2012.7

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  • 【メタアナリシスの意義-臨床にどういう影響を与えたか-】 メタアナリシスへの参加経験 論文ベースのメタアナリシスをする際の留意点

    児玉 暁, 田中 司朗, 大橋 靖雄, 曽根 博仁

    動脈硬化予防   11 ( 2 )   43 - 52   2012.7

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  • 医科栄養学教育の現状と展望 カリキュラム改革に向けて

    折茂 英生, 上野 高浩, 曽根 博仁, 田中 明, 田中 芳明, 西 理宏, 伴場 裕己, 松浦 達也, 吉田 博, 板倉 弘重

    医学教育   43 ( Suppl. )   116 - 116   2012.7

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  • 【最新臨床糖尿病学 下-糖尿病学の最新動向-】 糖尿病合併症・糖尿病関連疾患 各種糖尿病合併症の概念・成因・診断・治療 糖尿病大血管症 我が国の糖尿病大血管症の特徴

    曽根 博仁

    日本臨床   70 ( 増刊5 最新臨床糖尿病学(下) )   305 - 312   2012.7

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  • 【糖尿病合併症の成因と治療】 糖尿病大血管症のエビデンスに基づく治療戦略

    曽根 博仁

    Medical Science Digest   38 ( 8 )   354 - 357   2012.7

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    糖尿病治療の目標は合併症を予防し、患者の生活の質や健康寿命を非糖尿病者に限りなく近づけることである。多くの内外の大規模研究の結果から、血糖コントロールの是正が、網膜症や腎症などの細小血管合併症を抑制することは確立している。一方、糖尿病大血管症については、血清脂質、血圧など血糖以外の有力なリスクファクターがいくつも関与するため、単に血糖コントロールを厳格に行うのみでは不十分であることが指摘されてきた。本稿では、血糖、血清脂質、血圧、生活習慣、集学的治療のそれぞれの観点から糖尿病患者における大血管症予防戦略について、最近のエビデンスも含めて概説する。(著者抄録)

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  • 生活習慣病の疫学研究から動脈硬化を予防する 糖尿病性心血管病発症危険因子の年代別検討 HDL-CとLDL-C/HDL-Cの役割を中心に

    林 登志雄, 井藤 英喜, 荒木 厚, 川嶋 成乃亮, 曽根 博仁, 渡邉 裕司, 大類 孝, 横手 幸太郎, 竹本 稔, 服部 良之, 久保田 潔, 伊奈 孝一郎, 野村 秀樹

    日本動脈硬化学会総会プログラム・抄録集   44回   127 - 127   2012.7

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  • Prediction of Incident Diabetes by Measurements of both HbA1C and Fasting Plasma Glucose in Comparison With Use of HbA1c or FPG Alone: A Meta-Analysis

    Satoru Kodama, Chika Horikawa, Ryoko Tajima, Kazuya Fujihara, Sakiko Yoshizawa, Yoko Ibe, Reiko Hirasawa, Hitoshi Shimano, Kazumi Saito, Hirohito Sone

    DIABETES   61   A368 - A368   2012.6

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  • Fruit Intake and Incident Retinopathy in Japanese Patients With Type 2 Diabetes-Nutritional Analysis in the Japan Diabetes Complications Study (JDCS)

    Shiro Tanaka, Yukio Yoshimura, Ryo Kawasaki, Chiemi Kamada, Sachiko Tanaka, Chika Horikawa, Yasuo Ohashi, Atsushi Araki, Hideki Ito, Yasuo Akanuma, Nobuhiro Yamada, Hidetoshi Yamashita, Hirohito Sone

    DIABETES   61   A77 - A77   2012.6

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  • Differences in Relationships between Diabetes Duration and Diabetes-Related Psychological Distress: Japan Diabetes Clinical Data Management Study

    Ayumi Sugawara, Koichi Kawai, Atsuyoshi Yuhara, Mariko Oishi, Hidekatsu Sugimoto, Hiroki Yokoyama, Noriharu Yagi, Akira Okada, Koichi Iwasaki, Kazuhiro Miyazawa, Fuminobu Okuguchi, Fumihiko Dake, Aki Saito, Kazumi Saito, Hirohito Sone

    DIABETES   61   A172 - A172   2012.6

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  • Relationship between Dairy Intake and Risk of Metabolic Syndrome: A Meta-Analysis

    Chika Horikawa, Satoru Kodama, Yoriko Heianza, Ayumi Sugawara, Miho Maki, Sakiko Yoshizawa, Yoko Yachi, Kazumi Saito, Hirohito Sone

    DIABETES   61   A514 - A514   2012.6

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  • A Meta-Analysis of the Quantitative Relationship Between Fat Intake and Incident DM

    Ryoko Tajima, Satoru Kodama, Chika Horikawa, Yoko Yachi, Ayumi Sugawara, Yoriko Heianza, Reiko Hirasawa, Kazuya Fujiwara, Kazumi Saitou, Kaoruko Iida, Hirohito Sone

    DIABETES   61   A190 - A191   2012.6

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  • Effectiveness of Non-Diagnostic Levels of HbA1C or Fasting Plasma Glucose for Diagnosing and Predicting Diabetes Mellitus: Meta-Analysis

    Chika Horikawa, Satoru Kodama, Ryoko Tajima, Kazuya Fujihara, Sakiko Yoshizawa, Yoko Ibe, Reiko Hirasawa, Hitoshi Shimano, Hirohito Sone

    DIABETES   61   A366 - A366   2012.6

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  • Physical Activity and Lower Risk of All-Cause Death and Cardiovascular Disease in Diabetes: A Meta-Analysis

    Satoru Kodama, Chika Horikawa, Ryoko Tajima, Yoriko Heianza, Ayumi Sugawara, Miho Maki, Yoko Yachi, Kaoruko T. Iida, Kazumi Saito, Hirohito Sone

    DIABETES   61   A40 - A41   2012.6

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  • Relationship Between Obstructive Sleep Apnea and Diabetes Risk-A Meta-Analysis

    Kazuya Fujihara, Satoru Kodama, Chika Horikawa, Yoriko Heianza, Ayumi Sugawara, Miho Maki, Yoko Yachi, Hitoshi Shimano, Kazumi Saito, Hirohito Sone

    DIABETES   61   A5 - A5   2012.6

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  • The Role of Triglycerides for the Development of Cardiovascular Disease in Mild to Moderate Hypercholesterolemia With Abnormal Fasting Glucose

    Tomoko Nakagami, Rimei Nishimura, Hirohito Sone, Naoko Tajima

    DIABETES   61   A387 - A388   2012.6

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  • Quality and Accuracy of Internet Information Concerning a Healthy Diet

    Reiko Hirasawa, Ayumi Sugawara, Kazumi Saito, Satoru Kodama, Yoko Yachi, Sakiko Yoshizawa, Chika Horikawa, Yoriko Heianza, Yoko Ibe, Hirohito Sone

    DIABETES   61   A175 - A175   2012.6

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  • Both Lifetime Maximum BMI and BMI Change Since Age 20 Years to Maximum Were Strongly Associated With having Undiagnosed Diabetes in Japanese Women: Toranomon Hospital Health Management Center Study

    Sakiko Yoshizawa, Yoriko Heianza, Yasuji Arase, Hiroshi Tsuji, Kazumi Saito, Shiun Dong Hsieh, Satoru Kodama, Nobuhiro Yamada, Shigeko Hara, Hirohito Sone

    DIABETES   61   A512 - A512   2012.6

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  • Physical Activity is Associated With Lower Risk of Stroke but Not Coronary Heart Disease (CHD) in Japanese Patients With Type 2 Diabetes-Analysis of the Japan Diabetes Complications Study (JDCS)

    Hirohito Sone, Shiro Tanaka, Sachiko Tanaka, Hiroaki Seino, Shun Ishibashi, Hitoshi Shimano, Shinichi Oikawa, Shigehiro Katayama, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES   61   A181 - A182   2012.6

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  • 糖尿病性ケトアシドーシスに併発した肺アスペルギルス症の1例

    藤田 英理子, 黒澤 陽一, 濱田 治, 尾本 美代子, 藤原 和哉, 大原 原, 籠橋 克紀, 栗島 浩一, 曽根 博仁, 佐藤 浩昭

    日本内科学会関東地方会   588回   36 - 36   2012.6

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  • 横紋筋融解症、急性心筋炎から救命しえた劇症1型糖尿病の1例

    宜保 英彦, 藤原 和哉, 小林 和人, 矢藤 繁, 高橋 昭光, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    日本内分泌学会雑誌   88 ( Suppl. )   71 - 74   2012.6

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    劇症1型糖尿病に横紋筋融解症、急性腎不全、急性心筋炎を合併し、大量補液や血液透析を含む集学的治療により救命しえた症例を経験した。患者は35歳男で、ウイルス抗体検査でヒトヘルペスウイルス6型(HHV-6)抗体価の有意な上昇を認めた。劇症1型糖尿病と心筋炎の発症にはHHV-6感染が関与した可能性があり、文献的考察を加えて報告した。

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  • 【クリティカルケアに必要な糖代謝と栄養管理-SCCM/ASPEN栄養管理ガイドラインに準拠して-】 高血糖の急性毒性 糖化蛋白

    齋藤 あき, 曽根 博仁

    救急・集中治療   24 ( 5-6 )   521 - 527   2012.6

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    <point>●糖化蛋白とは、グルコースやフルクトースなどの糖が蛋白質に結合した状態である。●糖化により蛋白質は変性し、その蛋白質本来の働きを失う。●糖化蛋白は糖化反応を経てAGEs(advanced gycation endproducts:糖化最終産物)を生成する。糖尿病などの慢性的な高血糖状態では、AGEsの形成が促進される。●糖尿病では、血糖の高値そのものだけでなく、ジカルボニル化合物などの糖化蛋白や、AGEsの生成が合併症の進展に関わっている。●現在の糖尿病治療では糖尿病性合併症を完全に予防できないが、初期からの厳格な血糖コントロールや集約的な治療により合併症を抑制できると考えられる。(著者抄録)

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  • New Risk Score for Predicting 5-Year Incidence of Type 2 Diabetes in Japan: The Toranomon Hospital Health Management Center Study

    Yoriko Heianza, Yasuji Arase, Hiroshi Tsuji, Sakiko Yoshizawa, Kazumi Saito, Shiun Dong Hsieh, Satoru Kodama, Nobuhiro Yamada, Shigeko Hara, Hirohito Sone

    DIABETES   61   A81 - A81   2012.6

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  • Effect of web-based lifestyle modification on weight control: a meta-analysis

    S. Kodama, K. Saito, S. Tanaka, C. Horikawa, K. Fujiwara, R. Hirasawa, Y. Yachi, K. T. Iida, H. Shimano, Y. Ohashi, N. Yamada, H. Sone

    INTERNATIONAL JOURNAL OF OBESITY   36 ( 5 )   675 - 685   2012.5

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    Objective: Web-based treatment programs are attractive in primary care because of their ability to reach numerous individuals at low cost. Our aim of this meta-analysis is to systematically review the weight loss or maintenance effect of the Internet component in obesity treatment programs.
    Methods: MEDLINE and EMBASE literature searches were conducted to identify studies investigating the effect of Web-based individualized advice on lifestyle modification on weight loss. Randomized controlled trials that consisted of a Web-user experimental and non-Web user control group were included. Weight changes in the experimental group in comparison with the control group were pooled with a random-effects model.
    Results: A total of 23 studies comprising 8697 participants were included. Overall, using the Internet had a modest but significant additional weight-loss effect compared with non-Web user control groups (-0.68 kg, P = 0.03). In comparison with the control group, stratified analysis indicated that using the Internet as an adjunct to obesity care was effective (-1.00 kg, P&lt;0.001), but that using it as a substitute for face-to-face support was unfavorable (+1.27kg, P = 0.01). An additional effect on weight control was observed when the aim of using the Internet was initial weight loss (-1.01 kg; P = 0.03), but was not observed when the aim was weight maintenance (+0.68 kg; P = 0.26). The relative effect was diminished with longer educational periods (P-trend = 0.04) and was insignificant (-0.20 kg; P = 0.75) in studies with educational periods of 12 months or more.
    Conclusion: The current meta-analysis indicates that the Internet component in obesity treatment programs has a modest effect on weight control. However, the effect was inconsistent, largely depending on the type of usage of the Internet or the period of its use. International Journal of Obesity (2012) 36, 675-685; doi:10.1038/ijo.2011.121; published online 21 June 2011

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  • Comparison of Various Lipid Variables as Predictors of Coronary Heart Disease in Japanese Men and Women With Type 2 Diabetes Subanalysis of the Japan Diabetes Complications Study

    Hirohito Sone, Sachiko Tanaka, Shiro Tanaka, Satoshi Iimuro, Shun Ishibashi, Shinichi Oikawa, Hitoshi Shimano, Shigehiro Katayama, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES CARE   35 ( 5 )   1150 - 1157   2012.5

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    OBJECTIVE- To determine the best lipid variable to predict coronary heart disease (CHD) in Japanese patients with type 2 diabetes.
    RESEARCH DESIGN AND METHODS-Eligible Japanese men and women (1,771) aged 40-70 years with type 2 diabetes from 59 institutes nationwide were followed for a planned 8-year period. The performance of eight conventional lipid variables, i.e., total cholesterol (TC), LDL-cholesterol (LDLC), HDL-cholesterol (HDLC), triglycerides (TGs), non-HDLC, TC/HDLC ratio, LDLC/HDLC ratio, and TG/HDLC ratio, as predictors of incident CHD were evaluated by four methods: hazard ratio (HR) per one SD increment by multivariate Cox analysis, chi(2) likelihood ratio test, area under the receiver operating characteristic curve (AUC), and tertile analysis.
    RESULTS-Although all variables significantly predicted CHD events in men, non-HDLC (HR per one SD 1.78 [95% CI 1.43-2.21]; AUC 0.726) and TC/HDLC (HR 1.63 [1.36-1.95]; AUC 0.718) had the better predictive performances among the variables, including LDLC. In women, TGs (log-transformed; HR 1.72 [1.21-2.43]; AUC 0.708) were the best predictor according to results of tertile analysis (HR of the top tertile versus the bottom tertile 4.31 [1.53-12.16]). The associations with incident CHD were linear and continuous.
    CONCLUSIONS-For Japanese diabetic men, non-HDLC and TC/HDLC were the best predictors, whereas TGs were most predictive for women. These findings, which included prominent sex differences, should be considered among clinical approaches to risk reduction among East Asians with diabetes.

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  • Quality of Internet information related to the Mediterranean diet

    Reiko Hirasawa, Kazumi Saito, Yoko Yachi, Yoko Ibe, Satoru Kodama, Mihoko Asumi, Chika Horikawa, Aki Saito, Yoriko Heianza, Kazuo Kondo, Hitoshi Shimano, Hirohito Sone

    PUBLIC HEALTH NUTRITION   15 ( 5 )   885 - 893   2012.5

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    Objective: The present study aimed to evaluate the quality of Internet information on the Mediterranean diet and to determine the relationship between the quality of information and the website source.
    Design: Website sources were categorized as institutional, pharmaceutical, non-pharmaceutical commercial, charitable, support and alternative medicine. Content quality was evaluated using the DISCERN rating instrument, the Health On the Net Foundation's (HON) code principles, and Journal of the American Medical Association (JAMA) benchmarks. Readability was graded by the Flesch Reading Ease score and Flesch-Kincaid Grade Level score.
    Setting: The phrase 'Mediterranean diet' was entered as a search term into the six most commonly used English-language search engines.
    Subjects: The first thirty websites forthcoming by each engine were examined.
    Results: Of the 180 websites identified, thirty-two met our inclusion criteria. Distribution of the website sources was: institutional, n 8 (25 %); non-pharmaceutical commercial, n 12 (38 %); and support, n 12 (38 %). As evaluated by the DISCERN, thirty-one of the thirty-two websites were rated as fair to very poor. Non-pharmaceutical commercial sites scored significantly lower than institutional and support sites (P=0.002). The mean Flesch Reading Ease score and mean Flesch-Kincaid Grade Level were 55.9 (fairly difficult) and 7.2, respectively. The Flesch-Kincaid Grade Level score determines the difficulty of material by measuring the length of words and sentences and converting the results into a grade level ranging from 0 to 12 (US grade level).
    Conclusions: Due to the poor quality of website information on the Mediterranean diet, patients or consumers who are interested in the Mediterranean diet should get advice from physicians or dietitians.

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  • Longitudinal Trajectories of HbA(1c) and Fasting Plasma Glucose Levels During the Development of Type 2 Diabetes The Toranomon Hospital Health Management Center Study 7 (TOPICS 7)

    Yoriko Heianza, Yasuji Arase, Kazuya Fujhara, Shiun Dung Hsieh, Kazumi Saito, Hiroshi Tsuji, Satoru Kodama, Naoya Yahagi, Hitosh Shimano, Nobuhiro Yamada, Shigeko Hara, Hirohito Sone

    DIABETES CARE   35 ( 5 )   1050 - 1052   2012.5

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    OBJECTIVE-To describe the trajectory of HbA(1c), and glucose concentrations before the diagnosis of diabetes.
    RESEARCH DESIGN AND METHODS-The study comprised 1,722 nondiabetic Japanese individuals aged 26-80 years. Fasting plasma glucose (FPG) and HbA(1c) were measured annually for a mean of 9.5 (SD 1.8) years.
    RESULTS-Diabetes occurred in 193 individuals (FPG &gt;= 7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) &gt;= 6.5%). Mean HbA(1c) values were &gt;5.6% each year before diagnosis in diabetes cases. Mean HbA(1c) (5.69% [95% CI 5.50-5.88]) was higher in the 21 individuals who developed diabetes 10 years after the baseline examination than in nondiabetic individuals after 10 years (5.27% [5.25-5.28]). From 3 years to 1 year prediagriosis, HbA(1c) increased 0.09% (SE 0.01)/year, reaching 5.90% (5.84-5.96) 1 year prediagnosis. In the entire group, marked increases in HbA(1c) of 0.3% (SE 0.05%)/year and FPG of 0.63 (0.07) mmol/L/year predicted diabetes.
    CONCLUSIONS HbA(1c) trajectory increased sharply after gradual long-term increases in diabetic individuals.

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  • Quality of Internet information related to the Mediterranean diet

    Reiko Hirasawa, Kazumi Saito, Yoko Yachi, Yoko Ibe, Satoru Kodama, Mihoko Asumi, Chika Horikawa, Aki Saito, Yoriko Heianza, Kazuo Kondo, Hitoshi Shimano, Hirohito Sone

    PUBLIC HEALTH NUTRITION   15 ( 5 )   885 - 893   2012.5

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    Objective: The present study aimed to evaluate the quality of Internet information on the Mediterranean diet and to determine the relationship between the quality of information and the website source.
    Design: Website sources were categorized as institutional, pharmaceutical, non-pharmaceutical commercial, charitable, support and alternative medicine. Content quality was evaluated using the DISCERN rating instrument, the Health On the Net Foundation's (HON) code principles, and Journal of the American Medical Association (JAMA) benchmarks. Readability was graded by the Flesch Reading Ease score and Flesch-Kincaid Grade Level score.
    Setting: The phrase 'Mediterranean diet' was entered as a search term into the six most commonly used English-language search engines.
    Subjects: The first thirty websites forthcoming by each engine were examined.
    Results: Of the 180 websites identified, thirty-two met our inclusion criteria. Distribution of the website sources was: institutional, n 8 (25 %); non-pharmaceutical commercial, n 12 (38 %); and support, n 12 (38 %). As evaluated by the DISCERN, thirty-one of the thirty-two websites were rated as fair to very poor. Non-pharmaceutical commercial sites scored significantly lower than institutional and support sites (P=0.002). The mean Flesch Reading Ease score and mean Flesch-Kincaid Grade Level were 55.9 (fairly difficult) and 7.2, respectively. The Flesch-Kincaid Grade Level score determines the difficulty of material by measuring the length of words and sentences and converting the results into a grade level ranging from 0 to 12 (US grade level).
    Conclusions: Due to the poor quality of website information on the Mediterranean diet, patients or consumers who are interested in the Mediterranean diet should get advice from physicians or dietitians.

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  • Longitudinal Trajectories of HbA(1c) and Fasting Plasma Glucose Levels During the Development of Type 2 Diabetes The Toranomon Hospital Health Management Center Study 7 (TOPICS 7)

    Yoriko Heianza, Yasuji Arase, Kazuya Fujhara, Shiun Dung Hsieh, Kazumi Saito, Hiroshi Tsuji, Satoru Kodama, Naoya Yahagi, Hitosh Shimano, Nobuhiro Yamada, Shigeko Hara, Hirohito Sone

    DIABETES CARE   35 ( 5 )   1050 - 1052   2012.5

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    OBJECTIVE-To describe the trajectory of HbA(1c), and glucose concentrations before the diagnosis of diabetes.
    RESEARCH DESIGN AND METHODS-The study comprised 1,722 nondiabetic Japanese individuals aged 26-80 years. Fasting plasma glucose (FPG) and HbA(1c) were measured annually for a mean of 9.5 (SD 1.8) years.
    RESULTS-Diabetes occurred in 193 individuals (FPG &gt;= 7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) &gt;= 6.5%). Mean HbA(1c) values were &gt;5.6% each year before diagnosis in diabetes cases. Mean HbA(1c) (5.69% [95% CI 5.50-5.88]) was higher in the 21 individuals who developed diabetes 10 years after the baseline examination than in nondiabetic individuals after 10 years (5.27% [5.25-5.28]). From 3 years to 1 year prediagriosis, HbA(1c) increased 0.09% (SE 0.01)/year, reaching 5.90% (5.84-5.96) 1 year prediagnosis. In the entire group, marked increases in HbA(1c) of 0.3% (SE 0.05%)/year and FPG of 0.63 (0.07) mmol/L/year predicted diabetes.
    CONCLUSIONS HbA(1c) trajectory increased sharply after gradual long-term increases in diabetic individuals.

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  • Effect of web-based lifestyle modification on weight control: a meta-analysis

    S. Kodama, K. Saito, S. Tanaka, C. Horikawa, K. Fujiwara, R. Hirasawa, Y. Yachi, K. T. Iida, H. Shimano, Y. Ohashi, N. Yamada, H. Sone

    INTERNATIONAL JOURNAL OF OBESITY   36 ( 5 )   675 - 685   2012.5

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    Objective: Web-based treatment programs are attractive in primary care because of their ability to reach numerous individuals at low cost. Our aim of this meta-analysis is to systematically review the weight loss or maintenance effect of the Internet component in obesity treatment programs.
    Methods: MEDLINE and EMBASE literature searches were conducted to identify studies investigating the effect of Web-based individualized advice on lifestyle modification on weight loss. Randomized controlled trials that consisted of a Web-user experimental and non-Web user control group were included. Weight changes in the experimental group in comparison with the control group were pooled with a random-effects model.
    Results: A total of 23 studies comprising 8697 participants were included. Overall, using the Internet had a modest but significant additional weight-loss effect compared with non-Web user control groups (-0.68 kg, P = 0.03). In comparison with the control group, stratified analysis indicated that using the Internet as an adjunct to obesity care was effective (-1.00 kg, P&lt;0.001), but that using it as a substitute for face-to-face support was unfavorable (+1.27kg, P = 0.01). An additional effect on weight control was observed when the aim of using the Internet was initial weight loss (-1.01 kg; P = 0.03), but was not observed when the aim was weight maintenance (+0.68 kg; P = 0.26). The relative effect was diminished with longer educational periods (P-trend = 0.04) and was insignificant (-0.20 kg; P = 0.75) in studies with educational periods of 12 months or more.
    Conclusion: The current meta-analysis indicates that the Internet component in obesity treatment programs has a modest effect on weight control. However, the effect was inconsistent, largely depending on the type of usage of the Internet or the period of its use. International Journal of Obesity (2012) 36, 675-685; doi:10.1038/ijo.2011.121; published online 21 June 2011

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  • Comparison of Various Lipid Variables as Predictors of Coronary Heart Disease in Japanese Men and Women With Type 2 Diabetes Subanalysis of the Japan Diabetes Complications Study

    Hirohito Sone, Sachiko Tanaka, Shiro Tanaka, Satoshi Iimuro, Shun Ishibashi, Shinichi Oikawa, Hitoshi Shimano, Shigehiro Katayama, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES CARE   35 ( 5 )   1150 - 1157   2012.5

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    OBJECTIVE- To determine the best lipid variable to predict coronary heart disease (CHD) in Japanese patients with type 2 diabetes.
    RESEARCH DESIGN AND METHODS-Eligible Japanese men and women (1,771) aged 40-70 years with type 2 diabetes from 59 institutes nationwide were followed for a planned 8-year period. The performance of eight conventional lipid variables, i.e., total cholesterol (TC), LDL-cholesterol (LDLC), HDL-cholesterol (HDLC), triglycerides (TGs), non-HDLC, TC/HDLC ratio, LDLC/HDLC ratio, and TG/HDLC ratio, as predictors of incident CHD were evaluated by four methods: hazard ratio (HR) per one SD increment by multivariate Cox analysis, chi(2) likelihood ratio test, area under the receiver operating characteristic curve (AUC), and tertile analysis.
    RESULTS-Although all variables significantly predicted CHD events in men, non-HDLC (HR per one SD 1.78 [95% CI 1.43-2.21]; AUC 0.726) and TC/HDLC (HR 1.63 [1.36-1.95]; AUC 0.718) had the better predictive performances among the variables, including LDLC. In women, TGs (log-transformed; HR 1.72 [1.21-2.43]; AUC 0.708) were the best predictor according to results of tertile analysis (HR of the top tertile versus the bottom tertile 4.31 [1.53-12.16]). The associations with incident CHD were linear and continuous.
    CONCLUSIONS-For Japanese diabetic men, non-HDLC and TC/HDLC were the best predictors, whereas TGs were most predictive for women. These findings, which included prominent sex differences, should be considered among clinical approaches to risk reduction among East Asians with diabetes.

    DOI: 10.2337/dc11-1412

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  • 2型糖尿病における知識と負担感との関連の検討

    菅原 歩美, 曽根 博仁, 湯原 淳良, 大石 まり子, 杉本 英克, 横山 宏樹, 屋宜 宣治, 岡田 朗, 岩崎 皓一, 宮澤 一裕, 奥口 文宣, 嵩 文彦, 齋藤 あき, 西垣 結佳子, 川井 紘一

    成人病と生活習慣病   42 ( 5 )   605 - 606   2012.5

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  • 糖尿病診断および予測能におけるグリコヘモグロビンA1cと空腹時血糖のメタ解析

    児玉 暁, 堀川 千嘉, 平安座 依子, 菅原 歩美, 平澤 玲子, 谷内 洋子, 齋藤 和美, 曽根 博仁, 田中 司朗, 大橋 靖雄

    成人病と生活習慣病   42 ( 5 )   621 - 621   2012.5

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  • 【最新臨床糖尿病学 上-糖尿病学の最新動向-】 糖尿病の疫学とEBM 疫学研究・大規模臨床試験より得られたEBM JDCS

    曽根 博仁, 片山 茂裕, 山下 英俊, 赤沼 安夫, 山田 信博

    日本臨床   70 ( 増刊3 最新臨床糖尿病学(上) )   281 - 289   2012.5

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  • "Healthy diet"に関する国際的ウェブ情報のクオリティの検証

    平澤 玲子, 谷内 洋子, 伊部 陽子, 由澤 咲子, 堀川 千嘉, 斉藤 あき, 平安座 依子, 菅原 歩美, 戸塚 久美子, 齋藤 和美, 児玉 暁, 曽根 博仁

    成人病と生活習慣病   42 ( 5 )   606 - 606   2012.5

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  • 2型糖尿病発症予測に最適なHbA1cと空腹時血糖値の閾値の組み合わせの検討 TOPICS

    平安座 依子, 山田 信博, 齋藤 和美, 児玉 暁, 曽根 博仁, 原 茂子, 謝 勲東, 辻 裕之, 荒瀬 康司

    成人病と生活習慣病   42 ( 5 )   621 - 622   2012.5

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  • 健常妊婦における低出生体重児出産リスク因子の検討(TWC Study)

    谷内 洋子, 菅原 歩美, 児玉 暁, 齋藤 和美, 曽根 博仁, 田中 康弘, 松岡 隆, 西端 泉, 安原 眞知子, 小林 香織

    成人病と生活習慣病   42 ( 5 )   604 - 605   2012.5

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  • 【脳・心・腎連関を見逃さない】 脳・心・腎連関各論 脂質異常症と脳・心・腎連関

    藤原 和哉, 曽根 博仁

    糖尿病診療マスター   10 ( 4 )   313 - 320   2012.5

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    DOI: 10.11477/mf.1415101355

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  • HbA1cを導入した新しい2型糖尿病予測スコアリングシステムの開発

    平安座 依子, 藤原 和哉, 堀川 千嘉, 谷内 洋子, 山田 信博, 児玉 暁, 曽根 博仁, 謝 勲東, 原 茂子, 辻 裕之, 荒瀬 康司

    成人病と生活習慣病   42 ( 5 )   603 - 603   2012.5

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  • 2型糖尿病発症前のHbA1c値と空腹時血糖値の変化に関する大規模縦断的検討

    平安座 依子, 藤原 和哉, 山田 信博, 齋藤 和美, 児玉 暁, 曽根 博仁, 荒瀬 康司, 辻 裕之, 謝 勲東, 原 茂子

    成人病と生活習慣病   42 ( 5 )   602 - 603   2012.5

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  • 【最新臨床糖尿病学 上-糖尿病学の最新動向-】 糖尿病の予防・管理・治療 糖尿病における二次・三次予防の新しい考え方

    藤原 和哉, 曽根 博仁

    日本臨床   70 ( 増刊3 最新臨床糖尿病学(上) )   561 - 569   2012.5

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    Other Link: http://search.jamas.or.jp/link/ui/2012266117

  • 【日本人の糖尿病と欧米人の糖尿病】 糖尿病の合併症に関する相違 大血管症

    曽根 博仁

    ホルモンと臨床   60 ( 5 )   419 - 427   2012.5

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    Other Link: http://search.jamas.or.jp/link/ui/2014075697

  • TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice

    Hitoshi Iwasaki, Ayano Naka, Kaoruko Tada Iida, Yoshimi Nakagawa, Takashi Matsuzaka, Kiyo-aki Ishii, Kazuto Kobayashi, Akimitsu Takahashi, Shigeru Yatoh, Naoya Yahagi, Hirohito Sone, Hiroaki Suzuki, Nobuhiro Yamada, Hitoshi Shimano

    AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM   302 ( 7 )   E896 - E902   2012.4

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    Iwasaki H, Naka A, Iida KT, Nakagawa Y, Matsuzaka T, Ishii K, Kobayashi K, Takahashi A, Yatoh S, Yahagi N, Sone H, Suzuki H, Yamada N, Shimano H. TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice. Am J Physiol Endocrinol Metab 302: E896-E902, 2012. First published January 31, 2012; doi: 10.1152/ajpendo.00204.2011.-The role of transcription factor E3 (TFE3), a bHLH transcription factor, in immunology and cancer has been well characterized. Recently, we reported that TFE3 activates hepatic IRS-2 and hexokinase, participates in insulin signaling, and ameliorates diabetes. However, the effects of TFE3 in other organs are poorly understood. Herein, we examined the effects of TFE3 on skeletal muscle, an important organ involved in glucose metabolism. We generated transgenic mice that selectively express TFE3 in skeletal muscles. These mice exhibit a slight acceleration in growth prior to adulthood as well as a progressive increase in muscle mass. In TFE3 transgenic muscle, glycogen stores were more than twofold than in wild-type mice, and this was associated with an upregulation of genes involved in glucose metabolism, specifically glucose transporter 4, hexokinase II, and glycogen synthase. Consequently, exercise endurance capacity was enhanced in this transgenic model. Furthermore, insulin sensitivity was enhanced in transgenic mice and exhibited better improvement after 4 wk of exercise training, which was associated with increased IRS-2 expression. The effects of TFE3 on glucose metabolism in skeletal muscle were different from that in the liver, although they did, in part, overlap. The potential role of TFE3 in regulating metabolic genes and glucose metabolism within skeletal muscle suggests that it may be used for treating metabolic diseases as well as increasing endurance in sport.

    DOI: 10.1152/ajpendo.00204.2011

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  • Non-high-density lipoprotein cholesterol: An important predictor of stroke and diabetes-related mortality in Japanese elderly diabetic patients

    Atsushi Araki, Satoshi Iimuro, Takashi Sakurai, Hiroyuki Umegaki, Katsuya Iijima, Hiroshi Nakano, Kenzo Oba, Koichi Yokono, Hirohito Sone, Nobuhiro Yamada, Junya Ako, Koichi Kozaki, Hisayuki Miura, Atsunori Kashiwagi, Ryuichi Kikkawa, Yukio Yoshimura, Tadasumi Nakano, Yasuo Ohashi, Hideki Ito

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( Suppl1 )   18 - 28   2012.4

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    Aims: To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients.
    Methods: This study was carried out as a post-hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged &gt;= 65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry.
    Results: During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes-related deaths and 113 diabetes-related events. High low-density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, nonhigh- density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes-related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non-high-density lipoprotein cholesterol were 1.010 (1.001-1.018, P = 0.029) for stroke, 1.019 (1.007-1.031, P &lt; 0.001) for diabetes-related death and 1.008 (1.002-1.014; P &lt; 0.001) for total diabetes-related events.
    Conclusions: Higher non-high-density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes-related mortality and total events in elderly diabetes patients. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 18-28.

    DOI: 10.1111/j.1447-0594.2011.00809.x

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  • Non-high-density lipoprotein cholesterol: An important predictor of stroke and diabetes-related mortality in Japanese elderly diabetic patients

    Atsushi Araki, Satoshi Iimuro, Takashi Sakurai, Hiroyuki Umegaki, Katsuya Iijima, Hiroshi Nakano, Kenzo Oba, Koichi Yokono, Hirohito Sone, Nobuhiro Yamada, Junya Ako, Koichi Kozaki, Hisayuki Miura, Atsunori Kashiwagi, Ryuichi Kikkawa, Yukio Yoshimura, Tadasumi Nakano, Yasuo Ohashi, Hideki Ito

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( Suppl1 )   18 - 28   2012.4

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    Aims: To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients.
    Methods: This study was carried out as a post-hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged &gt;= 65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry.
    Results: During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes-related deaths and 113 diabetes-related events. High low-density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, nonhigh- density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes-related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non-high-density lipoprotein cholesterol were 1.010 (1.001-1.018, P = 0.029) for stroke, 1.019 (1.007-1.031, P &lt; 0.001) for diabetes-related death and 1.008 (1.002-1.014; P &lt; 0.001) for total diabetes-related events.
    Conclusions: Higher non-high-density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes-related mortality and total events in elderly diabetes patients. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 18-28.

    DOI: 10.1111/j.1447-0594.2011.00809.x

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  • Long-term multiple risk factor interventions in Japanese elderly diabetic patients: The Japanese Elderly Diabetes Intervention Trial - study design, baseline characteristics and effects of intervention

    Atsushi Araki, Satoshi Iimuro, Takashi Sakurai, Hiroyuki Umegaki, Katsuya Iijima, Hiroshi Nakano, Kenzo Oba, Koichi Yokono, Hirohito Sone, Nobuhiro Yamada, Junya Ako, Koichi Kozaki, Hisayuki Miura, Atsunori Kashiwagi, Ryuichi Kikkawa, Yukio Yoshimura, Tadasumi Nakano, Yasuo Ohashi, Hideki Ito

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( suppl1 )   7 - 17   2012.4

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    Aim: To evaluate long-term, multiple risk factor intervention on physical, psychological and mental prognosis, and development of complications and cardiovascular disease in elderly type 2 diabetes patients.
    Methods: Our randomized, controlled, multicenter, prospective intervention trial included 1173 elderly type 2 diabetes patients who were enrolled from 39 Japanese institutions and randomized to an intensive or conservative treatment group. Glycemic control, dyslipidemia, hypertension, obesity, diabetic complications and atherosclerotic disease were measured annually. Instrumental activity of daily living, cognitive impairment, depressive symptoms and diabetes burden were assessed at baseline and 3 years.
    Results: There was no significant difference in clinical or cognitive parameters at baseline between the two groups. The prevalence of low activities of daily living, depressive symptoms and cognitive impairment was 13%, 28% and 4%, respectively, and was similar in the two groups. A small, but significant difference in HbA1c between the two groups was observed at 1 year after the start of intervention (7.9% vs 8.1%, P &lt; 0.05), although this significant difference was not observed after the second year. With the exception of coronary revascularization, there was no significant difference in fatal or non-fatal events between the two groups. Composite events were also similar in the two groups.
    Conclusions: This study showed no significant differences in fatal or non-fatal events between intensive and conventional treatment. The present study might clarify whether treatment of risk factors influences function and quality of life in elderly diabetic patients. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 7-17.

    DOI: 10.1111/j.1447-0594.2011.00808.x

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  • Long-term multiple risk factor interventions in Japanese elderly diabetic patients: The Japanese Elderly Diabetes Intervention Trial - study design, baseline characteristics and effects of intervention

    Atsushi Araki, Satoshi Iimuro, Takashi Sakurai, Hiroyuki Umegaki, Katsuya Iijima, Hiroshi Nakano, Kenzo Oba, Koichi Yokono, Hirohito Sone, Nobuhiro Yamada, Junya Ako, Koichi Kozaki, Hisayuki Miura, Atsunori Kashiwagi, Ryuichi Kikkawa, Yukio Yoshimura, Tadasumi Nakano, Yasuo Ohashi, Hideki Ito

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( suppl1 )   7 - 17   2012.4

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    Aim: To evaluate long-term, multiple risk factor intervention on physical, psychological and mental prognosis, and development of complications and cardiovascular disease in elderly type 2 diabetes patients.
    Methods: Our randomized, controlled, multicenter, prospective intervention trial included 1173 elderly type 2 diabetes patients who were enrolled from 39 Japanese institutions and randomized to an intensive or conservative treatment group. Glycemic control, dyslipidemia, hypertension, obesity, diabetic complications and atherosclerotic disease were measured annually. Instrumental activity of daily living, cognitive impairment, depressive symptoms and diabetes burden were assessed at baseline and 3 years.
    Results: There was no significant difference in clinical or cognitive parameters at baseline between the two groups. The prevalence of low activities of daily living, depressive symptoms and cognitive impairment was 13%, 28% and 4%, respectively, and was similar in the two groups. A small, but significant difference in HbA1c between the two groups was observed at 1 year after the start of intervention (7.9% vs 8.1%, P &lt; 0.05), although this significant difference was not observed after the second year. With the exception of coronary revascularization, there was no significant difference in fatal or non-fatal events between the two groups. Composite events were also similar in the two groups.
    Conclusions: This study showed no significant differences in fatal or non-fatal events between intensive and conventional treatment. The present study might clarify whether treatment of risk factors influences function and quality of life in elderly diabetic patients. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 7-17.

    DOI: 10.1111/j.1447-0594.2011.00808.x

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  • Prevalence and risk factors for diabetic maculopathy, and its relationship to diabetic retinopathy in elderly Japanese patients with type 2 diabetes mellitus

    Teiko Yamamoto, Satoshi Iimuro, Yasuo Ohashi, Hirohito Sone, Hidetoshi Yamashita, Hideki Ito

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( Suppl1 )   134 - 140   2012.4

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    Aims: To determine the prevalence of diabetic retinopathy and diabetic maculopathy in Japanese patients older than 65 years-of-age with type 2 diabetes mellitus. In addition, to determine the relationship between the severity of retinopathy and maculopathy, and the risk factors for these conditions in Japanese patients with the same characteristics.
    Methods: This was a cross-sectional study carried out at the enrolment of patients who participated in a randomized controlled trial. A total of 960 eyes of 960 Japanese patients with type 2 diabetes who were &gt;= 65 years-of-age were analyzed.
    Results: Our data showed that there was a correlation between the severity of retinopathy and the severity of maculopathy. The risk factors for the severity of retinopathy were different from the risk factors for the severity of maculopathy. The age, duration of diabetes, systemic pulse pressure, fasting insulin, insulin treatment of diabetes, highdensity lipoprotein cholesterol, microalbumin-to-creatinine ratio and history of cerebrovascular disease all contributed significantly to the severity of retinopathy. The duration of diabetes, insulin treatment and microalbumin-to-creatinine ratio were correlated with the severity of maculopathy.
    Conclusions: The risk factors related to diabetic retinopathy and maculopathy in Japanese patients with type 2 diabetes mellitus aged 365 years were different from that in other countries. Our data also showed that the certain risk factors for retinopathy differ from those associated with maculopathy. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 134-140.

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  • Prevalence and risk factors for diabetic maculopathy, and its relationship to diabetic retinopathy in elderly Japanese patients with type 2 diabetes mellitus

    Teiko Yamamoto, Satoshi Iimuro, Yasuo Ohashi, Hirohito Sone, Hidetoshi Yamashita, Hideki Ito

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( Suppl1 )   134 - 140   2012.4

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    Aims: To determine the prevalence of diabetic retinopathy and diabetic maculopathy in Japanese patients older than 65 years-of-age with type 2 diabetes mellitus. In addition, to determine the relationship between the severity of retinopathy and maculopathy, and the risk factors for these conditions in Japanese patients with the same characteristics.
    Methods: This was a cross-sectional study carried out at the enrolment of patients who participated in a randomized controlled trial. A total of 960 eyes of 960 Japanese patients with type 2 diabetes who were &gt;= 65 years-of-age were analyzed.
    Results: Our data showed that there was a correlation between the severity of retinopathy and the severity of maculopathy. The risk factors for the severity of retinopathy were different from the risk factors for the severity of maculopathy. The age, duration of diabetes, systemic pulse pressure, fasting insulin, insulin treatment of diabetes, highdensity lipoprotein cholesterol, microalbumin-to-creatinine ratio and history of cerebrovascular disease all contributed significantly to the severity of retinopathy. The duration of diabetes, insulin treatment and microalbumin-to-creatinine ratio were correlated with the severity of maculopathy.
    Conclusions: The risk factors related to diabetic retinopathy and maculopathy in Japanese patients with type 2 diabetes mellitus aged 365 years were different from that in other countries. Our data also showed that the certain risk factors for retinopathy differ from those associated with maculopathy. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 134-140.

    DOI: 10.1111/j.1447-0594.2011.00821.x

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  • Long-term risk factors for diabetic retinopathy and diabetic maculopathy in elderly Japanese patients with type 2 diabetes mellitus

    Teiko Yamamoto, Satoshi Iimuro, Yasuo Ohashi, Hirohito Sone, Hideki Ito, Hidetoshi Yamashita

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( Suppl1 )   141 - 144   2012.4

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    DOI: 10.1111/j.1447-0594.2011.00822.x

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  • Long-term risk factors for diabetic retinopathy and diabetic maculopathy in elderly Japanese patients with type 2 diabetes mellitus

    Teiko Yamamoto, Satoshi Iimuro, Yasuo Ohashi, Hirohito Sone, Hideki Ito, Hidetoshi Yamashita

    GERIATRICS & GERONTOLOGY INTERNATIONAL   12 ( Suppl1 )   141 - 144   2012.4

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    DOI: 10.1111/j.1447-0594.2011.00822.x

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  • TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice

    Hitoshi Iwasaki, Ayano Naka, Kaoruko Tada Iida, Yoshimi Nakagawa, Takashi Matsuzaka, Kiyo-aki Ishii, Kazuto Kobayashi, Akimitsu Takahashi, Shigeru Yatoh, Naoya Yahagi, Hirohito Sone, Hiroaki Suzuki, Nobuhiro Yamada, Hitoshi Shimano

    AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM   302 ( 7 )   E896 - E902   2012.4

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    Iwasaki H, Naka A, Iida KT, Nakagawa Y, Matsuzaka T, Ishii K, Kobayashi K, Takahashi A, Yatoh S, Yahagi N, Sone H, Suzuki H, Yamada N, Shimano H. TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice. Am J Physiol Endocrinol Metab 302: E896-E902, 2012. First published January 31, 2012; doi: 10.1152/ajpendo.00204.2011.-The role of transcription factor E3 (TFE3), a bHLH transcription factor, in immunology and cancer has been well characterized. Recently, we reported that TFE3 activates hepatic IRS-2 and hexokinase, participates in insulin signaling, and ameliorates diabetes. However, the effects of TFE3 in other organs are poorly understood. Herein, we examined the effects of TFE3 on skeletal muscle, an important organ involved in glucose metabolism. We generated transgenic mice that selectively express TFE3 in skeletal muscles. These mice exhibit a slight acceleration in growth prior to adulthood as well as a progressive increase in muscle mass. In TFE3 transgenic muscle, glycogen stores were more than twofold than in wild-type mice, and this was associated with an upregulation of genes involved in glucose metabolism, specifically glucose transporter 4, hexokinase II, and glycogen synthase. Consequently, exercise endurance capacity was enhanced in this transgenic model. Furthermore, insulin sensitivity was enhanced in transgenic mice and exhibited better improvement after 4 wk of exercise training, which was associated with increased IRS-2 expression. The effects of TFE3 on glucose metabolism in skeletal muscle were different from that in the liver, although they did, in part, overlap. The potential role of TFE3 in regulating metabolic genes and glucose metabolism within skeletal muscle suggests that it may be used for treating metabolic diseases as well as increasing endurance in sport.

    DOI: 10.1152/ajpendo.00204.2011

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  • 2型糖尿病患者における果物摂取と網膜症発症率

    鎌田 智英実, 田中 司朗, 川崎 良, 奥村 亮太, 田中 佐智子, 堀川 千嘉, 山下 英俊, 山田 信博, 曽根 博仁, 吉村 幸雄

    日本栄養・食糧学会大会講演要旨集   66回   225 - 225   2012.4

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  • HbA1cを導入した新しい2型糖尿病リスクスコアの開発 The Toranomon Hospital Health Management Center Study(TOPICS)

    平安座 依子, 原 茂子, 齋藤 和美, 藤原 和哉, 辻 裕之, 児玉 暁, 謝 勲東, 島野 仁, 荒瀬 康司, 山田 信博, 曽根 博仁

    糖尿病   55 ( Suppl.1 )   S - 214   2012.4

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  • シタグリプチンによる血糖改善効果の減弱

    鈴木 美佑希, 高橋 直穂, 菅野 咲子, 奥田 昌恵, 山田 大志郎, 本庄 潤, 曽根 博仁, 清水 平, 横山 宏樹

    糖尿病   55 ( Suppl.1 )   S - 204   2012.4

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  • 2型糖尿病発症に至るまでのHbA1c値と空腹時血糖値の長期変化に関する検討 TOPICS

    原 茂子, 平安座 依子, 齋藤 和美, 藤原 和哉, 辻 裕之, 児玉 暁, 謝 勲東, 島野 仁, 荒瀬 康司, 山田 信博, 曽根 博仁

    糖尿病   55 ( Suppl.1 )   S - 214   2012.4

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  • 妊娠中期耐糖能スクリーニングは低出生体重児出産を予測する方法として有用である(TWC Study)

    谷内 洋子, 田中 康弘, 西端 泉, 菅原 歩美, 松岡 隆, 島野 仁, 児玉 暁, 齋藤 和美, 曽根 博仁

    糖尿病   55 ( Suppl.1 )   S - 186   2012.4

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  • フラミンガムリスクスコア、UKPDSリスクエンジン、max-IMT、LDL/HDL比による冠動脈病変予測能に関する検討

    藤原 和哉, 鈴木 浩明, 佐藤 明, 大崎 芳典, 尾本 美代子, 豊島 晶子, 平安座 依子, 児玉 暁, 斎藤 和美, 小林 和人, 矢藤 繁, 高橋 昭光, 山田 信博, 曽根 博仁, 島野 仁

    糖尿病   55 ( Suppl.1 )   S - 180   2012.4

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  • シタグリプチンとアログリプチンの血糖改善効果の比較

    今田 敦子, 菅野 咲子, 高橋 直穂, 山田 大志郎, 本庄 潤, 曽根 博仁, 清水 平, 横山 宏樹

    糖尿病   55 ( Suppl.1 )   S - 202   2012.4

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  • 茨城県央地区におけるシタグリプチン至適投与対象に関する検討について【最終報告】

    荷見 澄子, 遅野井 健, 仲本 信也, 水谷 正一, 曽根 博仁

    糖尿病   55 ( Suppl.1 )   S - 199   2012.4

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  • 2型糖尿病患者における心理的負担感と罹病期間の関連の検討

    菅原 歩美, 齋藤 あき, 湯原 淳良, 大石 まり子, 杉本 英克, 横山 宏樹, 屋宜 宣治, 岡田 朗, 岩崎 皓一, 宮澤 一裕, 奥口 文宣, 嵩 文彦, 齋藤 和美, 川井 紘一, 曽根 博仁

    糖尿病   55 ( Suppl.1 )   S - 106   2012.4

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  • 大規模試験からのメッセージ Japan Diabetes Complications Study(JDCS)

    曽根 博仁, 赤沼 安夫, 山田 信博

    糖尿病   55 ( Suppl.1 )   S - 39   2012.4

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  • マクロファージ泡沫化および動脈硬化における脂肪酸伸長酵素Elovl6の役割

    松坂 賢, 齋藤 亮, 唐澤 直義, 松森 理恵, 煙山 紀子, 中川 嘉, 石井 清朗, 岩崎 仁, 小林 和人, 矢藤 繁, 高橋 昭光, 曽根 博仁, 鈴木 浩明, 矢作 直也, 山田 信博, 島野 仁

    糖尿病   55 ( Suppl.1 )   S - 312   2012.4

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  • 生涯最大BMIならびに20歳から生涯最大までのBMI変化はいずれも2型糖尿病と強く関連する

    由澤 咲子, 平安座 依子, 荒瀬 康司, 齋藤 和美, 辻 裕之, 児玉 暁, 謝 勲東, 島野 仁, 山田 信博, 原 茂子, 曽根 博仁

    糖尿病   55 ( Suppl.1 )   S - 306   2012.4

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  • 糖尿病と難聴の関連性についてのメタ解析

    堀川 千嘉, 児玉 暁, 藤原 和哉, 平安座 依子, 菅原 歩美, 平澤 玲子, 谷内 洋子, 齋藤 和美, 曽根 博仁

    糖尿病   55 ( Suppl.1 )   S - 358   2012.4

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  • 脂肪酸伸長酵素ELOVL5のエンハンサー領域の同定とSREBPによる発現制御機構の解析

    篠崎 悠奈, 矢作 直也, 武内 謙憲, 西 真貴子, 中川 嘉, 石井 清朗, 松坂 賢, 岩崎 仁, 小林 和人, 矢藤 繁, 高橋 昭光, 曽根 博仁, 鈴木 浩明, 山田 信博, 島野 仁

    糖尿病   55 ( Suppl.1 )   S - 336   2012.4

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  • 当院における75gブドウ糖負荷試験の受診追跡者の検討

    菅野 咲子, 山下 りさ, 山田 智子, 高橋 直穂, 曽根 博仁, 山田 大志郎, 横山 宏樹

    糖尿病   55 ( Suppl.1 )   S - 266   2012.4

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  • 高脂肪食と糖尿病発症リスクの関連性についてのメタ解析

    田島 諒子, 児玉 暁, 藤原 和哉, 平安座 依子, 菅原 歩美, 平澤 玲子, 谷内 洋子, 齋藤 和美, 飯田 薫子, 曽根 博仁

    糖尿病   55 ( Suppl.1 )   S - 214   2012.4

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  • 糖尿病罹患者における心血管病発症リスクの年代別、性別検討成績 HDL-CとLDL-C/HDL-C比の意義について

    林 登志雄, 川嶋 成乃亮, 井藤 英喜, 荒木 厚, 曽根 博仁, 渡邉 裕司, 大類 孝, 横手 幸太郎, 竹本 稔, 服部 良之, 伊奈 孝太郎, 野村 秀樹

    糖尿病   55 ( Suppl.1 )   S - 290   2012.4

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  • 日本人2型糖尿病における顕性腎症発症と腎機能低下に対する糖尿病性網膜症および微量アルブミン尿の影響 JDCSサブ解析

    守屋 達美, 田中 司朗, 川崎 良, 大橋 靖雄, 赤沼 安夫, 山田 信博, 曽根 博仁, 山下 英俊, 片山 茂裕

    糖尿病   55 ( Suppl.1 )   S - 289   2012.4

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  • 抗GAD抗体が陽性であった高齢発症の劇症1型糖尿病の1例

    村山 友樹, 藤原 和哉, 宜保 英彦, 尾本 美代子, 小林 和人, 高橋 昭光, 矢藤 繁, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    日本内分泌学会雑誌   88 ( 1 )   290 - 290   2012.4

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  • 【糖尿病の血管合併症】 日本人2型糖尿病患者の合併症の現状 Japan Diabetes Complications Study(JDCS)のデータより

    曽根 博仁, 田中 司朗, 片山 茂裕, 山下 英俊, 山田 信博

    The Lipid   23 ( 2 )   138 - 146   2012.4

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    Japan Diabetes Complications Study(JDCS)は、わが国の2型糖尿病患者の特徴と現状を明らかにする目的で始められ、その病態背景や合併症の発症率・リスクファクターなどを報告してきた。これまでの解析から、腎症の発症率がかなり低く寛解も高率でみられること、喫煙が腎症のリスクになること、網膜症を予防するためにはかなり厳格な血糖コントロールが必要であること、血清トリグリセライド値がLDLコレステロール値に匹敵する強さを有する大血管症のリスクファクターであること、生活習慣介入が脳卒中を抑制したことなど、日本人2型糖尿病患者に関する新たなエビデンスが生み出されつつある。(著者抄録)

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  • 日本人高齢者における高感度CRPとメタボリックシンドロームおよび肥満との関連〜SAT195

    叔 びょう, 齋藤 和美, 児玉 暁, 田辺 解, 村上 晴香, 飯田 薫子, 田中 喜代次, 鰺坂 隆一, 久野 譜也, 曽根 博仁

    日本未病システム学会雑誌   18 ( 1 )   38 - 43   2012.2

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    [目的]日本人高齢者において、高感度CRP(high sensitivity C-reactive protein、hsCRP)濃度とメタボリックシンドローム(Metabolic Syndrome、MetS)構成因子および肥満指標との関係、MetSに対するhsCRP濃度のカットオフ値について検討する。[対象と方法]高齢者向け運動教室参加者251名(うち男性91名、平均年齢69.5±5.2歳)において、体格指数(BMI)、腹囲、腹部総脂肪面積、腹部皮下脂肪面積、内臓脂肪面積、血圧を測定し、採血検査を実施した。高血圧・糖尿病・脂質異常症の病歴を調査し、修正AHA/NHLBI基準によるMetS構成因子(糖尿病、高血圧、低HDLコレステロール血症、高トリグリセリド(triglyceride、TG)血圧、肥満(腹囲により判定))の保有状況について調査した。[結果]hsCRP値で四分位分割した際、最高四分位群の最低四分位群に対するMetS、および各MetS因子(糖尿病、高血圧、低HDLコレステロール血症、高TG血症、肥満)の保有リスクのハザード比(95%信頼区間)はそれぞれ、3.3(1.5-7.3)、1.8(0.8-3.8)、0.9(0.4-2.4)、1.7(0.7-4.2)、2.0(0.8-5.1)、3.5(1.6-7.9)であった。hsCRP濃度とBMI、腹囲、総脂肪量、内臓脂肪量、皮下脂肪量との相関係数(R)は、それぞれ0.26、0.21、0.17、0.18、0.12であり、皮下脂肪量以外との相関関係は統計学的に有意であった。MetSに対して最適と思われるhsCRP濃度のカットオフ値は、0.44mg/L(感度60%、特異度59%)であった。(著者抄録)

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  • 日本人高齢者における各種肥満度指数と心血管疾患危険因子との関連 SAT194

    叔 びょう, 齋藤 和美, 児玉 暁, 田辺 解, 村上 晴香, 飯田 薫子, 田中 喜代次, 鰺坂 隆一, 久野 譜也, 曽根 博仁

    日本未病システム学会雑誌   18 ( 1 )   32 - 37   2012.2

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    肥満を表す指標は多くあるが、どの指標が最も強く心血管疾患危険因子と関連するかは人種や年齢により異なる可能性が指摘されている。日本人高齢者における、体格指数(Body mass index(BMI)(kg/m2))、ウエスト(WC)(cm)、ウエストヒップ比(WHR)、ウエスト身長比(WHtR)、CTによる腹部脂肪面積(総脂肪面積(total fat area;TFA)、内臓脂肪面積(visceral fat area;VFA)、皮下脂肪面積(subcutaneous fat area;SFA)、単位はいずれも(cm2)と心血管疾患危険因子(高血圧、糖尿病、低HDLコレステロール血症、高トリグリセリド(TG)血症)との関連を検討した。運動教室に参加した251名の高齢者の心血管疾患危険因子の保有状況を調査し、心血管疾患危険因子の保有数別に、各肥満指標の平均値を比較した。また、各肥満指標を四分位にした際の、心血管疾患危険因子2個以上の保有頻度の差異を検討した。さらに各指標のうち、心血管疾患危険因子2個以上の保有に最も強く関連する因子をロジスティック回帰分析により検討し、強く関連した因子の閾値を求めた。検討した各肥満指標の平均値は、心血管疾患危険因子の保有個数により異なっていた。各肥満指標は高いほど心血管疾患危険因子を2個以上保有との関連が強く、肥満指標のうち、WCが心血管疾患危険因子2個以上の保有に最も強く関連した。WCの閾値は男性で85.5cm(感度66%、特異度69%)、女性で75.5cm(感度80%、特異度55%)であった。(著者抄録)

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  • Impact of introducing HbA1c into the diagnostic criteria on prevalence and cardiovascular risk profiles of individuals with newly diagnosed diabetes in Japan: The Toranomon Hospital Health Management Center Study 2 (TOPICS 2)

    Yoriko Heianza, Shigeko Hara, Yasuji Arase, Kazumi Saito, Hiroshi Tsuji, Satoru Kodama, Shiun Dong Hsieh, Yasumichi Mori, Minoru Okubo, Nobuhiro Yamada, Kinori Kosaka, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   95 ( 2 )   283 - 290   2012.2

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    Objective: To evaluate the impact of HbA1c for diagnosis of diabetes and investigate whether cardiovascular risks profiles differ among individuals with diabetes diagnosed by HbA1c or fasting plasma glucose (FPG).
    Methods: This cross-sectional study involved 26,884 participants (30.6% women; aged 20-91 years) without known diabetes. Subjects were categorized into 4 groups according to the presence or absence of FPG &gt;= 7.0 mmol/L and/or HbA1c &gt;= 6.5%, which were American Diabetes Association criteria. Oral glucose tolerance test data were not available.
    Results: Prevalence of undiagnosed diabetes was 3.6%. Of those individuals, 47.5% fulfilled both two criteria and 26.0% fulfilled only HbA1c criterion. Individuals with diabetes according to FPG &gt;= 7.0 mmol/L alone were characterized as having poorly controlled hypertension while those with HbA1c &gt;6.5% alone were characterized as older, female, and having lower blood pressure and gamma-glutamyltransferase values. Persons with newly diagnosed diabetes by HbA1c had low HDL cholesterol and high LDL or non-HDL cholesterol levels.
    Conclusions: Introducing HbA1c into the diagnosis allowed detection of many previously undiagnosed cases of diabetes in Japanese individuals. Those diagnosed by FPG were characterized by hypertension and those diagnosed by HbA1c had unfavorable lipid profiles, reflecting an atherosclerotic trait. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2011.10.024

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  • Impact of introducing HbA1c into the diagnostic criteria on prevalence and cardiovascular risk profiles of individuals with newly diagnosed diabetes in Japan: The Toranomon Hospital Health Management Center Study 2 (TOPICS 2)

    Yoriko Heianza, Shigeko Hara, Yasuji Arase, Kazumi Saito, Hiroshi Tsuji, Satoru Kodama, Shiun Dong Hsieh, Yasumichi Mori, Minoru Okubo, Nobuhiro Yamada, Kinori Kosaka, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   95 ( 2 )   283 - 290   2012.2

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    Objective: To evaluate the impact of HbA1c for diagnosis of diabetes and investigate whether cardiovascular risks profiles differ among individuals with diabetes diagnosed by HbA1c or fasting plasma glucose (FPG).
    Methods: This cross-sectional study involved 26,884 participants (30.6% women; aged 20-91 years) without known diabetes. Subjects were categorized into 4 groups according to the presence or absence of FPG &gt;= 7.0 mmol/L and/or HbA1c &gt;= 6.5%, which were American Diabetes Association criteria. Oral glucose tolerance test data were not available.
    Results: Prevalence of undiagnosed diabetes was 3.6%. Of those individuals, 47.5% fulfilled both two criteria and 26.0% fulfilled only HbA1c criterion. Individuals with diabetes according to FPG &gt;= 7.0 mmol/L alone were characterized as having poorly controlled hypertension while those with HbA1c &gt;6.5% alone were characterized as older, female, and having lower blood pressure and gamma-glutamyltransferase values. Persons with newly diagnosed diabetes by HbA1c had low HDL cholesterol and high LDL or non-HDL cholesterol levels.
    Conclusions: Introducing HbA1c into the diagnosis allowed detection of many previously undiagnosed cases of diabetes in Japanese individuals. Those diagnosed by FPG were characterized by hypertension and those diagnosed by HbA1c had unfavorable lipid profiles, reflecting an atherosclerotic trait. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2011.10.024

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  • 20歳時BMIおよび20歳以降のBMI変化量はGDM発症を予測する有用な指標

    田中 康弘, 谷内 洋子, 曽根 博仁

    日本産科婦人科学会雑誌   64 ( 2 )   522 - 522   2012.2

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    Other Link: https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=448199

  • 糖尿病患者の身体活動量と総死亡、心血管疾患発症リスクの関連性のメタ解析

    児玉 暁, 藤原 和哉, 齋藤 和美, 曽根 博仁

    日本内科学会雑誌   101 ( Suppl. )   290 - 290   2012.2

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  • 【糖尿病腎症と血糖コントロール】 厳格な血糖コントロールは糖尿病腎症(CKD)の発症・進展を抑制できるか?

    曽根 博仁

    臨床透析   28 ( 2 )   157 - 164   2012.2

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    糖尿病患者における厳格な血糖コントロールは,微量アルブミン尿やCKDの予防,さらには改善(寛解)に対しても,血圧コントロールと並びもっとも有効な治療の一つであると考えられ,しかもその効果は長期間にわたって持続することもわかってきた.一方,すでに進行してしまった腎症において,血糖コントロール単独では,透析導入を遅らせるほどの効果は期待できない.この時期においては,血圧コントロールなどを含む全身管理が必要になり,その予後改善のためには,さらに多くの日本人データを集めて検討していく必要がある.(著者抄録)

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  • 多臓器不全と横紋筋融解症をきたし、集学的治療によって救命し得た劇症1型糖尿病の一例

    飯谷 宗弘, 金井 貴夫, 今西 真実子, 湊谷 亮, 木下 賢輔, 酒井 俊介, 外山 昌弘, 宜保 英彦, 藤原 和哉, 曽根 博仁, 錦 健太, 小林 裕幸, 徳田 安春, 渡辺 重行

    日本病院総合診療医学会雑誌   3 ( 1 )   91 - 92   2012.2

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  • 異なる空腹時血糖値異常とHbA1c高値の判定基準を用いた2型糖尿病予測スクリーニング精度の比較:TOPICS

    平安座依子, 原茂子, 謝勲東, 児玉暁, 辻裕之, 藤原和哉, 由澤咲子, 伊部陽子, 齋藤和美, 山田信博, 荒瀬康司, 曽根博仁

    J Epidemiol   22 ( Supplement 1 )   122   2012.1

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  • 2型糖尿病発症10年間のHbA1c値の変化:TOPICS

    平安座依子, 荒瀬康司, 辻裕之, 齋藤和美, 藤原和哉, 謝勲東, 児玉暁, 山田信博, 原茂子, 曽根博仁

    Journal of Epidemiology   22 ( Supplement 1 )   122   2012.1

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  • HbA1cの変動が微量アルブミン尿発症に及ぼす影響の検討

    菅原歩美, 川井紘一, 齋藤和美, 本橋しのぶ, 島野仁, 山田信博, 曽根博仁

    J Epidemiol   22 ( Supplement 1 )   124   2012.1

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  • 成人における糖尿病と難聴の関連性:メタアナリシスにおける評価

    堀川千嘉, 児玉暁, 菅原歩美, 平安座依子, 由澤咲子, 齋藤あき, 伊部陽子, 平澤玲子, 谷内洋子, 齋藤和美, 曽根博仁

    J Epidemiol   22 ( Supplement 1 )   121   2012.1

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  • 2型糖尿病発症前のHbA1c値と空腹時血糖値の変化に関する大規模縦断的検討

    平安座 依子, 荒瀬 康司, 辻 裕之, 齋藤 和美, 藤原 和哉, 謝 勲東, 児玉 暁, 山田 信博, 原 茂子, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   38   53 - 53   2012.1

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  • 【動脈硬化予防における血糖管理】 (Part1)糖尿病と動脈硬化 疫学的知見

    曽根 博仁, 山田 信博

    動脈硬化予防   10 ( 4 )   5 - 13   2012.1

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  • 2型糖尿病発症予測に最適なHbA1cと空腹時血糖値の閾値の組み合わせの検討 TOPICS

    平安座 依子, 原 茂子, 謝 勲東, 齋藤 和美, 辻 裕之, 菅原 歩美, 齋藤 あき, 児玉 暁, 荒瀬 康司, 山田 信博, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   38   75 - 75   2012.1

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  • 2型糖尿病における知識と負担感との関連の検討

    菅原 歩美, 湯原 淳良, 大石 まり子, 杉本 英克, 横山 宏樹, 屋宜 宣治, 岡田 朗, 岩崎 皓一, 宮澤 一裕, 奥口 文宣, 嵩 文彦, 齋藤 あき, 西垣 結佳子, 川井 紘一, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   38   57 - 57   2012.1

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  • 健常妊婦における低出生体重児出産リスク因子の検討(TWC Study)

    谷内 洋子, 田中 康弘, 西端 泉, 菅原 歩美, 安原 眞知子, 小林 香織, 松岡 隆, 児玉 暁, 齋藤 和美, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   38   56 - 56   2012.1

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  • 糖尿病診断および予測能におけるグリコヘモグロビンA1cと空腹時血糖のメタ解析

    児玉 暁, 堀川 千嘉, 平安座 依子, 菅原 歩美, 平澤 玲子, 谷内 洋子, 齋藤 和美, 田中 司朗, 大橋 靖雄, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   38   74 - 74   2012.1

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  • "Healthy diet"に関する国際的ウェブ情報のクオリティの検証

    平澤 玲子, 谷内 洋子, 伊部 陽子, 由澤 咲子, 堀川 千嘉, 斉藤 あき, 平安座 依子, 菅原 歩美, 戸塚 久美子, 齋藤 和美, 児玉 暁, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   38   58 - 58   2012.1

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  • HbA1cを導入した新しい2型糖尿病予測スコアリングシステムの開発

    平安座 依子, 謝 勲東, 原 茂子, 辻 裕之, 藤原 和哉, 堀川 千嘉, 谷内 洋子, 児玉 暁, 山田 信博, 荒瀬 康司, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   38   54 - 54   2012.1

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  • 原発性高脂血症に関する調査研究 2型糖尿病患者の冠動脈病変予測と脂質異常

    島野仁, 鈴木浩明, 藤原和哉, 佐藤明, 曽根博仁

    原発性高脂血症に関する調査研究 平成23年度 総括研究報告書   54 - 62   2012

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  • Fasting and Post-Challenge Glucose as Quantitative Cardiovascular Risk Factors: A Meta-Analysis

    Satoru Kodama, Kazumi Saito, Shiro Tanaka, Chika Horikawa, Kazuya Fujiwara, Reiko Hirasawa, Yoko Yachi, Yasuko Sone, Kaoruko Tada Iida, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   19 ( 4 )   385 - 396   2012

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    Aim: The post-challenge glucose (PCG) level has been suggested to be superior to the fasting blood glucose (FG) level for predicting the risk of future cardiovascular disease (CVD); however, the extent of its superiority has not been consistently shown among previous cohort studies. Therefore, we conducted a meta-analysis to summarize the quantitative association of FG and PCG with CVD risk and compared the strengths of the two associations.
    Method: Electronic literature searches using MEDLINE and EMBASE with an additional manual search were conducted for prospective observational studies of the association of FG and PCG with CVD risk. Studies were included if they were prospective studies in which the relative risk (RR) of CVD per 1 standard deviation increase in both FG and PCG could be estimated. Pooled relative risks for the incremental increase were calculated as RRFG and RRPCG using a bivariate random-effects model.
    Result: Data were obtained from 14 eligible studies that included 70,889 participants and 2,927 cases. The pooled RRFG and RRPCG (95% confidence interval) were, respectively, 1.15 (1.06 to 1.26) and 1.24 (1.12 to 1.36); the difference was significant (P = 0.001). The association of PCG with CVD risk was stronger in studies that targeted participants with a baseline mean FG &lt;100 mg/dl (P &lt; 0.001) or mean age &gt;= 55 years (P = 0.004).
    Conclusions: Overall, the association of PCG with CVD risk was stronger than that of FG by approximately 50% on a log scale. Measuring PCG is especially important in populations with relatively low FG levels or in the elderly, although it is often burdensome in routine clinical practice.

    DOI: 10.5551/jat.10975

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  • Fasting and Post-Challenge Glucose as Quantitative Cardiovascular Risk Factors: A Meta-Analysis

    Satoru Kodama, Kazumi Saito, Shiro Tanaka, Chika Horikawa, Kazuya Fujiwara, Reiko Hirasawa, Yoko Yachi, Yasuko Sone, Kaoruko Tada Iida, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   19 ( 4 )   385 - 396   2012

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    Aim: The post-challenge glucose (PCG) level has been suggested to be superior to the fasting blood glucose (FG) level for predicting the risk of future cardiovascular disease (CVD); however, the extent of its superiority has not been consistently shown among previous cohort studies. Therefore, we conducted a meta-analysis to summarize the quantitative association of FG and PCG with CVD risk and compared the strengths of the two associations.
    Method: Electronic literature searches using MEDLINE and EMBASE with an additional manual search were conducted for prospective observational studies of the association of FG and PCG with CVD risk. Studies were included if they were prospective studies in which the relative risk (RR) of CVD per 1 standard deviation increase in both FG and PCG could be estimated. Pooled relative risks for the incremental increase were calculated as RRFG and RRPCG using a bivariate random-effects model.
    Result: Data were obtained from 14 eligible studies that included 70,889 participants and 2,927 cases. The pooled RRFG and RRPCG (95% confidence interval) were, respectively, 1.15 (1.06 to 1.26) and 1.24 (1.12 to 1.36); the difference was significant (P = 0.001). The association of PCG with CVD risk was stronger in studies that targeted participants with a baseline mean FG &lt;100 mg/dl (P &lt; 0.001) or mean age &gt;= 55 years (P = 0.004).
    Conclusions: Overall, the association of PCG with CVD risk was stronger than that of FG by approximately 50% on a log scale. Measuring PCG is especially important in populations with relatively low FG levels or in the elderly, although it is often burdensome in routine clinical practice.

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  • Management of Type IIb Dyslipidemia

    Hidenori Arai, Shun Ishibashi, Hideaki Bujo, Toshio Hayashi, Shinji Yokoyama, Shinichi Oikawa, Junji Kobayashi, Kohji Shirai, Takao Ota, Shizuya Yamashita, Takanari Gotoda, Mariko Harada-Shiba, Hirohito Sone, Masaaki Eto, Hiroaki Suzuki, Nobuhiro Yamada

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   19 ( 2 )   105 - 114   2012

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    Although the Japan Atherosclerosis Society guideline for the diagnosis and prevention of atherosclerosis cardiovascular diseases for the Japanese population provides targets for low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol to prevent cardiovascular disease in patients with dyslipidemia, there is no guideline specifically targeting the treatment of type IIb dyslipidemia, which is one of the most common types of dyslipidemia, along with type IIa and type IV dyslipidemia. Type IIb dyslipidemia is important because it sometimes accompanies atherogenic lipid profiles, such as small, dense LDL, remnants, low HDL cholesterolemia. It is also associated with type 2 diabetes mellitus, metabolic syndrome, and chronic kidney disease (CKD), and most patients with familial combined hyperlipidemia (FCHL) show this phenotype; therefore, it is assumed that patients with type IIb dyslipidemia have a high risk for cardiovascular disease. Thus, the management of type IIb dyslipidemia is very important for the prevention of cardiovascular disease, so we have attempted to provide a guideline for the management of type IIb dyslipidemia.

    DOI: 10.5551/jat.10447

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  • Background to Discuss Guidelines for Control of Plasma HDL-Cholesterol in Japan

    Shinji Yokoyama, Shizuya Yamashita, Shun Ishibashi, Hirohito Sone, Shinichi Oikawa, Kohji Shirai, Takao Ohta, Hideaki Bujo, Junji Kobayashi, Hidenori Arai, Mariko Harada-Shiba, Masaaki Eto, Toshio Hayashi, Takanari Gotoda, Hiroaki Suzuki, Nobuhiro Yamada

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   19 ( 3 )   207 - 212   2012

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    A decrease in high density lipoprotein-cholesterol (HDL-C) is a strong risk factor for atherosclerotic disorders in Japan, probably more important than an increase in low density lipoprotein-cholesterol (LDL-C). While there are rational grounds for the argument that elevation of HDL-C leads to decreased risk, there has as yet been no direct evidence of such an effect. If elevation of HDL-C decreases the risk, this effect is expected throughout the normal range of HDL-C or perhaps even higher than that. Simulation based on epidemiological data indicated that it may eventually reduce the incidence of ischemic heart disease by 60-70% in Japan. In the risk management guideline, "low" HDL-C is presently defined as 40 mg/dL or below. While there is no evidence that strongly urges a change in this definition, the results of epidemiological studies support "The higher the HDL-C level, the lower the risk," even in the "normal range". Elevation of the HDL-C level may reduce the risk, probably at least up to 70 mg/dL; however, there are no supportive data for this effect still being obtained over 80 mg/dL. Patients with homozygous CETP deficiency should be followed-up while controlling other risk factors, so as not to dismiss the possibility of a risk increase with an extremely elevated HDL-C level.

    DOI: 10.5551/jat.11452

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  • Background to Discuss Guidelines for Control of Plasma HDL-Cholesterol in Japan

    Shinji Yokoyama, Shizuya Yamashita, Shun Ishibashi, Hirohito Sone, Shinichi Oikawa, Kohji Shirai, Takao Ohta, Hideaki Bujo, Junji Kobayashi, Hidenori Arai, Mariko Harada-Shiba, Masaaki Eto, Toshio Hayashi, Takanari Gotoda, Hiroaki Suzuki, Nobuhiro Yamada

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   19 ( 3 )   207 - 212   2012

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    A decrease in high density lipoprotein-cholesterol (HDL-C) is a strong risk factor for atherosclerotic disorders in Japan, probably more important than an increase in low density lipoprotein-cholesterol (LDL-C). While there are rational grounds for the argument that elevation of HDL-C leads to decreased risk, there has as yet been no direct evidence of such an effect. If elevation of HDL-C decreases the risk, this effect is expected throughout the normal range of HDL-C or perhaps even higher than that. Simulation based on epidemiological data indicated that it may eventually reduce the incidence of ischemic heart disease by 60-70% in Japan. In the risk management guideline, "low" HDL-C is presently defined as 40 mg/dL or below. While there is no evidence that strongly urges a change in this definition, the results of epidemiological studies support "The higher the HDL-C level, the lower the risk," even in the "normal range". Elevation of the HDL-C level may reduce the risk, probably at least up to 70 mg/dL; however, there are no supportive data for this effect still being obtained over 80 mg/dL. Patients with homozygous CETP deficiency should be followed-up while controlling other risk factors, so as not to dismiss the possibility of a risk increase with an extremely elevated HDL-C level.

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  • 尿路結石による水腎症および無機能腎を呈し,同側腎からの高レニン血症により二次性高血圧を来たした1例

    五十野桃子, 藤原和哉, 鈴木智晴, 五十野博基, 志鎌明人, 宜保英彦, 尾本美代子, 曽根博仁

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   13th   52   2012

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  • Management of Type IIb Dyslipidemia

    Hidenori Arai, Shun Ishibashi, Hideaki Bujo, Toshio Hayashi, Shinji Yokoyama, Shinichi Oikawa, Junji Kobayashi, Kohji Shirai, Takao Ota, Shizuya Yamashita, Takanari Gotoda, Mariko Harada-Shiba, Hirohito Sone, Masaaki Eto, Hiroaki Suzuki, Nobuhiro Yamada

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   19 ( 2 )   105 - 114   2012

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    Although the Japan Atherosclerosis Society guideline for the diagnosis and prevention of atherosclerosis cardiovascular diseases for the Japanese population provides targets for low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol to prevent cardiovascular disease in patients with dyslipidemia, there is no guideline specifically targeting the treatment of type IIb dyslipidemia, which is one of the most common types of dyslipidemia, along with type IIa and type IV dyslipidemia. Type IIb dyslipidemia is important because it sometimes accompanies atherogenic lipid profiles, such as small, dense LDL, remnants, low HDL cholesterolemia. It is also associated with type 2 diabetes mellitus, metabolic syndrome, and chronic kidney disease (CKD), and most patients with familial combined hyperlipidemia (FCHL) show this phenotype; therefore, it is assumed that patients with type IIb dyslipidemia have a high risk for cardiovascular disease. Thus, the management of type IIb dyslipidemia is very important for the prevention of cardiovascular disease, so we have attempted to provide a guideline for the management of type IIb dyslipidemia.

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  • Diagnosis and management of type I and type V hyperlipoproteinemia

    Takanari Gotoda, Koji Shirai, Takao Ohta, Junji Kobayashi, Shinji Yokoyama, Shinichi Oikawa, Hideaki Bujo, Shun Ishibashi, Hidenori Arai, Shizuya Yamashita, Mariko Harada-Shiba, Masaaki Eto, Toshio Hayashi, Hirohito Sone, Hiroaki Suzuki, Nobuhiro Yamada

    Journal of Atherosclerosis and Thrombosis   19 ( 1 )   1 - 12   2012

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    Both type I and type V hyperlipoproteinemia are characterized by severe hypertriglyceridemia due to an increase in chylomicrons. Type I hyperlipoproteinemia is caused by a decisive abnormality of the lipoprotein lipase (LPL)-apolipoprotein C-II system, whereas the cause of type I V hyperlipoproteinemia is more complicated and more closely related to acquired environmental factors. Since the relationship of hypertriglyceridemia with atherosclerosis is not as clear as that of hypercholesterolemia, and since type I and V hyperlipoproteinemia are relatively rare, few guidelines for their diagnosis and treatment have been established
    however, type I and V hyperlipoproteinemia are clinically important as underlying disorders of acute pancreatitis, and appropriate management is necessary to prevent or treat such complications. Against such a background, here we propose guidelines primarily concerning the diagnosis and management of type I and V hyperlipoproteinemia in Japanese.

    DOI: 10.5551/jat.10702

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  • Diagnosis and management of type I and type V hyperlipoproteinemia

    Takanari Gotoda, Koji Shirai, Takao Ohta, Junji Kobayashi, Shinji Yokoyama, Shinichi Oikawa, Hideaki Bujo, Shun Ishibashi, Hidenori Arai, Shizuya Yamashita, Mariko Harada-Shiba, Masaaki Eto, Toshio Hayashi, Hirohito Sone, Hiroaki Suzuki, Nobuhiro Yamada

    Journal of Atherosclerosis and Thrombosis   19 ( 1 )   1 - 12   2012

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    Both type I and type V hyperlipoproteinemia are characterized by severe hypertriglyceridemia due to an increase in chylomicrons. Type I hyperlipoproteinemia is caused by a decisive abnormality of the lipoprotein lipase (LPL)-apolipoprotein C-II system, whereas the cause of type I V hyperlipoproteinemia is more complicated and more closely related to acquired environmental factors. Since the relationship of hypertriglyceridemia with atherosclerosis is not as clear as that of hypercholesterolemia, and since type I and V hyperlipoproteinemia are relatively rare, few guidelines for their diagnosis and treatment have been established
    however, type I and V hyperlipoproteinemia are clinically important as underlying disorders of acute pancreatitis, and appropriate management is necessary to prevent or treat such complications. Against such a background, here we propose guidelines primarily concerning the diagnosis and management of type I and V hyperlipoproteinemia in Japanese.

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  • The Level of Orally Ingested Vitamin C Affected the Expression of Vitamin C Transporters and Vitamin C Accumulation in the Livers of ODS Rats

    Yasuko Sone, Etsuko Ueta, Satoru Kodama, Yasuko Sannoumaru, Noriko Miyake, Hirohito Sone, Yoko Fujiwara, Yuzuru Otsuka, Kazuo Kondo, Masahiro Inagaki, Eiji Namba, Tadao Kurata, Emiko Suzuki

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   75 ( 12 )   2394 - 2397   2011.12

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    We investigated the effects of vitamin C administration on vitamin C-specific transporters in ODS/ShiJcl-od/od rat livers. The vitamin C-specific transporter levels increased in the livers of the rats not administered vitamin C and decreased in the livers of those administered vitamin C at 100 mg/d, indicating that these transporter levels can be influenced by the amount of vitamin C administered.

    DOI: 10.1271/bbb.110312

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  • Self-reported fast eating is a potent predictor of development of impaired glucose tolerance in Japanese men and women: Tsukuba Medical Center Study

    Kumiko Totsuka, Takami Maeno, Kazumi Saito, Satoru Kodama, Mihoko Asumi, Yoko Yachi, Yuri Hiranuma, Hitoshi Shimano, Nobuhiro Yamada, Yukio Ono, Takashi Naito, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   94 ( 3 )   E72 - E74   2011.12

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    We recorded self-reported eating patterns in 172 Japanese men and women who were subsequently followed for 3 years for the occurrence of impaired glucose tolerance (IGT).
    Incidence of IGT was significantly higher in those who reported eating fast. Self-reported eating fast is a potent risk factor for development of IGT. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2011.08.015

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  • Self-reported fast eating is a potent predictor of development of impaired glucose tolerance in Japanese men and women: Tsukuba Medical Center Study

    Kumiko Totsuka, Takami Maeno, Kazumi Saito, Satoru Kodama, Mihoko Asumi, Yoko Yachi, Yuri Hiranuma, Hitoshi Shimano, Nobuhiro Yamada, Yukio Ono, Takashi Naito, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   94 ( 3 )   E72 - E74   2011.12

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    We recorded self-reported eating patterns in 172 Japanese men and women who were subsequently followed for 3 years for the occurrence of impaired glucose tolerance (IGT).
    Incidence of IGT was significantly higher in those who reported eating fast. Self-reported eating fast is a potent risk factor for development of IGT. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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  • The Level of Orally Ingested Vitamin C Affected the Expression of Vitamin C Transporters and Vitamin C Accumulation in the Livers of ODS Rats

    Yasuko Sone, Etsuko Ueta, Satoru Kodama, Yasuko Sannoumaru, Noriko Miyake, Hirohito Sone, Yoko Fujiwara, Yuzuru Otsuka, Kazuo Kondo, Masahiro Inagaki, Eiji Namba, Tadao Kurata, Emiko Suzuki

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   75 ( 12 )   2394 - 2397   2011.12

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    We investigated the effects of vitamin C administration on vitamin C-specific transporters in ODS/ShiJcl-od/od rat livers. The vitamin C-specific transporter levels increased in the livers of the rats not administered vitamin C and decreased in the livers of those administered vitamin C at 100 mg/d, indicating that these transporter levels can be influenced by the amount of vitamin C administered.

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  • 【動脈硬化と運動・身体活動-予防・改善のための取り組み-】 疫学研究 運動と動脈硬化の疫学

    児玉 暁, 曽根 博仁

    臨床スポーツ医学   28 ( 12 )   1311 - 1316   2011.12

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  • 横紋筋融解症、急性心筋炎から救命しえた劇症1型糖尿病の1例

    宜保 英彦, 藤原 和哉, 小林 和人, 高橋 昭光, 矢藤 繁, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    日本内分泌学会雑誌   87 ( 3 )   963 - 963   2011.12

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  • 震災時の精神的ストレスが血糖に与える影響

    藤原 和哉, 宜保 英彦, 小林 和人, 高橋 昭光, 矢藤 繁, 鈴木 浩明, 山田 信博, 斎藤 和美, 曽根 博仁

    日本内分泌学会雑誌   87 ( 3 )   1005 - 1005   2011.12

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  • Accumulation of cardiovascular risks in Japanese women with abnormal glucose and mild to moderate hypercholesterolemia (vol 152, pg 254, 2011)

    Tomoko Nakagami, Rimei Nishimura, Hirohito Sone, Naoko Tajima

    INTERNATIONAL JOURNAL OF CARDIOLOGY   153 ( 2 )   238 - 238   2011.12

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  • Accumulation of cardiovascular risks in Japanese women with abnormal glucose and mild to moderate hypercholesterolemia (vol 152, pg 254, 2011)

    Tomoko Nakagami, Rimei Nishimura, Hirohito Sone, Naoko Tajima

    INTERNATIONAL JOURNAL OF CARDIOLOGY   153 ( 2 )   238 - 238   2011.12

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  • Dose of 3-methylcholanthrene enhances vitamin C accumulation and mRNA expression of its transporter in the liver of ODS rats and in HepG2 cells

    Yasuko Sone, Etsuko Ueta, Yasuko Sannomaru, Noriko Miyake, Hirohito Sone, Yuzuru Otsuka, Kazuo Kondo, Tadao Kurata, Emiko Suzuki

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY   25 ( 6 )   369 - 376   2011.11

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    Polycyclic aromatic hydrocarbon (PAH) compounds including 3-methylcholanthrene induce harmful reactive intermediates and reactive oxygen species. This study reports the effect of 3-methylcholanthrene on the accumulation of vitamin C and the expression of vitamin C transporters. ODS rats were given l-ascorbic acid daily and intraperitoneal injections of 10 mg 3-methylcholanthrene in total. On day 10, vitamin C concentrations and the expression of vitamin C transporter in the tissues were measured. As a result, the levels of sodium-dependent vitamin C transporter (SVCTs) 1 and the l-ascorbic acid concentration in 3-methylcholanthrene-treated livers and hepatocytes have increased significantly. However, the content of vitamin C in the urine and TBARS in the liver have not changed. These results suggest that the administration of 3-methylcholanthrene elevates the requirement for vitamin C via (SVCTs) 1 due to xenobitics-metabolizing, such as the induction of cytochrome P450 family. (c) 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:369376 2011; View this article online at . DOI 10.1002/jbt.20403

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  • Inhibition of Ubiquitin Ligase F-box and WD Repeat Domain-containing 7 alpha (Fbw7 alpha) Causes Hepatosteatosis through Kruppel-like Factor 5 (KLF5)/Peroxisome Proliferator-activated Receptor gamma 2 (PPAR gamma 2) Pathway but Not SREBP-1c Protein in Mice

    Shin Kumadaki, Tadayoshi Karasawa, Takashi Matsuzaka, Masatsugu Ema, Yoshimi Nakagawa, Masanori Nakakuki, Ryo Saito, Naoya Yahagi, Hitoshi Iwasaki, Hirohito Sone, Kazuhiro Takekoshi, Shigeru Yatoh, Kazuto Kobayashi, Akimitsu Takahashi, Hiroaki Suzuki, Satoru Takahashi, Nobuhiro Yamada, Hitoshi Shimano

    JOURNAL OF BIOLOGICAL CHEMISTRY   286 ( 47 )   40835 - 40846   2011.11

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    F-box and WD repeat domain-containing 7 alpha (Ebw7 alpha) is the substrate recognition component of a ubiquitin ligase that controls the degradation of factors involved in cellular growth, including c-Myc, cyclin E, and c-Jun. In addition, Fbw7 alpha degrades the nuclear form of sterol regulatory element-binding protein (SREBP)-1a, a global regulator of lipid synthesis, particularly during mitosis in cultured cells. This study investigated the in vivo role of Ebw7 alpha in hepatic lipid metabolism. siRNA knockdown of Ebw7 alpha in mice caused marked hepatosteatosis with the accumulation of triglycerides. However, inhibition of Ebw7 alpha did not change the level of nuclear SREBP-1 protein or the expression of genes involved in fatty acid synthesis and oxidation. In vivo experiments on the gain and loss of Fbw7 alpha function indicated that Fbw7 alpha regulated the expression of peroxisome proliferator-activated receptor (PPAR) gamma 2 and its target genes involved in fatty acid uptake and triglyceride synthesis. These genes included fatty acid transporter Cd36, diacylglycerol acyltransferase 1 (Dgatl), and fat-specific protein 27 (Cidec). The regulation of PPAR gamma 2 by Fbw7 alpha was mediated, at least in part, by the direct degradation of the Krtippel-like factor 5 (KI.F5) protein, upstream of PPAR gamma 2 expression. Hepatic Fbw7 alpha contributes to normal fatty acid and triglyceride metabolism, functions that represent novel aspects of this cell growth regulator.

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  • Inhibition of Ubiquitin Ligase F-box and WD Repeat Domain-containing 7 alpha (Fbw7 alpha) Causes Hepatosteatosis through Kruppel-like Factor 5 (KLF5)/Peroxisome Proliferator-activated Receptor gamma 2 (PPAR gamma 2) Pathway but Not SREBP-1c Protein in Mice

    Shin Kumadaki, Tadayoshi Karasawa, Takashi Matsuzaka, Masatsugu Ema, Yoshimi Nakagawa, Masanori Nakakuki, Ryo Saito, Naoya Yahagi, Hitoshi Iwasaki, Hirohito Sone, Kazuhiro Takekoshi, Shigeru Yatoh, Kazuto Kobayashi, Akimitsu Takahashi, Hiroaki Suzuki, Satoru Takahashi, Nobuhiro Yamada, Hitoshi Shimano

    JOURNAL OF BIOLOGICAL CHEMISTRY   286 ( 47 )   40835 - 40846   2011.11

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    F-box and WD repeat domain-containing 7 alpha (Ebw7 alpha) is the substrate recognition component of a ubiquitin ligase that controls the degradation of factors involved in cellular growth, including c-Myc, cyclin E, and c-Jun. In addition, Fbw7 alpha degrades the nuclear form of sterol regulatory element-binding protein (SREBP)-1a, a global regulator of lipid synthesis, particularly during mitosis in cultured cells. This study investigated the in vivo role of Ebw7 alpha in hepatic lipid metabolism. siRNA knockdown of Ebw7 alpha in mice caused marked hepatosteatosis with the accumulation of triglycerides. However, inhibition of Ebw7 alpha did not change the level of nuclear SREBP-1 protein or the expression of genes involved in fatty acid synthesis and oxidation. In vivo experiments on the gain and loss of Fbw7 alpha function indicated that Fbw7 alpha regulated the expression of peroxisome proliferator-activated receptor (PPAR) gamma 2 and its target genes involved in fatty acid uptake and triglyceride synthesis. These genes included fatty acid transporter Cd36, diacylglycerol acyltransferase 1 (Dgatl), and fat-specific protein 27 (Cidec). The regulation of PPAR gamma 2 by Fbw7 alpha was mediated, at least in part, by the direct degradation of the Krtippel-like factor 5 (KI.F5) protein, upstream of PPAR gamma 2 expression. Hepatic Fbw7 alpha contributes to normal fatty acid and triglyceride metabolism, functions that represent novel aspects of this cell growth regulator.

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  • Serum Level of Triglycerides Is a Potent Risk Factor Comparable to LDL Cholesterol for Coronary Heart Disease in Japanese Patients with Type 2 Diabetes: Subanalysis of the Japan Diabetes Complications Study (JDCS)

    Hirohito Sone, Sachiko Tanaka, Shiro Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shinichi Oikawa, Shun Ishibashi, Shigehiro Katayama, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   96 ( 11 )   3448 - 3456   2011.11

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    Context: Risk factors for cardiovascular complications in Japanese patients with diabetes have not been fully elucidated.
    Objective: Our objective was to determine incidence of and risk factors for coronary heart disease (CHD) and stroke in Japanese diabetic patients.
    Design and Settings: We conducted a prospective study at 59 hospitals throughout Japan.
    Patients: Patients included 940 men and 831 women with type 2 diabetes (mean age, 58.2 yr) without a history of cardiovascular complications who were followed for a median of 7.86 yr.
    Intervention: This was an observational study.
    Main Outcome Measures: Incidence of CHD and stroke was evaluated.
    Results: Incidences of CHD and stroke per 1000 person-years were 9.59 and 7.45, respectively, whereas those of myocardial and brain infarctions were 3.84 and 6.29, respectively. Multivariate Cox analysis revealed that the serum log-transformed triglyceride level was a potent and independent predictor of CHD [hazard ratio (HR) = 1.54; 95% confidence interval (CI) = 1.22-1.94 per 1 SD increase), comparable to low-density lipoprotein (LDL) cholesterol (HR = 1.49; 95% CI = 1.25-1.78 per 1 SD increase). Triglycerides and LDL cholesterol linearly and continuously increased CHD risk, and subjects in the top third for both had markedly high risks of CHD, and their effects were possibly additive. However, serum triglycerides worked independently of blood pressure levels. Systolic blood pressure was the only significant predictor for stroke except for age (HR = 1.31; 95% CI = 1.04-1.65, per 1 SD increase).
    Conclusions: In Japanese patients with type 2 diabetes, the serum triglyceride level was a leading predictor of CHD, comparable to LDL cholesterol. Because the serum triglyceride level is not a leading predictor of CHD in diabetic subjects in Western countries, ethnic group-specific strategies for prevention of diabetic macroangiopathy may be indicated. (J Clin Endocrinol Metab 96: 3448-3456, 2011)

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  • Dose of 3-methylcholanthrene enhances vitamin C accumulation and mRNA expression of its transporter in the liver of ODS rats and in HepG2 cells

    Yasuko Sone, Etsuko Ueta, Yasuko Sannomaru, Noriko Miyake, Hirohito Sone, Yuzuru Otsuka, Kazuo Kondo, Tadao Kurata, Emiko Suzuki

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY   25 ( 6 )   369 - 376   2011.11

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    Polycyclic aromatic hydrocarbon (PAH) compounds including 3-methylcholanthrene induce harmful reactive intermediates and reactive oxygen species. This study reports the effect of 3-methylcholanthrene on the accumulation of vitamin C and the expression of vitamin C transporters. ODS rats were given l-ascorbic acid daily and intraperitoneal injections of 10 mg 3-methylcholanthrene in total. On day 10, vitamin C concentrations and the expression of vitamin C transporter in the tissues were measured. As a result, the levels of sodium-dependent vitamin C transporter (SVCTs) 1 and the l-ascorbic acid concentration in 3-methylcholanthrene-treated livers and hepatocytes have increased significantly. However, the content of vitamin C in the urine and TBARS in the liver have not changed. These results suggest that the administration of 3-methylcholanthrene elevates the requirement for vitamin C via (SVCTs) 1 due to xenobitics-metabolizing, such as the induction of cytochrome P450 family. (c) 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:369376 2011; View this article online at . DOI 10.1002/jbt.20403

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  • Serum Level of Triglycerides Is a Potent Risk Factor Comparable to LDL Cholesterol for Coronary Heart Disease in Japanese Patients with Type 2 Diabetes: Subanalysis of the Japan Diabetes Complications Study (JDCS)

    Hirohito Sone, Sachiko Tanaka, Shiro Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shinichi Oikawa, Shun Ishibashi, Shigehiro Katayama, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   96 ( 11 )   3448 - 3456   2011.11

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    Context: Risk factors for cardiovascular complications in Japanese patients with diabetes have not been fully elucidated.
    Objective: Our objective was to determine incidence of and risk factors for coronary heart disease (CHD) and stroke in Japanese diabetic patients.
    Design and Settings: We conducted a prospective study at 59 hospitals throughout Japan.
    Patients: Patients included 940 men and 831 women with type 2 diabetes (mean age, 58.2 yr) without a history of cardiovascular complications who were followed for a median of 7.86 yr.
    Intervention: This was an observational study.
    Main Outcome Measures: Incidence of CHD and stroke was evaluated.
    Results: Incidences of CHD and stroke per 1000 person-years were 9.59 and 7.45, respectively, whereas those of myocardial and brain infarctions were 3.84 and 6.29, respectively. Multivariate Cox analysis revealed that the serum log-transformed triglyceride level was a potent and independent predictor of CHD [hazard ratio (HR) = 1.54; 95% confidence interval (CI) = 1.22-1.94 per 1 SD increase), comparable to low-density lipoprotein (LDL) cholesterol (HR = 1.49; 95% CI = 1.25-1.78 per 1 SD increase). Triglycerides and LDL cholesterol linearly and continuously increased CHD risk, and subjects in the top third for both had markedly high risks of CHD, and their effects were possibly additive. However, serum triglycerides worked independently of blood pressure levels. Systolic blood pressure was the only significant predictor for stroke except for age (HR = 1.31; 95% CI = 1.04-1.65, per 1 SD increase).
    Conclusions: In Japanese patients with type 2 diabetes, the serum triglyceride level was a leading predictor of CHD, comparable to LDL cholesterol. Because the serum triglyceride level is not a leading predictor of CHD in diabetic subjects in Western countries, ethnic group-specific strategies for prevention of diabetic macroangiopathy may be indicated. (J Clin Endocrinol Metab 96: 3448-3456, 2011)

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  • 【糖尿病網膜症-診断と治療の将来展望-】 糖尿病網膜症への内科的アプローチ

    川崎 良, 曽根 博仁, 山下 英俊

    プラクティス   28 ( 6 )   575 - 584   2011.11

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  • 生活習慣病の臨床エビデンス(第28回) Webを使用した減量指導効果のエビデンス

    児玉 暁, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   10 ( 6 )   921 - 924   2011.11

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  • 【糖尿病患者のトータルケア】 総論 日本人糖尿病患者の実態 JDCS

    曽根 博仁, 片山 茂裕, 山下 英俊, 赤沼 安夫, 山田 信博

    診断と治療   99 ( 11 )   1805 - 1812   2011.11

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  • Skipping breakfast and prevalence of overweight and obesity in Asian and Pacific regions: A meta-analysis

    Chika Horikawa, Satoru Kodama, Yoko Yachi, Yoriko Heianza, Reiko Hirasawa, Yoko Ibe, Kazumi Saito, Hitoshi Shimano, Nobuhiro Yamada, Hirohito Sone

    PREVENTIVE MEDICINE   53 ( 4-5 )   260 - 267   2011.10

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    Objective. In Western countries, skipping breakfast is associated with a high prevalence of overweight and obesity. This meta-analysis aimed to determine if the same relationship exists in Asian and Pacific regions.
    Methods. A systematic literature search was performed for observational studies using a cross-sectional design that examined the relationship between frequency of eating breakfast and overweight or obesity. Odds ratios (ORs) for overweight or obesity were pooled with a variance-based method.
    Results. Nineteen studies (93,108 total participants and 19,270 overweight or obese cases) were included. The pooled OR 95% confidence intervals (CI)] of overweight or obesity for the lowest vs. highest category of breakfast frequency was 1.75 [1.57 to 1.95] (P&lt;0.001). Between-study heterogeneity in the association&apos;s strength was highly significant (I-squared = 36.4%, P&lt;0.001), although a positive OR was shown in all but one included study. However, no study characteristics could be identified to explain the heterogeneity.
    Conclusion. This meta-analysis suggests that a positive association between skipping breakfast and overweight and obesity is globally observed regardless of cultural diversity among countries. Promoting the eating of breakfast in all populations may be beneficial. (c) 2011 Elsevier Inc. All rights reserved.

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  • Low incidence of cardiovascular events in Japanese patients with Type 2 diabetes in primary care settings: a prospective cohort study (JDDM 20)

    H. Yokoyama, M. Matsushima, K. Kawai, K. Hirao, M. Oishi, H. Sugimoto, H. Takeda, M. Minami, M. Kobayashi, H. Sone

    DIABETIC MEDICINE   28 ( 10 )   1221 - 1228   2011.10

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    Aims To investigate whether a reduced incidence of cardiovascular disease in Type 2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts.
    Methods A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type 2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts.
    Results There were 90 cardiovascular events over 10 827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P &lt; 0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA(1c), HDL cholesterol and urinary albumin.
    Conclusion The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type 2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors.

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  • Low incidence of cardiovascular events in Japanese patients with Type 2 diabetes in primary care settings: a prospective cohort study (JDDM 20)

    H. Yokoyama, M. Matsushima, K. Kawai, K. Hirao, M. Oishi, H. Sugimoto, H. Takeda, M. Minami, M. Kobayashi, H. Sone

    DIABETIC MEDICINE   28 ( 10 )   1221 - 1228   2011.10

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    Aims To investigate whether a reduced incidence of cardiovascular disease in Type 2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts.
    Methods A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type 2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts.
    Results There were 90 cardiovascular events over 10 827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P &lt; 0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA(1c), HDL cholesterol and urinary albumin.
    Conclusion The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type 2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors.

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  • Age, gender, insulin and blood glucose control status alter the risk of ischemic heart disease and stroke among elderly diabetic patients

    Toshio Hayashi, Seinosuke Kawashima, Hideki Nomura, Hideki Itoh, Hiroshi Watanabe, Takashi Ohrui, Koutaro Yokote, Hirohito Sone, Yoshiyuki Hattori, Masao Yoshizumi, Koichiro Ina, Kiyoshi Kubota

    CARDIOVASCULAR DIABETOLOGY   10   86   2011.10

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    Background: We analyzed the effects of insulin therapy, age and gender on the risk of ischemic heart disease (IHD) and cerebrovascular accident (CVA) according to glycemic control.
    Methods and Results: We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) of type 2 diabetes patients (n = 4014) for 2 years. The primary endpoint was the onset of fatal/non-fatal IHD and/or CVA, which occurred at rates of 7.9 and 7.2 per 1000 person-years, respectively. We divided diabetic patients into four groups based on age (&lt;= 70 and &gt; 70) and hemoglobin A1C levels (&lt;= 7.0 and &gt; 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure and low HDL-C in patients under 70 years of age with fair glycemic control and was associated with low diastolic blood pressure in the older/fair group. Interestingly, insulin use was associated with IHD in the older/poor group (OR = 2.27, 95% CI = 1.11-5.89; p = 0.026) and was associated with CVA in the older/fair group (OR = 2.09, 95% CI = 1.06-4.25; p = 0.028). CVA was associated with lower HDL-C and longer duration of diabetes in younger/poor glycemic control group. Results by stepwise analysis were similar. Next, patients were divided into four groups based on gender and diabetic control (hemoglobinA1C &lt; or &gt; 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure in male/fair glycemic control group, age in male/poor control group, and short duration of diabetic history in females in both glycemic control groups. Interestingly, insulin use was associated with IHD in the male/poor group(OR = 4.11, 95% CI = 1.22-8.12; p = 0.018) and with CVA in the female/poor group(OR = 3.26, 95% CI = 1.12-6.24; p = 0.02). CVA was associated with short duration of diabetes in both female groups.
    Conclusions: IHD and CVA risks are affected by specific factors in diabetics, such as treatment, gender and age. Specifically, insulin use has a potential role in preventing IHD but may also be a risk factor for CVA among the diabetic elderly, thus revealing a need to develop improved treatment strategies for diabetes in elderly patients. The Japan Cholesterol and Diabetes Mellitus Study was formulated to evaluate them(Umin Clinical Trials Registry, clinical trial reg. no. UMIN00000516; http://www.umin.ac.jp/ctr/index.htm).

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  • Age, gender, insulin and blood glucose control status alter the risk of ischemic heart disease and stroke among elderly diabetic patients

    Toshio Hayashi, Seinosuke Kawashima, Hideki Nomura, Hideki Itoh, Hiroshi Watanabe, Takashi Ohrui, Koutaro Yokote, Hirohito Sone, Yoshiyuki Hattori, Masao Yoshizumi, Koichiro Ina, Kiyoshi Kubota

    CARDIOVASCULAR DIABETOLOGY   10   86   2011.10

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    Background: We analyzed the effects of insulin therapy, age and gender on the risk of ischemic heart disease (IHD) and cerebrovascular accident (CVA) according to glycemic control.
    Methods and Results: We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) of type 2 diabetes patients (n = 4014) for 2 years. The primary endpoint was the onset of fatal/non-fatal IHD and/or CVA, which occurred at rates of 7.9 and 7.2 per 1000 person-years, respectively. We divided diabetic patients into four groups based on age (&lt;= 70 and &gt; 70) and hemoglobin A1C levels (&lt;= 7.0 and &gt; 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure and low HDL-C in patients under 70 years of age with fair glycemic control and was associated with low diastolic blood pressure in the older/fair group. Interestingly, insulin use was associated with IHD in the older/poor group (OR = 2.27, 95% CI = 1.11-5.89; p = 0.026) and was associated with CVA in the older/fair group (OR = 2.09, 95% CI = 1.06-4.25; p = 0.028). CVA was associated with lower HDL-C and longer duration of diabetes in younger/poor glycemic control group. Results by stepwise analysis were similar. Next, patients were divided into four groups based on gender and diabetic control (hemoglobinA1C &lt; or &gt; 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure in male/fair glycemic control group, age in male/poor control group, and short duration of diabetic history in females in both glycemic control groups. Interestingly, insulin use was associated with IHD in the male/poor group(OR = 4.11, 95% CI = 1.22-8.12; p = 0.018) and with CVA in the female/poor group(OR = 3.26, 95% CI = 1.12-6.24; p = 0.02). CVA was associated with short duration of diabetes in both female groups.
    Conclusions: IHD and CVA risks are affected by specific factors in diabetics, such as treatment, gender and age. Specifically, insulin use has a potential role in preventing IHD but may also be a risk factor for CVA among the diabetic elderly, thus revealing a need to develop improved treatment strategies for diabetes in elderly patients. The Japan Cholesterol and Diabetes Mellitus Study was formulated to evaluate them(Umin Clinical Trials Registry, clinical trial reg. no. UMIN00000516; http://www.umin.ac.jp/ctr/index.htm).

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  • Skipping breakfast and prevalence of overweight and obesity in Asian and Pacific regions: A meta-analysis

    Chika Horikawa, Satoru Kodama, Yoko Yachi, Yoriko Heianza, Reiko Hirasawa, Yoko Ibe, Kazumi Saito, Hitoshi Shimano, Nobuhiro Yamada, Hirohito Sone

    PREVENTIVE MEDICINE   53 ( 4-5 )   260 - 267   2011.10

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    Objective. In Western countries, skipping breakfast is associated with a high prevalence of overweight and obesity. This meta-analysis aimed to determine if the same relationship exists in Asian and Pacific regions.
    Methods. A systematic literature search was performed for observational studies using a cross-sectional design that examined the relationship between frequency of eating breakfast and overweight or obesity. Odds ratios (ORs) for overweight or obesity were pooled with a variance-based method.
    Results. Nineteen studies (93,108 total participants and 19,270 overweight or obese cases) were included. The pooled OR 95% confidence intervals (CI)] of overweight or obesity for the lowest vs. highest category of breakfast frequency was 1.75 [1.57 to 1.95] (P&lt;0.001). Between-study heterogeneity in the association&apos;s strength was highly significant (I-squared = 36.4%, P&lt;0.001), although a positive OR was shown in all but one included study. However, no study characteristics could be identified to explain the heterogeneity.
    Conclusion. This meta-analysis suggests that a positive association between skipping breakfast and overweight and obesity is globally observed regardless of cultural diversity among countries. Promoting the eating of breakfast in all populations may be beneficial. (c) 2011 Elsevier Inc. All rights reserved.

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  • 日本人の動脈硬化リスクファクターをどのように包括管理するか

    曽根 博仁, 土井 康文, 大久保 孝義

    動脈硬化予防   10 ( 3 )   68 - 81   2011.10

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  • わが国におけるメタボリックシンドロームのエビデンスと診断基準

    菅原 歩美, 曽根 博仁

    栄養学雑誌   69 ( 5 )   205 - 213   2011.10

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    国際的に統一されたメタボリックシンドローム(MetS)の診断基準はない。MetSの診断に用いられる基準値には、1)内臓脂肪蓄積、腹囲径、2)耐糖能異常、3)高血圧、4)脂質異常、5)インスリン抵抗性、6)アルブミン排泄率などがあり、これらの項目のうちの幾つかを満たしている場合にMetSと診断されるが、用いられる項目やその値は国によってまちまちである。この中で本邦の基準が他国の基準と大きく異なっている点は、女性の腹囲診断基準値が男性よりも大きいことである。

    DOI: 10.5264/eiyogakuzashi.69.205

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  • 20歳時BMIは妊娠糖尿病発症を予測する指標として有用である(Tanaka Women's Clinic Study)

    谷内 洋子, 田中 康弘, 西端 泉, 菅原 歩美, 児玉 暁, 斎藤 和美, 曽根 博仁

    糖尿病と妊娠   11 ( 2 )   S - 71   2011.10

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  • Factors associated with inappropriate weight loss attempts by early adolescent girls in Japan

    A. Sugawara, M. Sato, K. Totsuka, K. Saito, S. Kodama, A. Fukushi, Y. Yamanashi, E. Matsushima, Y. Fujiwara, E. Suzuki, K. Kondo, S. Yamamoto, H. Sone

    EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY   16 ( 3 )   E157 - E163   2011.9

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    Attempting to lose weight by normal or underweight adolescent girls is a serious issue in many countries. It has been reported that the mode of attempted weight loss does not differ between normal weight and overweight girls. These inappropriate weight loss attempts (IWLA) by normal or underweight adolescent girls is associated with various health issues, but factors associated with IWLA have only been marginally elucidated. In this study, we applied a single multivariate regression analysis to clarify independent factors for IWLA. Study subjects were 134 pairs of early adolescent girls (aged 12-15) and their mothers. In addition to IWLA, many factors including height, weight, body image, perceived weight status, depressive symptoms, media influence and self-esteem were surveyed in both mothers and daughters and subjected to multivariate analysis. Approximately half of girls surveyed had IWLA, even though all were of normal weight and 62.9% knew that they were of normal weight. IWLA were independently associated with depressive symptoms (OR (95% CI); 2.80 (1.21-6.50), p=0.016) independent of actual or perceived weight status. Factors significantly associated with IWLA by the girls were percentage deviation of weight from standard weight (%DW) and media influence on the girls themselves, and media influence on and self-esteem of their mothers. IWLA, which were frequently observed among early adolescent girls even among those of normal weight, were closely related to depressive status. IWLA were significantly associated with not only factors related to the girls (1.09 (1.04-1.14), p=0.001), but also with maternal psychological factors (1.06 (1.00-1.13), p=0.035) conveyed by the media. Future prospective or interventional studies are required to clarify whether these factors could be targeted in an effort to prevent IWLA. (Eating Weight Disord. 16: e157-e163, 2011). (C) 2011, Editrice Kurtis

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  • Screening using various cutoffs of HbA(1c) and impaired fasting plasma glucose for predicting future diabetes: the Toranomon hospital health management center study

    C. Horikawa, Y. Heianza, S. Hara, Y. Arase, K. Saito, K. Fujiwara, A. Sugawara, H. Tsuji, S. Kodama, S. D. Hsieh, H. Shimano, N. Yamada, H. Sone

    DIABETOLOGIA   54   S142 - S142   2011.9

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  • Low BMI at age 20 years predicts gestational diabetes independent of BMI in early pregnancy: Tanaka Women's Clinic Study

    Y. Yachi, C. Horikawa, Y. Heianza, A. Sugawara, A. Saito, K. Fujiwara, I. Nishibata, M. Yasuhara, K. Kobayashi, S. Kodama, K. Saito, Y. Tanaka, H. Sone

    DIABETOLOGIA   54   S479 - S479   2011.9

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  • Potential impact of elevated HbA(1c) and impaired fasting glucose on population for predicting risk of diabetes: the Toranomon Hospital Health Management Center Study

    Y. Heianza, S. Hara, C. Horikawa, K. Saito, A. Sugawara, K. Fujiwara, S. Kodama, S. D. Hsieh, H. Tsuji, H. Shimano, N. Yamada, Y. Arase, H. Sone

    DIABETOLOGIA   54   S368 - S368   2011.9

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  • Macrophage Elovl6 Deficiency Ameliorates Foam Cell Formation and Reduces Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

    Ryo Saito, Takashi Matsuzaka, Tadayoshi Karasawa, Motohiro Sekiya, Nazuki Okada, Masaki Igarashi, Rie Matsumori, Kiyoaki Ishii, Yoshimi Nakagawa, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Hirohito Sone, Hiroaki Suzuki, Naoya Yahagi, Nobuhiro Yamada, Hitoshi Shimano

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   31 ( 9 )   1973 - U143   2011.9

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    Objective-Elovl6, a long-chain fatty acid elongase, is a rate-limiting enzyme that elongates saturated and monounsaturated fatty acids and has been shown to be related to obesity-induced insulin resistance via modification of fatty acid composition. In this study, we investigated the roles of Elovl6 in foam cell formation in macrophages and atherosclerosis in mice.
    Methods and Results-To investigate the roles of Elovl6 in macrophages in the progression of atherosclerosis, we transplanted bone marrow cells of wild-type or Elovl6(-/-) mice into irradiated LDL-R(-/-) mice that were fed a western diet. Aortic atherosclerotic lesion areas and infiltration of macrophages were significantly smaller in Elovl6(-/-) bone marrow cells-transplanted LDL-R(-/-) mice than in wild-type. Accumulation of esterified cholesterol on exposure to acetylated-LDL was less severe in peritoneal macrophages from Elovl6(-/-) mice than those from wild-type. Cholesterol efflux and expression of cholesterol efflux transporters were increased in Elovl6(-/-) macrophages, although no difference in uptake of acetylated-LDL was found between the two groups. On analysis of fatty acid composition of the esterified cholesterol fraction in macrophages, n-6 polyunsaturated fatty acids were decreased by absence of Elovl6.
    Conclusion-These findings suggest that Elovl6 in macrophages may contribute to foam cell formation and progression of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2011;31:1973-1979.)

    DOI: 10.1161/ATVBAHA.110.221663

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  • Macrophage Elovl6 Deficiency Ameliorates Foam Cell Formation and Reduces Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

    Ryo Saito, Takashi Matsuzaka, Tadayoshi Karasawa, Motohiro Sekiya, Nazuki Okada, Masaki Igarashi, Rie Matsumori, Kiyoaki Ishii, Yoshimi Nakagawa, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Hirohito Sone, Hiroaki Suzuki, Naoya Yahagi, Nobuhiro Yamada, Hitoshi Shimano

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   31 ( 9 )   1973 - U143   2011.9

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    Objective-Elovl6, a long-chain fatty acid elongase, is a rate-limiting enzyme that elongates saturated and monounsaturated fatty acids and has been shown to be related to obesity-induced insulin resistance via modification of fatty acid composition. In this study, we investigated the roles of Elovl6 in foam cell formation in macrophages and atherosclerosis in mice.
    Methods and Results-To investigate the roles of Elovl6 in macrophages in the progression of atherosclerosis, we transplanted bone marrow cells of wild-type or Elovl6(-/-) mice into irradiated LDL-R(-/-) mice that were fed a western diet. Aortic atherosclerotic lesion areas and infiltration of macrophages were significantly smaller in Elovl6(-/-) bone marrow cells-transplanted LDL-R(-/-) mice than in wild-type. Accumulation of esterified cholesterol on exposure to acetylated-LDL was less severe in peritoneal macrophages from Elovl6(-/-) mice than those from wild-type. Cholesterol efflux and expression of cholesterol efflux transporters were increased in Elovl6(-/-) macrophages, although no difference in uptake of acetylated-LDL was found between the two groups. On analysis of fatty acid composition of the esterified cholesterol fraction in macrophages, n-6 polyunsaturated fatty acids were decreased by absence of Elovl6.
    Conclusion-These findings suggest that Elovl6 in macrophages may contribute to foam cell formation and progression of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2011;31:1973-1979.)

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  • Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan Diabetes Complications Study (JDCS)

    R. Kawasaki, S. Tanaka, S. Tanaka, T. Yamamoto, H. Sone, Y. Ohashi, Y. Akanuma, N. Yamada, H. Yamashita

    DIABETOLOGIA   54 ( 9 )   2288 - 2294   2011.9

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    The aim of this study was to determine the incidence and progression rates of diabetic retinopathy and their associations in Japanese individuals with type 2 diabetes.
    This is a part of the Japan Diabetic Complications Study (JDCS), a multi-centred randomised trial of type 2 diabetes patients aged 40-70 years with an 8 year follow-up. There were 1,221 patients without diabetic retinopathy at baseline; incidence of diabetic retinopathy was defined as the development of any diabetic retinopathy. There were 410 patients with mild non-proliferative diabetic retinopathy at baseline; progression of diabetic retinopathy was defined as the development of severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy. We used multivariate proportional Cox hazard models, and generalised additive models were also applied to identify potential threshold effect.
    The incidence and progression rate of diabetic retinopathy was 38.3/1,000 person-years and 21.1/1,000 person-years, respectively. Higher HbA(1c) (adjusted HR [aHR] per 1% [10.9 mmol/mol] 1.36 [95% CI 1.28-1.45]), longer duration of diabetes (aHR per 5 year period 1.26 [95% CI 1.17-1.35]), higher systolic blood pressure (aHR per +10 mmHg 1.01 [95% CI 1.00-1.02]) and higher body mass index (aHR per 1 kg/m(2) 1.05 [95% CI 1.00-1.09]) were associated with incident diabetic retinopathy. The association between HbA(1c) and incident diabetic retinopathy was linear; the association with duration of diabetes increased rapidly between 5 and 10 years. Higher HbA(1c) was also associated with progression of diabetic retinopathy (aHR per 1% [10.9 mmol/mol] 1.66 [95% CI 1.41-1.96]).
    Observed incidence and progression rates of diabetic retinopathy seemed lower than that in western populations. HbA(1c) was the only factor associated with both incidence and progression of diabetic retinopathy. The strength of the association between duration of diabetes and incidence of diabetic retinopathy increased rapidly during a period of 5 to 10 years duration of diabetes.

    DOI: 10.1007/s00125-011-2199-0

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  • Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan Diabetes Complications Study (JDCS)

    R. Kawasaki, S. Tanaka, S. Tanaka, T. Yamamoto, H. Sone, Y. Ohashi, Y. Akanuma, N. Yamada, H. Yamashita

    DIABETOLOGIA   54 ( 9 )   2288 - 2294   2011.9

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    The aim of this study was to determine the incidence and progression rates of diabetic retinopathy and their associations in Japanese individuals with type 2 diabetes.
    This is a part of the Japan Diabetic Complications Study (JDCS), a multi-centred randomised trial of type 2 diabetes patients aged 40-70 years with an 8 year follow-up. There were 1,221 patients without diabetic retinopathy at baseline; incidence of diabetic retinopathy was defined as the development of any diabetic retinopathy. There were 410 patients with mild non-proliferative diabetic retinopathy at baseline; progression of diabetic retinopathy was defined as the development of severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy. We used multivariate proportional Cox hazard models, and generalised additive models were also applied to identify potential threshold effect.
    The incidence and progression rate of diabetic retinopathy was 38.3/1,000 person-years and 21.1/1,000 person-years, respectively. Higher HbA(1c) (adjusted HR [aHR] per 1% [10.9 mmol/mol] 1.36 [95% CI 1.28-1.45]), longer duration of diabetes (aHR per 5 year period 1.26 [95% CI 1.17-1.35]), higher systolic blood pressure (aHR per +10 mmHg 1.01 [95% CI 1.00-1.02]) and higher body mass index (aHR per 1 kg/m(2) 1.05 [95% CI 1.00-1.09]) were associated with incident diabetic retinopathy. The association between HbA(1c) and incident diabetic retinopathy was linear; the association with duration of diabetes increased rapidly between 5 and 10 years. Higher HbA(1c) was also associated with progression of diabetic retinopathy (aHR per 1% [10.9 mmol/mol] 1.66 [95% CI 1.41-1.96]).
    Observed incidence and progression rates of diabetic retinopathy seemed lower than that in western populations. HbA(1c) was the only factor associated with both incidence and progression of diabetic retinopathy. The strength of the association between duration of diabetes and incidence of diabetic retinopathy increased rapidly during a period of 5 to 10 years duration of diabetes.

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  • Risks for glomerular filtration rate decline in association with progression of albuminuria in type 2 diabetes

    Hiroki Yokoyama, Sakiko Kanno, Suguho Takahashi, Daishiro Yamada, Jun Honjo, Kazumi Saito, Hirohito Sone, Masakazu Haneda

    NEPHROLOGY DIALYSIS TRANSPLANTATION   26 ( 9 )   2924 - U1513   2011.9

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    Background. The aim of this study was to investigate the annual rate of glomerular filtration rate (GFR) decline and risks for this decline in association with albuminuria progression in type 2 diabetes.Methods. An observational 4-year cohort study was performed on 1002 subjects with preserved GFR (699 normoalbuminuric), and the predictive value of baseline variables on the GFR slope was investigated. GFR decliner and albuminuria progressor were defined as a GFR slope < -4.0%/year and changes in the geometric mean of urinary albumin from baseline to follow-up > 150%, respectively.Results. Annual rates of GFR decline (percent per year, median and interquartile range) were -2.58 (-4.70 to -0.48) in normoalbuminuria, -3.49 (-5.93 to -1.11) in microalbuminuria and -6.58 (-10.64 to -3.53) in macroalbuminuria. Subjects cross-classified according to GFR decliner/albuminuria progressor consisted of 51% (-/-), 13% (-/+), 28% (+/-) and 8% (+/+). Common risks for GFR decline and albuminuria progression were retinopathy, neuropathy, hemoglobin A(1C) (HbA(1C)) and urinary albumin. Independent significant risks for GFR decline were baseline GFR, systolic blood pressure (SBP), total protein (TP) and hypertension. Proportions with progression to albuminuria were similar between GFR decliners and non-decliners. Multiple linear regression analysis indicated that GFR slope was predicted by baseline variables of urinary albumin, GFR, HbA(1C), SBP, plasma TP and retinopathy. These risks appeared variable according to high or low levels of urinary albumin and GFR.Conclusions. Urinary albumin excretion is only one risk factor for albuminuria progression and GFR decline, and other important factors were implicated as important for prevention of end-stage renal disease.

    DOI: 10.1093/ndt/gfq774

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  • Risks for glomerular filtration rate decline in association with progression of albuminuria in type 2 diabetes

    Hiroki Yokoyama, Sakiko Kanno, Suguho Takahashi, Daishiro Yamada, Jun Honjo, Kazumi Saito, Hirohito Sone, Masakazu Haneda

    NEPHROLOGY DIALYSIS TRANSPLANTATION   26 ( 9 )   2924 - U1513   2011.9

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    Background. The aim of this study was to investigate the annual rate of glomerular filtration rate (GFR) decline and risks for this decline in association with albuminuria progression in type 2 diabetes.Methods. An observational 4-year cohort study was performed on 1002 subjects with preserved GFR (699 normoalbuminuric), and the predictive value of baseline variables on the GFR slope was investigated. GFR decliner and albuminuria progressor were defined as a GFR slope < -4.0%/year and changes in the geometric mean of urinary albumin from baseline to follow-up > 150%, respectively.Results. Annual rates of GFR decline (percent per year, median and interquartile range) were -2.58 (-4.70 to -0.48) in normoalbuminuria, -3.49 (-5.93 to -1.11) in microalbuminuria and -6.58 (-10.64 to -3.53) in macroalbuminuria. Subjects cross-classified according to GFR decliner/albuminuria progressor consisted of 51% (-/-), 13% (-/+), 28% (+/-) and 8% (+/+). Common risks for GFR decline and albuminuria progression were retinopathy, neuropathy, hemoglobin A(1C) (HbA(1C)) and urinary albumin. Independent significant risks for GFR decline were baseline GFR, systolic blood pressure (SBP), total protein (TP) and hypertension. Proportions with progression to albuminuria were similar between GFR decliners and non-decliners. Multiple linear regression analysis indicated that GFR slope was predicted by baseline variables of urinary albumin, GFR, HbA(1C), SBP, plasma TP and retinopathy. These risks appeared variable according to high or low levels of urinary albumin and GFR.Conclusions. Urinary albumin excretion is only one risk factor for albuminuria progression and GFR decline, and other important factors were implicated as important for prevention of end-stage renal disease.

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  • JDCSからみたわが国の糖尿病大血管障害の特徴

    曽根 博仁

    糖尿病合併症   25 ( Suppl.1 )   129 - 129   2011.9

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  • 糖尿病診療に必要な知識 2型糖尿病の血管合併症 JDCSの成果

    曽根 博仁, 片山 茂裕, 山下 英俊, 赤沼 安夫, 山田 信博

    糖尿病学の進歩   ( 45 )   1 - 7   2011.9

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  • 胴身長比(Waist-to-stature ratio:WSR)と2型糖尿病発症(T2DM)との関連性のメタ解析

    児玉 暁, 堀川 千嘉, 平安座 依子, 斎藤 あき, 菅原 歩美, 谷内 洋子, 平澤 玲子, 藤原 和哉, 斎藤 和美, 曽根 博仁

    肥満研究   17 ( Suppl. )   166 - 166   2011.9

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  • 生活習慣病の臨床エビデンス(第27回) 米国糖尿病学会の新しいPre-diabetes(前糖尿病状態)診断基準におけるHbA1c(国際標準値)5.7〜6.4%と空腹時血糖値異常による糖尿病発症の予測

    平安座 依子, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   10 ( 5 )   771 - 776   2011.9

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  • CKD categories by KDIGO and the progression rate in GFR, albuminuria and cardiovascular disease in type 2 diabetes without prevalent cardiovascular disease: prospective cohort study

    H. Yokoyama, M. Matsushima, K. Kawai, M. Oishi, K. Hirao, H. Sugimoto, H. Sone, S. -I. Araki, A. Kashiwagi

    DIABETOLOGIA   54   S437 - S437   2011.9

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  • Sterol Regulatory Element-Binding Protein-1 Determines Plasma Remnant Lipoproteins and Accelerates Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

    Tadayoshi Karasawa, Akimitsu Takahashi, Ryo Saito, Motohiro Sekiya, Masaki Igarashi, Hitoshi Iwasaki, Shoko Miyahara, Saori Koyasu, Yoshimi Nakagawa, Kiyoaki Ishii, Takashi Matsuzaka, Kazuto Kobayashi, Naoya Yahagi, Kazuhiro Takekoshi, Hirohito Sone, Shigeru Yatoh, Hiroaki Suzuki, Nobuhiro Yamada, Hitoshi Shimano

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   31 ( 8 )   1788 - U201   2011.8

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    Objective-Sterol regulatory element-binding protein-1 (SREBP-1) is nutritionally regulated and is known to be a key transcription factor regulating lipogenic enzymes. The goal of this study was to evaluate the roles of SREBP-1 in dyslipidemia and atherosclerosis.
    Methods and Results-Transgenic mice that overexpress SREBP-1c in the liver and SREBP-1-deficient mice were crossed with low-density lipoprotein receptor (LDLR)-deficient mice, and the plasma lipids and atherosclerosis were analyzed. Hepatic SREBP-1c overexpression in LDLR-deficient mice caused postprandial hypertriglyceridemia, increased very-low-density lipoprotein (VLDL) cholesterol, and decreased high-density lipoprotein cholesterol in plasma, which resulted in accelerated aortic atheroma formation. Conversely, absence of SREBP-1 suppressed Western diet-induced hyperlipidemia in LDLR-deficient mice and ameliorated atherosclerosis. In contrast, bone marrow-specific SREBP-1 deficiency did not alter the development of atherosclerosis. The size of nascent VLDL particles secreted from the liver was increased in SREBP-1c transgenic mice and reduced in SREBP-1-deficient mice, accompanied by upregulation and downregulation of phospholipid transfer protein expression, respectively.
    Conclusion-Hepatic SREBP-1c determines plasma triglycerides and remnant cholesterol and contributes to atherosclerosis in hyperlipidemic states. Hepatic SREBP-1c also regulates the size of nascent VLDL particles. (Arterioscler Thromb Vasc Biol. 2011;31:1788-1795.)

    DOI: 10.1161/ATVBAHA.110.219659

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  • Sterol Regulatory Element-Binding Protein-1 Determines Plasma Remnant Lipoproteins and Accelerates Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

    Tadayoshi Karasawa, Akimitsu Takahashi, Ryo Saito, Motohiro Sekiya, Masaki Igarashi, Hitoshi Iwasaki, Shoko Miyahara, Saori Koyasu, Yoshimi Nakagawa, Kiyoaki Ishii, Takashi Matsuzaka, Kazuto Kobayashi, Naoya Yahagi, Kazuhiro Takekoshi, Hirohito Sone, Shigeru Yatoh, Hiroaki Suzuki, Nobuhiro Yamada, Hitoshi Shimano

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   31 ( 8 )   1788 - U201   2011.8

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    Objective-Sterol regulatory element-binding protein-1 (SREBP-1) is nutritionally regulated and is known to be a key transcription factor regulating lipogenic enzymes. The goal of this study was to evaluate the roles of SREBP-1 in dyslipidemia and atherosclerosis.
    Methods and Results-Transgenic mice that overexpress SREBP-1c in the liver and SREBP-1-deficient mice were crossed with low-density lipoprotein receptor (LDLR)-deficient mice, and the plasma lipids and atherosclerosis were analyzed. Hepatic SREBP-1c overexpression in LDLR-deficient mice caused postprandial hypertriglyceridemia, increased very-low-density lipoprotein (VLDL) cholesterol, and decreased high-density lipoprotein cholesterol in plasma, which resulted in accelerated aortic atheroma formation. Conversely, absence of SREBP-1 suppressed Western diet-induced hyperlipidemia in LDLR-deficient mice and ameliorated atherosclerosis. In contrast, bone marrow-specific SREBP-1 deficiency did not alter the development of atherosclerosis. The size of nascent VLDL particles secreted from the liver was increased in SREBP-1c transgenic mice and reduced in SREBP-1-deficient mice, accompanied by upregulation and downregulation of phospholipid transfer protein expression, respectively.
    Conclusion-Hepatic SREBP-1c determines plasma triglycerides and remnant cholesterol and contributes to atherosclerosis in hyperlipidemic states. Hepatic SREBP-1c also regulates the size of nascent VLDL particles. (Arterioscler Thromb Vasc Biol. 2011;31:1788-1795.)

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  • 【糖尿病性腎症-病態の解明と最新治療戦略】 コホート研究からの最新知見 JDCS(Japan Diabetes Complications Study)

    片山 茂裕, 守屋 達美, 田中 司朗, 大橋 靖雄, 曽根 博仁

    医学のあゆみ   238 ( 9 )   829 - 832   2011.8

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    &quot;糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDCS)&quot;において、尿アルブミン(Alb)/クレアチニン(Cr)が&lt;150mg/g Crの正常(&lt;30)あるいは軽度-微量アルブミン尿(30-&lt;150)の2型糖尿病患者1,558例を対象として、糖尿病性腎症(以下、腎症;尿Alb/Crが連続2回&gt;300)の発症・進展を検討した。8年後までの腎症発症率は6.67/1,000人・年と低値であった。ライフスタイルへの介入の効果は明らかでなかった(ハザード比1.01)。腎症発症の危険因子としてアルブミン尿が高値、HbA1cが高値、収縮期血圧が高値、喫煙があげられた。逆に、登録時の軽度-微量アルブミン尿群の452例中の30.3%が&lt;30に正常化(remission)した。腎症発症の高リスク群である日本人でも、正常あるいは軽度-微量アルブミン尿の病期までに早期に診断をして現状のわが国の治療をすれば、腎症の発症・進展を低く抑えられることが示された。(著者抄録)

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  • 【動脈硬化リスク因子のupdate】 糖尿病・耐糖能異常

    藤原 和哉, 曽根 博仁

    循環器内科   70 ( 2 )   148 - 156   2011.8

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    Other Link: http://search.jamas.or.jp/link/ui/2011347521

  • HbA(1c) 5.7-6.4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study

    Yoriko Heianza, Shigeko Hara, Yasuji Arase, Kazumi Saito, Kazuya Fujiwara, Hiroshi Tsuji, Satoru Kodama, Shiun Dong Hsieh, Yasumichi Mori, Hitoshi Shimano, Nobuhiro Yamada, Kinori Kosaka, Hirohito Sone

    LANCET   378 ( 9786 )   147 - 155   2011.7

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    Background The clinical relevance of the diagnostic criteria for prediabetes to prediction of progression to diabetes has been little studied. We aimed to compare the prevalence of prediabetes when assessed by the new glycated haemoglobin A(1c) (HbA(1c)) 5.7-6.4% criterion or by impaired fasting glucose, and assessed differences in progression rate to diabetes between these two criteria for prediabetes in a Japanese population.
    Methods Our longitudinal cohort study included 4670 men and 1571 women aged 24-82 years without diabetes at baseline (diabetes was defined as fasting plasma glucose &gt;= 7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) &gt;= 6.5%) who attended Toranomon Hospital (Tokyo, Japan) for a routine health check between 1997 and 2003. Participants with a baseline diagnosis of prediabetes according to impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/L) or HbA(1c) 5.7-6.4%, or both, were divided into four groups on the basis of baseline diagnosis of prediabetes. Rate of progression to diabetes was assessed annually.
    Findings Mean follow-up was 4.7 (SD 0.7) years. 412 (7%) of 6241 participants were diagnosed with prediabetes on the basis of the HbA(1c) 5.7-6.4% criterion. Screening by HbA(1c) alone missed 1270 (61%) of the 2092 prediabetic individuals diagnosed by a combination of impaired fasting glucose and HbA(1c) 5.7-6.4%. Overall cumulative probability of progression to diabetes did not differ significantly between participants with prediabetes discordantly diagnosed by either HbA(1c) or impaired fasting glucose alone (incidence was 7% for HbA(1c) alone [n=412 individuals and 30 incident cases] and 9% for impaired fasting glucose alone [n=1270,108 cases]; log-rank test, p=0.3317). Multivariate-adjusted hazard ratios for incident diabetes were 6.16 (95% CI 4.33-8.77) for those diagnosed with prediabetes by impaired fasting glucose alone and 6.00 (3.76-9.56) for diagnosis by HbA(1c) alone, and were substantially increased to 31.9 (22.6-45.0) for diagnosis by both impaired fasting glucose and HbA(1c) compared with normoglycaemic individuals.
    Interpretation Diagnosis of prediabetes by both the new HbA(1c) criterion and impaired fasting glucose identified individuals with an increased risk of progression to diabetes. Although the new HbA(1c) criterion identified fewer individuals at high risk than did impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA(1c) 5.7-6.4% was similar to that assessed by impaired fasting glucose alone. The two tests used together could efficiently target people who are most likely to develop diabetes and allow for early intervention.

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  • HbA(1c) 5.7-6.4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study

    Yoriko Heianza, Shigeko Hara, Yasuji Arase, Kazumi Saito, Kazuya Fujiwara, Hiroshi Tsuji, Satoru Kodama, Shiun Dong Hsieh, Yasumichi Mori, Hitoshi Shimano, Nobuhiro Yamada, Kinori Kosaka, Hirohito Sone

    LANCET   378 ( 9786 )   147 - 155   2011.7

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    Background The clinical relevance of the diagnostic criteria for prediabetes to prediction of progression to diabetes has been little studied. We aimed to compare the prevalence of prediabetes when assessed by the new glycated haemoglobin A(1c) (HbA(1c)) 5.7-6.4% criterion or by impaired fasting glucose, and assessed differences in progression rate to diabetes between these two criteria for prediabetes in a Japanese population.
    Methods Our longitudinal cohort study included 4670 men and 1571 women aged 24-82 years without diabetes at baseline (diabetes was defined as fasting plasma glucose &gt;= 7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) &gt;= 6.5%) who attended Toranomon Hospital (Tokyo, Japan) for a routine health check between 1997 and 2003. Participants with a baseline diagnosis of prediabetes according to impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/L) or HbA(1c) 5.7-6.4%, or both, were divided into four groups on the basis of baseline diagnosis of prediabetes. Rate of progression to diabetes was assessed annually.
    Findings Mean follow-up was 4.7 (SD 0.7) years. 412 (7%) of 6241 participants were diagnosed with prediabetes on the basis of the HbA(1c) 5.7-6.4% criterion. Screening by HbA(1c) alone missed 1270 (61%) of the 2092 prediabetic individuals diagnosed by a combination of impaired fasting glucose and HbA(1c) 5.7-6.4%. Overall cumulative probability of progression to diabetes did not differ significantly between participants with prediabetes discordantly diagnosed by either HbA(1c) or impaired fasting glucose alone (incidence was 7% for HbA(1c) alone [n=412 individuals and 30 incident cases] and 9% for impaired fasting glucose alone [n=1270,108 cases]; log-rank test, p=0.3317). Multivariate-adjusted hazard ratios for incident diabetes were 6.16 (95% CI 4.33-8.77) for those diagnosed with prediabetes by impaired fasting glucose alone and 6.00 (3.76-9.56) for diagnosis by HbA(1c) alone, and were substantially increased to 31.9 (22.6-45.0) for diagnosis by both impaired fasting glucose and HbA(1c) compared with normoglycaemic individuals.
    Interpretation Diagnosis of prediabetes by both the new HbA(1c) criterion and impaired fasting glucose identified individuals with an increased risk of progression to diabetes. Although the new HbA(1c) criterion identified fewer individuals at high risk than did impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA(1c) 5.7-6.4% was similar to that assessed by impaired fasting glucose alone. The two tests used together could efficiently target people who are most likely to develop diabetes and allow for early intervention.

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  • 大脳深部白質高信号所見(DSWMH)の臨床的意義 大きさ個数と年齢との関連

    山口 龍生, 阿隅 美保子, 鶉橋 弘子, 古川 豊, 齋藤 和美, 児玉 暁, 松井 博滋, 宮澤 英充, 曽根 博仁, 福田 寛

    日本老年医学会雑誌   48 ( 4 )   404 - 404   2011.7

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  • 採血を用いない未診断糖尿病患者簡易発見法の妥当性の検討

    児玉 暁, 平安座 依子, 原 茂子, 辻 裕之, 謝 勲東, 荒瀬 康司, 曽根 博仁

    人間ドック   26 ( 2 )   410 - 410   2011.7

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  • HbA1cと空腹時血糖による糖代謝異常の評価とその後の糖尿病発症リスク

    原 茂子, 平安座 依子, 大本 由樹, 小川 恭子, 天川 和久, 謝 勲東, 辻 裕之, 曽根 博仁, 荒瀬 康司

    人間ドック   26 ( 2 )   415 - 415   2011.7

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  • 生活習慣病の臨床エビデンス(第26回) 妊娠中の耐糖能異常と周産期予後 妊娠中の耐糖能異常スクリーニング

    谷内 洋子, 田中 康弘, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   10 ( 4 )   631 - 634   2011.7

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  • 血清コレステロール値と無症候性脳梗塞の関連 横断的検討

    阿隅 美保子, 山口 龍生, 鶉橋 弘子, 古川 豊, 齋藤 和美, 児玉 暁, 松井 博滋, 宮澤 英充, 曽根 博仁, 福田 寛

    日本老年医学会雑誌   48 ( 4 )   404 - 404   2011.7

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  • 大脳深部白質高信号所見(DSWMH)の臨床的意義 大きさおよび個数とIMTmax値との関連

    山口 龍生, 阿隅 美保子, 鶉橋 弘子, 古川 豊, 齋藤 和美, 児玉 暁, 松井 博滋, 宮澤 英充, 曽根 博仁, 福田 寛

    日本老年医学会雑誌   48 ( 4 )   404 - 404   2011.7

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  • Diabetes and Risk of Hearing Impairment: A Meta-Analysis

    Chika Horikawa, Satoru Kodama, Yoriko Heianza, Aki Saito, Reiko Hira Sawa, Ayumi Sugawara, Kumiko Totsuka, Miho Maki, Kazumi Saito, Hirohito Sone

    DIABETES   60   A118 - A118   2011.7

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  • Is the Waist-to-Stature Ratio a Better Predictor Than Other Anthropometric Indicators To Predict Future Diabetes Risk? A Meta-Analysis

    Satoru Kodama, Chika Horikawa, Yoriko Heianza, Ayumi Sugawara, Yoko Ibe, Yoko Yachi, Miho Maki, Miao Shu, Kazumi Saito, Hirohito Sone

    DIABETES   60   A514 - A514   2011.7

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  • Dietary Intake in Japanese Patients with Type 2 Diabetes: Japan Diabetes Complication Study (JDCS)

    Chika Horikawa, Yukio Yoshimura, Yukako Nishigaki, Shiro Tanaka, Sachiko Tanaka, Chiemi Kamada, Ryota Okumura, Hideki Ito, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone, Japan Diabetes

    DIABETES   60   A33 - A34   2011.7

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  • Alcohol Consumption and Risk of Atrial Fibrillation Reply

    Satoru Kodama, Hirohito Sone

    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY   57 ( 25 )   2545 - 2546   2011.6

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    DOI: 10.1016/j.jacc.2011.02.035

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  • Relationship between hemoglobin A1c and cardiovascular disease in mild-to-moderate hypercholesterolemic Japanese individuals: subanalysis of a large-scale randomized controlled trial

    Rimei Nishimura, Tomoko Nakagami, Hirohito Sone, Yasuo Ohashi, Naoko Tajima

    CARDIOVASCULAR DIABETOLOGY   10   58   2011.6

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    Background: Although the ADA/EASD/IDF International Expert Committee recommends using hemoglobin A1c (HbA1c) to define diabetes, the relation between HbA1c and cardiovascular disease (CVD) has not been thoroughly investigated. We analyzed this relation using clinical data on Japanese individuals with hypercholesterolemia.
    Methods: In the large-scale MEGA Study 7832 patients aged 40 to 70 years old with mild-to-moderate hypercholesterolemia without CVD were randomized to diet alone or diet plus pravastatin and followed for &gt;5 years. In the present subanalysis of that study a total of 4002 patients with baseline and follow-up HbA1c data were stratified according to having an average HbA1c during the first year of follow-up &lt;6.0%, 6.0%-&lt;6.5%, or &gt;= 6.5% and their subsequent 5-year incidence rates of CVD compared according to sex, low-density lipoprotein cholesterol (LDL-C), and treatment arm.
    Results: Overall, risk of CVD was significantly 2.4 times higher in individuals with HbA1c &gt;= 6.5% versus &lt;6.0%. A similar relation was noted in men and women (hazard ratio [HR], 2.1; p &lt;0.01 and HR, 3.0; p &lt;0.01, respectively) and was regardless of treatment arm (diet alone group: HR, 2.2; p &lt;0.001; diet plus pravastatin group: HR, 1.8; p = 0.02). Spline curves showed a continuous risk increase according to HbA1c level in all subpopulations studied.
    Conclusions: In hypercholesterolemic individuals the risk of CVD increases linearly with HbA1c level. This significant contribution by elevated HbA1c to increased CVD is independent of pravastatin therapy, and thus requires appropriate HbA1c management in addition to lipids reduction.

    DOI: 10.1186/1475-2840-10-58

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  • Relationship between hemoglobin A1c and cardiovascular disease in mild-to-moderate hypercholesterolemic Japanese individuals: subanalysis of a large-scale randomized controlled trial

    Rimei Nishimura, Tomoko Nakagami, Hirohito Sone, Yasuo Ohashi, Naoko Tajima

    CARDIOVASCULAR DIABETOLOGY   10   58   2011.6

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    Background: Although the ADA/EASD/IDF International Expert Committee recommends using hemoglobin A1c (HbA1c) to define diabetes, the relation between HbA1c and cardiovascular disease (CVD) has not been thoroughly investigated. We analyzed this relation using clinical data on Japanese individuals with hypercholesterolemia.
    Methods: In the large-scale MEGA Study 7832 patients aged 40 to 70 years old with mild-to-moderate hypercholesterolemia without CVD were randomized to diet alone or diet plus pravastatin and followed for &gt;5 years. In the present subanalysis of that study a total of 4002 patients with baseline and follow-up HbA1c data were stratified according to having an average HbA1c during the first year of follow-up &lt;6.0%, 6.0%-&lt;6.5%, or &gt;= 6.5% and their subsequent 5-year incidence rates of CVD compared according to sex, low-density lipoprotein cholesterol (LDL-C), and treatment arm.
    Results: Overall, risk of CVD was significantly 2.4 times higher in individuals with HbA1c &gt;= 6.5% versus &lt;6.0%. A similar relation was noted in men and women (hazard ratio [HR], 2.1; p &lt;0.01 and HR, 3.0; p &lt;0.01, respectively) and was regardless of treatment arm (diet alone group: HR, 2.2; p &lt;0.001; diet plus pravastatin group: HR, 1.8; p = 0.02). Spline curves showed a continuous risk increase according to HbA1c level in all subpopulations studied.
    Conclusions: In hypercholesterolemic individuals the risk of CVD increases linearly with HbA1c level. This significant contribution by elevated HbA1c to increased CVD is independent of pravastatin therapy, and thus requires appropriate HbA1c management in addition to lipids reduction.

    DOI: 10.1186/1475-2840-10-58

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  • 糖尿病と脳卒中 疫学の面から予防法を探る

    曽根 博仁

    糖尿病合併症   25 ( 1 )   71 - 79   2011.6

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  • Contribution of first trimester fasting plasma insulin levels to the incidence of glucose intolerance in later pregnancy: Tanaka women's clinic study

    Yoko Yachi, Yasuhiro Tanaka, Yui Anasako, Izumi Nishibata, Kazumi Saito, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   92 ( 2 )   293 - 298   2011.5

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    Aims: To clarify risk factors predictive of glucose intolerance in later pregnancy.
    Methods: We prospectively studied 509 pregnant women who visited the obstetrics clinic in Tokyo prior to week 13 of gestation, between September 2008 and January 2010. Biochemical parameters were measured in fasting plasma samples collected at week 8.0 +/- 2.0 of gestation. A 50 g glucose challenge test (GCT) was performed between weeks 26 and 29: plasma glucose levels &gt;= 7.8 mmol/l 1 h after ingestion indicated a positive GCT. Logistic regression was performed, adjusting for relevant covariates.
    Results: We identified 114 patients with positive GCTs, including 8 with gestational diabetes mellitus (GDM). After correcting for baseline body mass index, only the homeostasis model assessment of insulin resistance value remained a significant predictor of GCT positivity (OR 2.07; 1.21-3.55). We identified threshold values of fasting plasma glucose (FPG) &gt;= 3.66 mmol/l and fasting plasma insulin (FPI) &gt;= 36.69 pmol/l as indicative of a higher risk of positive GCT (OR 2.38; 1.49-3.80).
    Conclusions: First trimester FPI levels improve the predictive ability of FPG level on subsequent GCT positivity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2011.02.012

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  • Low transition rate from normo- and low microalbuminuria to proteinuria in Japanese type 2 diabetic individuals: the Japan Diabetes Complications Study (JDCS)

    S. Katayama, T. Moriya, S. Tanaka, S. Tanaka, Y. Yajima, H. Sone, S. Iimuro, Y. Ohashi, Y. Akanuma, N. Yamada

    DIABETOLOGIA   54 ( 5 )   1025 - 1031   2011.5

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    The aim of the study was to determine the transition rate and factors associated with the progression of normo- and low microalbuminuria to diabetic nephropathy (overt proteinuria).
    For 8 years we prospectively observed 1,558 Japanese patients with type 2 diabetes mellitus whose basal urinary albumin:creatinine ratio (UACR) had been measured as &lt; 17.0 mg/mmol at entry. The incidence of nephropathy (UACR &gt; 33.9 mg/mmol) was determined by measuring UACR twice a year.
    Progression to nephropathy occurred in 74 patients. The annual transition rate was 0.67%, and was substantially higher for the low-microalbuminuric group than for the normoalbuminuric group (1.85% and 0.23%, respectively; hazard ratio for the low-microalbuminuric group 8.45, p &lt; 0.01). The hazard ratio for an HbA(1c) of 7-9% or a parts per thousand yen9% was 2.72 (p &lt; 0.01) or 5.81 (p &lt; 0.01) relative to HbA(1c) &lt; 7.0%, respectively. In comparison with individuals with a systolic blood pressure (SBP) of &lt; 120 mmHg, the hazard ratios for patients with an SBP of 120-140 mmHg or a parts per thousand yen140 mmHg were 2.31 (p = 0.06) and 3.54 (p &lt; 0.01), respectively. Smoking also affected progression to proteinuria (hazard ratio 1.99, p &lt; 0.01). In contrast, 30.3% of the low-microalbuminuric group returned to normoalbuminuria (i.e. were in remission).
    These results suggest that if patients with type 2 diabetes mellitus are receiving treatment from diabetologists for hyperglycaemia and hypertension when they are in the early stages of nephropathy (i.e. normo- or low microalbuminuria), their rate of transition to proteinuria is considerably lowered, and that differentiating patients with low microalbuminuria from those with high microalbuminuria might be clinically useful.
    UMIN Clinical Trials Registry C000000222
    The study was funded by the Ministry of Health, Labour and Welfare, Japan.

    DOI: 10.1007/s00125-010-2025-0

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  • Contribution of first trimester fasting plasma insulin levels to the incidence of glucose intolerance in later pregnancy: Tanaka women's clinic study

    Yoko Yachi, Yasuhiro Tanaka, Yui Anasako, Izumi Nishibata, Kazumi Saito, Hirohito Sone

    DIABETES RESEARCH AND CLINICAL PRACTICE   92 ( 2 )   293 - 298   2011.5

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    Aims: To clarify risk factors predictive of glucose intolerance in later pregnancy.
    Methods: We prospectively studied 509 pregnant women who visited the obstetrics clinic in Tokyo prior to week 13 of gestation, between September 2008 and January 2010. Biochemical parameters were measured in fasting plasma samples collected at week 8.0 +/- 2.0 of gestation. A 50 g glucose challenge test (GCT) was performed between weeks 26 and 29: plasma glucose levels &gt;= 7.8 mmol/l 1 h after ingestion indicated a positive GCT. Logistic regression was performed, adjusting for relevant covariates.
    Results: We identified 114 patients with positive GCTs, including 8 with gestational diabetes mellitus (GDM). After correcting for baseline body mass index, only the homeostasis model assessment of insulin resistance value remained a significant predictor of GCT positivity (OR 2.07; 1.21-3.55). We identified threshold values of fasting plasma glucose (FPG) &gt;= 3.66 mmol/l and fasting plasma insulin (FPI) &gt;= 36.69 pmol/l as indicative of a higher risk of positive GCT (OR 2.38; 1.49-3.80).
    Conclusions: First trimester FPI levels improve the predictive ability of FPG level on subsequent GCT positivity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2011.02.012

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  • Low transition rate from normo- and low microalbuminuria to proteinuria in Japanese type 2 diabetic individuals: the Japan Diabetes Complications Study (JDCS)

    S. Katayama, T. Moriya, S. Tanaka, S. Tanaka, Y. Yajima, H. Sone, S. Iimuro, Y. Ohashi, Y. Akanuma, N. Yamada

    DIABETOLOGIA   54 ( 5 )   1025 - 1031   2011.5

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    The aim of the study was to determine the transition rate and factors associated with the progression of normo- and low microalbuminuria to diabetic nephropathy (overt proteinuria).
    For 8 years we prospectively observed 1,558 Japanese patients with type 2 diabetes mellitus whose basal urinary albumin:creatinine ratio (UACR) had been measured as &lt; 17.0 mg/mmol at entry. The incidence of nephropathy (UACR &gt; 33.9 mg/mmol) was determined by measuring UACR twice a year.
    Progression to nephropathy occurred in 74 patients. The annual transition rate was 0.67%, and was substantially higher for the low-microalbuminuric group than for the normoalbuminuric group (1.85% and 0.23%, respectively; hazard ratio for the low-microalbuminuric group 8.45, p &lt; 0.01). The hazard ratio for an HbA(1c) of 7-9% or a parts per thousand yen9% was 2.72 (p &lt; 0.01) or 5.81 (p &lt; 0.01) relative to HbA(1c) &lt; 7.0%, respectively. In comparison with individuals with a systolic blood pressure (SBP) of &lt; 120 mmHg, the hazard ratios for patients with an SBP of 120-140 mmHg or a parts per thousand yen140 mmHg were 2.31 (p = 0.06) and 3.54 (p &lt; 0.01), respectively. Smoking also affected progression to proteinuria (hazard ratio 1.99, p &lt; 0.01). In contrast, 30.3% of the low-microalbuminuric group returned to normoalbuminuria (i.e. were in remission).
    These results suggest that if patients with type 2 diabetes mellitus are receiving treatment from diabetologists for hyperglycaemia and hypertension when they are in the early stages of nephropathy (i.e. normo- or low microalbuminuria), their rate of transition to proteinuria is considerably lowered, and that differentiating patients with low microalbuminuria from those with high microalbuminuria might be clinically useful.
    UMIN Clinical Trials Registry C000000222
    The study was funded by the Ministry of Health, Labour and Welfare, Japan.

    DOI: 10.1007/s00125-010-2025-0

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  • 動脈硬化の予防と治療 動脈硬化の予防と治療 糖尿病

    曽根 博仁

    日本老年医学会雑誌   48 ( 3 )   253 - 256   2011.5

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    DOI: 10.3143/geriatrics.48.253

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  • 喫煙状況と無症候性脳梗塞との関連性 脳ドック受診者における横断的検討

    阿隅 美保子, 齋藤 和美, 児玉 暁, 曽根 博仁, 飯田 薫子, 鈴木 恵美子, 近藤 和雄, 山口 龍生, 松井 博滋, 宮澤 英充

    成人病と生活習慣病   41 ( 5 )   608 - 609   2011.5

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  • 採血不要の臨床指標による未診断糖尿病スクリーニングのための基礎的検討 TOPICS

    平安座 依子, 齋藤 和美, 児玉 暁, 山田 信博, 曽根 博仁, 原 茂子, 齋藤 和美, 辻 裕之, 謝 勲東, 荒瀬 康司, 小坂 樹徳

    成人病と生活習慣病   41 ( 5 )   602 - 603   2011.5

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  • 産後のうつ症状と妊娠期の生活習慣との関連(Tanaka Women's Clinic Study)

    穴迫 唯衣, 谷内 洋子, 児玉 暁, 齋藤 和美, 曽根 博仁, 鈴木 恵美子, 近藤 和雄, 赤松 利恵, 飯田 薫子, 田中 康弘, 西端 泉, 安原 眞知子, 小林 香織

    成人病と生活習慣病   41 ( 5 )   622 - 623   2011.5

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  • HbA1cと空腹時血糖値それぞれにより糖尿病型と判定された者の特徴 TOPICS

    平安座 依子, 齋藤 和美, 藤原 和哉, 児玉 暁, 山田 信博, 曽根 博仁, 平安座 依子, 原 茂子, 齋藤 和美, 辻 裕之, 児玉 暁, 謝 勲東, 荒瀬 康司, 小坂 樹徳, 曽根 博仁, 原 茂子, 辻 裕之, 謝 勲東, 荒瀬 康司, 小坂 樹徳

    成人病と生活習慣病   41 ( 5 )   600 - 601   2011.5

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  • 妊娠時までのBMI変化と妊娠中の耐糖能異常発症リスクとの関連(TWC Study)

    谷内 洋子, 穴迫 唯衣, 齊藤 和美, 曽根 博仁, 谷内 洋子, 穴迫 唯衣, 赤松 利恵, 近藤 和雄, 鈴木 恵美子, 田中 康弘, 松岡 隆, 西端 泉

    成人病と生活習慣病   41 ( 5 )   600 - 600   2011.5

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  • 生活習慣病に対する食育指導 特に日本人女性のやせ過ぎを中心に

    曽根 博仁, 菅原 歩美

    成人病と生活習慣病   41 ( 5 )   568 - 572   2011.5

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    ・食や栄養は健康の基本であり、その知識や経験を通じて、健全な食生活を実践するための「食育」が提唱されてきた。本稿では、わが国において肥満と並び、今後特に食育が力を入れるべき分野である若年女性のやせ過ぎの問題について、その実態や背景、心身に対する影響などについて、これまでの研究結果を整理する。・わが国において、女性の平均BMIが10歳代後半から低下する傾向は他国にはみられない独特のものであり、骨密度や寿命、摂食障害など本人の身体的・精神的健康のみならず、出産数や出生時体重の低下などを通じて、次世代の国民にも影響を与えうる問題である。・その原因はいまだ完全に解明されていないが、雑誌、テレビなどのメディアや母親をはじめとする周囲の人間関係などが影響していることが最近の研究からも示唆されている。・食育をはじめとする啓発活動を通じた、一層の対策充実が求められている。(著者抄録)

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    Other Link: http://search.jamas.or.jp/link/ui/2011263640

  • 脂質異常症診断基準の臨床的意義 男性における体重管理指標との関連

    阿隅 美保子, 齋藤 和美, 児玉 暁, 曽根 博仁, 飯田 薫子, 鈴木 恵美子, 近藤 和雄, 山口 龍生, 松井 博滋, 宮澤 英充

    成人病と生活習慣病   41 ( 5 )   598 - 599   2011.5

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  • 卵の摂取量と心血管疾患リスクとの関連

    堀川 千嘉, 児玉 暁, 齋藤 あき, 平安座 依子, 西垣 結佳子, 穴迫 唯衣, 伊部 陽子, 平澤 玲子, 谷内 陽子, 齋藤 和美, 曽根 博仁

    成人病と生活習慣病   41 ( 5 )   597 - 597   2011.5

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  • 過去の体重歴は未診断糖尿病や前糖尿病状態を発見する指標として有用である TOPICS

    平安座 依子, 齋藤 和美, 児玉 暁, 山田 信博, 曽根 博仁, 原 茂子, 齋藤 和美, 辻 裕之, 児玉 暁, 謝 勲東, 荒瀬 康司, 小坂 樹徳, 曽根 博仁, 原 茂子, 辻 裕之

    成人病と生活習慣病   41 ( 5 )   599 - 599   2011.5

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  • 生活習慣病の臨床エビデンス(第25回) 若年女性の減量行動とその関連因子

    菅原 歩美, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   10 ( 3 )   490 - 492   2011.5

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  • 【脂質異常症 動脈硬化症を予防するためのStrategy】 動脈硬化症と脂質異常症の理解のために 【動脈硬化症発症に及ぼす各危険因子の影響】 糖尿病が果たす役割

    藤原 和哉, 曽根 博仁

    Medicina   48 ( 5 )   734 - 738   2011.5

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    <ポイント>★糖尿病患者では初期から大血管症が認められ,非糖尿病患者と比較して心血管疾患発症が2〜4倍高く,重症度も高い.★糖尿病患者では,高TG血症,低HDL血症といった動脈硬化を促進する危険因子が重複しやすい.★糖尿病患者では,small dense LDL,酸化LDL,糖化LDLなど動脈硬化を惹起する物質の増加を含む脂質代謝の質的異常を有する.★食後高血糖,負荷後高血糖は冠動脈疾患の危険因子であり,耐糖能障害の段階から心血管疾患の危険因子となる.(著者抄録)

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  • Low serum potassium levels and risk of type 2 diabetes: the Toranomon Hospital Health Management Center Study 1 (TOPICS 1)

    Y. Heianza, S. Hara, Y. Arase, K. Saito, K. Totsuka, H. Tsuji, S. Kodama, S. D. Hsieh, N. Yamada, K. Kosaka, H. Sone

    DIABETOLOGIA   54 ( 4 )   762 - 766   2011.4

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    Evidence has suggested that low serum potassium concentrations decrease insulin secretion, leading to glucose intolerance, and that hypokalaemia induced by diuretics increases the risk for diabetes in hypertensive individuals. However, no prospective study has investigated the association between serum potassium and the development of type 2 diabetes in a healthy cohort comprised of Asian individuals not being administered antihypertensive medications. This study aimed to investigate whether low serum potassium is associated with increased risk of type 2 diabetes in apparently healthy Japanese men.
    We followed 4,409 Japanese men with no history of diabetes, use of antihypertensives, renal dysfunction or liver dysfunction (mean +/- SD age, 48.4 +/- 8.4 years). Cox proportional hazards regression was used to estimate HRs for incident diabetes (fasting plasma glucose level a parts per thousand yen7.0 mmol/l, HbA(1c) a parts per thousand yenaEuro parts per thousand 6.5% or self-reported) including serum potassium concentration as either a categorical or a continuous variable.
    During a 5 year follow-up, 250 individuals developed type 2 diabetes. The lowest tertile of serum potassium (2.8-3.9 mmol/l) was independently associated with the development of diabetes after adjustment for known predictors (HR 1.57 [95% CI, 1.15-2.15]) compared with the highest tertile (4.2-5.4 mmol/l). Every 0.5 mmol/l lower increment in the baseline serum potassium level was associated with a 45% (12-87%) increased risk of diabetes.
    Mild to moderately low serum potassium levels, within the normal range and without frank hypokalaemia, could be predictive of type 2 diabetes in apparently healthy Japanese men.

    DOI: 10.1007/s00125-010-2029-9

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  • Low serum potassium levels and risk of type 2 diabetes: the Toranomon Hospital Health Management Center Study 1 (TOPICS 1)

    Y. Heianza, S. Hara, Y. Arase, K. Saito, K. Totsuka, H. Tsuji, S. Kodama, S. D. Hsieh, N. Yamada, K. Kosaka, H. Sone

    DIABETOLOGIA   54 ( 4 )   762 - 766   2011.4

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    Evidence has suggested that low serum potassium concentrations decrease insulin secretion, leading to glucose intolerance, and that hypokalaemia induced by diuretics increases the risk for diabetes in hypertensive individuals. However, no prospective study has investigated the association between serum potassium and the development of type 2 diabetes in a healthy cohort comprised of Asian individuals not being administered antihypertensive medications. This study aimed to investigate whether low serum potassium is associated with increased risk of type 2 diabetes in apparently healthy Japanese men.
    We followed 4,409 Japanese men with no history of diabetes, use of antihypertensives, renal dysfunction or liver dysfunction (mean +/- SD age, 48.4 +/- 8.4 years). Cox proportional hazards regression was used to estimate HRs for incident diabetes (fasting plasma glucose level a parts per thousand yen7.0 mmol/l, HbA(1c) a parts per thousand yenaEuro parts per thousand 6.5% or self-reported) including serum potassium concentration as either a categorical or a continuous variable.
    During a 5 year follow-up, 250 individuals developed type 2 diabetes. The lowest tertile of serum potassium (2.8-3.9 mmol/l) was independently associated with the development of diabetes after adjustment for known predictors (HR 1.57 [95% CI, 1.15-2.15]) compared with the highest tertile (4.2-5.4 mmol/l). Every 0.5 mmol/l lower increment in the baseline serum potassium level was associated with a 45% (12-87%) increased risk of diabetes.
    Mild to moderately low serum potassium levels, within the normal range and without frank hypokalaemia, could be predictive of type 2 diabetes in apparently healthy Japanese men.

    DOI: 10.1007/s00125-010-2029-9

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  • 2型糖尿病患者における食べる速さの糖尿病コントロールに及ぼす影響

    齋藤 あき, 西垣 結佳子, 川井 紘一, 柳澤 守文, 栗林 伸一, 横山 宏樹, 杉本 英克, 大石 まり子, 和田 崇子, 屋宜 宣治, 宮澤 一裕, 岩崎 皓一, 新井 桂子, 藤原 和哉, 齋藤 和美, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   65回   233 - 233   2011.4

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  • インターネットを用いた生活習慣改善教育における、肥満改善効果の検討 メタ解析による評価

    堀川 千嘉, 児玉 暁, 谷口 絵里香, 谷内 洋子, 平澤 玲子, 伊部 陽子, 西垣 結佳子, 齋藤 あき, 平安座 依子, 飯田 薫子, 藤原 葉子, 齋藤 和美, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   65回   232 - 232   2011.4

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  • 栄養指導法を参考にした新しい運動指導の試み 脂質代謝異常症患者での検討

    進藤 弥生, 皆川 健太, 曽根 博仁, 飯田 薫子

    日本栄養・食糧学会大会講演要旨集   65回   144 - 144   2011.4

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  • 食生活に関する国際的ウェブ情報のクオリティの検証 Mediterranean dietを例に

    平澤 玲子, 谷内 洋子, 堀川 千嘉, 平安座 依子, 齋藤 あき, 藤原 和哉, 菅原 歩美, 齋藤 和美, 飯田 薫子, 藤原 葉子, 近藤 和雄, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   65回   141 - 141   2011.4

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  • 2型糖尿病患者における、糖・脂質摂取比(C/F比)が糖・脂質代謝に及ぼす影響のメタアナリシス

    菅原 歩美, 児玉 暁, 牧 美保, 堀川 千嘉, 藤原 和哉, 平安座 依子, 齊藤 あき, 西垣 結佳子, 伊部 陽子, 平澤 玲子, 谷内 洋子, 齊藤 和美, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   65回   196 - 196   2011.4

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  • 日本人男性における喫煙状況と無症候性脳梗塞の関連性 喫煙指数を用いた横断的検討

    阿隅 美保子, 山口 龍生, 松井 博滋, 宮澤 英充, 児玉 暁, 齋藤 和美, 飯田 薫子, 近藤 和雄, 曽根 博仁, 鈴木 恵美子

    日本栄養・食糧学会大会講演要旨集   65回   152 - 152   2011.4

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  • 二十歳時から妊娠時までのBMI変化と妊娠糖尿病発症リスクとの関連(TWC Study)

    谷内 洋子, 田中 康弘, 穴迫 唯衣, 菅原 歩美, 戸塚 久美子, 赤松 利恵, 近藤 和雄, 鈴木 恵美子, 飯田 薫子, 児玉 暁, 齋藤 和美, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   65回   109 - 109   2011.4

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  • 生涯最大体重や20歳時の体重はその後の未診断糖尿病や前糖尿病状態の発症と関連する(TOPICS)

    平安座 依子, 原 茂子, 齋藤 和美, 児玉 暁, 飯田 薫子, 赤松 利恵, 鈴木 恵美子, 近藤 和雄, 荒瀬 康司, 山田 信博, 小坂 樹徳, 曽根 博仁

    日本栄養・食糧学会大会講演要旨集   65回   108 - 108   2011.4

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  • Japan Diabetes Complication Study(JDCS)における日本人2型糖尿病患者の栄養素及び食品摂取状況

    鎌田 智英実, 西垣 結佳子, 奥村 亮太, 田中 司朗, 井藤 英喜, 田中 佐智子, 堀川 千嘉, 高橋 あかね, 大橋 靖雄, 赤沼 安夫, 山田 信博, 曽根 博仁, 吉村 幸雄, JDCSグループ

    日本栄養・食糧学会大会講演要旨集   65回   233 - 233   2011.4

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  • HbA1cとFPGによる糖代謝異常評価とその後の糖尿病発症リスク(TOPICS)

    原 茂子, 平安座 依子, 齋藤 和美, 辻 裕之, 児玉 暁, 謝 勲東, 島野 仁, 荒瀬 康司, 山田 信博, 小坂 樹徳, 曽根 博仁

    糖尿病   54 ( Suppl.1 )   S - 202   2011.4

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  • 【血糖管理と心血管病を考える】 わが国の糖尿病患者における心血管病の発症とそのリスクをみる 欧米人との比較を含めて

    曽根 博仁

    Vascular Medicine   7 ( 1 )   2 - 9   2011.4

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    糖尿病患者は非糖尿病者と比較して、心血管疾患の発症率の高さが数倍以上で重症度も高い。糖尿病に合併する心血管疾患すなわち大血管合併症の発症率やリスクファクターは、人種や国によって異なる。これまで、世界の糖尿病人口の半分以上を占めるアジア人患者、とくに東アジア人患者を含む疫学研究は少なかったため、おもに欧米でおこなわれてきた研究結果が日本人糖尿病患者にあてはまるか否かは明らかでなかった。しかし、最近はわが国における合併症のリスクファクターや治療効果に関する研究も充実しつつあり、今後の積み重ねにより大血管症予防の実診療に反映させることができるものと期待される。(著者抄録)

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  • 糖尿病網膜症重症度と大血管症発症の関連 JDCS

    阿部 さち, 田中 佐智子, 山本 禎子, 大橋 靖雄, 曽根 博仁, 山田 信博, 山下 英俊

    日本眼科学会雑誌   115 ( 臨増 )   229 - 229   2011.4

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  • リラグルチドの多数例での有効無効の検討

    菅野 咲子, 奥田 昌江, 佐藤 舞菜見, 山下 りさ, 曽根 博仁, 本庄 潤, 山田 大志郎, 横山 宏樹

    糖尿病   54 ( Suppl.1 )   S - 179   2011.4

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  • IMTの規定因子とIMT変化へ影響する介入因子の検討

    猪苅 冬樹, 奥田 昌恵, 高橋 直穂, 菅野 咲子, 本庄 潤, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( Suppl.1 )   S - 120   2011.4

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  • 1,5AGと受診時血糖値、A1cの関連 食後血糖抑制剤使用を含めた検討

    今田 敦子, 菅野 咲子, 高橋 直穂, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( Suppl.1 )   S - 187   2011.4

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  • HbA1cと空腹時血糖値による糖尿病型の判定基準と臨床指標の比較(TOPICS)

    平安座 依子, 原 茂子, 齋藤 和美, 藤原 和哉, 辻 裕之, 児玉 暁, 謝 勲東, 島野 仁, 荒瀬 康司, 山田 信博, 小坂 樹徳, 曽根 博仁

    糖尿病   54 ( Suppl.1 )   S - 102   2011.4

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  • 採血不要の臨床指標による未診断糖尿病予測スコアリングシステムの開発(TOPICS)

    由澤 咲子, 平安座 依子, 原 茂子, 齋藤 和美, 飯田 薫子, 児玉 暁, 謝 勲東, 荒瀬 康司, 山田 信博, 小坂 樹徳, 曽根 博仁

    糖尿病   54 ( Suppl.1 )   S - 101   2011.4

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  • 生涯最大体重や20歳時の体重はその後の未診断糖尿病や前糖尿病状態の発症と関連する(TOPICS)

    齋藤 あき, 平安座 依子, 原 茂子, 齋藤 和美, 辻 裕之, 児玉 暁, 近藤 和雄, 荒瀬 康司, 山田 信博, 小坂 樹徳, 曽根 博仁

    糖尿病   54 ( Suppl.1 )   S - 108   2011.4

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  • PWVの改善に影響する介入因子の検討

    奥田 昌恵, 猪苅 冬樹, 高橋 直穂, 佐藤 舞菜見, 菅野 咲子, 本庄 潤, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( Suppl.1 )   S - 102   2011.4

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  • 【糖尿病診療においてよく出くわす疑問点と考慮のポイントupdate】 糖尿病症例に対するLDLコレステロール(C)管理基準値 現行のガイドライン(120/100mg/dl)でよいか?

    藤原 和哉, 曽根 博仁

    内分泌・糖尿病・代謝内科   32 ( 4 )   370 - 379   2011.4

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  • 当院における治療中断者の臨床像(第4報) 経済的理由により治療中断した2型糖尿病患者の臨床像

    菅原 歩美, 本橋 しのぶ, 曽根 博仁, 川井 紘一

    糖尿病   54 ( Suppl.1 )   S - 336   2011.4

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  • 妊娠時までのBMI変化と妊娠糖尿病発症リスクとの関連(TWC Study)

    谷内 洋子, 田中 康弘, 穴迫 唯衣, 西端 泉, 近藤 和雄, 松岡 隆, 島野 仁, 児玉 暁, 齋藤 和美, 曽根 博仁

    糖尿病   54 ( Suppl.1 )   S - 312   2011.4

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  • シタグリプチンの血糖改善効果は? 単剤投与、上乗せ、他剤交換の比較

    佐藤 舞菜見, 高橋 直穂, 今田 敦子, 鈴木 美佑希, 山田 大志郎, 本庄 潤, 曽根 博仁, 中村 公英, 横山 宏樹

    糖尿病   54 ( Suppl.1 )   S - 283   2011.4

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  • CT coronary angiography(CTA)による冠動脈不安定プラーク(VP)と関連する臨床指標に関する検討

    藤原 和哉, 鈴木 浩明, 佐藤 明, 大崎 芳典, 尾本 美代子, 豊崎 晶子, 平安座 依子, 児玉 暁, 斎藤 和美, 小林 和人, 矢藤 繁, 高橋 昭光, 山田 信博, 曽根 博仁, 島野 仁

    糖尿病   54 ( Suppl.1 )   S - 220   2011.4

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  • 茨城県央地区におけるシタグリプチン至適投与対象に関する検討について(中間報告)

    仲本 信也, 遅野井 健, 水谷 正一, 荷見 澄子, 曽根 博仁

    糖尿病   54 ( Suppl.1 )   S - 290   2011.4

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  • 2型糖尿病のインスリン導入率とインスリン導入予知因子の探索

    山下 りさ, 菅野 咲子, 高橋 直穂, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( Suppl.1 )   S - 288   2011.4

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  • 患者動向の10年間の推移

    畑中 麻梨恵, 菅野 咲子, 高橋 直穂, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( Suppl.1 )   S - 199   2011.4

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  • わが国における2型糖尿病患者の食事摂取の状況 Japan Diabetes Complication Study(JDCS)

    西垣 結佳子, 田中 司朗, 井藤 英喜, 田中 佐智子, 鎌田 智英実, 奥村 亮太, 堀川 千嘉, 片桐 あかね, 大橋 靖雄, 島野 仁, 赤沼 安夫, 山田 信博, 曽根 博仁, 吉村 幸雄

    糖尿病   54 ( Suppl.1 )   S - 190   2011.4

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  • 経口ブドウ糖負荷前・負荷後血糖の心血管疾患リスクの量的関係の解析(メタアナリシス)

    齋藤 和美, 児玉 曉, 堀川 千嘉, 伊部 陽子, 平澤 玲子, 谷内 洋子, 菅原 歩美, 小林 和人, 高橋 昭光, 島野 仁, 山田 信博, 曽根 博仁

    糖尿病   54 ( Suppl.1 )   S - 219   2011.4

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  • 眼科医のための知ってもらいたい糖尿病合併症 糖尿病大血管合併症の現状と課題

    曽根 博仁

    日本糖尿病眼学会誌   15   18 - 22   2011.3

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  • 生活習慣病の臨床エビデンス(第24回) 血清カリウム低値と2型糖尿病発症リスク

    平安座 依子, 原 茂子, 荒瀬 康司, 山田 信博, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   10 ( 2 )   284 - 287   2011.3

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  • 【糖尿病合併症の心血管疾患 focusすべき病態を識る】 診る 臨床現場での診断のポイント わが国の臨床疫学研究JDCSの成果 何を診るか?

    曽根 博仁

    Heart View   15 ( 3 )   224 - 228   2011.3

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  • Contribution of glimepiride to basal-prandial insulin therapy in patients with type 2 diabetes

    Hiroki Yokoyama, Hirohito Sone, Daishiro Yamada, Jun Honjo, Masakazu Haneda

    DIABETES RESEARCH AND CLINICAL PRACTICE   91 ( 2 )   148 - 153   2011.2

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    Aim: To investigate the efficacy of continuing glimepiride in combination with basal-prandial insulin therapy in type 2 diabetes.Methods: An open crossover study was performed with arms of discontinuation and continuation of glimepiride in 25 subjects with mean diabetes duration of 17 years and 5 years of insulin treatment combined with glimepiride plus metformin. At entry and at the end of each 3-month arm, meal tolerance tests were performed for measurements of blood glucose and C-peptide.Results: In terms of between-treatment differences (discontinuation vs. continuation arm of glimepiride) during meal tolerance tests performed at the ends of arms, significant increases in plasma glucose were seen on the discontinuation arm at 0-, 30-, and 60-min, while significant decreases in serum C-peptide were observed at 60- and 120-min. A1C values of the discontinuation arm significantly increased (from 6.6 +/- 0.6 at baseline to 7.7 +/- 0.8 at 3-months, p < 0.0001). Increases in A1C were closely correlated with decreases in area under the curve of meal-stimulated serum C-peptide (r = -0.61, p < 0.0001).Conclusions: Since endogenous insulin secretion is more physiological than subcutaneous insulin injection, continuing glimepiride may remain beneficial, partly through enhancing insulin secretion, in individuals with a long duration of diabetes and basal-prandial insulin therapy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2010.10.007

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  • Contribution of glimepiride to basal-prandial insulin therapy in patients with type 2 diabetes

    Hiroki Yokoyama, Hirohito Sone, Daishiro Yamada, Jun Honjo, Masakazu Haneda

    DIABETES RESEARCH AND CLINICAL PRACTICE   91 ( 2 )   148 - 153   2011.2

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    Aim: To investigate the efficacy of continuing glimepiride in combination with basal-prandial insulin therapy in type 2 diabetes.Methods: An open crossover study was performed with arms of discontinuation and continuation of glimepiride in 25 subjects with mean diabetes duration of 17 years and 5 years of insulin treatment combined with glimepiride plus metformin. At entry and at the end of each 3-month arm, meal tolerance tests were performed for measurements of blood glucose and C-peptide.Results: In terms of between-treatment differences (discontinuation vs. continuation arm of glimepiride) during meal tolerance tests performed at the ends of arms, significant increases in plasma glucose were seen on the discontinuation arm at 0-, 30-, and 60-min, while significant decreases in serum C-peptide were observed at 60- and 120-min. A1C values of the discontinuation arm significantly increased (from 6.6 +/- 0.6 at baseline to 7.7 +/- 0.8 at 3-months, p < 0.0001). Increases in A1C were closely correlated with decreases in area under the curve of meal-stimulated serum C-peptide (r = -0.61, p < 0.0001).Conclusions: Since endogenous insulin secretion is more physiological than subcutaneous insulin injection, continuing glimepiride may remain beneficial, partly through enhancing insulin secretion, in individuals with a long duration of diabetes and basal-prandial insulin therapy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2010.10.007

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  • 妊婦における耐糖能異常発症のリスクファクターの検討 妊娠初期空腹時インスリン値の測定意義 Tanaka Women's Clinic Study

    田中 康弘, 谷内 洋子, 曽根 博仁

    日本産科婦人科学会雑誌   63 ( 2 )   561 - 561   2011.2

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    Other Link: https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=446215

  • メタ解析からみた卵摂取と心血管疾患リスク上昇との関連性の考察

    児玉 暁, 齋藤 和美, 藤原 和哉, 小林 和人, 矢藤 繁, 高橋 昭光, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    日本内科学会雑誌   100 ( Suppl. )   208 - 208   2011.2

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  • 【糖尿病大血管症の最新医療】 わが国の糖尿病大血管症の現状

    曽根 博仁

    Pharma Medica   29 ( 2 )   9 - 15   2011.2

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  • 両側肺にsubpleural curvilinear shadowを認めた好酸球性肺炎の1例

    服部 一哉, 籠橋 克紀, 角田 義弥, 小林 克誠, 松田 洋祐, 木下 賢輔, 山本 昌良, 渋谷 正俊, 錦 健太, 佐藤 匡美, 千野 祐介, 黒田 裕久, 小林 裕幸, 曽根 博仁, 徳田 安春, 渡邊 重行, 佐藤 浩昭

    茨城県臨床医学雑誌   ( 46 )   12 - 12   2011.2

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  • 手根骨転移を来した肺腺癌の1例

    木下 賢輔, 佐藤 浩昭, 小林 克誠, 角田 義弥, 服部 一哉, 松田 洋祐, 山本 昌良, 渋谷 正俊, 錦 健太, 千野 裕介, 曽根 博仁, 小林 裕幸, 渡辺 重行, 佐藤 匡美, 黒田 裕久, 徳田 安春

    茨城県臨床医学雑誌   ( 46 )   6 - 6   2011.2

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  • DPP4製剤シタグリプチンの使用経験 単剤投与、上乗せ、他剤交換の比較

    佐藤 舞菜見, 高橋 直穂, 今田 敦子, 鈴木 美佑希, 山田 大志郎, 本庄 潤, 曽根 博仁, 中村 公英, 横山 宏樹

    糖尿病   54 ( 2 )   149 - 149   2011.2

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  • IMTの規定因子とIMT変化へ影響する介入因子の検討

    猪苅 冬樹, 奥田 昌恵, 高橋 直穂, 菅野 咲子, 本庄 潤, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( 2 )   139 - 139   2011.2

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  • PWVの改善に影響する介入因子の検討

    奥田 昌恵, 猪狩 冬樹, 高橋 直穂, 菅野 咲子, 本庄 潤, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( 2 )   139 - 139   2011.2

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  • 2型糖尿病のインスリン導入率とインスリン導入予知因子の探索

    山下 りさ, 菅野 咲子, 高橋 直穂, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( 2 )   147 - 147   2011.2

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  • 2型糖尿病におけるGFR低下とアルブミン尿進行の共通、独立した危険因子

    菅野 咲子, 高橋 直穂, 本庄 潤, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( 2 )   144 - 144   2011.2

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  • 食後血糖抑制剤による食後血糖と1,5AG、A1c、随時血糖の検討

    今田 敦子, 菅野 咲子, 高橋 直穂, 山田 大志朗, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( 2 )   139 - 139   2011.2

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  • 患者動向の10年間の推移

    畑中 麻梨恵, 菅野 咲子, 高橋 直穂, 本庄 潤, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   54 ( 2 )   138 - 138   2011.2

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  • Alcohol Consumption and Risk of Atrial Fibrillation A Meta-Analysis

    Satoru Kodama, Kazumi Saito, Shiro Tanaka, Chika Horikawa, Aki Saito, Yoriko Heianza, Yui Anasako, Yukako Nishigaki, Yoko Yachi, Kaoruko Tada Iida, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY   57 ( 4 )   427 - 436   2011.1

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    Objectives The purpose of this meta-analysis is to summarize the estimated risk of atrial fibrillation (AF) related to alcohol consumption.
    Background Results from observational studies examining the relationship between alcohol consumption and AF are inconsistent.
    Methods A systematic electronic search of Medline (January 1966 to December 2009) and Embase (January 1974 to December 2009) databases was conducted for studies using key words related to alcohol and AF. Studies were included if data on effect measures for AF associated with habitual alcohol intake were reported or could be calculated. The effect measures for AF for the highest versus lowest alcohol intake in individual studies were pooled with a variance-based method. Linear and spline regression analyses were conducted to quantify the relationship between alcohol intake and AF risk.
    Results Fourteen eligible studies were included in this meta-analysis. The pooled estimate of AF for the highest versus the lowest alcohol intake was 1.51 (95% confidence interval: 1.31 to 1.74). A linear regression model showed that the pooled estimate for an increment of 10 g per day alcohol intake was 1.08 (95% confidence interval: 1.05 to 1.10; R-2 = 0.43, p &lt; 0.001). A spline regression model also indicated that the AF risk increased with increasing levels of alcohol consumption.
    Conclusions Results of this meta-analysis suggest that not consuming alcohol is most favorable in terms of AF risk reduction. (J Am Coll Cardiol 2011; 57: 427-36) (C) 2011 by the American College of Cardiology Foundation

    DOI: 10.1016/j.jacc.2010.08.641

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  • Alcohol Consumption and Risk of Atrial Fibrillation A Meta-Analysis

    Satoru Kodama, Kazumi Saito, Shiro Tanaka, Chika Horikawa, Aki Saito, Yoriko Heianza, Yui Anasako, Yukako Nishigaki, Yoko Yachi, Kaoruko Tada Iida, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY   57 ( 4 )   427 - 436   2011.1

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    Objectives The purpose of this meta-analysis is to summarize the estimated risk of atrial fibrillation (AF) related to alcohol consumption.
    Background Results from observational studies examining the relationship between alcohol consumption and AF are inconsistent.
    Methods A systematic electronic search of Medline (January 1966 to December 2009) and Embase (January 1974 to December 2009) databases was conducted for studies using key words related to alcohol and AF. Studies were included if data on effect measures for AF associated with habitual alcohol intake were reported or could be calculated. The effect measures for AF for the highest versus lowest alcohol intake in individual studies were pooled with a variance-based method. Linear and spline regression analyses were conducted to quantify the relationship between alcohol intake and AF risk.
    Results Fourteen eligible studies were included in this meta-analysis. The pooled estimate of AF for the highest versus the lowest alcohol intake was 1.51 (95% confidence interval: 1.31 to 1.74). A linear regression model showed that the pooled estimate for an increment of 10 g per day alcohol intake was 1.08 (95% confidence interval: 1.05 to 1.10; R-2 = 0.43, p &lt; 0.001). A spline regression model also indicated that the AF risk increased with increasing levels of alcohol consumption.
    Conclusions Results of this meta-analysis suggest that not consuming alcohol is most favorable in terms of AF risk reduction. (J Am Coll Cardiol 2011; 57: 427-36) (C) 2011 by the American College of Cardiology Foundation

    DOI: 10.1016/j.jacc.2010.08.641

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  • 脂質異常症診断基準の臨床的意義 男性における体重管理指標との関連

    阿隅 美保子, 山口 龍生, 斎藤 和美, 児玉 暁, 松井 博滋, 宮澤 英充, 飯田 薫子, 鈴木 恵美子, 近藤 和雄, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   55 - 55   2011.1

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  • 卵の摂取量と心血管疾患リスクとの関連

    堀川 千嘉, 児玉 暁, 齋藤 あき, 平安座 依子, 西垣 結佳子, 穴迫 唯衣, 伊部 陽子, 平澤 玲子, 谷内 陽子, 齋藤 和美, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   53 - 53   2011.1

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  • 生活習慣病に対する食育指導について 現代日本の肥満とやせを中心に

    曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   31 - 31   2011.1

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  • 【糖尿病における動脈硬化治療戦略 大規模臨床研究から学ぶ】 日本人2型糖尿病患者における大血管合併症の疫学

    曽根 博仁, 山田 信博, 赤沼 安夫

    糖尿病   54 ( 1 )   2 - 5   2011.1

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    DOI: 10.11213/tonyobyo.54.2

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  • 喫煙状況と無症候性脳梗塞との関連性 脳ドック受診者における横断的検討

    阿隅 美保子, 山口 龍生, 齋藤 和美, 児玉 暁, 松井 博滋, 宮澤 英充, 飯田 薫子, 鈴木 恵美子, 近藤 和雄, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   66 - 66   2011.1

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  • 【メタボリックシンドローム(第2版) 基礎・臨床の最新知見】 疫学 コホート研究から得られたメタボリックシンドロームに関する知見 疫学研究からみた糖尿病とメタボリックシンドロームとの関係

    曽根 博仁

    日本臨床   69 ( 増刊1 メタボリックシンドローム )   93 - 100   2011.1

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  • 妊娠時までのBMI変化と妊娠中の耐糖能異常発症リスクとの関連(TWC Study)

    谷内 洋子, 田中 康弘, 穴迫 唯衣, 西端 泉, 赤松 利恵, 近藤 和雄, 鈴木 恵美子, 松岡 隆, 齊藤 和美, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   56 - 56   2011.1

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  • 過去の体重歴は未診断糖尿病や前糖尿病状態を発見する指標として有用である TOPICS

    平安座 依子, 原 茂子, 齋藤 和美, 辻 裕之, 児玉 暁, 謝 勲東, 荒瀬 康司, 山田 信博, 小坂 樹徳, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   55 - 55   2011.1

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  • 採血不要の臨床指標による未診断糖尿病スクリーニングのための基礎的検討 TOPICS

    平安座 依子, 原 茂子, 齋藤 和美, 辻 裕之, 児玉 暁, 謝 勲東, 荒瀬 康司, 山田 信博, 小坂 樹徳, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   59 - 59   2011.1

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  • HbA1cと空腹時血糖値それぞれにより糖尿病型と判定された者の特徴 TOPICS

    平安座 依子, 原 茂子, 齋藤 和美, 藤原 和哉, 辻 裕之, 児玉 暁, 謝 勲東, 荒瀬 康司, 山田 信博, 小坂 樹徳, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   57 - 57   2011.1

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  • 糖尿病 臨床分野での進歩 日本人の糖尿病血管合併症

    曽根 博仁

    Annual Review糖尿病・代謝・内分泌   2011   58 - 66   2011.1

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    糖尿病の有病率や病態が人種や国によって異なるように,合併症の発症率やリスクファクターについても地域・人種差がある.糖尿病診療の最終目標は合併症予防であり,合併症の有病率,発症率,リスクファクター,治療効果などは,治療対策上の重要な基礎資料となる.従来の欧米の糖尿病臨床疫学研究は,主に白人,黒人,ヒスパニック系患者などが対象で,世界の糖尿病人口の半数以上を占めるアジア人患者,特に東アジア人患者を含む研究は少なかった.それら欧米の研究結果が日本人糖尿病患者にあてはまるとは限らず,可能な限り日本人のエビデンスを確立する必要があるが,近年は,わが国における合併症のリスクファクターや治療効果に関する研究も充実しつつある. (著者抄録)

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  • 生活習慣病の臨床エビデンス(第23回) 飲酒と心房細動リスクの関連

    児玉 暁, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   10 ( 1 )   144 - 147   2011.1

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  • 産後のうつ症状と妊娠期の生活習慣との関連(Tanaka Women's Clinic Study)

    穴迫 唯衣, 田中 康弘, 谷内 洋子, 西端 泉, 安原 眞知子, 小林 香織, 鈴木 恵美子, 近藤 和雄, 赤松 利恵, 飯田 薫子, 児玉 暁, 齋藤 和美, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   37   82 - 82   2011.1

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  • 診断に難渋した低血糖の一例

    向山和彦, 藤原和哉, 宜保英彦, 小林和人, 高橋昭光, 矢藤繁, 鈴木浩明, 島野仁, 山田信博, 曽根博仁

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   11th   52   2011

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  • 自覚症状に乏しく低血糖による意識障害で診断に至ったACTH単独欠損症の一例

    斎藤祥子, 藤原和哉, 宜保英彦, 小林和人, 高橋昭光, 矢藤繁, 鈴木浩明, 島野仁, 山田信博, 曽根博仁

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   11th   44   2011

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  • 痙性斜頸を契機に発見されたバセドウ病の一例

    宜保英彦, 藤原和哉, 小林和人, 高橋昭光, 矢藤繁, 鈴木浩明, 島野仁, 山田信博, 曽根博仁

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   11th   63   2011

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  • うつ病と鑑別が困難であり診断に長期間を要したGitelman症候群の一例

    志鎌明人, 藤原和哉, 宜保英彦, 小林和人, 高橋昭光, 矢藤繁, 鈴木浩明, 島野仁, 山田信博, 曽根博仁

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   11th   60   2011

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  • 原発性高脂血症に関する調査研究 2型糖尿病における冠動脈不安定プラークと脂質パラメーターとの関連

    鈴木浩明, 藤原和哉, 佐藤明, 曽根博仁

    原発性高脂血症に関する調査研究 平成22年度 総括研究報告書   81 - 84   2011

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  • Comparison of Education-Only versus Group-Based Intervention in Promoting Weight Loss: A Randomised Controlled Trial Reviewed

    Yoshio Nakata, Masafumi Okada, Koichi Hashimoto, Yoshinori Harada, Hirohito Sone, Kiyoji Tanaka

    Obesity Facts   4 ( 3 )   222 - 228   2011

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    Aim: To compare the effectiveness of education-only versus group-based intervention in promoting weight loss. Methods: Between April and October 2009, a 6-month randomised controlled trial was conducted at Mito Kyodo General Hospital in Japan (UMIN000001259). The participants were 188 overweight adults (145 women, 43 men) aged 40-65 years. They were randomly assigned to one of three groups: control, moderate or intensive intervention. A single motivational lecture was provided to all three groups, educational materials (textbooks, notebooks, and a pedometer) to the moderate and intensive intervention groups, and group-based support to the intensive intervention group. Amount of weight loss was the primary outcome measure. Secondary outcome measures were components of metabolic syndrome. Results: Mean +/- SD weight loss of participants in the control, moderate and intensive intervention groups was 2.9 +/- 4.1, 4.7 +/- 4.0 and 7.7 +/- 4.1 kg, respectively. Bonferroni post-hoc comparisons revealed all between-group differences to be significant (p &lt; 0.05). Waist circumference decreased in the intensive intervention group more than in the other groups, whereas no significant differences were observed in the other secondary outcome measures. Conclusion: Education-only intervention is a cost-effective method to promote weight loss. Adding group-based intervention further promotes weight loss.

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  • 日本女性のBMIとやせの現状

    曽根 博仁, 菅原 歩美, 谷内 洋子

    茨城県母性衛生学会誌   ( 29 )   19 - 24   2011

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  • Flow-mediated dilation is associated with microalbuminuria independent of cardiovascular risk factors in type 2 diabetes: Interrelations with arterial thickness and stiffness

    Hiroki Yokoyama, Hirohito Sone, Kazumi Saito, Daishiro Yamada, Jun Honjo, Masakazu Haneda

    Journal of Atherosclerosis and Thrombosis   18 ( 9 )   744 - 752   2011

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    Aims: To investigate whether endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is associated with urinary albumin excretion (UAE) and is interrelated with carotid intima- media thickness (IMT) and pulse-wave velocity (PWV) in type 2 diabetes. Methods: We measured FMD, IMT and PWV in 158 subjects with type 2 diabetes (normo- 49, micro- 64, macroalbuminuria 45), explored the determinants of FMD, and analyzed the relationship of FMD with traditional cardiovascular risk factors according to IMT and PWV levels. Results: Microalbuminuria was significantly associated with lower FMD, higher IMT and higher PWV compared to normoalbuminuria (p&lt
    0.001 for all). FMD was significantly correlated with IMT and PWV, and also with traditional risk factors, UAE, glomerular filtration rate, diabetic retinopathy, and neuropathy. Multivariate regression analysis revealed that UAE remained a significant determinant of FMD independent of traditional risk factors, metabolic control, and renal function. The relationship of FMD with IMT and PWV was less pronounced in subjects with increased IMT and PWV. Conclusions: In individuals with type 2 diabetes, FMD is impaired in subjects with microalbuminuria and is associated with IMT and PWV only when these values are not increased, i.e., at an early stage of atherosclerosis.

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  • Flow-mediated dilation is associated with microalbuminuria independent of cardiovascular risk factors in type 2 diabetes: Interrelations with arterial thickness and stiffness

    Hiroki Yokoyama, Hirohito Sone, Kazumi Saito, Daishiro Yamada, Jun Honjo, Masakazu Haneda

    Journal of Atherosclerosis and Thrombosis   18 ( 9 )   744 - 752   2011

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    Aims: To investigate whether endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is associated with urinary albumin excretion (UAE) and is interrelated with carotid intima- media thickness (IMT) and pulse-wave velocity (PWV) in type 2 diabetes. Methods: We measured FMD, IMT and PWV in 158 subjects with type 2 diabetes (normo- 49, micro- 64, macroalbuminuria 45), explored the determinants of FMD, and analyzed the relationship of FMD with traditional cardiovascular risk factors according to IMT and PWV levels. Results: Microalbuminuria was significantly associated with lower FMD, higher IMT and higher PWV compared to normoalbuminuria (p&lt
    0.001 for all). FMD was significantly correlated with IMT and PWV, and also with traditional risk factors, UAE, glomerular filtration rate, diabetic retinopathy, and neuropathy. Multivariate regression analysis revealed that UAE remained a significant determinant of FMD independent of traditional risk factors, metabolic control, and renal function. The relationship of FMD with IMT and PWV was less pronounced in subjects with increased IMT and PWV. Conclusions: In individuals with type 2 diabetes, FMD is impaired in subjects with microalbuminuria and is associated with IMT and PWV only when these values are not increased, i.e., at an early stage of atherosclerosis.

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  • 原因究明に難渋した遷延性低血糖の一例

    藤原 和哉, 宜保 英彦, 小林 和人, 高橋 昭光, 矢藤 繁, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    日本内分泌学会雑誌   86 ( 3 )   724 - 724   2010.12

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  • 痙性斜頸を合併したBasedow病の一例

    宜保 英彦, 藤原 和哉, 小林 和人, 高橋 昭光, 矢藤 繁, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    日本内分泌学会雑誌   86 ( 3 )   727 - 727   2010.12

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  • Comparison of Lipid Parameters as a Predictor of Cardiovascular Disease and Effects of Low Dose Pravastatin in Japanese Patients With and Without Diabetes Mellitus.

    Hirohito Sone, Rimei Nishimura, Tomoko Nakagami, Yasuo Ohashi, Naoko Tajima

    CIRCULATION   122 ( 21 )   2010.11

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  • 【肥満と漢方】 日本人の肥満の特徴

    菅原 歩美, 曽根 博仁

    漢方と最新治療   19 ( 4 )   269 - 279   2010.11

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  • 【糖尿病治療の最前線】 糖尿病の治療 食事・運動療法と生活習慣の改善

    曽根 博仁

    カレントテラピー   28 ( 11 )   1008 - 1013   2010.11

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  • 【糖尿病診療の将来展望 10 Topics】 動脈硬化を克服する 現状と将来展望

    藤原 和哉, 曽根 博仁

    糖尿病診療マスター   8 ( 6 )   613 - 621   2010.11

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    DOI: 10.11477/mf.1415101114

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  • 日本人糖尿病患者の特徴と病態に関する臨床疫学的研究

    曽根 博仁

    糖尿病   53 ( 11 )   791 - 794   2010.11

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    DOI: 10.11213/tonyobyo.53.791

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  • 【αグルコシダーゼ阻害薬】 αグルコシダーゼ阻害薬の特徴と種類、食後血糖のエビデンス

    藤原 和哉, 曽根 博仁

    糖尿病の最新治療   2 ( 1 )   6 - 15   2010.11

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    αグルコシダーゼ阻害薬は、上部小腸からの炭水化物の吸収を遅らせ、食後血糖値の上昇を抑制する薬物である。単独投与において低血糖の頻度が低く、体重増加を来しにくいという特性を持ち、他の糖尿病治療薬との併用効果もあり、幅広い使い方が可能である。さらに、食後高血糖を是正することにより2型糖尿病発症抑制や、心血管疾患を抑制することも報告されている。以前より食後高血糖が心血管疾患の危険因子である可能性が指摘されてきたが、24時間持続血糖モニタリングの普及にて食後血糖を含めた1日の血糖変動の測定が可能となり、今後は低血糖を回避するとともに、食後高血糖を意識したきめ細かい血糖コントロールを行うことが重要となる。本稿では、αグルコシダーゼ阻害薬の種類と特徴、食後血糖のエビデンスについて述べる。(著者抄録)

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  • 【高血圧の管理と脳卒中】 生活習慣と脳卒中予防の関係は? 生活習慣を改善することで脳卒中を予防することはできますか?

    曽根 博仁, 山田 信博

    Q&Aでわかる肥満と糖尿病   9 ( 6 )   918 - 919   2010.11

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  • 【糖尿病性細小血管症(第2版) 発症・進展制御の最前線】 糖尿病性細小血管症の定義、疫学、診断 糖尿病性細小血管症の本邦における疫学 欧米との比較

    曽根 博仁

    日本臨床   68 ( 増刊9 糖尿病性細小血管症 )   13 - 20   2010.11

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  • 糖尿病と脳卒中 疫学の面から予防法を探る

    曽根 博仁

    糖尿病合併症   24 ( Suppl.1 )   55 - 55   2010.10

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  • 【多リスク時代の新しいストラテジー トータル血管マネージメント】 動脈硬化の抑制および心血管疾患の予防を目ざした生活習慣改善のエビデンス

    児玉 暁, 曽根 博仁

    Mebio   27 ( 10 )   46 - 55   2010.10

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  • 【糖尿病診療2010】 糖尿病へのアプローチ 糖尿病発症予防のために ライフスタイルの是正

    曽根 博仁

    日本医師会雑誌   139 ( 特別2 )   S90 - S93   2010.10

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  • 臨床現場が求めるHbA1c基準値

    平安座 依子, 曽根 博仁

    検査と技術   38 ( 11 )   1108 - 1111   2010.10

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    DOI: 10.11477/mf.1543102974

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  • 【糖尿病診療2010】 糖尿病対策 JDCS

    曽根 博仁, 山田 信博

    日本医師会雑誌   139 ( 特別2 )   S322 - S324   2010.10

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  • 【糖尿病の血管病変を再考する】 糖尿病血管合併症の疫学

    曽根 博仁

    脈管学   50 ( 5 )   523 - 531   2010.10

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    糖尿病の血管合併症は、網膜症、腎症、神経障害といった細小血管合併症と、冠動脈疾患や脳卒中、末梢動脈疾患などの動脈硬化性疾患いわゆる大血管合併症に大別される。糖尿病性網膜症、腎症、神経障害および大血管合併症の有病率・発症率と危険因子について概説した。血管合併症の発症パターンや危険因子には地域差・人種差がみられるため、日本人の治療を考える上で、日本人の大規模前向きデータのさらなる蓄積が必要である。

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  • アジア人における朝食欠食と肥満リスクの関係のメタ分析

    堀川千嘉, 児玉暁, 西垣結佳子, 齋藤あき, 穴迫唯衣, 平安座依子, 平澤玲子, 島野仁, 齋藤和美, 曽根博仁

    栄養学雑誌   68 ( 5 Supplement )   305   2010.9

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  • 「地中海食」に関するインターネット情報のクオリティ評価

    平澤玲子, 西垣結佳子, 平安座依子, 伊部陽子, 飯田薫子, 近藤和雄, 島野仁, 児玉暁, 斎藤和美, 曽根博仁

    栄養学雑誌   68 ( 5 Supplement )   305   2010.9

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  • 大学生の食物摂取状況および食に関する知識・態度・行動等の実態調査

    伊部陽子, 飯島和子, 平安座依子, 穴迫唯衣, 齋藤あき, 齋藤和美, 児玉暁, 曽根博仁

    栄養学雑誌   68 ( 5 Supplement )   232   2010.9

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  • 【ここが問題 若年女性のやせ・肥満】 若年女性のやせ願望の実態とその問題点

    菅原 歩美, 曽根 博仁

    臨床婦人科産科   64 ( 9 )   1263 - 1267   2010.9

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  • インターネットによる生活習慣指導の肥満に対する効果の定量的検討

    児玉 暁, 斉藤 和美, 堀川 千嘉, 谷口 絵里香, 斉藤 あき, 平安座 依子, 西垣 結佳子, 穴迫 唯衣, 菅原 歩美, 戸塚 久美子, 平澤 玲子, 阿隅 美保子, 牧 美保, 谷内 洋子, 伊部 陽子, 曽根 博仁

    肥満研究   16 ( Suppl. )   123 - 123   2010.9

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  • 慢性合併症の臨床(糖尿病合併症のエビデンス) Japan Diabetes Complications Study(JDCS)

    曽根 博仁

    糖尿病学の進歩   ( 44 )   338 - 343   2010.9

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  • 【禁煙支援と歯周病予防】

    曽根 博仁, 中村 正和, 稲垣 幸司

    Q&Aでわかる肥満と糖尿病   9 ( 5 )   659 - 675   2010.9

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  • 【禁煙支援と歯周病予防】 喫煙と合併症の関係は? 糖尿病患者が喫煙するとどんな合併症になりやすいですか

    齋藤 和美, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   9 ( 5 )   713 - 714   2010.9

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  • 肝細胞癌術後の慢性C型肝炎に対しインターフェロン施行後、1型糖尿病を発症した1例

    小俣 勝哉, 浅野 康治郎, 鈴木 浩明, 高橋 昭光, 小林 和人, 矢藤 繁, 曽根 博仁, 島野 仁, 山田 信博

    糖尿病   53 ( 8 )   647 - 647   2010.8

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  • 生活習慣病の臨床エビデンス(第20回) 脂質パラメータの特長と最近の研究動向 心血管イベント発症予測能の比較から

    阿隅 美保子, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   9 ( 4 )   623 - 626   2010.7

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  • 【運動と生活習慣病のかかわりにせまる】 運動と糖尿病のかかわりにせまる 糖尿病の一次予防・二次予防における身体活動・運動の意義

    穴迫 唯衣, 曽根 博仁

    Life Style Medicine   4 ( 3 )   197 - 203   2010.7

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    糖尿病の蔓延が深刻化する近年、その一次予防・二次予防における運動の役割が注目され、運動療法の効果に関するエビデンスも増えてきた。運動は、インスリン抵抗性を改善し、良好な血糖コントロールの維持に貢献する。さらに、薬物療法より副作用や費用も少なく、精神的な面も含むQOL改善などの効果も期待できる。このような効果や必要性が理解されていても、臨床現場における運動指導は十分とはいえず、運動療法教室などを実施している施設もわずかである。本稿では最近の研究結果から、身体活動の増加、歩行を含む有酸素運動や、最近注目を集めているレジスタンス運動の意義、生活介入などの効果を、一次予防と二次予防に分けて概説する。(著者抄録)

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  • 【糖尿病合併症とその治療に関するエポックメーキングトピックスの展開】 日本人糖尿病患者の合併症についての長期研究JDCSは何を明らかにしてきたか

    曽根 博仁

    糖尿病診療マスター   8 ( 4 )   385 - 389   2010.7

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    DOI: 10.11477/mf.1415101072

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  • Serum Triglyceride Level Is the Strongest Predictor of Coronary Heart Disease (CHD) in Japanese Women with Type 2 Diabetes. The Japan Diabetes Complications Study (JDCS)

    Hirohito Sone, Sachiko Tanaka, Shiro Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shun Ishibashi, Shigehiro Katayama, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES   59   A223 - A223   2010.6

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  • Fasting Insulin Level in the First Trimester Is a More Sensitive Predictor of Glucose Intolerance in Later Pregnancy Than the Fasting Glucose Level in Japanese Pregnant Women: Tanaka Women&apos;s Clinic Study

    Yoko Yachi, Yasuhiro Tanaka, Yui Anasako, Ayumi Sugawara, Izumi Nishibata, Machiko Yasuhara, Kaori Kobayashi, Hirohito Sone

    DIABETES   59   A509 - A509   2010.6

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  • Association between Sleep Duration and Diabetes Control Status among Japanese Men and Women with Type 2 Diabetes: The Japan Diabetes Clinical Data Management (JDDM) Study

    Aki Saito, Yukako Nishigaki, Morifumi Yanagisawa, Koichi Kawai, Nobuichi Kuribayashi, Hiroki Yokoyama, Hidekatsu Sugimoto, Mariko Oishi, Takako Wada, Koichi Iwasaki, Noriharu Yagi, Fuminobu Okuguchi, Kazuhiro Miyazawa, Keiko Arai, Kazumi Saito, Hirohito Sone

    DIABETES   59   A513 - A513   2010.6

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  • Smoking Cessation Can Prevent the Development of Type 2 Diabetes (T2DM) Independent of a History of Heavy Smoking:Toranomon Hospital Health Management Center Study (TOPICS)

    Yoriko Heianza, Kazumi Saito, Kumiko Totsuka, Chika Horikawa, Satoru Kodama, Shiun Dong Hsieh, Shigeko Hara, Yasuji Arase, Kinori Kosaka, Hirohito Sone

    DIABETES   59   A294 - A294   2010.6

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  • Insulin Therapy Does Not Adversely Affect Diabetes-Specific Quality of Life (dsQOL) When Glycemic Control Is Good in Japanese Patients with Type 2 Diabetes: Japan Diabetes Clinical Data Management (JDDM) Study

    Yukako Nishigaki, Aki Saito, Mariko Oishi, Atsuyoshi Yuhara, Hidekatsu Sugimoto, Koichi Kawai, Hiroki Yokoyama, Noriharu Yagi, Akira Okada, Koichi Iwasaki, Kazuhiro Miyazawa, Fuminobu Okuguchi, Fumihiko Dake, Kazumi Saito, Hirohito Sone

    DIABETES   59   A517 - A517   2010.6

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  • Simple Self-Report Questions on Behavioral or Psychological Symptoms Can Effectively Predict Future Type2 Diabetes (T2DM): Toranomon Hospital Health Management Center Study (TOPICS)

    Yoriko Heianza, Yukako Nishigaki, Kazumi Saito, Kumiko Totsuka, Satoru Kodama, Hiroshi Tsuji, Shigeko Hara, Yasuji Arase, Nobuhiro Yamada, Kinori Kosaka, Hirohito Sone

    DIABETES   59   A114 - A114   2010.6

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  • Are serum cholesterol levels associated with silent brain infarcts? The Seiryo Clinic Study

    Mihoko Asumi, Tatsuo Yamaguchi, Kazumi Saito, Satoru Kodama, Hidemitsu Miyazawa, Hiroshige Matsui, Emiko Suzuki, Hiroshi Fukuda, Hirohito Sone

    ATHEROSCLEROSIS   210 ( 2 )   674 - 677   2010.6

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    Objective: High levels of serum cholesterol are associated with the risk of stroke. However, the association of serum cholesterol with silent brain infarcts (SBIs) is unclear. We investigated the association between SBI and various clinical factors.
    Methods: We conducted a cross-sectional study that included 324 apparently healthy Japanese men(mean age 53.8 +/- 9.2 years). Combinations of three types of scan (T1-weighted, T2-weighted and FLAIR images) were used to detect and discriminate SBI.
    Results: Serum cholesterol was significantly associated with SBI [total cholesterol, odds ratio (OR) 3.75 (95% confidence interval (CI) 1.45-9.68); LDL-cholesterol, OR 2.54 (95% CI 1.03-6.27), and non-HDL-cholesterol, OR 2.54 (95% CI 1.03-6.27)] after adjustment for age, smoking status, serum triglycerides, maximal-intima-media thickness, obesity, hypertension, diabetes mellitus, hyperuricemia, coronary heart disease and lipid-lowering agent use.
    Conclusion: Our cross-sectional data suggest that serum cholesterol levels are associated with SBI independently of known confounders. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.atherosclerosis.2010.01.008

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  • 【運動基準づくりへの新エビデンス】 生活習慣病発症リスクと最大酸素摂取量

    児玉 暁, 曽根 博仁

    体育の科学   60 ( 6 )   379 - 383   2010.6

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  • Are serum cholesterol levels associated with silent brain infarcts? The Seiryo Clinic Study

    Mihoko Asumi, Tatsuo Yamaguchi, Kazumi Saito, Satoru Kodama, Hidemitsu Miyazawa, Hiroshige Matsui, Emiko Suzuki, Hiroshi Fukuda, Hirohito Sone

    ATHEROSCLEROSIS   210 ( 2 )   674 - 677   2010.6

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    Objective: High levels of serum cholesterol are associated with the risk of stroke. However, the association of serum cholesterol with silent brain infarcts (SBIs) is unclear. We investigated the association between SBI and various clinical factors.
    Methods: We conducted a cross-sectional study that included 324 apparently healthy Japanese men(mean age 53.8 +/- 9.2 years). Combinations of three types of scan (T1-weighted, T2-weighted and FLAIR images) were used to detect and discriminate SBI.
    Results: Serum cholesterol was significantly associated with SBI [total cholesterol, odds ratio (OR) 3.75 (95% confidence interval (CI) 1.45-9.68); LDL-cholesterol, OR 2.54 (95% CI 1.03-6.27), and non-HDL-cholesterol, OR 2.54 (95% CI 1.03-6.27)] after adjustment for age, smoking status, serum triglycerides, maximal-intima-media thickness, obesity, hypertension, diabetes mellitus, hyperuricemia, coronary heart disease and lipid-lowering agent use.
    Conclusion: Our cross-sectional data suggest that serum cholesterol levels are associated with SBI independently of known confounders. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.atherosclerosis.2010.01.008

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  • 生活習慣病の臨床エビデンス(第19回) 無症候性脳梗塞と血清コレステロール値との関係

    阿隅 美保子, 山口 龍生, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   9 ( 3 )   465 - 468   2010.5

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  • 【糖尿病大血管症 エビデンスに基づく発症・進展制御】 我が国における糖尿病大血管症発症・進展制御のエビデンス 発症・進展予防に対する介入試験からの知見 日本人2型糖尿病患者における血管合併症の発症予防と進展抑制に関する研究:JDCS

    曽根 博仁, 山田 信博

    日本臨床   68 ( 5 )   865 - 871   2010.5

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    Other Link: http://search.jamas.or.jp/link/ui/2010166098

  • 無症候性脳梗塞と血清コレステロール値に関する横断的検討

    阿隅 美保子, 山口 龍生, 鶉橋 弘子, 古川 豊, 松井 博滋, 宮澤 英充, 鈴木 恵美子, 近藤 和雄, 福田 寛, 齋藤 和美, 児玉 暁, 曽根 博仁

    成人病と生活習慣病   40 ( 5 )   567 - 567   2010.5

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  • アルコール摂取と心房細動リスクの関連性についてのメタ解析

    児玉 暁, 齋藤 和美, 松坂 賢, 小林 和人, 矢藤 繁, 高橋 昭光, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    成人病と生活習慣病   40 ( 5 )   566 - 566   2010.5

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  • 2型糖尿病患者における就寝・起床時刻と血糖コントロールの関連についての探索的検討

    齋藤 あき, 西垣 結佳子, 齋藤 和美, 児玉 暁, 曽根 博仁, 川井 紘一, 大石 まり子, 杉本 英克, 栗林 伸一, 和田 崇子

    成人病と生活習慣病   40 ( 5 )   583 - 583   2010.5

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  • 大脳深部白質高信号所見(DSWMH)の年齢別出現状況と頸動脈硬化との関連

    阿隅 美保子, 山口 龍生, 鶉橋 弘子, 古川 豊, 松井 博滋, 宮澤 英充, 鈴木 恵美子, 近藤 和雄, 福田 寛, 齋藤 和美, 児玉 暁, 曽根 博仁

    成人病と生活習慣病   40 ( 5 )   568 - 568   2010.5

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  • インターネットを用いた生活習慣指導の肥満改善効果のメタ解析

    谷口 絵里香, 児玉 暁, 齋藤 和美, 堀川 千嘉, 齋藤 あき, 平安座 依子, 西垣 結佳子, 穴迫 唯衣, 谷内 洋子, 牧 美保, 平澤 玲子, 曽根 博仁, 鈴木 恵美子, 近藤 和雄

    成人病と生活習慣病   40 ( 5 )   546 - 546   2010.5

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  • 血清カリウム低値は2型糖尿病発症の新たな独立した危険因子である Toranomon Hospital Health Management Center Study 1(TOPICS-1)

    平安座 依子, 齋藤 和美, 戸塚 久美子, 児玉 暁, 山田 信博, 曽根 博仁, 原 茂子, 荒瀬 康司, 辻 裕之, 謝 勲東, 小坂 樹徳

    成人病と生活習慣病   40 ( 5 )   545 - 545   2010.5

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  • 2型糖尿病患者における診療の主観的説明理解度と心理的ストレスとの関連

    西垣 結佳子, 齋藤 あき, 齋藤 和美, 児玉 暁, 曽根 博仁, 横山 宏樹, 川井 紘一, 大石 まり子, 杉本 英克

    成人病と生活習慣病   40 ( 5 )   550 - 551   2010.5

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  • 朝食欠食と肥満リスクとの関係に関するメタ解析

    堀川 千嘉, 児玉 暁, 齋藤 和美, 平澤 玲子, 伊部 陽子, 谷内 洋子, 平安座 依子, 斉藤 あき, 菅原 歩美, 戸塚 久美子, 阿隅 美保子, 曽根 博仁, 鈴木 恵美子, 近藤 和雄

    成人病と生活習慣病   40 ( 5 )   546 - 547   2010.5

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  • 動脈硬化の予防と治療 動脈硬化の予防と治療 糖尿病

    曽根 博仁

    日本老年医学会雑誌   47 ( Suppl. )   7 - 7   2010.5

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  • 【睡眠と生活習慣病】 睡眠と脂質異常症

    齋藤 あき, 曽根 博仁

    成人病と生活習慣病   40 ( 4 )   441 - 445   2010.4

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    睡眠時間は、2型糖尿病の発症、肥満、高血圧をはじめとした生活習慣病やCVD(心血管疾患)に関連し、生活習慣病の発症に影響する重要な因子として注目されている。睡眠時間と脂質異常症との関連については、報告は増加しつつあるが、まだ一致した見解は得られていない。しかし、睡眠不足状態が食欲調整システムに影響し、過食や肥満などを通じて、脂質代謝に悪影響を及ぼしている可能性が考えられる。睡眠時呼吸障害をはじめとする睡眠の質の低下も脂質異常症に関連することを示唆する報告が増えており、睡眠時無呼吸症候群の治療や睡眠の質の評価も重要視する必要がある。睡眠は、脂質異常症を含む生活習慣病の発症、増悪に影響を与えうるため、臨床現場でも睡眠時間と質を考慮した睡眠習慣の指導が重視されるべきである。(著者抄録)

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  • 【喫煙と生活習慣病のかかわりを探る】 喫煙はCKDにどのようなかかわりをもっているか?

    齋藤 和美, 曽根 博仁

    Life Style Medicine   4 ( 2 )   147 - 155   2010.4

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    喫煙が心血管系疾患、呼吸器疾患や多くの悪性腫瘍のリスクを上昇させ、健康や寿命に悪影響を与えることは広く知られている。CKDについても、喫煙は、高血圧・糖尿病などCKDの危険因子を発症・増悪させることが知られていたが、喫煙そのものもCKDの発症・進行の両方の独立した危険因子でもあることが、観察研究などで明らかになりつつある。喫煙により腎障害をきたすメカニズムはさまざまで、いまだ不明な部分も多い。また、禁煙が腎障害に好影響を与え得るかも十分に解析されてはいない。しかし、CKD患者においても、喫煙は心血管障害の危険因子であり、いずれにしても禁煙を積極的に勧めるべきである。(著者抄録)

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  • 2型糖尿病患者における睡眠時間と糖尿病コントロールとの関連

    齋藤 あき, 川井 紘一, 柳澤 守文, 栗林 伸一, 横山 宏樹, 杉本 英克, 大石 まり子, 和田 崇子, 屋宜 宣治, 宮澤 一裕, 岩崎 皓一, 新井 桂子, 児玉 暁, 曽根 博仁

    糖尿病   53 ( Suppl.1 )   S - 115   2010.4

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  • 2型糖尿病に認められる脂肪肝改善率と奏功因子の探索

    藤井 恵理, 佐藤 舞菜見, 辻 景子, 田川 聖子, 宮腰 千晴, 高橋 直穂, 山田 大志郎, 曽根 博仁, 本庄 潤, 中村 公英, 横山 宏樹

    糖尿病   53 ( Suppl.1 )   S - 109   2010.4

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  • eGFR値、アルブミン尿から見た心血管イベントと早期動脈硬化症指標

    佐藤 舞菜見, 高橋 直穂, 菅野 咲子, 横田 友紀, 辻 景子, 田川 聖子, 本庄 潤, 山田 大志郎, 曽根 博仁, 中村 公英, 横山 宏樹

    糖尿病   53 ( Suppl.1 )   S - 305   2010.4

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  • インスリン療法が心理的負担に与える影響およびそれに関連する因子の検討

    西垣 結佳子, 川井 紘一, 大石 まり子, 湯原 淳良, 杉本 英克, 横山 宏樹, 屋宜 宣治, 岡田 朗, 宮澤 一裕, 奥口 文宣, 嵩 文彦, 岩崎 皓一, 齋藤 和美, 曽根 博仁

    糖尿病   53 ( Suppl.1 )   S - 265   2010.4

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  • 2型糖尿病患者における安静時CVRR低下の発症率

    齋藤 和美, 川井 紘一, 菅原 歩美, 平澤 玲子, 本橋 しのぶ, 児玉 暁, 小林 和人, 島野 仁, 山田 信博, 曽根 博仁

    糖尿病   53 ( Suppl.1 )   S - 307   2010.4

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  • ピオグリタゾンの肝機能検査値への影響

    菅野 咲子, 佐藤 舞菜見, 藤井 恵里, 横田 友紀, 石村 郁恵, 曽根 博仁, 中村 公英, 本庄 潤, 山田 大志郎, 横山 宏樹

    糖尿病   53 ( Suppl.1 )   S - 214   2010.4

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  • 血管保護に重点をおいたチーム医療による糖尿病の集約的治療 達成率、施行率の追跡調査

    横田 友紀, 宮腰 千晴, 菅野 咲子, 佐藤 舞菜見, 石村 郁恵, 山下 りさ, 高橋 直穂, 本庄 潤, 山田 大志郎, 中村 公英, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( Suppl.1 )   S - 194   2010.4

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  • 早期腎症からFMD(Flow mediated vasodilatation)は既に低下している

    辻 景子, 藤井 恵理, 菅野 咲子, 本庄 潤, 山田 大志郎, 中村 公英, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( Suppl.1 )   S - 263   2010.4

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  • わが国における糖尿病運動療法の実施状況に関する調査研究(第二報) 糖尿病患者からみた現状について

    佐藤 祐造, 曽根 博仁, 小林 正, 河盛 隆造, 渥美 義仁, 押田 芳治, 田中 史朗, 鈴木 進, 牧田 茂, 大沢 功, 田村 好史, 渡邉 智之, 糖尿病運動療法, 運動処方確立のための学術調査研究委員会

    糖尿病   53 ( Suppl.1 )   S - 252   2010.4

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  • 国内大規模臨床試験 The Japan Diabetes Complications Study(JDCS)

    曽根 博仁, 赤沼 安夫, 山田 信博

    糖尿病   53 ( Suppl.1 )   S - 21   2010.4

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  • 低カリウム血症は2型糖尿病発症の新たな独立した危険因子である Toranomon Hospital Health Management Center Study(TOPICS)

    平安座 依子, 原 茂子, 荒瀬 康司, 齋藤 和美, 戸塚 久美子, 辻 裕之, 児玉 暁, 謝 勲東, 山田 信博, 小坂 樹徳, 曽根 博仁

    糖尿病   53 ( Suppl.1 )   S - 106   2010.4

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  • 2型糖尿病の肥満への減量介入

    畑中 麻梨恵, 山下 りさ, 石村 郁恵, 横田 友紀, 菅野 咲子, 佐藤 舞菜見, 山田 大志郎, 本庄 潤, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( Suppl.1 )   S - 170   2010.4

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  • インスリン導入のタイミングと方法に関する観察研究

    石村 郁恵, 山下 りさ, 横田 友紀, 菅野 咲子, 佐藤 舞菜見, 高橋 直穂, 本庄 潤, 山田 大志郎, 曽根 博仁, 中村 公英, 横山 宏樹

    糖尿病   53 ( Suppl.1 )   S - 154   2010.4

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  • 女性2型糖尿病患者における食事指導後の摂取/指示カロリー比と5年後の血糖コントロール状況

    菅原 歩美, 酒井 百合子, 本橋 しのぶ, 佐藤 睦美, 曽根 博仁, 川井 紘一

    糖尿病   53 ( Suppl.1 )   S - 188   2010.4

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  • Effects of long-term lifestyle intervention on vascular complications in Japanese patients with type 2 diabetes. The Japan Diabetes Complications Study (JDCS)

    Hirohito Sone, Sachiko Tanaka, Shiro Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shun Ishibashi, Shigehiro Katayama, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    ENDOCRINE JOURNAL   57   S388 - S388   2010.3

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  • Long-term lifestyle intervention lowers the incidence of stroke in Japanese patients with type 2 diabetes: a nationwide multicentre randomised controlled trial (the Japan Diabetes Complications Study)

    H. Sone, S. Tanaka, S. Iimuro, S. Tanaka, K. Oida, Y. Yamasaki, S. Oikawa, S. Ishibashi, S. Katayama, H. Yamashita, H. Ito, Y. Yoshimura, Y. Ohashi, Y. Akanuma, N. Yamada

    DIABETOLOGIA   53 ( 3 )   419 - 428   2010.3

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    The aim of the study was to clarify whether a therapeutic intervention focused on lifestyle modification affected the incidence of vascular complications in patients with established diabetes.
    A total of 2,033 eligible Japanese men and women aged 40-70 years with type 2 diabetes from 59 institutes were randomised to a conventional treatment group (CON), which continued to receive the usual care, and a lifestyle intervention group (INT), which received education on lifestyle modification regarding dietary habits, physical activities and adherence to treatment by telephone counselling and at each outpatient clinic visit, in addition to the usual care. Randomisation and open-label allocation were done by a central computer system. Primary analysis regarding measurements of control status and occurrence of macro- and microvascular complications was based on 1,304 participants followed for an 8 year period.
    Although status of control of most classic cardiovascular risk factors, including body weight, glycaemia, serum lipids and BP, did not differ between groups during the study period, the incidence of stroke in the INT group (5.48/1,000 patient-years) was significantly lower than in the CON group (9.52/1,000 patient-years) by Kaplan-Meier analysis (p = 0.02 by logrank test) and by multivariate Cox analysis (HR 0.62, 95% CI 0.39-0.98, p = 0.04). The incidence of CHD, retinopathy and nephropathy did not differ significantly between groups. Lipoprotein(a) was another significant independent risk factor for stroke.
    These findings suggest that lifestyle modification had limited effects on most typical control variables, but did have a significant effect on stroke incidence in patients with established type 2 diabetes.
    Clinical Trial Registration: UMIN-CTR C000000222
    Funding: The Ministry of Health, Labour and Welfare, Japan.

    DOI: 10.1007/s00125-009-1622-2

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  • 【脂質異常症 明日からの実地診療に役立つ最新の知識】 新しい指標と活用法 nonHDL-Cと脂質比(LDL-C/HDL-C、TC/HDL-C)

    阿隅 美保子, 曽根 博仁

    Medical Practice   27 ( 3 )   441 - 447   2010.3

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  • 糖尿病患者の喫煙の現状と合併症への関与

    横田 友紀, 菅野 咲子, 佐藤 舞菜見, 本庄 潤, 山田 大志郎, 中村 公英, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( 3 )   211 - 211   2010.3

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  • 糖尿病性ケトーシスの外来加療への検討

    石村 郁恵, 横田 友紀, 菅野 咲子, 佐藤 舞菜見, 高橋 直穂, 本庄 潤, 山田 大志郎, 中村 公英, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( 3 )   209 - 209   2010.3

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  • 食事講習会の不参加者へのアプローチの検討

    山下 りさ, 石村 郁恵, 畑中 麻梨絵, 高橋 直穂, 本庄 潤, 山田 大志郎, 中村 公英, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( 3 )   214 - 214   2010.3

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  • 2型糖尿病の肥満への減量介入

    畑中 麻梨恵, 山下 りさ, 石村 郁恵, 横田 友紀, 菅野 咲子, 佐藤 舞菜見, 本庄 潤, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( 3 )   211 - 211   2010.3

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  • 多剤併用療法によりアルブミン尿の低下を認めたネフローゼ症候群を呈した1型糖尿病の1症例

    北川 明子, 菅野 咲子, 横田 友紀, 佐藤 舞菜見, 辻 景子, 本庄 潤, 山田 大志郎, 中村 公英, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( 3 )   203 - 203   2010.3

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  • 糖尿病性腎症とFMD(Flow mediated vasodilatation)の関連

    辻 景子, 菅野 咲子, 田川 聖子, 本庄 潤, 中村 公英, 山田 大志郎, 曽根 博仁, 横山 宏樹

    糖尿病   53 ( 3 )   202 - 202   2010.3

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  • 2型糖尿病に認められる脂肪肝改善率と奏功因子の探索

    藤井 恵理, 佐藤 舞菜見, 辻 景子, 田川 聖子, 宮腰 千晴, 高橋 直穂, 山田 大志郎, 曽根 博仁, 本庄 潤, 中村 公英, 横山 宏樹

    糖尿病   53 ( 3 )   205 - 205   2010.3

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  • ピオグリタゾンの肝機能検査値への影響

    菅野 咲子, 佐藤 舞菜見, 横田 友紀, 塚本 祐美子, 石村 郁恵, 辻 景子, 本庄 潤, 山田 大志郎, 曽根 博仁, 中村 公英, 横山 宏樹

    糖尿病   53 ( 3 )   205 - 205   2010.3

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  • Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages

    Yoshimi Kishimoto, Mariko Tani, Harumi Uto-Kondo, Maki Iizuka, Emi Saita, Hirohito Sone, Hideaki Kurata, Kazuo Kondo

    EUROPEAN JOURNAL OF NUTRITION   49 ( 2 )   119 - 126   2010.3

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    Astaxanthin is a red carotenoid pigment which has significant potential for antioxidant activity. The macrophages in atherosclerotic lesions, known as activated macrophages, express scavenger receptors responsible for the clearance of pathogenic lipoproteins. In addition, the expression and secretion of proteolytic enzymes, matrix metalloproteinases (MMPs), and pro-inflammatory cytokines are remarkably promoted in activated macrophages.
    In this study, we investigated the effects of astaxanthin on the expression of scavenger receptors, MMPs, and pro-inflammatory cytokines in macrophages.
    THP-1 macrophages were incubated with 5-10 mu M astaxanthin for 24 h. The expression levels of scavenger receptors, MMPs, and pro-inflammatory cytokines were determined by Western blot analysis or real-time RT-PCR. The MMP-9 and -2 activities were examined by gelatin zymography and total MMP activity was measured by fluorometry.
    We found that astaxanthin remarkably decreased the class A scavenger receptor and CD36 expression in the protein and mRNA levels. Astaxanthin also reduced MMP-1, -2, -3, -9, -12, and -14 activity and expression. The mRNA expression of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 were significantly suppressed by astaxanthin. Furthermore, astaxanthin inhibited the phosphorylation of nuclear factor-kappa B.
    These results indicate that astaxanthin has inhibitory effects on macrophage activation, such as scavenger receptors up-regulation, MMPs activation, and pro-inflammatory cytokines secretion.

    DOI: 10.1007/s00394-009-0056-4

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  • Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages

    Yoshimi Kishimoto, Mariko Tani, Harumi Uto-Kondo, Maki Iizuka, Emi Saita, Hirohito Sone, Hideaki Kurata, Kazuo Kondo

    EUROPEAN JOURNAL OF NUTRITION   49 ( 2 )   119 - 126   2010.3

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    Astaxanthin is a red carotenoid pigment which has significant potential for antioxidant activity. The macrophages in atherosclerotic lesions, known as activated macrophages, express scavenger receptors responsible for the clearance of pathogenic lipoproteins. In addition, the expression and secretion of proteolytic enzymes, matrix metalloproteinases (MMPs), and pro-inflammatory cytokines are remarkably promoted in activated macrophages.
    In this study, we investigated the effects of astaxanthin on the expression of scavenger receptors, MMPs, and pro-inflammatory cytokines in macrophages.
    THP-1 macrophages were incubated with 5-10 mu M astaxanthin for 24 h. The expression levels of scavenger receptors, MMPs, and pro-inflammatory cytokines were determined by Western blot analysis or real-time RT-PCR. The MMP-9 and -2 activities were examined by gelatin zymography and total MMP activity was measured by fluorometry.
    We found that astaxanthin remarkably decreased the class A scavenger receptor and CD36 expression in the protein and mRNA levels. Astaxanthin also reduced MMP-1, -2, -3, -9, -12, and -14 activity and expression. The mRNA expression of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 were significantly suppressed by astaxanthin. Furthermore, astaxanthin inhibited the phosphorylation of nuclear factor-kappa B.
    These results indicate that astaxanthin has inhibitory effects on macrophage activation, such as scavenger receptors up-regulation, MMPs activation, and pro-inflammatory cytokines secretion.

    DOI: 10.1007/s00394-009-0056-4

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  • Long-term lifestyle intervention lowers the incidence of stroke in Japanese patients with type 2 diabetes: a nationwide multicentre randomised controlled trial (the Japan Diabetes Complications Study)

    H. Sone, S. Tanaka, S. Iimuro, S. Tanaka, K. Oida, Y. Yamasaki, S. Oikawa, S. Ishibashi, S. Katayama, H. Yamashita, H. Ito, Y. Yoshimura, Y. Ohashi, Y. Akanuma, N. Yamada

    DIABETOLOGIA   53 ( 3 )   419 - 428   2010.3

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    The aim of the study was to clarify whether a therapeutic intervention focused on lifestyle modification affected the incidence of vascular complications in patients with established diabetes.
    A total of 2,033 eligible Japanese men and women aged 40-70 years with type 2 diabetes from 59 institutes were randomised to a conventional treatment group (CON), which continued to receive the usual care, and a lifestyle intervention group (INT), which received education on lifestyle modification regarding dietary habits, physical activities and adherence to treatment by telephone counselling and at each outpatient clinic visit, in addition to the usual care. Randomisation and open-label allocation were done by a central computer system. Primary analysis regarding measurements of control status and occurrence of macro- and microvascular complications was based on 1,304 participants followed for an 8 year period.
    Although status of control of most classic cardiovascular risk factors, including body weight, glycaemia, serum lipids and BP, did not differ between groups during the study period, the incidence of stroke in the INT group (5.48/1,000 patient-years) was significantly lower than in the CON group (9.52/1,000 patient-years) by Kaplan-Meier analysis (p = 0.02 by logrank test) and by multivariate Cox analysis (HR 0.62, 95% CI 0.39-0.98, p = 0.04). The incidence of CHD, retinopathy and nephropathy did not differ significantly between groups. Lipoprotein(a) was another significant independent risk factor for stroke.
    These findings suggest that lifestyle modification had limited effects on most typical control variables, but did have a significant effect on stroke incidence in patients with established type 2 diabetes.
    Clinical Trial Registration: UMIN-CTR C000000222
    Funding: The Ministry of Health, Labour and Welfare, Japan.

    DOI: 10.1007/s00125-009-1622-2

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  • 生活習慣病の臨床エビデンス(第18回) 2型糖尿病発症関連因子としての尿酸値

    児玉 暁, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   9 ( 2 )   321 - 323   2010.3

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  • Effects of magnesium on postprandial serum lipid responses in healthy human subjects

    Yoshimi Kishimoto, Mariko Tani, Harumi Uto-Kondo, Emi Saita, Maki Iizuka, Hirohito Sone, Kuninobu Yokota, Kazuo Kondo

    BRITISH JOURNAL OF NUTRITION   103 ( 4 )   469 - 472   2010.2

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    Postprandial hyperlipidaemia has been recognised to be a risk factor for atherosclerosis development. Epidemiological and animal studies have shown that Mg intake is inversely associated with some risk factors of atherosclerosis, including lipid metabolism. The present study was performed to determine the effects of Mg supplementation on postprandial responses in serum lipid levels. We used bittern (Nigari, in Japanese), a natural MgCl(2) Solution from sea or salt lake water, for Mg Supplementation. In it two-way, randomised, crossover study, sixteen healthy male Volunteers consumed 30g butter with or without 5 ml bittern containing 500 mg of Mg. Fasting and postprandial blood samples were taken 2, 3, 4 and 6 h after ingestion. Postprandial lipid responses were evaluated by serum TAG, chylomicron TAG, apo-B48, remnant-like particle cholesterol (RLP-C) and NEFA concentrations. We found that the serum and the chylomicron TAG responses after the fat load were reduced and delayed by Mg supplementation. The concentrations of apo-B48 (P&lt;0.05), RLP-C (P&lt;0.05) and NEFA (P&lt;0.05) were significantly lower at 2 h after the fat-with-Mg meal compared with the fat-only meal. The present study indicated that Mg. supplementation could inhibit fat absorption and improve postprandial hyperlipidaemia in healthy subjects.

    DOI: 10.1017/S0007114509992716

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  • 血中尿酸値と2型糖尿病発症の関連についてのメタ解析

    児玉 暁, 齋藤 和美, 小林 和人, 矢藤 繁, 高橋 昭光, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    日本内科学会雑誌   99 ( Suppl. )   185 - 185   2010.2

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  • Effects of magnesium on postprandial serum lipid responses in healthy human subjects

    Yoshimi Kishimoto, Mariko Tani, Harumi Uto-Kondo, Emi Saita, Maki Iizuka, Hirohito Sone, Kuninobu Yokota, Kazuo Kondo

    BRITISH JOURNAL OF NUTRITION   103 ( 4 )   469 - 472   2010.2

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    Postprandial hyperlipidaemia has been recognised to be a risk factor for atherosclerosis development. Epidemiological and animal studies have shown that Mg intake is inversely associated with some risk factors of atherosclerosis, including lipid metabolism. The present study was performed to determine the effects of Mg supplementation on postprandial responses in serum lipid levels. We used bittern (Nigari, in Japanese), a natural MgCl(2) Solution from sea or salt lake water, for Mg Supplementation. In it two-way, randomised, crossover study, sixteen healthy male Volunteers consumed 30g butter with or without 5 ml bittern containing 500 mg of Mg. Fasting and postprandial blood samples were taken 2, 3, 4 and 6 h after ingestion. Postprandial lipid responses were evaluated by serum TAG, chylomicron TAG, apo-B48, remnant-like particle cholesterol (RLP-C) and NEFA concentrations. We found that the serum and the chylomicron TAG responses after the fat load were reduced and delayed by Mg supplementation. The concentrations of apo-B48 (P&lt;0.05), RLP-C (P&lt;0.05) and NEFA (P&lt;0.05) were significantly lower at 2 h after the fat-with-Mg meal compared with the fat-only meal. The present study indicated that Mg. supplementation could inhibit fat absorption and improve postprandial hyperlipidaemia in healthy subjects.

    DOI: 10.1017/S0007114509992716

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  • 【糖尿病と網膜症】 糖尿病網膜症のリスク因子

    曽根 博仁, 山田 信博, 山下 英俊

    月刊糖尿病   2 ( 3 )   19 - 24   2010.2

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  • 肥満症(第2版) 基礎・臨床研究の進歩 肥満基礎研究の進歩 肥満・肥満症の成因と発症機序 行動要因 運動不足・低身体活動

    戸塚 久美子, 曽根 博仁

    日本臨床   68 ( 増刊2 肥満症 )   297 - 301   2010.2

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  • 肥満症(第2版) 基礎・臨床研究の進歩 肥満症の予防・治療学の進歩 介入研究から得られた肥満症診療のEBM 生活習慣介入による肥満の一次予防

    齋藤 あき, 戸塚 久美子, 曽根 博仁

    日本臨床   68 ( 増刊2 肥満症 )   575 - 581   2010.2

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  • 無症候性脳梗塞と血清コレステロール値に関する横断的検討

    阿隅 美保子, 山口 龍生, 鶉橋 弘子, 古川 豊, 齋藤 和美, 児玉 暁, 松井 博滋, 宮澤 英充, 鈴木 恵美子, 近藤 和雄, 福田 寛, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   36   84 - 84   2010.1

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  • 2型糖尿病患者における就寝・起床時刻と血糖コントロールの関連についての探索的検討

    齋藤 あき, 西垣 結佳子, 川井 紘一, 大石 まり子, 杉本 英克, 栗林 伸一, 和田 崇子, 齋藤 和美, 児玉 暁, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   36   100 - 100   2010.1

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  • アルコール摂取と心房細動リスクの関連性についてのメタ解析

    児玉 暁, 斉藤 和美, 松坂 賢, 小林 和人, 矢藤 繁, 高橋 昭光, 鈴木 浩明, 島野 仁, 山田 信博, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   36   82 - 82   2010.1

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  • 2型糖尿病患者における診療の説明理解度と心理的ストレスの関連

    西垣 結佳子, 川井 紘一, 大石 まり子, 杉本 英克, 湯原 淳良, 屋宜 宣治, 齋藤 和美, 児玉 暁, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   36   66 - 66   2010.1

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  • 大脳深部白質高信号所見(DSWMH)の年齢別出現状況と頸動脈硬化との関連

    阿隅 美保子, 山口 龍生, 鶉橋 弘子, 古川 豊, 齋藤 和美, 児玉 暁, 松井 博滋, 宮澤 英充, 鈴木 恵美子, 近藤 和雄, 福田 寛, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   36   84 - 84   2010.1

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  • 生活習慣病の臨床エビデンス(第17回) 生活習慣指導介入に糖尿病合併症を防ぐ効果はあるか?

    曽根 博仁, 山田 信博

    Q&Aでわかる肥満と糖尿病   9 ( 1 )   154 - 156   2010.1

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  • インターネットを用いた生活習慣指導の肥満改善効果のメタ解析

    谷口 絵里香, 児玉 暁, 齋藤 和美, 堀川 千嘉, 齋藤 あき, 平安座 依子, 西垣 結佳子, 穴迫 唯衣, 谷内 洋子, 牧 美保, 平澤 玲子, 鈴木 恵美子, 近藤 和雄, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   36   61 - 61   2010.1

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  • 低カリウム血症は2型糖尿病発症の新たな独立した危険因子である

    平安座 依子, 齋藤 和美, 児玉 暁, 戸塚 久美子, 辻 裕之, 謝 勲東, 小坂 樹徳, 山田 信博, 原 茂子, 荒瀬 康司, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   36   60 - 60   2010.1

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  • 朝食欠食と肥満リスクのメタ解析

    堀川 千嘉, 児玉 暁, 斉藤 和美, 平澤 玲子, 伊部 陽子, 谷内 洋子, 平安座 依子, 斉藤 あき, 菅原 歩美, 戸塚 久美子, 阿隅 美保子, 鈴木 恵美子, 近藤 和雄, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   36   61 - 61   2010.1

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  • 戦中の女学校生徒の64年後を追跡調査 大和なでしこ、長寿の秘密は?

    曽根 博仁, 佐藤 睦美, 菅原 歩美

    栄養と料理   76 ( 1 )   95 - 101   2010.1

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  • 糖尿病療養指導の主観的理解度と心理的ストレスとの関連

    西垣結佳子, 西垣結佳子, 斎藤あき, 斎藤あき, 横山宏樹, 川井紘一, 大石まり子, 鈴木恵美子, 近藤和雄, 斎藤和美, 曽根博仁

    栄養学雑誌   68 ( 5 Supplement )   2010

  • 睡眠習慣と糖尿病コントロールとの関連の検討

    齋藤あき, 齋藤あき, 西垣結佳子, 西垣結佳子, 川井紘一, 大石まり子, 栗林伸一, 和田崇子, 杉本英克, 鈴木恵美子, 齋藤和美, 曽根博仁

    栄養学雑誌   68 ( 5 Supplement )   2010

  • 続発性副腎機能低下症による低Na血症に伴う横紋筋融解症が疑われた一例

    藤原和哉, 宜保英彦, 渋谷正俊, 小林和人, 高橋昭光, 矢藤繁, 鈴木浩明, 島野仁, 山田信博, 曽根博仁

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   10th   31   2010

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  • 両側基底核,小脳歯状核,大脳皮質下白質,深部白質に石灰化を来たした一例

    宜保英彦, 藤原和哉, 渋谷正俊, 小林和人, 高橋昭光, 矢藤繁, 鈴木浩明, 島野仁, 山田信博, 曽根博仁

    日本内分泌学会関東甲信越支部学術集会プログラム抄録集   10th   51   2010

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  • Effect of Endurance Exercise Training on Oxidative Stress in Spontaneously Hypertensive Rats (SHR) After Emergence of Hypertension

    Hiroko Kimura, Nobuko Kon, Satoshi Furukawa, Masahiro Mukaida, Fumiyuki Yamakura, Kazuko Matsumoto, Hirohito Sone, Kimiko Murakami-Murofushi

    CLINICAL AND EXPERIMENTAL HYPERTENSION   32 ( 7 )   407 - 415   2010

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    The purpose of this study is to elucidate the effect of wheel training on oxidative stress maker levels in spontaneous hypertensive rats (SHR). 4-hydroxynonenal and 3-nitrotyrosine levels in the aorta of SHRs were allowed to run for 10 weeks from the age of 15 weeks were measured and compared with those of nonexercised SHRs. The 4-hydroxynonenal and 3-nitrotyrosine levels in the exercised group were significantly lower than those in the nonexercised group. The exercised group showed a significant increase of manganese-containing superoxide dismutase. Endurance exercise showed a possible suppressing effect on the arteriosclerosis development by reducing oxidative stress, even after emergence of hypertension.

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  • A Hierarchical Regression Model for Dietary Data Adjusting for Covariates Measurement Error by Regression Calibration: An Application to a Large Prospective Study for Diabetic Complications Reviewed

    Masataka Taguri, Yutaka Matsuyama, Yasuo Ohashi, Hirohito Sone, Yukio Yoshimura, Nobuhiro Yamada

    Japanese Journal of Biometrics   31 ( 2 )   49 - 62   2010

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    DOI: 10.5691/jjb.31.49

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  • Effect of Endurance Exercise Training on Oxidative Stress in Spontaneously Hypertensive Rats (SHR) After Emergence of Hypertension

    Hiroko Kimura, Nobuko Kon, Satoshi Furukawa, Masahiro Mukaida, Fumiyuki Yamakura, Kazuko Matsumoto, Hirohito Sone, Kimiko Murakami-Murofushi

    CLINICAL AND EXPERIMENTAL HYPERTENSION   32 ( 7 )   407 - 415   2010

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    The purpose of this study is to elucidate the effect of wheel training on oxidative stress maker levels in spontaneous hypertensive rats (SHR). 4-hydroxynonenal and 3-nitrotyrosine levels in the aorta of SHRs were allowed to run for 10 weeks from the age of 15 weeks were measured and compared with those of nonexercised SHRs. The 4-hydroxynonenal and 3-nitrotyrosine levels in the exercised group were significantly lower than those in the nonexercised group. The exercised group showed a significant increase of manganese-containing superoxide dismutase. Endurance exercise showed a possible suppressing effect on the arteriosclerosis development by reducing oxidative stress, even after emergence of hypertension.

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  • 動脈硬化高リスク病態としての糖尿病とメタボリックシンドローム

    曽根 博仁

    痛風と核酸代謝   33 ( 2 )   189 - 196   2009.12

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    DOI: 10.6032/gnam.33.189

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  • 【糖尿病の血糖管理と血管合併症】 わが国の糖尿病患者の血管合併症の現況 JDCSからの知見

    曽根 博仁

    Angiology Frontier   8 ( 4 )   385 - 392   2009.12

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    Japan Diabetes Complication Study(JDCS)は、日本人2型糖尿病患者を対象にした前向き大規模臨床研究である。全国の糖尿病専門施設59ヶ所に通院する2型糖尿病患者2033名を対象に、コントロールや合併症などについて調査されている。この研究により、日本人糖尿病患者の合併症の頻度やリスクファクターなどが解明されつつあり、血管合併症予防のためには血糖だけではなく血清コレステロールや血圧、生活習慣など多くの因子について、バランスの取れた総合的管理を心がける必要があることが明らかになりつつある。(著者抄録)

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  • 【慢性疾患における身体活動・運動】 運動と脂質異常症

    児玉 暁, 曽根 博仁

    実験治療   ( 696 )   14 - 18   2009.12

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  • 高グルコース刺激による血管内皮機能障害に対するアスタキサンチンの影響

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 鈴木 佳織, 豊崎 美紅, 永井 美宇, 村上 香純, 杉原 規恵, 竹中 香織, 田口 千恵, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    機能性食品と薬理栄養   6 ( 1 )   45 - 45   2009.12

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  • 日本人における1型糖尿病と自己免疫性甲状腺疾患 合併頻度とその発症様式

    大崎 芳典, 川井 紘一, 本橋 しのぶ, 曽根 博仁, 山田 信博

    糖尿病   52 ( 11 )   887 - 893   2009.11

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    1型糖尿病(DM)の自己免疫性甲状腺疾患(AITD:バセドウ病またはホルモン補充療法を要する橋本病)合併率および発症様式について,川井クリニックを受診した全1型および2型DM患者3,540名を対象に検討した.1型DM159名中,54名(女性27名)が緩徐進行性1型DM(SPIDDM),105名(女性61名)が急性発症1型DMであった.1型DMのAITD合併率は8.8%で,2型DMの0.8%に比し有意に高かった.SPIDDMのAITD合併率は18.6%,急性発症1型DMのAITD合併率は3.9%であり,いずれも女性での合併率が高かった.抗GAD抗体(GADA)陽性1型DMのAITD合併率は14.2%,陰性では1.5%で,特にGADA価≧50U/ml群では,&lt;50U/ml群に比しAITD合併率が高かった.AITD合併の1型DM14名中,13名でAITDが先行発症していた.以上より,1型DM,中でも女性,GADA陽性群,GADA高値群,SPIDDMでAITD合併率が高く,発症の順序としては大部分でAITDが1型DMに先行した.(著者抄録)

    DOI: 10.11213/tonyobyo.52.887

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  • Multi-state Modelを用いた糖尿病合併症の予後予測

    田中 司朗, 飯室 聡, 田中 佐智子, 曽根 博仁, 山田 信博, 大橋 靖雄

    臨床研究・生物統計研究会誌   29 ( 1 )   15 - 18   2009.11

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  • 【運動療法の新展開】 糖尿病の予防・治療のための運動療法の新展開

    曽根 博仁

    Q&Aでわかる肥満と糖尿病   8 ( 6 )   781 - 783   2009.11

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  • 運動による中高齢者の生活機能向上支援の実際(第11回) 生活機能の維持および身体活動増進と糖尿病予防

    西垣 結佳子, 曽根 博仁

    臨床スポーツ医学   26 ( 11 )   1445 - 1450   2009.11

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  • 生活習慣病の臨床エビデンス(第16回) 体格指数(Body Mass Index)と死亡率との関係

    佐藤 睦美, 鈴木 恵美子, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   8 ( 6 )   911 - 913   2009.11

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  • Determinants of Decline in Glomerular Filtration Rate in Nonproteinuric Subjects with or without Diabetes and Hypertension

    Hiroki Yokoyama, Sakiko Kanno, Suguho Takahashi, Daishiro Yamada, Hiroshi Itoh, Kazumi Saito, Hirohito Sone, Masakazu Haneda

    CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   4 ( 9 )   1432 - 1440   2009.9

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    Background and objectives: This study investigated whether the slope of estimated GFR is different between nonproteinuric subjects with and without diabetes, and what clinical factors are associated with the GFR slope.Design, setting, participants, & measurements: An observational cohort study was performed in 923 subjects, and the predictive value of baseline variables on the GFR slope was investigated.Results: On the basis of the median 3-yr follow-up and 7 measurements of GFR, GFR slope (%/yr, median and interquartile range) was significantly larger in subjects with diabetes (-2.39 (-4.86 to 0.15), n = 729) than in those without diabetes (-1.02 (-4.28 to 1.37), n = 194), and this difference remained significant with or without presence of hypertension. After adjustments for confounding factors, predictors of GFR decline were found to be baseline high values of glycosylated hemoglobin A(1C) (HbA(1C)), GFR, systolic blood pressure, and low plasma total protein in subjects with diabetes, whereas only the latter two were significant in subjects without diabetes. In subjects with diabetes, the high GFR was accounted for by high HbA(1C) at baseline, and the predictors of GFR decline differed between those with and without hypertension, or with high and low baseline GFR. Any combination of the predictors showed increased risk for GFR decline.Conclusions: GFR slope is substantially affected by multiple factors at various stages. The degree of chronic hyperglycemia is likely to play a crucial role in elevating GFR and accelerating the decline in patients with type 2 diabetes even from the normoalbuminuric stage. Clin J Am Soc Nephrol 4: 1432-1440, 2009. doi: 10.2215/CJN.06511208

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  • Determinants of Decline in Glomerular Filtration Rate in Nonproteinuric Subjects with or without Diabetes and Hypertension

    Hiroki Yokoyama, Sakiko Kanno, Suguho Takahashi, Daishiro Yamada, Hiroshi Itoh, Kazumi Saito, Hirohito Sone, Masakazu Haneda

    CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   4 ( 9 )   1432 - 1440   2009.9

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    Background and objectives: This study investigated whether the slope of estimated GFR is different between nonproteinuric subjects with and without diabetes, and what clinical factors are associated with the GFR slope.Design, setting, participants, & measurements: An observational cohort study was performed in 923 subjects, and the predictive value of baseline variables on the GFR slope was investigated.Results: On the basis of the median 3-yr follow-up and 7 measurements of GFR, GFR slope (%/yr, median and interquartile range) was significantly larger in subjects with diabetes (-2.39 (-4.86 to 0.15), n = 729) than in those without diabetes (-1.02 (-4.28 to 1.37), n = 194), and this difference remained significant with or without presence of hypertension. After adjustments for confounding factors, predictors of GFR decline were found to be baseline high values of glycosylated hemoglobin A(1C) (HbA(1C)), GFR, systolic blood pressure, and low plasma total protein in subjects with diabetes, whereas only the latter two were significant in subjects without diabetes. In subjects with diabetes, the high GFR was accounted for by high HbA(1C) at baseline, and the predictors of GFR decline differed between those with and without hypertension, or with high and low baseline GFR. Any combination of the predictors showed increased risk for GFR decline.Conclusions: GFR slope is substantially affected by multiple factors at various stages. The degree of chronic hyperglycemia is likely to play a crucial role in elevating GFR and accelerating the decline in patients with type 2 diabetes even from the normoalbuminuric stage. Clin J Am Soc Nephrol 4: 1432-1440, 2009. doi: 10.2215/CJN.06511208

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  • Association Between Serum Uric Acid and Development of Type 2 Diabetes

    Satoru Kodama, Kazumi Saito, Yoko Yachi, Mihoko Asumi, Ayumi Sugawara, Kumiko Totsuka, Aki Saito, Hirohito Sone

    DIABETES CARE   32 ( 9 )   1737 - 1742   2009.9

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    OBJECTIVE - To systematically evaluate the association between serum uric acid (SUA) level and subsequent development of type 2 diabetes.
    RESEARCH DESIGN AND METHODS - We searched Medline (31 March from 1966 to 2009) and Embase (31 March from 1980 to 2009) for observational cohort studies examining the association between SUA and the risk of type 2 diabetes by manual literature search. Relative risks (RRs) for each 1 mg/dl increase in SUA were pooled by using a random-effects model. The studies included were stratified into subgroups representing different study characteristics, and meta-regression analyses were performed to investigate the effect of these characteristics on the association between SUA level and type 2 diabetes risk.
    RESULTS - The search yielded 11 cohort studies (42,834 participants) that reported 3,305 incident cases of type 2 diabetes during follow-up periods ranging from 2.0 to 13.5 years. The pooled RR of a 1 mg/dl increase in SUA was 1.17 (95% CI 1.09-1.25). Study results were consistently significant (i.e., &gt;1) across characteristics of participants and study design. Publication bias was both visually and statistically suggested (P = 0.03 for Egger&apos;s test, 0.06). Adjustment for publication bias attenuated the pooled RR per mg/dI increase in SUA (RR 1.11 [95% CI 1.03-1.20]), but the association remained statistically significant (P = 0.009).
    CONCLUSIONS - The current meta-analysis suggests that SUA level is positively associated with the development of type 2 diabetes regardless of various study characteristics. Further research should attempt to determine whether it is effective to utilize SUA level as a predictor of type 2 diabetes for its primary prevention.

    DOI: 10.2337/dc09-0288

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  • Association Between Serum Uric Acid and Development of Type 2 Diabetes

    Satoru Kodama, Kazumi Saito, Yoko Yachi, Mihoko Asumi, Ayumi Sugawara, Kumiko Totsuka, Aki Saito, Hirohito Sone

    DIABETES CARE   32 ( 9 )   1737 - 1742   2009.9

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    OBJECTIVE - To systematically evaluate the association between serum uric acid (SUA) level and subsequent development of type 2 diabetes.
    RESEARCH DESIGN AND METHODS - We searched Medline (31 March from 1966 to 2009) and Embase (31 March from 1980 to 2009) for observational cohort studies examining the association between SUA and the risk of type 2 diabetes by manual literature search. Relative risks (RRs) for each 1 mg/dl increase in SUA were pooled by using a random-effects model. The studies included were stratified into subgroups representing different study characteristics, and meta-regression analyses were performed to investigate the effect of these characteristics on the association between SUA level and type 2 diabetes risk.
    RESULTS - The search yielded 11 cohort studies (42,834 participants) that reported 3,305 incident cases of type 2 diabetes during follow-up periods ranging from 2.0 to 13.5 years. The pooled RR of a 1 mg/dl increase in SUA was 1.17 (95% CI 1.09-1.25). Study results were consistently significant (i.e., &gt;1) across characteristics of participants and study design. Publication bias was both visually and statistically suggested (P = 0.03 for Egger&apos;s test, 0.06). Adjustment for publication bias attenuated the pooled RR per mg/dI increase in SUA (RR 1.11 [95% CI 1.03-1.20]), but the association remained statistically significant (P = 0.009).
    CONCLUSIONS - The current meta-analysis suggests that SUA level is positively associated with the development of type 2 diabetes regardless of various study characteristics. Further research should attempt to determine whether it is effective to utilize SUA level as a predictor of type 2 diabetes for its primary prevention.

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  • 糖尿病の血管合併症のトータルケア 早期診断、そして予防へ わが国の糖尿病血管合併症の実態 Japan Diabetes Complication Study(JDCS)の結果より

    曽根 博仁, 赤沼 安夫, 山田 信博

    日本内科学会雑誌   98 ( 9 )   2208 - 2215   2009.9

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    DOI: 10.2169/naika.98.2208

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  • 高血糖による血管内皮機能障害に対するアスタキサンチンの影響

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 鈴木 佳織, 豊崎 美紅, 永井 美宇, 村上 香純, 杉原 規恵, 竹中 香織, 田中 千恵, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    肥満研究   15 ( Suppl. )   254 - 254   2009.9

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  • 糖尿病療養指導に必要な知識 大血管症

    曽根 博仁, 山田 信博, 赤沼 安夫

    糖尿病の療養指導: 糖尿病学の進歩   43回   25 - 31   2009.9

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  • 生活習慣病の臨床エビデンス 全死亡および冠動脈疾患リスクにおける心肺機能の意義

    児玉 暁, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   8 ( 5 )   754 - 757   2009.9

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  • No Relationship Between Body Mass Index During Adolescence and All-Cause Mortality in Japanese Women-A 56.5-Year Observational Study

    Mutsumi Sato, Satoru Kodama, Ayumi Sugawara, Kumiko Totsuka, Kazumi Saito, Hirohito Sone

    ANNALS OF EPIDEMIOLOGY   19 ( 8 )   590 - 591   2009.8

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    DOI: 10.1016/j.annepidem.2009.03.020

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  • No Relationship Between Body Mass Index During Adolescence and All-Cause Mortality in Japanese Women-A 56.5-Year Observational Study

    Mutsumi Sato, Satoru Kodama, Ayumi Sugawara, Kumiko Totsuka, Kazumi Saito, Hirohito Sone

    ANNALS OF EPIDEMIOLOGY   19 ( 8 )   590 - 591   2009.8

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  • アスタキサンチンは高血糖刺激による血管内皮機能障害を改善する

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 鈴木 佳織, 豊崎 美紅, 永井 美宇, 村上 香純, 杉原 規恵, 竹中 香織, 田口 千恵, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    New Diet Therapy   25 ( 2 )   208 - 208   2009.8

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  • 頸動脈内膜中膜複合体厚(IMT)と大脳白質変化の関連性 横断的検討

    山口 龍生, 阿隅 美保子, 鶉橋 弘子, 古川 豊, 齋藤 和美, 児玉 暁, 宮澤 英充, 松井 博滋, 福田 寛, 曽根 博仁

    人間ドック   24 ( 2 )   347 - 347   2009.8

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  • 未病と生活習慣病 生活習慣病における運動の意義とエビデンス

    曽根 博仁

    日本未病システム学会雑誌   15 ( 1 )   30 - 34   2009.7

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    Other Link: http://search.jamas.or.jp/link/ui/2009345742

  • 【糖尿病と中枢神経障害】 糖尿病と脳血管障害の疫学 わが国のデータを中心に

    曽根 博仁

    内分泌・糖尿病科   29 ( 1 )   2 - 9   2009.7

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  • 糖尿病患者における心・脳-腎連関 日本人2型糖尿病における糖尿病性腎症および大血管障害の発症について 糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDC Study)から

    守屋 達美, 田中 司朗, 飯室 聡, 大橋 靖雄, 山田 信博, 曽根 博仁, 赤沼 安夫, 片山 茂裕

    糖尿病合併症   23 ( 1 )   26 - 30   2009.7

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    「糖尿病における血管合併症の発症予防と進展抑制に関する研究」の対象例を用い、2型糖尿病患者1558例については腎症を、1771例については大血管障害を追跡した。その結果、1)登録時の1996年から2005年までに74例が顕性腎症を発症し、発症率は1000人年あたり6.67であった。微量アルブミン尿期(452例)から正常アルブミン尿期に寛解したのは137例で、顕性腎症へ移行するリスク因子はHbA1c、収縮期血圧、喫煙であった。2)心疾患の発症は113例、脳血管疾患の発症は90例で、発症率は1000人年あたり、それぞれ9.42、7.45であった。心疾患単独ではHbA1cはリスク因子であったが、尿アルブミン・クレアチニン比(ACR)、収縮期血圧、eGFRは有意なリスク因子ではなかった。一方、脳血管疾患単独でもACR、収縮期血圧との有意な関連は認められなかった。尚、本検討では尿アルブミン排泄量30mg/gCr未満の範囲に大血管障害のリスク因子としてのアルブミン尿のcut-off levelを決定することはできなかった。

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  • 糖尿病網膜症の治療戦略 より良い視力予後を目指した治療戦略確立への道

    山下 英俊, 山田 信博, 曽根 博仁, 山本 禎子, 川崎 良, 中野 早紀子, 嘉山 孝正

    あたらしい眼科   26 ( 7 )   911 - 915   2009.7

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  • 生活習慣病の臨床エビデンス 日本人女性のやせすぎの現状およびやせすぎが引き起こしうる健康リスク

    菅原 歩美, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   8 ( 4 )   598 - 600   2009.7

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  • Non-HDL-Cholesterol Is a Simple and Useful Predictor of Cardiovascular Complications in Japanese Patients with Type 2 Diabetes. The Japan Diabetes Complications Study (JDCS)

    Hirohito Sone, Sachiko Tanaka, Satoshi Iimuro, Shiro Tanaka, Koji Oida, Yoshimitsu Yamasaki, Shinichi Oikawa, Shun Ishibashi, Shigehiro Katayama, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES   58   A191 - A191   2009.6

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  • Self-Reported Eating Fast Is a Potent Predictor of Development of Impaired Glucose Tolerance in Japanese Men and women: Tsukuba Medical Center Study

    Kumiko Totsuka, Kimi Maeno, Kazumi Saito, Satoru Kodama, Ayumi Sugawara, Mihoko Asumi, Yoko Yachi, Miho Make, Hitoshi Shimano, Nobuhiro Yamada, Yukio Ono, Takashi Naito, Hirohito Sone

    DIABETES   58   A432 - A432   2009.6

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  • Is Serum Uric Acid Level a Predictor of Development of Type 2 Diabetes Mellitus? A Meta-Analysis

    Satoru Kodama, Kazumi Saito, Mihoko Asumi, Aki Saito, Yoko Yachi, Miho Maki, Yukako Nishigaki, Nobuhiro Yamada, Hirohito Sone

    DIABETES   58   A264 - A265   2009.6

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  • Low HDL-Cholesterol Is Associated with the Risk of Stroke in Elderly Diabetic Individuals: Changes in the Risk for Atherosclerotic Diseasas at Various Ages

    Toshio Hayashi, Hideki Itoh, Yoshiyuki Hattori, Koutaro Yokote, Nobuhiro Yamada, Hirohito Sone, Seinosuke Kawashima, Hiroshi Watanabe, Takashi Ohrui, Hideki Nomura, Hiroyuki Umegaki, Akihisa Iguchi

    DIABETES   58   A189 - A189   2009.6

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    DOI: 10.2337/dc08-1677

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  • Low HDL-Cholesterol Is Associated with the Risk of Stroke in Elderly Diabetic Individuals: Changes in the Risk for Atherosclerotic Diseasas at Various Ages

    Toshio Hayashi, Hideki Itoh, Yoshiyuki Hattori, Koutaro Yokote, Nobuhiro Yamada, Hirohito Sone, Seinosuke Kawashima, Hiroshi Watanabe, Takashi Ohrui, Hideki Nomura, Hiroyuki Umegaki, Akihisa Iguchi

    DIABETES   58   A189 - A189   2009.6

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    DOI: 10.2337/dc08-1677

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  • 【糖尿病の運動療法 理論と指導方法】 糖尿病の発症予防と治療における運動の意義 大規模臨床研究のエビデンス

    西垣 結佳子, 曽根 博仁

    プラクティス   26 ( 3 )   271 - 277   2009.5

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  • 日本人糖尿病患者における心臓自律神経障害の発症率

    齋藤 和美, 児玉 暁, 菅原 歩美, 戸塚 久美子, 齋藤 あき, 西垣 結佳子, 曽根 博仁, 川井 紘一, 本橋 しのぶ, 小林 和人, 山田 信博

    成人病と生活習慣病   39 ( 5 )   582 - 582   2009.5

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  • 耐糖能異常及び糖尿病発症予測因子としての脂肪肝、肝機能検査異常の意義の検討

    戸塚 久美子, 齋藤 和美, 谷内 洋子, 菅原 歩美, 穴迫 唯衣, 曽根 博仁, 前野 貴美, 平沼 ゆり, 小野 幸雄, 内藤 隆志

    成人病と生活習慣病   39 ( 5 )   580 - 581   2009.5

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  • 主観的ストレス状況と短期の体重変化に関する縦断研究

    伊部 陽子, 曽根 博仁, 高橋 征子

    成人病と生活習慣病   39 ( 5 )   592 - 592   2009.5

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  • 食品群別摂取状況とその後の体重変化に関する縦断研究 食物ベースの栄養教育の検討

    伊部 陽子, 曽根 博仁, 高橋 征子

    成人病と生活習慣病   39 ( 5 )   592 - 592   2009.5

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  • 健常者における運動耐容能と心血管疾患発症リスクとの数量的関係についてのメタ解析

    児玉 暁, 牧 美保, 齋藤 和美, 佐藤 睦美, 穴迫 唯衣, 阿隅 美保子, 谷内 洋子, 曽根 保子, 曽根 博仁, 山田 信博

    成人病と生活習慣病   39 ( 5 )   571 - 571   2009.5

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  • 若年期のう歯数とその後の死亡率に関する長期縦断研究

    佐藤 睦美, 菅原 歩美, 福士 亜矢子, 戸塚 久美子, 阿隅 美保子, 牧 美保, 谷内 洋子, 齋藤 和美, 児玉 暁, 曽根 博仁

    成人病と生活習慣病   39 ( 5 )   566 - 567   2009.5

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  • 耐糖能異常および糖尿病発症における食習慣の意義に関する検討

    戸塚 久美子, 児玉 暁, 阿隅 美保子, 牧 美保, 穴迫 唯衣, 伊部 陽子, 曽根 博仁, 前野 貴美, 小野 幸雄, 内藤 隆志

    成人病と生活習慣病   39 ( 5 )   579 - 580   2009.5

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  • 若年期の体力(全身持久力)が生活習慣病罹患状況および全死亡率に与える影響の検討

    佐藤 睦美, 児玉 暁, 阿隅 美保子, 西垣 結佳子, 叔 森, 不老 美也子, 曽根 保子, 鈴木 恵美子, 曽根 博仁

    成人病と生活習慣病   39 ( 5 )   577 - 578   2009.5

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  • Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and Women A Meta-analysis

    Satoru Kodama, Kazumi Saito, Shiro Tanaka, Miho Maki, Yoko Yachi, Mihoko Asumi, Ayumi Sugawara, Kumiko Totsuka, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION   301 ( 19 )   2024 - 2035   2009.5

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    Context Epidemiological studies have indicated an inverse association between cardiorespiratory fitness (CRF) and coronary heart disease (CHD) or all-cause mortality in healthy participants.
    Objective To define quantitative relationships between CRF and CHD events, cardiovascular disease (CVD) events, or all-cause mortality in healthy men and women.
    Data Sources and Study Selection A systematic literature search was conducted for observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008). The Medical Subject Headings search terms used included exercise tolerance, exercise test, exercise/physiology, physical fitness, oxygen consumption, cardiovascular diseases, myocardial ischemia, mortality, mortalities, death, fatality, fatal, incidence, or morbidity. Studies reporting associations of baseline CRF with CHD events, CVD events, or all-cause mortality in healthy participants were included.
    Data Extraction Two authors independently extracted relevant data. CRF was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units. Participants were categorized as low CRF (&lt;7.9 METs), intermediate CRF (7.9-10.8 METs), or high CRF (&gt;= 10.9 METs). CHD and CVD were combined into 1 outcome (CHD/CVD). Risk ratios (RRs) for a 1-MET higher level of MAC and for participants with lower vs higher CRF were calculated with a random-effects model.
    Data Synthesis Data were obtained from 33 eligible studies (all-cause mortality, 102 980 participants and 6910 cases; CHD/CVD, 84 323 participants and 4485 cases). Pooled RRs of all-cause mortality and CHD/CVD events per 1-MET higher level of MAC (corresponding to 1-km/h higher running/jogging speed) were 0.87 (95% confidence interval [CI], 0.84-0.90) and 0.85 (95% CI, 0.82-0.88), respectively. Compared with participants with high CRF, those with low CRF had an RR for all-cause mortality of 1.70 (95% CI, 1.51-1.92; P &lt; .001) and for CHD/CVD events of 1.56 (95% CI, 1.39-1.75; P &lt; .001), adjusting for heterogeneity of study design. Compared with participants with intermediate CRF, those with low CRF had an RR for all-cause mortality of 1.40 (95% CI, 1.32-1.48; P &lt; .001) and for CHD/CVD events of 1.47 (95% CI, 1.35-1.61; P &lt; .001), adjusting for heterogeneity of study design.
    Conclusions Better CRF was associated with lower risk of all-cause mortality and CHD/CVD. Participants with a MAC of 7.9 METs or more had substantially lower rates of all-cause mortality and CHD/CVD events compared with those with aMAC of less 7.9 METs.

    DOI: 10.1001/jama.2009.681

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  • Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and Women A Meta-analysis

    Satoru Kodama, Kazumi Saito, Shiro Tanaka, Miho Maki, Yoko Yachi, Mihoko Asumi, Ayumi Sugawara, Kumiko Totsuka, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION   301 ( 19 )   2024 - 2035   2009.5

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    Authorship:Corresponding author   Language:English   Publishing type:Book review, literature introduction, etc.   Publisher:AMER MEDICAL ASSOC  

    Context Epidemiological studies have indicated an inverse association between cardiorespiratory fitness (CRF) and coronary heart disease (CHD) or all-cause mortality in healthy participants.
    Objective To define quantitative relationships between CRF and CHD events, cardiovascular disease (CVD) events, or all-cause mortality in healthy men and women.
    Data Sources and Study Selection A systematic literature search was conducted for observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008). The Medical Subject Headings search terms used included exercise tolerance, exercise test, exercise/physiology, physical fitness, oxygen consumption, cardiovascular diseases, myocardial ischemia, mortality, mortalities, death, fatality, fatal, incidence, or morbidity. Studies reporting associations of baseline CRF with CHD events, CVD events, or all-cause mortality in healthy participants were included.
    Data Extraction Two authors independently extracted relevant data. CRF was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units. Participants were categorized as low CRF (&lt;7.9 METs), intermediate CRF (7.9-10.8 METs), or high CRF (&gt;= 10.9 METs). CHD and CVD were combined into 1 outcome (CHD/CVD). Risk ratios (RRs) for a 1-MET higher level of MAC and for participants with lower vs higher CRF were calculated with a random-effects model.
    Data Synthesis Data were obtained from 33 eligible studies (all-cause mortality, 102 980 participants and 6910 cases; CHD/CVD, 84 323 participants and 4485 cases). Pooled RRs of all-cause mortality and CHD/CVD events per 1-MET higher level of MAC (corresponding to 1-km/h higher running/jogging speed) were 0.87 (95% confidence interval [CI], 0.84-0.90) and 0.85 (95% CI, 0.82-0.88), respectively. Compared with participants with high CRF, those with low CRF had an RR for all-cause mortality of 1.70 (95% CI, 1.51-1.92; P &lt; .001) and for CHD/CVD events of 1.56 (95% CI, 1.39-1.75; P &lt; .001), adjusting for heterogeneity of study design. Compared with participants with intermediate CRF, those with low CRF had an RR for all-cause mortality of 1.40 (95% CI, 1.32-1.48; P &lt; .001) and for CHD/CVD events of 1.47 (95% CI, 1.35-1.61; P &lt; .001), adjusting for heterogeneity of study design.
    Conclusions Better CRF was associated with lower risk of all-cause mortality and CHD/CVD. Participants with a MAC of 7.9 METs or more had substantially lower rates of all-cause mortality and CHD/CVD events compared with those with aMAC of less 7.9 METs.

    DOI: 10.1001/jama.2009.681

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  • 生活習慣病の臨床エビデンス 2型糖尿病における低脂肪食

    児玉 暁, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   8 ( 3 )   451 - 453   2009.5

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    2型糖尿病患者において糖・脂質比の異なる食事の代謝への影響を比較した無作為化対照試験の文献を検索し、19個の研究を抽出した。糖・脂質比が高いほうに分類された食事群における糖質の総エネルギーに占める割合は51〜73%(中央値60%)、糖・脂質比は1.7〜7.3(中央値2.4)であった。各研究の結果をまとめると、糖代謝についてはHbA1cや空腹時血糖への効果には群間差がみられなかったが、空腹時インスリンや血糖、インスリンの食後2時間値はいずれも、糖・脂質比の高い食事が低い食事と比較して有意に大きな上昇を示した。また、脂質代謝においては、総コレステロールやLDLコレステロールは群間差がなく、トリグリセリド(TG)上昇、HDLコレステロール低下が糖・脂質比の高い食事でみられた。この傾向は、比較的若年、非肥満者に対し糖・脂質比が特に高い食事介入を行った研究で顕著であった。減量を含めた介入を行った場合には、TG上昇が抑制されていた。

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  • 高血糖刺激による炎症反応に対するアスタキサンチンの影響

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 鈴木 佳織, 豊崎 美紅, 永井 美宇, 村上 香純, 杉原 規恵, 竹中 香織, 田口 千恵, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    日本栄養・食糧学会大会講演要旨集   63回   180 - 180   2009.5

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  • Influence of Fat and Carbohydrate Proportions on the Metabolic Profile in Patients With Type 2 Diabetes: A Meta-Analysis

    Satoru Kodama, Kazumi Saito, Shiro Tanaka, Miho Maki, Yoko Yachi, Mutsumi Sato, Ayumi Sugawara, Kumiko Totsuka, Hitoshi Shimano, Yasuo Ohashi, Nubuhiro Yamada, Hirohito Sone

    DIABETES CARE   32 ( 5 )   959 - 965   2009.5

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    OBJECTIVE- The effects of dietary macronutrient Composition oil metabolic profiles In patients with type 2 diabetes have been inconsistent. This meta-analysis aimed to elucidate the effect of replacing dietary fat with carbohydrate on glucose and lipid parameters in patients with type 2 diabetes.
    RESEARCH DESIGN AND METHODS- We searched for randomized trials that investigated the effects of two kinds of prescribed diets (a low-fat, high-carbohydrate [LFHC] diet and a high-fat, low-carbohydrate [HFLC] diet); in these studies, energy and protein intake dietary groups, Nineteen studies that included 306 did not differ significantly between the two, patients met our inclusion criteria. Median diet composition of carbohydrate/fat in the LFHC and HFLC diets was 58%/24% and 40%/40%, respectively.
    RESULTS- Changes in values for A1C, fasting plasma glucose (FPG), and total and LDL cholesterol did not differ significantly between the LFHC and HFLC groups. However,the LFHC diet significantly increased fasting insulin and triglycerides by 8% (P = 0.02) and 13% (P &lt; 0.001), respectively, and lowered HDL cholesterol by 6% (P &lt; 0.001)compared with the HFLC diet. There were Positive associations among the magnitude of changes in FPG, fasting insulin, and triglycerides for the diets analyzed. However, stratified analysis indicated that the increase in triglycerides was insignificant when accompanied by energy intake restriction.
    CONCLUSIONS- Our findings suggested that replacing fat with carbohydrate could deteriorate insulin resistance while the adverse effect on triglycerides from the LFHC diet. could be avoided by restricting energy intake to a degree sufficient for the attainment of weight reduction.

    DOI: 10.2337/dc08-1716

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  • Thinness in Japanese Young Women

    Ayumi Sugawara, Kazumi Saito, Mutsumi Sato, Satoru Kodama, Hirohito Sone

    EPIDEMIOLOGY   20 ( 3 )   464 - 465   2009.5

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    DOI: 10.1097/EDE.0b013e31819ed4ed

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  • Physical Fitness During Adolescence and Adult Mortality Reviewed

    Mutsumi Sato, Satoru Kodama, Ayumi Sugawara, Kazumi Saito, Hirohito Sone

    Epidemiology   20 ( 3 )   463 - 464   2009.5

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    DOI: 10.1097/ede.0b013e31819ed09f

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  • Influence of Fat and Carbohydrate Proportions on the Metabolic Profile in Patients With Type 2 Diabetes: A Meta-Analysis

    Satoru Kodama, Kazumi Saito, Shiro Tanaka, Miho Maki, Yoko Yachi, Mutsumi Sato, Ayumi Sugawara, Kumiko Totsuka, Hitoshi Shimano, Yasuo Ohashi, Nubuhiro Yamada, Hirohito Sone

    DIABETES CARE   32 ( 5 )   959 - 965   2009.5

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    OBJECTIVE- The effects of dietary macronutrient Composition oil metabolic profiles In patients with type 2 diabetes have been inconsistent. This meta-analysis aimed to elucidate the effect of replacing dietary fat with carbohydrate on glucose and lipid parameters in patients with type 2 diabetes.
    RESEARCH DESIGN AND METHODS- We searched for randomized trials that investigated the effects of two kinds of prescribed diets (a low-fat, high-carbohydrate [LFHC] diet and a high-fat, low-carbohydrate [HFLC] diet); in these studies, energy and protein intake dietary groups, Nineteen studies that included 306 did not differ significantly between the two, patients met our inclusion criteria. Median diet composition of carbohydrate/fat in the LFHC and HFLC diets was 58%/24% and 40%/40%, respectively.
    RESULTS- Changes in values for A1C, fasting plasma glucose (FPG), and total and LDL cholesterol did not differ significantly between the LFHC and HFLC groups. However,the LFHC diet significantly increased fasting insulin and triglycerides by 8% (P = 0.02) and 13% (P &lt; 0.001), respectively, and lowered HDL cholesterol by 6% (P &lt; 0.001)compared with the HFLC diet. There were Positive associations among the magnitude of changes in FPG, fasting insulin, and triglycerides for the diets analyzed. However, stratified analysis indicated that the increase in triglycerides was insignificant when accompanied by energy intake restriction.
    CONCLUSIONS- Our findings suggested that replacing fat with carbohydrate could deteriorate insulin resistance while the adverse effect on triglycerides from the LFHC diet. could be avoided by restricting energy intake to a degree sufficient for the attainment of weight reduction.

    DOI: 10.2337/dc08-1716

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  • Thinness in Japanese Young Women

    Ayumi Sugawara, Kazumi Saito, Mutsumi Sato, Satoru Kodama, Hirohito Sone

    EPIDEMIOLOGY   20 ( 3 )   464 - 465   2009.5

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    DOI: 10.1097/EDE.0b013e31819ed4ed

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  • 【がん 肥満・糖尿病との関係】 太りすぎるとどんながんになりやすいですか?肥満とがん発症リスクとの関係について教えてください

    菅原 歩美, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   8 ( 3 )   333 - 335   2009.5

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  • 若年女性のやせの現状とその減量行動に影響する要因の検討

    菅原 歩美, 阿隅 美保子, 谷内 洋子, 牧 美保, 伊部 陽子, 穴迫 唯衣, 西垣 結佳子, 齋藤 あき, 齋藤 和美, 曽根 博仁

    成人病と生活習慣病   39 ( 5 )   593 - 593   2009.5

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  • マグネシウム高含有にがりの脂肪細胞分化に及ぼす影響

    岸本 良美, 近藤 春美, 宇都, 谷 真理子, 吉岡 絵理, 才田 恵美, 平田 悠美子, 飯塚 麻貴, 野本 佳世子, 田口 千恵, 澤, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    機能性食品と薬理栄養   5 ( 5 )   339 - 342   2009.5

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    マグネシウム高含有にがり(MAG21)の3T3-L1前駆脂肪細胞の分化に及ぼす影響とそのメカニズムを検討した。にがり及び、MgCl2が3T3-L1前駆脂肪細胞の分化に及ぼす影響を検討するため、分化後の細胞内トリグリセリド量、脂肪滴の蓄積の増加を確認し、にがり及び、MgCl2単独の作用でコントロールに比べて、顕著な増加を認めた。細胞内の脂肪蓄積と同様に、にがり及び、MgCl2の作用によりPPARγ、aP2等のmRNA発現量が有意な上昇を認め、にがり及び、MgCl2は前駆脂肪細胞からの分化を促進することが示された。インスリン共存下では、にがり及び、MgCl2はインスリンによる糖の取り込みをさらに亢進させることが明らかとなり、にがりはインスリン感受性を高める可能性が示唆された。

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  • 【身体活動・運動と生活習慣病 運動生理学と最新の予防・治療】 運動療法 運動療法総論 効果と限界

    曽根 博仁

    日本臨床   67 ( 増刊2 身体活動・運動と生活習慣病 )   335 - 342   2009.4

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    Other Link: http://search.jamas.or.jp/link/ui/2009195237

  • 【糖尿病 診断と治療の進歩】 合併症対策の進歩 大血管障害

    曽根 博仁, 山田 信博

    日本内科学会雑誌   98 ( 4 )   794 - 801   2009.4

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    DOI: 10.2169/naika.98.794

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  • 【HDLを再考する】 わが国におけるHDLとCardiovascular Riskの疫学を知る

    曽根 博仁

    Vascular Medicine   5 ( 2 )   93 - 99   2009.4

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    血中HDLコレステロール(HDL-C)レベルとCHD発症との関係については、日本人を対象としたものも含めて、すでに多くの観察疫学データが存在している。同時に心血管イベントの発症・進展を目的とした多くの介入試験において、HDL-Cがどの程度上昇したかについても検討されている。しかしこれらの研究からHDL-C上昇単独の効果を知ることは難しく、治療介入によりHDL-Cを増加させた際にCHD発症をどの程度抑制できるかについては、まだエビデンスが不十分である。CETP阻害薬が期待された効果を上げられなかったことからも生活習慣改善の重要性は高まっており、それに関するエビデンスの充実が望まれる。(著者抄録)

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  • アスタキサンチンのマクロファージにおける抗動脈硬化作用の検討

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 野本 佳世子, 平田 悠美子, 永井 美宇, 村上 香純, 田口 千恵, 澤, 曽根 博仁, 蔵田 英明, 近藤 和雄

    機能性食品と薬理栄養   5 ( 4 )   298 - 298   2009.4

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  • アスコルビン酸濃度の違いによる遺伝子発現変化の検討

    曽根 保子, 丑田 晴菜, 児玉 暁, 齋藤 和美, 山王丸 靖子, 三宅 紀子, 曽根 博仁, 倉田 忠男, 鈴木 恵美子

    ビタミン   83 ( 4 )   198 - 198   2009.4

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  • ラットに対する2,3-ジケトグロン酸の影響について

    大野 友莉子, 北村 香織, 曽根 保子, 曽根 博仁, 山王丸 靖子, 佐藤 眞治, 三宅 紀子, 倉田 忠男, 鈴木 恵美子

    ビタミン   83 ( 4 )   198 - 198   2009.4

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  • わが国における糖尿病運動療法の実施状況に関する調査研究(第一報) 日本医師会との共同企画

    佐藤 祐造, 曽根 博仁, 小林 正, 河盛 隆造, 渥美 義仁, 押田 芳治, 田中 史朗, 鈴木 進, 牧田 茂, 大沢 功, 田村 好史, 今村 聡, 渡邉 智之, 糖尿病運動療法, 運動処方確立のための学術調査研究委員会

    糖尿病   52 ( Suppl.1 )   S - 293   2009.4

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  • 2型糖尿病インスリン4回法における持効型の1回から2回への有効性

    辻 景子, 宮腰 千晴, 奥田 昌恵, 山田 大志郎, 曽根 博仁, 伊藤 博史, 横山 宏樹

    糖尿病   52 ( Suppl.1 )   S - 241   2009.4

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  • 糖尿病ラットにおけるアスコルビン酸の体内動態について

    北村 香織, 大野 友莉子, 曽根 保子, 曽根 博仁, 山王丸 靖子, 佐藤 眞治, 三宅 紀子, 倉田 忠男, 鈴木 恵美子

    ビタミン   83 ( 4 )   197 - 197   2009.4

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  • 糖尿病患者の頸動脈病変をめぐって 糖尿病と脳卒中の疫学 日本の研究から

    曽根 博仁

    糖尿病   52 ( Suppl.1 )   S - 69   2009.4

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  • 2型糖尿病におけるeGFR低下速度に影響を及ぼす因子の検討

    菅野 咲子, 横田 友紀, 高橋 直穂, 山田 大志郎, 伊藤 博史, 曽根 博仁, 横山 宏樹

    糖尿病   52 ( Suppl.1 )   S - 221   2009.4

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  • インスリン強化療法におけるグリメピリドの必要性の検討

    横田 友紀, 星 由紀子, 菅野 咲子, 山田 大志郎, 伊藤 博史, 曽根 博仁, 横山 宏樹

    糖尿病   52 ( Suppl.1 )   S - 200   2009.4

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  • Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15)

    Hiroki Yokoyama, Hirohito Sone, Mariko Oishi, Koichi Kawai, Yoshihide Fukumoto, Masashi Kobayashi

    NEPHROLOGY DIALYSIS TRANSPLANTATION   24 ( 4 )   1212 - 1219   2009.4

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    Background. Microalbuminuria is widely accepted as the first clinical sign of diabetic nephropathy. However, normoalbuminuric type 2 diabetic patients who have renal insufficiency (RI), i.e. low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), exist. We explored the prevalence of such patients and associated clinical factors.Methods. We investigated the distribution of patients when stratified by albuminuria stages and chronic kidney disease (CKD) stages in a large-scale population of Japanese type 2 diabetic patients (N = 3297), and the common and independent factors for albuminuria and low eGFR.Results. The proportion of subjects with low eGFR was 15.3% (506/3297), which was 11.4% among those with normoalbuminuria (NA) (262/2298), 14.9% among those with microalbuminuria (105/705) and 47.3% among those with macroalbuminuria (139/294). There were 262 patients with NA and low eGFR, and 63.4% of them had neither diabetic retinopathy nor neuropathy. They were older and included a higher proportion of women and patients with hypertension, hyperlipidaemia and cardiovascular disease (CVD), and fewer smokers compared with those with NA and preserved eGFR. Multiple logistic regression analysis revealed that factors commonly associated with RI and albuminuria were hypertension, CVD and proliferative retinopathy. Factors independently associated with RI were age, duration of diabetes, A1C (negative), hyperlipidaemia, smoking (negative) and macroalbuminuria, whereas those associated with albuminuria were male sex, BMI, A1C, simple retinopathy and RI.Conclusions. A significant proportion of type 2 diabetic patients have normoalbuminuric RI. Renal disease in type 2 diabetes could be heterogeneous, implying the possibility of involvement of renal atherosclerosis and lipid toxicity.

    DOI: 10.1093/ndt/gfn603

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  • Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15)

    Hiroki Yokoyama, Hirohito Sone, Mariko Oishi, Koichi Kawai, Yoshihide Fukumoto, Masashi Kobayashi

    NEPHROLOGY DIALYSIS TRANSPLANTATION   24 ( 4 )   1212 - 1219   2009.4

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    Background. Microalbuminuria is widely accepted as the first clinical sign of diabetic nephropathy. However, normoalbuminuric type 2 diabetic patients who have renal insufficiency (RI), i.e. low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), exist. We explored the prevalence of such patients and associated clinical factors.Methods. We investigated the distribution of patients when stratified by albuminuria stages and chronic kidney disease (CKD) stages in a large-scale population of Japanese type 2 diabetic patients (N = 3297), and the common and independent factors for albuminuria and low eGFR.Results. The proportion of subjects with low eGFR was 15.3% (506/3297), which was 11.4% among those with normoalbuminuria (NA) (262/2298), 14.9% among those with microalbuminuria (105/705) and 47.3% among those with macroalbuminuria (139/294). There were 262 patients with NA and low eGFR, and 63.4% of them had neither diabetic retinopathy nor neuropathy. They were older and included a higher proportion of women and patients with hypertension, hyperlipidaemia and cardiovascular disease (CVD), and fewer smokers compared with those with NA and preserved eGFR. Multiple logistic regression analysis revealed that factors commonly associated with RI and albuminuria were hypertension, CVD and proliferative retinopathy. Factors independently associated with RI were age, duration of diabetes, A1C (negative), hyperlipidaemia, smoking (negative) and macroalbuminuria, whereas those associated with albuminuria were male sex, BMI, A1C, simple retinopathy and RI.Conclusions. A significant proportion of type 2 diabetic patients have normoalbuminuric RI. Renal disease in type 2 diabetes could be heterogeneous, implying the possibility of involvement of renal atherosclerosis and lipid toxicity.

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  • 健常者の脂肪負荷後血中トリグリセリド値に影響を与える因子の検討

    福士 亜矢子, 児玉 暁, 齋藤 和美, 谷内 洋子, 菅原 歩美, 戸塚 久美子, 叔 びょう, 齋藤 和典, 近藤 和雄, 曽根 博仁

    日本未病システム学会雑誌   14 ( 2 )   260 - 263   2009.3

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    食後高脂血症は、冠動脈疾患をはじめとする動脈硬化疾患との関連が指摘されている。食後高脂血症は、経口脂肪負荷試験(OFTT)におけるトリグリセリド(TG)反応により診断されることが多いが、検査が繁雑で長時間を要するため被験者の負担が大きい。その上、標準化された方法や正常値なども確立していない。本研究では基礎的検討として健常者を対象とし、(1)脂肪負荷後TG反応に影響を及ぼす因子は何か、(2)OFTTを簡略化し、あるいはOFTTを行わずに、脂肪負荷後TG反応を予測することは可能か、の2点を目的とした。健常人男女40人を対象としてOFTTを実施し、インスリン抵抗性関連指標(HOMA-IR、HOMA-β、QUICKI)をはじめとする他の各種空腹時採血指標や対象者の特徴とともに重回帰分析を用いて検討した。その結果、TGの曲線下面積(TG AUC)は空腹時のTG値、apoA-II、HOMA-β、HDL-Cが、それぞれ独立した有意な予測因子であった。TGのピーク値(TG peak)には空腹時のTG値、apoA-II、インスリンが関与していた。以上の結果より、今回のOFTT時TG反応には、空腹時TGとともにインスリン抵抗性や血中アポ蛋白A-IIなどが独立して関連していることが示された。これらの結果より、対象者の特徴と空腹時単回採血結果より、OFTT時TG反応はOFTTを実施しなくてもかなり予測し得ることが示唆された。今後は有疾患者も含め、多数例で検討する必要があるものの、本研究の結果は食後高脂血症の病態の解明、また診断法確立の一助となると考えられる。(著者抄録)

    DOI: 10.11288/mibyou1998.14.260

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  • 生活習慣病の臨床エビデンス 体力(有酸素運動能力)がその後の健康と寿命に与える影響

    佐藤 睦美, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   8 ( 2 )   285 - 287   2009.3

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  • 頸動脈内中膜複合体厚(IMT)に関連する因子の横断的検討

    阿隅 美保子, 佐伯 晃, 古川 豊, 秋山 朋子, 大泉 卓美, 鶉橋 弘子, 齋藤 和美, 児玉 暁, 宮澤 英充, 松井 博滋, 山口 龍生, 福田 寛, 曽根 博仁

    日本未病システム学会雑誌   14 ( 2 )   234 - 236   2009.3

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    2005年5月〜2006年3月に動脈硬化度健診を受診した188名(男87名、女101名、平均59±1歳)を対象に、頸動脈内中膜複合体厚(IMT)を測定し、対象者を最大値(IMT-max)により低値群(1.1mm未満)50名、高値群(1.1mm以上)138名に分け、IMTと関連する因子について検討した。女性は全員が非喫煙者で、喫煙者は男性のみであるため男女別の解析を行った。女性ではLDLコレステロールが動脈硬化の指標として有用であることがわかった。一方、男性では下肢血管の動脈硬化と脳動脈硬化が並行して観察される傾向があり、喫煙が脳動脈硬化の進行に重要であることが示された。従来の動脈硬化疾患危険因子が、潜在的な脳動脈硬化とどの程度関連しているかが明らかになった。

    DOI: 10.11288/mibyou1998.14.234

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  • 早食い習慣は糖尿病を含む耐糖能異常発症のリスクファクターである

    戸塚 久美子, 前野 貴美, 齋藤 和美, 谷内 洋子, 菅原 歩美, 佐藤 睦美, 西垣 結佳子, 齋藤 あき, 小野 幸雄, 内藤 隆志, 曽根 博仁

    日本未病システム学会雑誌   14 ( 2 )   195 - 198   2009.3

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    目的:人間ドックのデータを活用して、食習慣が耐糖能異常(IGT)および2型糖尿病(DM)発症に与える影響を前向きに検討した。方法:75g経口糖負荷試験を含む人間ドックを3年間の間隔で2回以上受診した男女230名のうち、初回ドック受診時にIGTまたはDMと判定された者、DMの既往(治療中を含む)をもつ者を除いた計172名(男性120名、女性52名、平均年齢49.4±5.0歳)を対象者とした。IGTとDMの診断にはWHOの判定基準を用いた。初回受診時に、「早食い」「欠食」「間食」「夜食」「外食」の各食習慣の有無を二択法により自己申告させ、その結果とその後のIGT、DMのいずれかの発症との関係を多変量解析により解析した。結果:3年間の追跡期間中、合計39名(男性33名、女性6名)が、IGT(37名)またはDM(2名)を発症した。IGTまたはDMの発症を目的変数とし、観察開始時の性別、年齢、喫煙、アルコール摂取量、糖尿病家族歴、収縮期血圧、総コレステロール、HDLコレステロール、中性脂肪、C反応性タンパク、早朝空腹時血糖を説明変数としてロジスティック回帰分析を行った結果、「早食い」の者のオッズ比(95%信頼区間)は、2.63(1.15-6.02、P=0.02)と有意であったのに対し、その他の食習慣はいずれも有意な関連を認めなかった。結論:自己評価に基づく「早食い」は、独立したIGT/DMの危険因子となることが示された。(著者抄録)

    DOI: 10.11288/mibyou1998.14.195

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  • 【熟練医から"日常診療のさまざまなコツ"を伝授】 "疾患への対応"のコツ 2型糖尿病診療のコツ

    曽根 博仁

    治療   91 ( 臨増 )   94 - 95   2009.3

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  • Waist Circumference as a Cardiovascular and Metabolic Risk in Japanese Patients With Type 2 Diabetes

    Hirohito Sone, Sachiko Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shun Ishibashi, Shinichi Oikawa, Shigehiro Katayama, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    OBESITY   17 ( 3 )   585 - 592   2009.3

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    Excess waist circumference (WC) is a frequently used indicator of abdominal obesity and/or cardiovascular disease (CVD) risk. Nonetheless, search of the literature revealed no prospective studies on the association between WC and CVD events in diabetic patients. In this study, the clinical significance and implications of WC as a cardiovascular and metabolic risk indicator was prospectively investigated in Japanese patients with type 2 diabetes. For this purpose, baseline data on WC, hypertension, and dyslipidemia were collected and subsequent CVD (coronary heart disease and stroke) events during the following 8 years were studied in 1,424 Japanese type 2 diabetic patients, and the cross-sectional/longitudinal associations between WC and CVD risk factors/events were analyzed. Mean WC levels were significantly increased according to the number of coexisting risk factors. However, no significant difference in mean WC between subgroups with and without CVD events was noted, and excess WC alone was not predictive of subsequent CVD events either in male or female subjects even after adjustment for age, smoking, hypertension, and dyslipidemia. In female patients, excess WC (&gt;= 80 cm) was predictive of CVD events only with the coexistence of hypertension. In Japanese diabetic patients, excess WC alone, although a good marker for clustering of CVD risk factors, did not raise the risk of CVD events unless accompanied by hypertension in female patients. Further investigations are necessary before WC as a risk factor can be utilized in clinical settings for the management of diabetes in this population.

    DOI: 10.1038/oby.2008.481

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  • Waist Circumference as a Cardiovascular and Metabolic Risk in Japanese Patients With Type 2 Diabetes

    Hirohito Sone, Sachiko Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shun Ishibashi, Shinichi Oikawa, Shigehiro Katayama, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    OBESITY   17 ( 3 )   585 - 592   2009.3

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    Excess waist circumference (WC) is a frequently used indicator of abdominal obesity and/or cardiovascular disease (CVD) risk. Nonetheless, search of the literature revealed no prospective studies on the association between WC and CVD events in diabetic patients. In this study, the clinical significance and implications of WC as a cardiovascular and metabolic risk indicator was prospectively investigated in Japanese patients with type 2 diabetes. For this purpose, baseline data on WC, hypertension, and dyslipidemia were collected and subsequent CVD (coronary heart disease and stroke) events during the following 8 years were studied in 1,424 Japanese type 2 diabetic patients, and the cross-sectional/longitudinal associations between WC and CVD risk factors/events were analyzed. Mean WC levels were significantly increased according to the number of coexisting risk factors. However, no significant difference in mean WC between subgroups with and without CVD events was noted, and excess WC alone was not predictive of subsequent CVD events either in male or female subjects even after adjustment for age, smoking, hypertension, and dyslipidemia. In female patients, excess WC (&gt;= 80 cm) was predictive of CVD events only with the coexistence of hypertension. In Japanese diabetic patients, excess WC alone, although a good marker for clustering of CVD risk factors, did not raise the risk of CVD events unless accompanied by hypertension in female patients. Further investigations are necessary before WC as a risk factor can be utilized in clinical settings for the management of diabetes in this population.

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  • 【糖尿病食事療法のエビデンス】 糖尿病とアルコールに関するエビデンス

    曽根 博仁

    内分泌・糖尿病科   28 ( 2 )   128 - 133   2009.2

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  • 運動耐容能が冠動脈疾患発症に及ぼす影響に関する定量的メタ解析

    児玉 暁, 齋藤 和美, 牧 美保, 阿隅 美保子, 谷内 洋子, 小林 和人, 高橋 昭光, 島野 仁, 山田 信博, 曽根 博仁

    日本内科学会雑誌   98 ( Suppl. )   130 - 130   2009.2

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  • 糖尿病の血管合併症のトータルケア 早期診断、そして予防へ わが国の血管合併症の実態 JDCSの結果より

    曽根 博仁, 赤沼 安夫, 山田 信博

    日本内科学会雑誌   98 ( Suppl. )   84 - 84   2009.2

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  • 若年期の体力(全身持久力)が生活習慣病罹患状況および全死亡率に与える影響の検討

    佐藤 睦美, 児玉 暁, 阿隅 美保子, 西垣 結佳子, 叔 森, 不老 美也子, 曽根 保子, 鈴木 恵美子, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   63 - 63   2009.1

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  • 若年女性のやせの現状とその減量行動に影響する要因の検討

    菅原 歩美, 阿隅 美保子, 谷内 洋子, 牧 美保, 伊部 陽子, 穴迫 唯衣, 西垣 結佳子, 齋藤 あき, 齋藤 和美, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   77 - 77   2009.1

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  • 日本人糖尿病患者における心臓自律神経障害の発症率

    齋藤 和美, 川井 紘一, 児玉 暁, 本橋 しのぶ, 菅原 歩美, 戸塚 久美子, 齋藤 あき, 西垣 結佳子, 小林 和人, 山田 信博, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   67 - 67   2009.1

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  • 耐糖能異常及び糖尿病発症予測因子としての脂肪肝、肝機能検査異常の意義の検討

    戸塚 久美子, 前野 貴美, 齊藤 和美, 谷内 洋子, 菅原 歩美, 穴迫 結衣, 平沼 ゆり, 小野 幸雄, 内藤 隆志, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   66 - 66   2009.1

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  • 主観的ストレス状況と短期の体重変化に関する縦断研究

    伊部 陽子, 高橋 征子, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   76 - 76   2009.1

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  • 食品群別摂取状況とその後の体重変化に関する縦断研究 食物ベースの栄養教育の検討

    伊部 陽子, 高橋 征子, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   76 - 76   2009.1

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  • 健常者における運動耐容能と心血管疾患発症リスクとの数量的関係についてのメタ解析

    児玉 暁, 牧 美保, 斉藤 和美, 佐藤 睦美, 戸塚 久美子, 穴迫 唯衣, 阿隅 美保子, 谷内 洋子, 曽根 保子, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   55 - 55   2009.1

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  • 若年期の損失歯数とその後の死亡率に関する長期縦断研究

    佐藤 睦美, 菅原 歩美, 福士 亜矢子, 戸塚 久美子, 阿隅 美保子, 牧 美保, 谷内 洋子, 斎藤 和美, 児玉 暁, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   51 - 51   2009.1

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  • 耐糖能異常および糖尿病発症における食習慣の意義に関する検討

    戸塚 久美子, 前野 貴美, 児玉 暁, 阿隅 美保子, 牧 美保子, 穴迫 結衣, 伊部 陽子, 小野 幸雄, 内藤 隆志, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   35   65 - 65   2009.1

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  • 生活習慣病の臨床エビデンス 胎児期からの成人疾病予防 胎生期低栄養とメタボリックシンドローム

    谷内 洋子, 菅原 歩美, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   8 ( 1 )   109 - 111   2009.1

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  • 【メタボリックシンドロームのその後を考察する】 保険診療では糖尿病にどのようにアプローチするか?

    曽根 博仁

    Vascular Medicine   5 ( 1 )   36 - 42   2009.1

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    国際的にも高く評価されているわが国の健康保険制度は、少子高齢社会の到来によって見直しを余儀なくされている。糖尿病診療も例外でなく、限られた医療資源でいかに効率的に患者のQOLや寿命の向上を実現するかは、国民・政府・医療従事者のすべてにとって重要な課題となっている。糖尿病患者においては、合併症の進行や累積により医療費は明らかに増加するので、糖尿病そのものの一次予防とともに、合併症(細小血管合併症、大血管合併症とも)予防を目標としたアプローチが重要であり、そのための説得力あるエビデンスが求められている。(著者抄録)

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  • INFLUENCE OF VITAMIN C LEVEL ON THE GENE EXPRESSION IN PRIMARY HEPATOCYTE OF ODS RAT

    Yasuko Sone, Kazumi Saitou, Fumiko Onitake, Yasuko Sannoumaru, Etsuko Ueta, Noriko Miyake, Hirohito Sone, Eiji Namba, Masahiro Inagaki, Yuzuru Otsuka, Kazuo Kondo, Tadao Kurata, Emiko Suzuki, Miao Shu, Satoru Kodama

    ANNALS OF NUTRITION AND METABOLISM   55   445 - 445   2009

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  • Components of Metabolic Syndrome and their Combinations as Predictors of Cardiovascular Disease in Japanese Patients with Type 2 Diabetes. Implications for Improved Definition. Analysis from Japan Diabetes Complications Study (JDCS)

    Hirohito Sone, Sachiko Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shinichi Oikawa, Shun Ishibashi, Shigehiro Katayama, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS   16 ( 4 )   380 - 387   2009

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    Aim: The prognostic power of metabolic syndrome (MetS) in patients with diabetes has been studied with inconsistent results depending on the definition of MetS. To clarify the best combination of MetS components to predict future cardiovascular disease (CVD) events, we estimated CVD risk in Japanese patients with type 2 diabetes according to MetS components.
    Methods: Patients were categorized according to the presence three MetS components in addition to hyperglycemia. hypertension, dyslipidemia and excess waist circumference (WC) (according to either Japanese or Asian cut-off values). Hazard ratios for CVD events were compared in patients with various categories of MetS components.
    Results: At least two components of MetS were required for a significantly elevated risk for CVD; however, component combinations with significantly increased risk differed depending on gender or the WC cut-off value. Any two among 1) excess WC (men &gt;= 90 cm, women &gt;= 80 cm); 2) hypertension (systolic blood pressure &gt;= 130 mmHg or diastolic blood pressure &gt;= 85 mmHg or use of an antihypertensive agent); and 3) dyslipidemia (triglycerides &gt;= 150 mg/dL or HDL-cholesterol &lt; 40 mg/dL or use of drug treatment) could be used to identify significantly higher risk (approximately twice) for CVD regardless of gender.
    Conclusions: The results suggest that the current MetS criteria should be modified when applied to patients with type 2 diabetes.

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  • Familial predisposition to cardiovascular risk and disease contributes to cardiovascular risk and disease interacting with other cardiovascular risk factors in diabetes-Implication for common soil (JDDM 14)

    Hiroki Yokoyama, Koichi Kawai, Mariko Ohishi, Hirohito Sone

    ATHEROSCLEROSIS   201 ( 2 )   332 - 338   2008.12

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    In diabetic population cardiovascular morbidity is high and the effects of genetic predisposition remain elucidated. In a large-scale multicenter-based diabetic population, clinical parameters including conventional cardiovascular risk factors and first-degree family history (FH) of diabetes, hypertension, coronary heart disease (CHD) and stroke were investigated in association with presence of CHD and stroke. Among 3611 diabetic patients, 181 (5.0%) had CHD and 118 (3.3%) had stroke. After adjustment for conventional risk factors, FH of CHD (OR 2.32, p &lt; 0.0001) and of diabetes (OR 1.44, p &lt; 0.05) were associated with CHD, and FH of stroke (OR 1.86, p &lt; 0.01) was associated with stroke. FH of hypertension was significantly associated with presence of hypertension and obesity. Synergistic effect of FH of CHD in combination with hypertension or aging on increasing CHD. and that of FH of stroke in combination with microalbuminuria on increasing stroke were found. FH of diabetes, of hypertension, of CHD and of stroke were significantly associated with FH of each disease, indicating clustering, of FH. In diabetic population, FH of CHD and FH of stroke doubled the risk of CHD and stroke, respectively, and had synergistic effect in combination with other risk factors. Clustering of FH may indicate interrelation of genetic predisposition. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

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  • Reduced GFR and microalbuminuria are independently associated with prevalent cardiovascular disease in Type 2 diabetes: JDDM study 16

    H. Yokoyama, M. Oishi, K. Kawai, H. Sone

    DIABETIC MEDICINE   25 ( 12 )   1426 - 1432   2008.12

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    We investigated whether a reduced estimated glomerular filtration rate (eGFR) was associated with cardiovascular disease (CVD) prevalence, independent of the effect of microalbuminuria in patients with diabetes.
    In a multicentre, large-scale cohort including 3002 Japanese patients with Type 2 diabetes without macroalbuminuria, the relationship of a reduced eGFR and microalbuminuria with CVD was investigated.
    Of those patients, 4.8% had a reduced eGFR and microalbuminuria, 12.7% had a reduced eGFR without microalbuminuria and 18.7% had microalbuminuria but normal eGFR. A reduced eGFR and microalbuminuria were each associated with a doubling of the prevalence of CVD. Compared with patients with no microalbuminuria/normal eGFR [odds ratio (OR) 1.0], the OR for CVD was significantly higher in those with a reduced eGFR without microalbuminuria (OR 1.97) and similarly higher in those with microalbuminuria without a reduced eGFR (OR 1.85). The OR was highest in those with both a reduced eGFR and microalbuminuria (OR 3.97, 95% confidence interval 2.55-6.20). The OR for CVD remained significant after adjustments for age, sex, hypertension, dyslipidaemia, smoking, body mass index, glycated haemoglobin and the duration of diabetes, and remained significant if the cut-off point for microalbuminuria was set at the median albumin : creatinine ratio (13.7 mg/g creatinine). In patients without microalbuminuria, a reduced eGFR was associated with CVD only in the older and male groups.
    A reduced eGFR and the presence of microalbuminuria were each associated with a near doubling of the prevalence of CVD, independently of traditional CVD risk factors and glycaemic control in patients with Type 2 diabetes.
    Diabet. Med. 25, 1426-1432 (2008).

    DOI: 10.1111/j.1464-5491.2008.02592.x

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  • Reduced GFR and microalbuminuria are independently associated with prevalent cardiovascular disease in Type 2 diabetes: JDDM study 16

    H. Yokoyama, M. Oishi, K. Kawai, H. Sone

    DIABETIC MEDICINE   25 ( 12 )   1426 - 1432   2008.12

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    We investigated whether a reduced estimated glomerular filtration rate (eGFR) was associated with cardiovascular disease (CVD) prevalence, independent of the effect of microalbuminuria in patients with diabetes.
    In a multicentre, large-scale cohort including 3002 Japanese patients with Type 2 diabetes without macroalbuminuria, the relationship of a reduced eGFR and microalbuminuria with CVD was investigated.
    Of those patients, 4.8% had a reduced eGFR and microalbuminuria, 12.7% had a reduced eGFR without microalbuminuria and 18.7% had microalbuminuria but normal eGFR. A reduced eGFR and microalbuminuria were each associated with a doubling of the prevalence of CVD. Compared with patients with no microalbuminuria/normal eGFR [odds ratio (OR) 1.0], the OR for CVD was significantly higher in those with a reduced eGFR without microalbuminuria (OR 1.97) and similarly higher in those with microalbuminuria without a reduced eGFR (OR 1.85). The OR was highest in those with both a reduced eGFR and microalbuminuria (OR 3.97, 95% confidence interval 2.55-6.20). The OR for CVD remained significant after adjustments for age, sex, hypertension, dyslipidaemia, smoking, body mass index, glycated haemoglobin and the duration of diabetes, and remained significant if the cut-off point for microalbuminuria was set at the median albumin : creatinine ratio (13.7 mg/g creatinine). In patients without microalbuminuria, a reduced eGFR was associated with CVD only in the older and male groups.
    A reduced eGFR and the presence of microalbuminuria were each associated with a near doubling of the prevalence of CVD, independently of traditional CVD risk factors and glycaemic control in patients with Type 2 diabetes.
    Diabet. Med. 25, 1426-1432 (2008).

    DOI: 10.1111/j.1464-5491.2008.02592.x

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  • Familial predisposition to cardiovascular risk and disease contributes to cardiovascular risk and disease interacting with other cardiovascular risk factors in diabetes-Implication for common soil (JDDM 14)

    Hiroki Yokoyama, Koichi Kawai, Mariko Ohishi, Hirohito Sone

    ATHEROSCLEROSIS   201 ( 2 )   332 - 338   2008.12

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    In diabetic population cardiovascular morbidity is high and the effects of genetic predisposition remain elucidated. In a large-scale multicenter-based diabetic population, clinical parameters including conventional cardiovascular risk factors and first-degree family history (FH) of diabetes, hypertension, coronary heart disease (CHD) and stroke were investigated in association with presence of CHD and stroke. Among 3611 diabetic patients, 181 (5.0%) had CHD and 118 (3.3%) had stroke. After adjustment for conventional risk factors, FH of CHD (OR 2.32, p &lt; 0.0001) and of diabetes (OR 1.44, p &lt; 0.05) were associated with CHD, and FH of stroke (OR 1.86, p &lt; 0.01) was associated with stroke. FH of hypertension was significantly associated with presence of hypertension and obesity. Synergistic effect of FH of CHD in combination with hypertension or aging on increasing CHD. and that of FH of stroke in combination with microalbuminuria on increasing stroke were found. FH of diabetes, of hypertension, of CHD and of stroke were significantly associated with FH of each disease, indicating clustering, of FH. In diabetic population, FH of CHD and FH of stroke doubled the risk of CHD and stroke, respectively, and had synergistic effect in combination with other risk factors. Clustering of FH may indicate interrelation of genetic predisposition. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.atherosclerosis.2008.02.025

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  • 【新時代の糖尿病学 病因・診断・治療研究の進歩】 糖尿病に起因する合併症 糖尿病合併症の概論的事項 我が国における糖尿病合併症に関する大規模臨床研究のエビデンス 欧米との比較

    曽根 博仁, 山田 信博

    日本臨床   66 ( 増刊9 新時代の糖尿病学(4) )   22 - 30   2008.11

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  • 生活習慣病の臨床エビデンス 糖尿病患者においてウエスト周囲径を測定する意義は?

    曽根 博仁, 山田 信博

    Q&Aでわかる肥満と糖尿病   7 ( 6 )   921 - 923   2008.11

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  • 【食後高血糖と食後高脂血症】 食後高血糖に対する運動療法の効果は? 食後高血糖に対する運動療法の効果について教えてください

    曽根 博仁

    Q&Aでわかる肥満と糖尿病   7 ( 6 )   875 - 877   2008.11

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  • 【新時代の糖尿病学 病因・診断・治療研究の進歩】 糖尿病に起因する合併症 慢性合併症 細小血管症 発症の主な危険因子 環境要因

    齋藤 和美, 曽根 博仁

    日本臨床   66 ( 増刊9 新時代の糖尿病学(4) )   140 - 143   2008.11

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  • 【わが国における最近の糖尿病メガスタディ】 Japan Diabetes Complications Study:JDCS

    曽根 博仁, 山田 信博

    Diabetes Frontier   19 ( 5 )   601 - 607   2008.10

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  • 【糖尿病の冠動脈疾患に対する治療戦略 内科の立場から】 糖尿病の冠疾患とそのリスクファクターの疫学 わが国と欧米のエビデンス

    曽根 博仁, 山田 信博

    日本冠疾患学会雑誌   14 ( 3 )   232 - 238   2008.10

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  • 人間ドックデータを活用した2型糖尿病発症における食習慣の意義の検討

    戸塚 久美子, 前野 貴美, 齊藤 和美, 牧 美保, 菅原 歩美, 佐藤 睦美, 平沼 ゆり, 小野 幸雄, 内藤 隆志, 曽根 博仁

    健康管理事業団研究助成論文集   XXIV ( 24 )   45 - 52   2008.10

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    「早食い」、「欠食」、「間食」、「夜食」、「外食」という、一般に好ましくないとされる典型的な食習慣が、耐糖能障害(IGT)や2型糖尿病(DM)の発症に与える影響を前向きに検討した。75g経口糖負荷試験を含む宿泊型人間ドックを、3年間の間隔で2回以上受診した男女230例中、初回ドック受診時にIGT、DMと判定された者、DMの既往を持つ者を除いた172例を対象とした。3年間の追跡期間中、39例が、IGTまたはDMを発症した。IGTまたはDMの発症を目的変数とし、観察開始時の性別、年齢、喫煙、アルコール摂取量、糖尿病家族歴、最大血圧、血清総コレステロール、HDLコレステロール、中性脂肪、CRP、早朝空腹時血糖を説明変数としてロジスティック回帰分析を行い、「早食い」の者のオッズ比は1.63と有意であった。「早食い」は、独立したIGT/DMの危険因子となることが示唆された。

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  • 【大規模臨床試験 循環・代謝系を中心に】 糖尿病 大規模臨床試験 二次予防 JDCS

    曽根 博仁, 山田 信博, JDCSグループ

    日本臨床   66 ( 増刊8 大規模臨床試験 )   642 - 651   2008.10

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDC Study) 糖尿病腎症の発症について

    田中 司朗, 飯室 聡, 大橋 靖雄, 田中 佐智子, 守屋 達美, 矢島 義忠, 山田 信博, 曽根 博仁, 赤沼 安夫, 片山 茂裕

    Diabetes Frontier   19 ( 5 )   699 - 700   2008.10

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  • 微量アルブミン尿、推算GFRと心血管疾患 JDDMスタデイーでみた日本人2型糖尿病から

    横山 宏樹, 平尾 紘一, 川井 紘一, 杉本 英克, 武田 浩, 大石 まり子, 南 昌江, 宮澤 一裕, 工藤 幹彦, 大河原 久子, 高村 宏, 高井 昌彦, 高橋 千恵子, 土井 邦紘, 岩崎 皓一, 福元 良英, 曽根 博仁, 松島 雅人, 高木 廣文, 小林 正

    Diabetes Frontier   19 ( 5 )   699 - 699   2008.10

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  • 青少年期における有酸素運動能力(総合体力)とその後の寿命および生活習慣病罹患に関する長期縦断研究

    佐藤睦美, 児玉暁, 穴迫唯衣, 牧美保, 戸塚久美子, 斎藤あき, 増田かやの, 石井朋子, 室岡和彦, 鈴木恵美子, 近藤和雄, 曽根博仁

    日本未病システム学会学術総会抄録集   15th   140   2008.9

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  • 頸動脈内中膜複合体厚(IMT)に関連する因子の横断的検討

    阿隅美保子, 佐伯晃, 古川豊, 秋山朋子, 大泉卓美, 鶉橋弘子, 齋藤和美, 児玉暁, 宮澤英充, 松井博滋, 山口龍生, 福田寛, 曽根博仁

    日本未病システム学会学術総会抄録集   15th   95   2008.9

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  • 一般健常者における運動耐用能が心血管疾患発症リスクに及ぼす影響のメタアナリシス

    児玉暁, 牧美保, 斉藤和美, 佐藤睦美, 穴迫唯衣, 阿隅美保子, 谷内洋子, 曽根保子, 山田信博, 曽根博仁

    日本未病システム学会学術総会抄録集   15th   91   2008.9

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  • 耐糖能異常及び糖尿病発症の予測因子として脂肪肝は肝機能検査異常よりも優れた指標である

    戸塚久美子, 前野貴美, 児玉暁, 阿隅美保子, 佐藤睦美, 西垣結佳子, 齊藤あき, 平沼ゆり, 小野幸雄, 内藤隆志, 曽根博仁

    日本未病システム学会学術総会抄録集   15th   142   2008.9

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  • 早食い習慣は耐糖能異常および糖尿病発症のリスクファクターである

    戸塚久美子, 前野貴美, 齊藤和美, 谷内洋子, 菅原歩美, 佐藤睦美, 西垣結佳子, 齊藤あき, 小野幸雄, 内藤隆志, 曽根博仁

    日本未病システム学会学術総会抄録集   15th   70   2008.9

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  • 健常者の脂肪負荷後血中トリグリセリド値に影響を与える因子の検討

    FUKUSHI AYAKO, KODAMA AKIRA, SAITO KAZUMI, TANIUCHI YOKO, SUGAWARA AYUMI, TOTSUKA KUMIKO, SHUKU BYO, SAITO KAZUNORI, KONDO KAZUO, SONE HIROHITO

    日本未病システム学会学術総会抄録集   15th   115   2008.9

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  • 思春期女性の減量行動に関与する因子の検討

    菅原歩美, 佐藤睦美, 福士亜矢子, 齋藤和美, 松島悦子, 藤原葉子, 栗原恵美子, 山梨八重子, 増田かやの, 佐藤道幸, 石井朋子, 米田俊彦, 山本茂, 近藤和雄, 曽根博仁

    日本未病システム学会学術総会抄録集   15th   87   2008.9

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  • 青少年期のBMIとその後の寿命に関する長期縦断研究

    佐藤睦美, 斎藤和美, 菅原歩美, 阿隅美保子, 西垣結佳子, 叔森, 増田かやの, 石井朋子, 室岡和彦, 鈴木恵美子, 近藤和雄, 曽根博仁

    日本未病システム学会学術総会抄録集   15th   141   2008.9

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  • 思春期女性におけるボディーイメージの現状とその関連因子の検討

    菅原歩美, 佐藤睦美, 戸塚久美子, 児玉暁, 松島悦子, 藤原葉子, 栗原恵美子, 山梨八重子, 佐藤道幸, 石井朋子, 田中京子, 菊池美千世, 山本茂, 近藤和雄, 曽根博仁

    日本未病システム学会学術総会抄録集   15th   86   2008.9

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  • 【新時代の糖尿病学 病因・診断・治療研究の進歩】 糖尿病治療学の進歩 メガスタディから得られた糖尿病診療のEBM 日本人を対象にした糖尿病診療に関する大規模前向き臨床研究

    曽根 博仁, 山田 信博

    日本臨床   66 ( 増刊7 新時代の糖尿病学(3) )   39 - 45   2008.9

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  • 生活習慣病の臨床エビデンス サプリメントとしてのビタミンと心血管疾患のリスク

    佐藤 睦美, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   7 ( 5 )   745 - 747   2008.9

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  • 【新時代の糖尿病学 病因・診断・治療研究の進歩】 糖尿病治療学の進歩 糖尿病治療概論 治療目標 血管合併症の発症・進展の阻止

    曽根 博仁, 山田 信博

    日本臨床   66 ( 増刊7 新時代の糖尿病学(3) )   81 - 88   2008.9

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  • アスタキサンチンのマクロファージにおける抗動脈硬化作用の検討

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 野本 佳世子, 平田 悠美子, 永井 美宇, 村上 香純, 鈴木 佳織, 豊崎 美紅, 田口 千恵, 貴堂 としみ, 曽根 博仁, 蔵田 英明, 近藤 和雄

    肥満研究   14 ( Suppl. )   279 - 279   2008.9

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  • 青少年期の全身持久力および総合運動能力がその後の健康状態に及ぼす影響

    SATO MUTSUMI, SUGAWARA AYUMI, TOTSUKA KUMIKO, FUKUSHI AYAKO, TANIUCHI YOKO, IBE YOKO, SAITO KAZUMI, KODAMA AKIRA, SONE HIROHITO

    栄養学雑誌   66 ( 5 Supplement )   206   2008.9

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  • 健常人男女における脂肪負荷後血中トリグリセリド変化に関与する因子の探索

    FUKUSHI AYAKO, SATO MUTSUMI, SUGAWARA AYUMI, TANIUCHI YOKO, IBE YOKO, KODAMA AKIRA, SAITO KAZUMI, KONDO KAZUO, SONE HIROHITO

    栄養学雑誌   66 ( 5 Supplement )   143   2008.9

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  • Palmitate impairs and eieosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets

    Toyonori Kato, Hitoshi Shimano, Takashi Yamamoto, Mayumi Ishikawa, Shin Kumadaki, Takashi Matsuzaka, Yoshimi Nakagawa, Naoya Yahagi, Masanori Nakakuki, Alyssa H. Hasty, Yoshinori Takeuchi, Kazuto Kobayashi, Akimitsu Takahashi, Shigeru Yatoh, Hiroaki Suzuki, Hirohito Sone, Nobuhiro Yamada

    DIABETES   57 ( 9 )   2382 - 2392   2008.9

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    OBJECTIVE-Chronic exposure to fatty acids causes beta-cell failure, often referred to as lipotoxicity. We investigated its mechanisms, focusing on contribution of SREBP-1c, a key transcription factor for Lipogenesis.
    RESEARCH DESIGN AND METHODS-We studied in vitro and in vivo effects of saturated and polyunsaturated acids on insulin secretion, insulin signaling, and expression of genes involved in beta-cell functions. Pancreatic islets isolated from C57BL/6 control and SREBP-1-null mice and adenoviral gene delivery or knockdown systems of related genes were used.
    RESULTS-Incubation of C57BL/6 islets with palmitate caused inhibition of both glucose- and potassium-stimidated insulin secretion, but addition of eicosapentaenoate (EPA) restored both inhibitions. Concomitantly, palmitate activated and EPA abolished both mRNA and nuclear protein of SREBP-1c, accompanied by reciprocal changes of SREBP-1c target genes such as insulin receptor substrate-2 (IRS-2) and granuphilin. These palmitate-EPA effects on insulin secretion were abolished in SREBP-1-null islets. Suppression of IRS-2/Akt pathway could be a part of the downstream mechanism for the SREBP-1c-mediated insulin secretion defect because adenoviral constitutively active Akt compensated it. Uncoupling protein-2 (UCP-2) also plays a crucial role in the palmitate inhibition of insulin secretion, as confirmed by knockdown experiments, but SREBP-1c contribution to UCP-2 regulation was partial. The palmitate-EPA regulation of insulin secretion was similarly observed in islets from C57BL/6 mice pretreated with dietary manipulations. Furthermore, administration of EPA to diabetic KK-Ay mice ameliorated impairment of insulin secretion in their islets.
    CONCLUSIONS-SREBP-1c plays a dominant role in palmitate-mediated insulin secretion defect, and EPA prevents it through SREBP-1c inhibition, implicating a therapeutic potential for treating diabetes related to lipotoxicity.

    DOI: 10.2337/db06-1806

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  • 青年期および若年日本人女性のやせの現状と関連要因の検討

    SUGAWARA AYUMI, SATO MUTSUMI, FUKUSHI AYAKO, TOTSUKA KUMIKO, IBE YOKO, TANIUCHI YOKO, SAITO KAZUMI, KODAMA AKIRA, SONE HIROHITO

    栄養学雑誌   66 ( 5 Supplement )   162   2008.9

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  • 糖尿病患者における心・脳 腎連関 日本人2型糖尿病における糖尿病性腎症および大血管障害の発症について 糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDC Study)から

    守屋 達美, 田中 司朗, 飯室 聡, 大橋 靖雄, 山田 信博, 曽根 博仁, 片山 茂裕

    糖尿病合併症   22 ( Suppl.1 )   41 - 41   2008.9

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  • 大血管合併症の克服をめざして 大規模臨床研究からの新しいエビデンス マルチプルリスクファクターとその管理の重要性

    曽根 博仁, 山田 信博

    糖尿病学の進歩   ( 42 )   157 - 164   2008.9

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  • マクロファージにおけるアスタキサンチンの抗動脈硬化作用の検討

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 野本 佳世子, 平田 悠美子, 永井 美宇, 村上 香純, 鈴木 佳織, 豊崎 美紅, 田口 千恵, 貴堂 としみ, 曽根 博仁, 蔵田 英明, 近藤 和雄

    New Diet Therapy   24 ( 2 )   204 - 204   2008.9

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  • 心血管、腎臓からみたメタボリックシンドローム 糖尿病患者におけるメタボリックシンドロームと心血管イベントとCKD JDCS研究より

    曽根 博仁, 片山 茂裕, 山田 信博, JDCSグループ

    肥満研究   14 ( Suppl. )   100 - 100   2008.9

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  • Palmitate impairs and eieosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets

    Toyonori Kato, Hitoshi Shimano, Takashi Yamamoto, Mayumi Ishikawa, Shin Kumadaki, Takashi Matsuzaka, Yoshimi Nakagawa, Naoya Yahagi, Masanori Nakakuki, Alyssa H. Hasty, Yoshinori Takeuchi, Kazuto Kobayashi, Akimitsu Takahashi, Shigeru Yatoh, Hiroaki Suzuki, Hirohito Sone, Nobuhiro Yamada

    DIABETES   57 ( 9 )   2382 - 2392   2008.9

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    OBJECTIVE-Chronic exposure to fatty acids causes beta-cell failure, often referred to as lipotoxicity. We investigated its mechanisms, focusing on contribution of SREBP-1c, a key transcription factor for Lipogenesis.
    RESEARCH DESIGN AND METHODS-We studied in vitro and in vivo effects of saturated and polyunsaturated acids on insulin secretion, insulin signaling, and expression of genes involved in beta-cell functions. Pancreatic islets isolated from C57BL/6 control and SREBP-1-null mice and adenoviral gene delivery or knockdown systems of related genes were used.
    RESULTS-Incubation of C57BL/6 islets with palmitate caused inhibition of both glucose- and potassium-stimidated insulin secretion, but addition of eicosapentaenoate (EPA) restored both inhibitions. Concomitantly, palmitate activated and EPA abolished both mRNA and nuclear protein of SREBP-1c, accompanied by reciprocal changes of SREBP-1c target genes such as insulin receptor substrate-2 (IRS-2) and granuphilin. These palmitate-EPA effects on insulin secretion were abolished in SREBP-1-null islets. Suppression of IRS-2/Akt pathway could be a part of the downstream mechanism for the SREBP-1c-mediated insulin secretion defect because adenoviral constitutively active Akt compensated it. Uncoupling protein-2 (UCP-2) also plays a crucial role in the palmitate inhibition of insulin secretion, as confirmed by knockdown experiments, but SREBP-1c contribution to UCP-2 regulation was partial. The palmitate-EPA regulation of insulin secretion was similarly observed in islets from C57BL/6 mice pretreated with dietary manipulations. Furthermore, administration of EPA to diabetic KK-Ay mice ameliorated impairment of insulin secretion in their islets.
    CONCLUSIONS-SREBP-1c plays a dominant role in palmitate-mediated insulin secretion defect, and EPA prevents it through SREBP-1c inhibition, implicating a therapeutic potential for treating diabetes related to lipotoxicity.

    DOI: 10.2337/db06-1806

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  • 生活習慣病の臨床エビデンス やせすぎ、太り過ぎとがんのリスク

    菅原 歩美, 齋藤 和美, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   7 ( 4 )   599 - 601   2008.7

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  • 糖尿病性網膜症 病態研究および治療の最前線 糖尿病合併症における網膜症の位置づけ JDCSの中間結果を含めて

    曽根 博仁, 山田 信博, 山下 英俊

    糖尿病合併症   22 ( 1 )   71 - 75   2008.7

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  • 当院2型糖尿病患者における平均血糖コントロール状況と合併症進展状況 探索的検討

    川井 紘一, 本橋 しのぶ, 岩永 志律子, 井川 茅野, 齋藤 和美, 曽根 博仁

    糖尿病   51 ( 7 )   661 - 661   2008.7

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  • Long-term lifestyle intervention lowers incidence of stroke in Japanese patients with type 2 diabetes. The Japan Diabetes Complications Study (JDCS)

    Hirohito Sone, Sachiko Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shun Ishibashi, Shi-Gehiro Katayama, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES   57   A50 - A50   2008.6

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  • Significance of waist circumference as a cardiovascular and metabolic risk in Japanese patients with type 2 diabetes. The Japan diabetes complications study (JDCS)

    Hirohito Sone, Sachiko Tanaka, Satoshi Iimuro, Koji Oida, Yoshimitsu Yamasaki, Shun Ishibashi, Shinichi Oikawa, Shigehiro Katayama, Hideki Ito, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES   57   A624 - A624   2008.6

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  • 【新時代の糖尿病学 病因・診断・治療研究の進歩】 肥満 我が国における肥満の動向 メタボリックシンドロームとの関連で

    曽根 博仁

    日本臨床   66 ( 増刊4 新時代の糖尿病学(2) )   611 - 620   2008.6

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  • マクロファージ機能に対するアスタキサンチンの影響

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 野本 佳世子, 平田 悠美子, 田口 千恵, 澤, 曽根 博仁, 蔵田 英明, 近藤 和雄

    日本動脈硬化学会総会プログラム・抄録集   40回   203 - 203   2008.6

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  • Early intervention is effective to prevent the progression to proteinuria in diabetics with normo- and low-microalbuminuria: Japan Diabete&apos;s Complications Study (JDCS) Reviewed

    Shigehiro Katayama, Shiro Tanaka, Sachiko Tanaka, Tatsumi Moriya, Yoshitada Yajima, Hirohito Sone, Yasuo Ohashi, Nobuhiro Yamada

    DIABETES   57   A210 - A210   2008.6

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  • 日本人2型糖尿病患者の微量アルブミン尿の寛解に影響する因子の検討

    齋藤 和美, 児玉 暁, 姫野 彰子, 近藤 和雄, 曽根 博仁, 川井 紘一, 田中 司朗, 大橋 靖雄, 山田 信博

    成人病と生活習慣病   38 ( 5 )   562 - 562   2008.5

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  • 生活習慣病の臨床エビデンス 糖尿病大血管合併症と血糖コントロール

    曽根 博仁

    Q&Aでわかる肥満と糖尿病   7 ( 3 )   459 - 461   2008.5

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  • 【産業医のための生活習慣病と動脈硬化、リスクとその管理】 糖尿病における動脈硬化症とそのリスクファクター管理

    曽根 博仁, 山田 信博

    成人病と生活習慣病   38 ( 5 )   490 - 496   2008.5

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    糖尿病患者には初期から動脈硬化症(すなわち大血管合併症)が頻発し、その予後に悪影響を及ぼしている。脂質異常症や高血圧など、心血管リスクファクターが重責する糖尿病患者において、大血管合併症を未然に防ぐためには、血糖、血清脂質、血圧など多項目について同時に十分なコントロールを要することが、エビデンスとして確立している。これに基づき、糖尿病患者に対する血圧や血清脂質のガイドライン目標値は、一般より厳しく設定してあるが、日本でも欧米でもその目標値に達しない患者がかなり多く、それらのコントロールと患者管理には世界的に改善の余地が大きい。(著者抄録)

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  • 2型糖尿病における食事の糖・脂質(C/F)比の変化が血糖コントロールに及ぼす影響のメタアナリシス

    児玉 暁, 斉藤 和美, 姫野 彰子, 鈴木 恵美子, 曽根 博仁, 田中 司朗, 大橋 靖雄, 山田 信博

    成人病と生活習慣病   38 ( 5 )   564 - 565   2008.5

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  • 2型糖尿病患者の早期腎症の改善因子に関する前向き研究

    齋藤 和美, 川井 紘一, 児玉 暁, 本橋 しのぶ, 坂巻 顕太郎, 田中 司朗, 大橋 靖雄, 高橋 昭光, 島野 仁, 山田 信博, 曽根 博仁

    糖尿病   51 ( Suppl.1 )   S - 133   2008.4

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  • ODSラットにおけるアスコルビン酸の栄養状態の違いによる輸送担体の発現変動

    曽根 保子, 谷口 サチ, 児玉 暁, 齋藤 和美, 曽根 博仁, 山王丸 靖子, 三宅 紀子, 倉田 忠男, 鈴木 恵美子

    ビタミン   82 ( 4 )   308 - 308   2008.4

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  • 【糖尿病 最近の話題】 日本人の糖尿病と血管合併症 JDCS研究

    曽根 博仁, 山田 信博

    成人病と生活習慣病   38 ( 4 )   421 - 428   2008.4

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    現在の糖尿病診療エビデンスの多くは、欧米の大規模研究から得られたものであり、日本を含むアジア人糖尿病患者の特徴は十分に検討されたとはいえない。Japan Diabetes Complications Study(JDCS)は、日本人2型糖尿病患者を対象にした大規模臨床研究である。全国の糖尿病専門施設59ヶ所に通院する2型糖尿病患者2,033名を対象に1996年以来、コントロールや合併症の発症状況などについて毎年調査されている。本研究の中間報告より、日本人糖尿病患者の病態的背景や特徴が欧米人とはかなり異なることが明らかにされてきた。このような相違は、東アジア人糖尿病患者の治療や療養指導においては、東アジア人患者自身のデータによるエビデンスが必要であることを強く示唆している。(著者抄録)

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  • 【動脈硬化の危険因子 治療基準と方法】 糖尿病と動脈硬化 その管理と効果

    曽根 博仁, 山田 信博

    The Lipid   19 ( 2 )   145 - 155   2008.4

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    糖尿病患者には初期から動脈硬化性疾患(すなわち糖尿病大血管合併症)が多発し、その予後を悪化させている。脂質異常症や高血圧が高頻度に合併する糖尿病患者の動脈硬化性疾患を予防するには、血糖、血清脂質、血圧など多項目について十分な治療を要する必要があることが、エビデンスとして確立している。これに基づき、糖尿病患者に対する血圧や血清脂質のガイドライン目標値は、一般より厳しく設定してあるが、日本でも欧米でもその目標値に達しない患者がかなり多い。一方、糖尿病患者における動脈硬化性疾患の発症パターンやリスクファクターには性別や人種差がみられるが、これまでの大規模臨床研究は欧米人患者を主体としており、東アジア人における糖尿病患者に対する介入研究はまだ十分でない。日本人の治療対策を考える上でも、日本人の大規模前向きデータを今後さらに蓄積する必要がある。同時に糖尿病患者における食事療法や運動療法による動脈硬化性疾患予防効果についてもエビデンスを充実させる必要がある。(著者抄録)

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDC Study):糖尿病性腎症の発症について

    田中 司朗, 飯室 聡, 大橋 靖雄, 田中 佐智子, 守屋 達美, 矢島 義忠, 山田 信博, 曽根 博仁, 赤沼 安夫, 片山 茂裕

    糖尿病   51 ( Suppl.1 )   S - 301   2008.4

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  • 糖尿病の動脈硬化 基礎から臨床まで 虚血性心疾患・脳卒中のリスクファクター JDCSから学ぶこと

    曽根 博仁, 山田 信博

    糖尿病   51 ( Suppl.1 )   S - 62   2008.4

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  • 各腎症病期におけるCKD病期の割合および正常アルブミン尿CKDの特徴 JDDMスタディ

    横山 宏樹, 川井 紘一, 杉本 英克, 平尾 紘一, 武田 浩, 大石 まり子, 南 昌江, 宮澤 一裕, 工藤 幹彦, 大河原 久子, 高村 宏, 高井 昌彦, 高橋 千恵子, 土井 邦紘, 岩崎 皓一, 福元 良英, 曽根 博仁, 松島 雅人, 高木 廣文, 小林 正

    糖尿病   51 ( Suppl.1 )   S - 299   2008.4

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  • アスタキサンチンのマクロファージ機能に及ぼす影響

    岸本 良美, 谷 真理子, 飯塚 麻貴, 才田 恵美, 野本 佳世子, 平田 悠美子, 永井 美宇, 村上 香純, 田口 千恵, 澤, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    日本栄養・食糧学会大会講演要旨集   62回   273 - 273   2008.4

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  • 生活習慣病の臨床エビデンス 2型糖尿病患者の肥満度 断面調査の結果から

    曽根 博仁, 山田 信博

    Q&Aでわかる肥満と糖尿病   7 ( 2 )   292 - 293   2008.3

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  • 【見えてきたニッポン・エビデンス】 糖尿病領域で見えてきたニッポン・エビデンス

    福士 亜矢子, 齋藤 和美, 曽根 博仁

    糖尿病診療マスター   6 ( 2 )   143 - 153   2008.3

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    DOI: 10.11477/mf.1415100785

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  • 糖尿病早期腎症の寛解に関する時間依存性Coxの比例ハザードモデルによる検討

    齋藤 和美, 川井 紘一, 児玉 暁, 本橋 しのぶ, 坂巻 顕太郎, 田中 司朗, 大橋 靖雄, 高橋 昭光, 島野 仁, 山田 信博, 曽根 博仁

    日本内分泌学会雑誌   83 ( 4 )   1014 - 1014   2008.3

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  • 【メタボリックシンドローム エビデンスから実地診療へ】 メタボリックシンドロームの心血管リスク因子に与える影響はどの程度か? 糖尿病発症リスクとしてのメタボリックシンドローム

    曽根 博仁, 山田 信博

    EBMジャーナル   9 ( 2 )   182 - 186   2008.2

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  • 2型糖尿病食事療法における糖・脂質比の変化と血糖コントロール改善効果のメタ解析

    児玉 暁, 齋藤 和美, 田中 司朗, 鈴木 恵美子, 大橋 靖雄, 島野 仁, 高橋 昭光, 山田 信博, 曽根 博仁

    日本内科学会雑誌   97 ( Suppl. )   234 - 234   2008.2

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  • 【メタボリックシンドローム】 日本におけるメタボリックシンドロームの疫学 日本人糖尿病患者におけるメタボリックシンドローム JDCSの結果より

    曽根 博仁, 山田 信博

    診断と治療   96 ( 2 )   303 - 308   2008.2

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  • Importance of lipid levels in elderly diabetic individuals - Baseline characteristics and 1-year - Survey of cardiovascular events

    Toshio Hayashi, Seinosuke Kawashima, Hideki Itoh, Nobuhiro Yamada, Hirohito Sone, Hiroshi Watanabe, Yoshiyuki Hattori, Takashi Ohrui, Masashi Yoshizumi, Koutaro Yokote, Kiyoshi Kubota, Hideki Nomura, Hiroyuki Umegaki, Akihisa Iguchi

    CIRCULATION JOURNAL   72 ( 2 )   218 - 225   2008.2

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    Background The respective incidences of ischemic heart and cerebrovascular disease (IHD, CVD) are high in diabetic individuals. Complications of dyslipidemia increase the risk, but direct evidence is limited, so a cohort prospective study (Japan-CDM) was conducted.
    Methods and Results The study group comprised 4,014 subjects with type 2 diabetes (1,936 women, 2,078 men; mean age 67.4 +/- 9.5 years) who were divided into dyslipidemic patients (79.1%) with or without medication (medicated, 50.9%; not medicated, 28.2%) and normo-lipidemic patients (20.9%). The incidence of IHD, CVD, arteriosclerosis obliterans (ASO), congestive heart failure (CHF) and death was assessed. IHD and CVD occurred in 0.82 and 0.67%, respectively, during the first year following registration. CHF, ASO and sudden death occurred in 0.27%, 0.12% and 0.12%, respectively. There was a significant statistical difference in the relation of elevated levels of high-density lipoprotein-cholesterol to lower rates of IHD and CVD. IHD and CVD in males were dependent on the level of low-density lipoprotein-cholesterol (LDL-C): 0.45%, 1.56%, 1.78%, 1.91% and 2.34% were observed in less than 2.11, 2.11 - 2.62, 2.63 - 3.15, 3.16 - 3.67, and more than 3.68 mol/L of LDL-C. In the lowest LDL-C group, death other than from vascular diseases was increased. Age, sex (male) and complicated hypertension increased the risk of events. Patients who were prescribed anti hyperlipidemic agents suffered less events than patients who were not being treated, which suggests direct effects of therapy.
    Conclusion Strict lipid control may be effective for reducing the incidence of vascular events in Japanese diabetic individuals.

    DOI: 10.1253/circj.72.218

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  • Importance of lipid levels in elderly diabetic individuals - Baseline characteristics and 1-year - Survey of cardiovascular events

    Toshio Hayashi, Seinosuke Kawashima, Hideki Itoh, Nobuhiro Yamada, Hirohito Sone, Hiroshi Watanabe, Yoshiyuki Hattori, Takashi Ohrui, Masashi Yoshizumi, Koutaro Yokote, Kiyoshi Kubota, Hideki Nomura, Hiroyuki Umegaki, Akihisa Iguchi

    CIRCULATION JOURNAL   72 ( 2 )   218 - 225   2008.2

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    Background The respective incidences of ischemic heart and cerebrovascular disease (IHD, CVD) are high in diabetic individuals. Complications of dyslipidemia increase the risk, but direct evidence is limited, so a cohort prospective study (Japan-CDM) was conducted.
    Methods and Results The study group comprised 4,014 subjects with type 2 diabetes (1,936 women, 2,078 men; mean age 67.4 +/- 9.5 years) who were divided into dyslipidemic patients (79.1%) with or without medication (medicated, 50.9%; not medicated, 28.2%) and normo-lipidemic patients (20.9%). The incidence of IHD, CVD, arteriosclerosis obliterans (ASO), congestive heart failure (CHF) and death was assessed. IHD and CVD occurred in 0.82 and 0.67%, respectively, during the first year following registration. CHF, ASO and sudden death occurred in 0.27%, 0.12% and 0.12%, respectively. There was a significant statistical difference in the relation of elevated levels of high-density lipoprotein-cholesterol to lower rates of IHD and CVD. IHD and CVD in males were dependent on the level of low-density lipoprotein-cholesterol (LDL-C): 0.45%, 1.56%, 1.78%, 1.91% and 2.34% were observed in less than 2.11, 2.11 - 2.62, 2.63 - 3.15, 3.16 - 3.67, and more than 3.68 mol/L of LDL-C. In the lowest LDL-C group, death other than from vascular diseases was increased. Age, sex (male) and complicated hypertension increased the risk of events. Patients who were prescribed anti hyperlipidemic agents suffered less events than patients who were not being treated, which suggests direct effects of therapy.
    Conclusion Strict lipid control may be effective for reducing the incidence of vascular events in Japanese diabetic individuals.

    DOI: 10.1253/circj.72.218

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  • 2型糖尿病食事療法の糖・脂質比の変化が血糖コントロールに及ぼす影響のメタアナリシス

    児玉暁, 田中司朗, 斉藤和美, 牧美保, 谷内洋子, 阿隅美保子, 伊部陽子, 大橋靖雄, 曽根博仁

    Journal of Epidemiology   18 ( 1 Supplement )   183   2008.1

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  • 生活習慣病の臨床エビデンス 糖尿病患者は肥満か? 肥満糖尿病患者は食べ過ぎか?

    曽根 博仁, 山田 信博

    Q&Aでわかる肥満と糖尿病   7 ( 1 )   146 - 149   2008.1

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  • 【世界の介入研究から何を学んだか?】 UKPDS

    曽根 博仁

    Q&Aでわかる肥満と糖尿病   7 ( 1 )   64 - 66   2008.1

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  • 産業医のための生活習慣病と動脈硬化、リスクとその管理 糖尿病における動脈硬化症とそのリスクファクター管理

    曽根 博仁

    日本成人病(生活習慣病)学会会誌   34   38 - 38   2008.1

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  • 糖尿病食事療法における糖・脂質比の変化が血糖コントロールに及ぼす影響のメタ解析

    児玉 暁, 斉藤 和美, 田中 司朗, 姫野 彰子, 鈴木 恵美子, 大橋 靖雄, 山田 信博, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   34   51 - 51   2008.1

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  • 【糖尿病に伴う血管病に迫る 各種病因と主要血管の病像まで】 病因から迫る メタボリックシンドロームと血管病はどのようにかかわるか?

    曽根 博仁, 山田 信博

    Vascular Medicine   4 ( 1 )   8 - 15   2008.1

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    耐糖能障害を含む糖尿病は心血管疾患の強いリスクファクターであるとともに、メタボリックシンドロームの構成因子の1つでもあり、メタボリックシンドロームの病態背景とされるインスリン抵抗性とも関係が深い。欧米を中心としたこれまでの研究結果によると、メタボリックシンドロームは2型糖尿病の発症予知に有用であり、2型糖尿病に匹敵する心血管疾患発症リスクを有し、2型糖尿病に合併した場合、心血管疾患のリスクをさらに上昇させることが知られていた。ただし日本人2型糖尿病患者においては、現行のメタボリックシンドローム診断基準(とくに腹囲による腹部肥満を必須項目とした場合)が、必ずしも将来の心血管疾患発症リスクの評価に適していないことも判明しており、日本人糖尿病患者に適した心血管合併症リスクの評価法をさらに検討する必要がある。(著者抄録)

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  • 日本人2型糖尿病患者の微量アルブミン尿の寛解に影響する因子の検討

    齋藤 和美, 川井 紘一, 児玉 暁, 田中 司朗, 姫野 彰子, 近藤 和雄, 大橋 靖雄, 山田 信博, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   34   49 - 49   2008.1

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  • JDCSからみた日本人2型糖尿病患者の特徴

    曽根 博仁, 吉村 幸雄, 田中 明, 山田 信博

    栄養学雑誌   65 ( 6 )   269 - 279   2007.12

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    Type 2 diabetes is one of the most challenging health problems throughout the world and is increasing at an alarming rate. Most clinical evidence involved in therapeutic guidelines for diabetes is derived from European or American cohort studies, and the characteristics of diabetes in Asians, including Japanese, have been only poorly investigated to date, despite Asians constituting approximately half of the world diabetes population. The Japan Diabetes Complications Study (JDCS) is a nationwide multi-center prospective study of type 2 diabetic patients. In 1996, 2, 205 patients aged 40-70 years with previously diagnosed type 2 diabetes were recruited from 59 Japanese institutes that specialize in diabetes care. Parameters related to their diet, exercise, glycemic control, diabetic complication events, dyslipidemia, hypertension, obesity and quality of life have been measured and collected every year until now. It was clarified from the interim results of JDCS that the characteristics and pathophysiological backgrounds of diabetes in East Asians were quite different from those in Caucasian subjects. Compared with Caucasian diabetic patients, the JDCS patients had a much lower body mass index (BMI). Moreover, whereas the mean BMI of Caucasian diabetic patients was higher than that reported for non-diabetics of the same ethnic origin, the mean BMI of Japanese diabetic patients was normal in comparison with the Japanese non-diabetic population. Other differences between Japanese and Caucasian patients with type 2 diabetes could be found in the incidence rate and risk factors of complications, the effects of moderate alcohol drinking on cardiovascular disease, and the clinical significance of the diagnosis of metabolic syndrome. These profound differences demonstrate the necessity for obtaining clinical evidence based on a large-scale study of East Asian patients in order to establish and provide management and care specific to this particular population.

    DOI: 10.5264/eiyogakuzashi.65.269

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  • 【脂質異常症の臨床的意義 HDLは予防・治療の標的か、指標か】 生活習慣(ライフスタイル)の変化とHDL-Cの改善

    児玉 暁, 曽根 博仁

    Progress in Medicine   27 ( 12 )   2829 - 2834   2007.12

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  • 【血栓・塞栓症の病態・検査・治療】 おもな血栓・塞栓症の病態と検査 血栓・塞栓症のリスクファクターとしてのメタボリックシンドローム

    曽根 博仁, 伊部 洋子, 齋藤 和美

    Medical Technology   35 ( 13 )   1450 - 1455   2007.12

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  • Involvement of glomerular SREBP-1c in diabetic nephropathy

    Naomi Ishigaki, Takashi Yamamoto, Yoshio Shimizu, Kazuto Kobayashi, Shigeru Yatoh, Hirohito Sone, Akimitsu Takahashi, Hiroaki Suzuki, Kunihiro Yamagata, Nobuhiro Yamada, Hitoshi Shimano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   364 ( 3 )   502 - 508   2007.12

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    The role of glomerular SREBP-1c in diabetic nephropathy was investigated. PEPCK-promoter transgenic mice overexpressing nuclear SREBP-1c exhibited enhancement of proteinuria with mesangial proliferation and matrix accumulation, mimicking diabetic nephropathy, despite the absence of hyperglycemia or hyperlipidemia. Isolated transgenic glomeruli had higher expression of TGF beta-1, fibronectin, and SPARC in the absence of marked lipid accumulation. Gene expression of P47(phox), p67(phox), and PU.1 were also activated, accompanying increased 8-OHdG in urine and kidney, demonstrating that glomerular SREBP-1c could directly cause oxidative stress through induced NADPH oxidase. Similar changes were observed in STZ-treated diabetic mice with activation of endogenous SREBP-1c. Finally, diabetic proteinuria and oxidative stress were ameliorated in SREBP-1-null mice. Adenoviral overexpression of active and dominant-negative SREBP-I c caused consistent reciprocal changes in expression of both profibrotic and oxidative stress genes in MESI3 mesangial cells. These data suggest that activation of glomerular SREBP-1c could contribute to emergence and/or progression of diabetic nephropathy. (C) 2007 Elsevier Inc. All rights reserved.

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  • Involvement of glomerular SREBP-1c in diabetic nephropathy

    Naomi Ishigaki, Takashi Yamamoto, Yoshio Shimizu, Kazuto Kobayashi, Shigeru Yatoh, Hirohito Sone, Akimitsu Takahashi, Hiroaki Suzuki, Kunihiro Yamagata, Nobuhiro Yamada, Hitoshi Shimano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   364 ( 3 )   502 - 508   2007.12

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    The role of glomerular SREBP-1c in diabetic nephropathy was investigated. PEPCK-promoter transgenic mice overexpressing nuclear SREBP-1c exhibited enhancement of proteinuria with mesangial proliferation and matrix accumulation, mimicking diabetic nephropathy, despite the absence of hyperglycemia or hyperlipidemia. Isolated transgenic glomeruli had higher expression of TGF beta-1, fibronectin, and SPARC in the absence of marked lipid accumulation. Gene expression of P47(phox), p67(phox), and PU.1 were also activated, accompanying increased 8-OHdG in urine and kidney, demonstrating that glomerular SREBP-1c could directly cause oxidative stress through induced NADPH oxidase. Similar changes were observed in STZ-treated diabetic mice with activation of endogenous SREBP-1c. Finally, diabetic proteinuria and oxidative stress were ameliorated in SREBP-1-null mice. Adenoviral overexpression of active and dominant-negative SREBP-I c caused consistent reciprocal changes in expression of both profibrotic and oxidative stress genes in MESI3 mesangial cells. These data suggest that activation of glomerular SREBP-1c could contribute to emergence and/or progression of diabetic nephropathy. (C) 2007 Elsevier Inc. All rights reserved.

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  • Influence of adiponectin gene polymorphism SNP276 (G/T) on adiponectin in response to exercise training

    Hu Huang, Kaoruko Tada Iida, Haruka Murakami, Yoko Saito, Takeshi Otsuki, Motoyuki Iemitsu, Seiji Maeda, Hirohito Sone, Shinya Kuno, Ryuichi Ajisaka

    ENDOCRINE JOURNAL   54 ( 6 )   879 - 886   2007.12

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    Adiponectin is an adipocytokine that is involved in insulin sensitivity. The adiponectin gene contains a single nucleotide polymorphism (SNP) at position 276 (G/T). The GG genotype of SNP276 (G/T) is associated with lower plasma adiponectin levels and a higher insulin resistance index. Therefore, we examined the influence of SNP276 (G/T) on the plasma level of adiponectin in response to exercise training. Thirty healthy Japanese (M12/F18; 56 to 79 years old) performed both resistance and endurance training, 5 times a week for 6 months. The work rate per kg of weight at double-product break-point (DPBP) was measured. Blood samples were obtained before and after the experiment. Plasma concentrations of adiponectin, HbA1c, insulin, glucose, total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, and triglyceride were measured. Genotypes of SNP276 were specified. Student's t-test for paired values and unpaired values was used. After the 6-month training period, the work rate per kg of weight at DPBP and the plasma HDL-cholesterol level were significantly improved (P&lt;0.05), while no change was observed in the total plasma adiponectin level. However, the plasma adiponectin level in those with the GT + TT genotype had significantly increased (P&lt;0.05). Additionally, the degree of the decrease in the HOMA-R level was significantly greater in the subjects with the GT + TT genotype than those with the GG genotype (p&lt;0.05). Our results suggest that subjects with the genotype GT + TT at SNP276 (G/T) have a greater adiponectin-related response to exercise training than those with the GG genotype.

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  • Influence of adiponectin gene polymorphism SNP276 (G/T) on adiponectin in response to exercise training

    Hu Huang, Kaoruko Tada Iida, Haruka Murakami, Yoko Saito, Takeshi Otsuki, Motoyuki Iemitsu, Seiji Maeda, Hirohito Sone, Shinya Kuno, Ryuichi Ajisaka

    ENDOCRINE JOURNAL   54 ( 6 )   879 - 886   2007.12

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    Adiponectin is an adipocytokine that is involved in insulin sensitivity. The adiponectin gene contains a single nucleotide polymorphism (SNP) at position 276 (G/T). The GG genotype of SNP276 (G/T) is associated with lower plasma adiponectin levels and a higher insulin resistance index. Therefore, we examined the influence of SNP276 (G/T) on the plasma level of adiponectin in response to exercise training. Thirty healthy Japanese (M12/F18; 56 to 79 years old) performed both resistance and endurance training, 5 times a week for 6 months. The work rate per kg of weight at double-product break-point (DPBP) was measured. Blood samples were obtained before and after the experiment. Plasma concentrations of adiponectin, HbA1c, insulin, glucose, total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, and triglyceride were measured. Genotypes of SNP276 were specified. Student's t-test for paired values and unpaired values was used. After the 6-month training period, the work rate per kg of weight at DPBP and the plasma HDL-cholesterol level were significantly improved (P&lt;0.05), while no change was observed in the total plasma adiponectin level. However, the plasma adiponectin level in those with the GT + TT genotype had significantly increased (P&lt;0.05). Additionally, the degree of the decrease in the HOMA-R level was significantly greater in the subjects with the GT + TT genotype than those with the GG genotype (p&lt;0.05). Our results suggest that subjects with the genotype GT + TT at SNP276 (G/T) have a greater adiponectin-related response to exercise training than those with the GG genotype.

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  • 【慢性疾患に対する身体活動のすすめ方 QOL向上への新しい具体策】 糖尿病 運動により糖尿病患者の糖代謝はどのように変わるか

    児玉 暁, 曽根 博仁

    臨床スポーツ医学   24 ( 臨増 )   103 - 110   2007.11

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  • マグネシウム高含有にがりの脂肪細胞分化に及ぼす影響

    岸本 良美, 近藤 春美, 吉岡 絵理, 才田 恵美, 平田 悠美子, 飯塚 麻貴, 野本 佳世子, 田口 千恵, 澤, 貴堂 としみ, 谷 真理子, 横田 邦信, 曽根 博仁, 近藤 和雄

    機能性食品と薬理栄養   4 ( 5 )   353 - 353   2007.11

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  • 糖尿病からみた機能性食品 糖尿病専門医の立場からみた機能性食品への期待

    曽根 博仁

    機能性食品と薬理栄養   4 ( 5 )   316 - 316   2007.11

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  • 生活習慣病の臨床エビデンス 歯周病と糖尿病

    姫野 彰子, 児玉 暁, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   6 ( 6 )   1038 - 1040   2007.11

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  • 【糖尿病網膜症 一次予防、二次予防、三次予防の戦略】 糖尿病網膜症一次および二次予防のエビデンス 他の合併症との関連ならびにJDCS中間報告から

    曽根 博仁, 山田 信博, 山下 英俊

    あたらしい眼科   24 ( 10 )   1281 - 1285   2007.10

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  • 3T3-L1前駆脂肪細胞の分化に対するにがりの影響

    岸本 良美, 近藤 春美, 都, 吉岡 絵理, 才田 恵美, 平田 悠美子, 飯塚 麻貴, 野本 佳世子, 田口 千恵, 澤, 谷 真理子, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    New Diet Therapy   23 ( 2 )   217 - 217   2007.10

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  • Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance

    Takashi Matsuzaka, Hitoshi Shimano, Naoya Yahagi, Toyonori Kato, Ayaka Atsumi, Takashi Yamamoto, Noriyuki Inoue, Mayumi Ishikawa, Sumiyo Okada, Naomi Ishigaki, Hitoshi Iwasaki, Yuko Iwasaki, Tadayoshi Karasawa, Shin Kumadaki, Toshiyuki Matsui, Motohiro Sekiya, Ken Ohashi, Alyssa H. Hasty, Yoshimi Nakagawa, Akimitsu Takahashi, Hiroaki Suzuki, Sigeru Yatoh, Hirohito Sone, Hideo Toyoshima, Jun-ichi Osuga, Nobuhiro Yamada

    NATURE MEDICINE   13 ( 10 )   1193 - 1202   2007.10

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    Insulin resistance is often associated with obesity and can precipitate type 2 diabetes. To date, most known approaches that improve insulin resistance must be preceded by the amelioration of obesity and hepatosteatosis. Here, we show that this provision is not mandatory; insulin resistance and hyperglycemia are improved by the modification of hepatic fatty acid composition, even in the presence of persistent obesity and hepatosteatosis. Mice deficient for Elovl6, the gene encoding the elongase that catalyzes the conversion of palmitate to stearate, were generated and shown to become obese and develop hepatosteatosis when fed a high- fat diet or mated to leptin- deficient ob/ ob mice. However, they showed marked protection from hyperinsulinemia, hyperglycemia and hyperleptinemia. Amelioration of insulin resistance was associated with restoration of hepatic insulin receptor substrate- 2 and suppression of hepatic protein kinase C e activity resulting in restoration of Akt phosphorylation. Collectively, these data show that hepatic fatty acid composition is a new determinant for insulin sensitivity that acts independently of cellular energy balance and stress. Inhibition of this elongase could be a new therapeutic approach for ameliorating insulin resistance, diabetes and cardiovascular risks, even in the presence of a continuing state of obesity.

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  • Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance

    Takashi Matsuzaka, Hitoshi Shimano, Naoya Yahagi, Toyonori Kato, Ayaka Atsumi, Takashi Yamamoto, Noriyuki Inoue, Mayumi Ishikawa, Sumiyo Okada, Naomi Ishigaki, Hitoshi Iwasaki, Yuko Iwasaki, Tadayoshi Karasawa, Shin Kumadaki, Toshiyuki Matsui, Motohiro Sekiya, Ken Ohashi, Alyssa H. Hasty, Yoshimi Nakagawa, Akimitsu Takahashi, Hiroaki Suzuki, Sigeru Yatoh, Hirohito Sone, Hideo Toyoshima, Jun-ichi Osuga, Nobuhiro Yamada

    NATURE MEDICINE   13 ( 10 )   1193 - 1202   2007.10

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    Insulin resistance is often associated with obesity and can precipitate type 2 diabetes. To date, most known approaches that improve insulin resistance must be preceded by the amelioration of obesity and hepatosteatosis. Here, we show that this provision is not mandatory; insulin resistance and hyperglycemia are improved by the modification of hepatic fatty acid composition, even in the presence of persistent obesity and hepatosteatosis. Mice deficient for Elovl6, the gene encoding the elongase that catalyzes the conversion of palmitate to stearate, were generated and shown to become obese and develop hepatosteatosis when fed a high- fat diet or mated to leptin- deficient ob/ ob mice. However, they showed marked protection from hyperinsulinemia, hyperglycemia and hyperleptinemia. Amelioration of insulin resistance was associated with restoration of hepatic insulin receptor substrate- 2 and suppression of hepatic protein kinase C e activity resulting in restoration of Akt phosphorylation. Collectively, these data show that hepatic fatty acid composition is a new determinant for insulin sensitivity that acts independently of cellular energy balance and stress. Inhibition of this elongase could be a new therapeutic approach for ameliorating insulin resistance, diabetes and cardiovascular risks, even in the presence of a continuing state of obesity.

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  • Effect of weight reduction on concentration of plasma total homocysteine in obese Japanese men

    Tomohiro Okura, Yoshio Nakata, Kazunori Ohkawara, Shigeharu Numao, Yasutomi Katayama, Yohei Ono, Tomoaki Matsuo, Hirohito Sone, Kiyoji Tanaka

    OBESITY RESEARCH & CLINICAL PRACTICE   1 ( 3 )   213 - 221   2007.10

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    Objective: To test whether weight reduction would lower tHcys concentration, and whether adding exercise training to dietary weight reduction would further reduce tHcys concentration over diet alone.
    Design: A randomized, controlled, prospective, 14-week weight-loss intervention.
    Setting and participants: Forty-eight obese Japanese men aged 27-66 years were assigned to 2 subgroups depending on the type of treatment: diet alone (DA) and diet plus exercise training (DE). Concentration of tHcy was measured in frozen plasma samples by an HPLC method.
    Results: Body weight decreased significantly for both groups: DA -7.8 +/- 3.2 kg and DE -9.1 +/- 3.6 kg. A significant decrease was found in tHcys concentration of the DE group (-2.3 +/- 5.0 mu mol/L) but not of the DA (-0.3 +/- 2.7 mu mol/L). For subjects with hyperhomocysteinemia (&gt;= 15 mu mol/L, n=17), tHcys concentration decreased from 20.1 +/- 7.0 to 13.9 +/- 3.0 mu mol/L (p&lt;0.01) for the DE group (n = 8) but did not change for the DA group (16.6 +/- 1.9 mu mol/L -&gt; 15.4 +/- 2.3 mu mol/L, n=9). Furthermore, to consider a statistical phenomenon "regression to the mean", we excluded two subjects with the highest two tHcys values of the DE group. The DE group (n=7) still displayed a significant reduction after the exclusion.
    Conclusions: A weight reduction with diet alone did not improve tHcy levels. Adding aerobic exercise training to a dietary weight-reduction program may be effective for a reduction in tHcy. (C) 2007 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

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  • Effect of weight reduction on concentration of plasma total homocysteine in obese Japanese men

    Tomohiro Okura, Yoshio Nakata, Kazunori Ohkawara, Shigeharu Numao, Yasutomi Katayama, Yohei Ono, Tomoaki Matsuo, Hirohito Sone, Kiyoji Tanaka

    OBESITY RESEARCH & CLINICAL PRACTICE   1 ( 3 )   213 - 221   2007.10

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    Objective: To test whether weight reduction would lower tHcys concentration, and whether adding exercise training to dietary weight reduction would further reduce tHcys concentration over diet alone.
    Design: A randomized, controlled, prospective, 14-week weight-loss intervention.
    Setting and participants: Forty-eight obese Japanese men aged 27-66 years were assigned to 2 subgroups depending on the type of treatment: diet alone (DA) and diet plus exercise training (DE). Concentration of tHcy was measured in frozen plasma samples by an HPLC method.
    Results: Body weight decreased significantly for both groups: DA -7.8 +/- 3.2 kg and DE -9.1 +/- 3.6 kg. A significant decrease was found in tHcys concentration of the DE group (-2.3 +/- 5.0 mu mol/L) but not of the DA (-0.3 +/- 2.7 mu mol/L). For subjects with hyperhomocysteinemia (&gt;= 15 mu mol/L, n=17), tHcys concentration decreased from 20.1 +/- 7.0 to 13.9 +/- 3.0 mu mol/L (p&lt;0.01) for the DE group (n = 8) but did not change for the DA group (16.6 +/- 1.9 mu mol/L -&gt; 15.4 +/- 2.3 mu mol/L, n=9). Furthermore, to consider a statistical phenomenon "regression to the mean", we excluded two subjects with the highest two tHcys values of the DE group. The DE group (n=7) still displayed a significant reduction after the exclusion.
    Conclusions: A weight reduction with diet alone did not improve tHcy levels. Adding aerobic exercise training to a dietary weight-reduction program may be effective for a reduction in tHcy. (C) 2007 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.orcp.2007.07.003

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  • 【各種ガイドラインの効果的な活用法 Up dateな糖尿病ガイドラインへのナビゲーション】 糖尿病対策を生活習慣病からアプローチ 糖尿病対策を生活習慣病からアプローチ

    田嶼 尚子, 片山 茂裕, 曽根 博仁, 宮崎 滋

    糖尿病UP-DATE   ( 23 )   40 - 56   2007.9

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  • 糖尿病性網膜症 病態研究および治療の最前線 糖尿病合併症における網膜症の位置づけ JDCSの中間結果より

    曽根 博仁, 山田 信博, 山下 英俊

    糖尿病合併症   21 ( Suppl.1 )   47 - 47   2007.9

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  • 生活習慣病の臨床エビデンス 禁煙の重要性 糖尿病患者を例にして

    齋藤 和美, 姫野 彰子, 曽根 博仁

    Q&Aでわかる肥満と糖尿病   6 ( 5 )   851 - 853   2007.9

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  • にがりの3T3-L1前駆脂肪細胞の分化に及ぼす影響

    岸本 良美, 近藤 春美, 都, 吉岡 絵理, 才田 恵美, 平田 悠美子, 飯塚 麻貴, 野本 佳世子, 田口 千恵, 沢, 谷 真理子, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    肥満研究   13 ( Suppl. )   279 - 279   2007.9

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  • 【各種ガイドラインの効果的な活用法 Up dateな糖尿病ガイドラインへのナビゲーション】 糖尿病対策を生活習慣病からアプローチ 高脂血症からみた糖尿病とガイドラインの効果的活用

    曽根 博仁

    糖尿病UP-DATE   ( 23 )   24 - 31   2007.9

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    糖尿病患者の冠動脈疾患予防において、LDL-Cのコントロールは血糖コントロールと同等以上のメリットがある。昨今の研究結果から、特に米国では非常にアグレッシブなガイドラインに変化しつつある。JDCS(主任研究者:筑波大山田信博教授)のデータでは日本人男性では、LDL-Cと共に、dyslipidemia特に高TG血症を単独で満たしている群が冠動脈疾患の危険性が高いという結果も得られている。今後は人種ごとのエビデンスを考慮したガイドラインの充実が必要であろう。(著者抄録)

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  • Cross-sectional association between BMI glycemic control and energy intake in Japanese patients with type 2 diabetes analysis from the Japan Diabetes Complications Study

    Hirohito Sone, Yukio Yoshimura, Sachiko Tanaka, Satoshi Iimuro, Yasuo Ohashi, Hideki Ito, Hiroaki Seino, Shun Ishibashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES RESEARCH AND CLINICAL PRACTICE   77 ( 1 )   S23 - S29   2007.9

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    Although. weight loss is associated with improved glycemic control in diabetic patients, the relationships between patient weight. daily energy intake (EI), and glycemic or other control status have been poorly investigated. Baseline characteristics of the Japan Diabetes Complications Study, a representative cohort of Japanese diabetic patients, were used for quartile analysis stratified according to patient body mass index (BMI) and EI. Despite a 1.4-fold discrepancy in BMI between the highest and the lowest quartiles, no significant linear trend in HbA(1C) levels or EI between quartiles was seen, although, waist/hip ratio, blood pressure, total cholesterol and triglycerides increased and HDL cholesterol decreased with the increase in BMI. Quartile analysis, according to EI., revealed a 1.8-fold elevation in EI between the lowest and the highest quartile. Nevertheless, the differences in patient BMI between the lowest and the highest quartile were no more than 3% and there were no significant linear trends among the four quartiles in most parameters including HbA(1c), blood pressure, serum lipids. These results revealed only very limited cross-sectional correlations among BMI, EI and other parameters suggesting that it is necessary to consider much wider variations in ideal weight and optimal dietary prescription when making assessments of diabetic patients. (c) 2007 Published by Elsevier Ireland Ltd.

    DOI: 10.1016/j.diabres.2007.01.029

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  • Cross-sectional association between BMI glycemic control and energy intake in Japanese patients with type 2 diabetes analysis from the Japan Diabetes Complications Study

    Hirohito Sone, Yukio Yoshimura, Sachiko Tanaka, Satoshi Iimuro, Yasuo Ohashi, Hideki Ito, Hiroaki Seino, Shun Ishibashi, Yasuo Akanuma, Nobuhiro Yamada

    DIABETES RESEARCH AND CLINICAL PRACTICE   77 ( 1 )   S23 - S29   2007.9

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    Although. weight loss is associated with improved glycemic control in diabetic patients, the relationships between patient weight. daily energy intake (EI), and glycemic or other control status have been poorly investigated. Baseline characteristics of the Japan Diabetes Complications Study, a representative cohort of Japanese diabetic patients, were used for quartile analysis stratified according to patient body mass index (BMI) and EI. Despite a 1.4-fold discrepancy in BMI between the highest and the lowest quartiles, no significant linear trend in HbA(1C) levels or EI between quartiles was seen, although, waist/hip ratio, blood pressure, total cholesterol and triglycerides increased and HDL cholesterol decreased with the increase in BMI. Quartile analysis, according to EI., revealed a 1.8-fold elevation in EI between the lowest and the highest quartile. Nevertheless, the differences in patient BMI between the lowest and the highest quartile were no more than 3% and there were no significant linear trends among the four quartiles in most parameters including HbA(1c), blood pressure, serum lipids. These results revealed only very limited cross-sectional correlations among BMI, EI and other parameters suggesting that it is necessary to consider much wider variations in ideal weight and optimal dietary prescription when making assessments of diabetic patients. (c) 2007 Published by Elsevier Ireland Ltd.

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  • 危険因子 糖尿病 喫煙

    齋藤 和美, 曽根 博仁

    動脈硬化予防   6 ( 2 )   101 - 103   2007.8

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  • 【運動と健康推進プロジェクト】 運動による糖尿病予防・治療とQOLの向上

    佐藤 睦美, 児玉 暁, 曽根 博仁

    体育の科学   57 ( 8 )   603 - 608   2007.8

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    Other Link: http://search.jamas.or.jp/link/ui/2007339964

  • 【高脂血症・脂質異常症 メタボリックリスクとしての高脂血症・脂質異常症の実地診療】 高脂血症・脂質異常症・セミナー 高脂血症がもたらす臓器障害 マルチプルリスク管理としての高脂血症

    齋藤 和美, 曽根 博仁

    Medical Practice   24 ( 7 )   1221 - 1225   2007.7

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  • 生活習慣病の臨床エビデンス 運動とHDLコレステロール

    曽根 博仁, 児玉 暁

    Q&Aでわかる肥満と糖尿病   6 ( 4 )   687 - 689   2007.7

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  • 【糖尿病網膜症 基礎と臨床の最新動向】 日本と世界における糖尿病網膜症の現状 大規模臨床研究JDCSの成果を含めて

    曽根 博仁, 山下 英俊, 山田 信博

    医学のあゆみ   222 ( 4 )   235 - 239   2007.7

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    日本人2型糖尿病患者の大規模研究であるJapan Diabetes Complications Study(JDCS)を始めとするわが国の検討を通して、日本人糖尿病患者において網膜症が、どのくらいの頻度で起こるか、どのような因子をもつ患者に起こりやすいかなどが次第に明らかになりつつある。とくに血糖コントロールは、網膜症の予防においてとりわけ重要であることが日本人患者においても確認されており、今後その管理をさらに強化していく必要がある。(著者抄録)

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  • 【脂質代謝異常 高脂血症・低脂血症】 脂質代謝異常の臨床 高脂血症 高脂血症の臨床疫学 大規模臨床介入試験成績による治療効果のエビデンス HDLコレステロールに対する介入試験

    児玉 暁, 曽根 博仁

    日本臨床   65 ( 増刊7 脂質代謝異常 )   264 - 269   2007.7

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  • インスリン注射手技に起因すると考えられる菌血症から黄色ブドウ球菌性眼内炎を来した症例

    宮原 尚子, 岩崎 祐子, 岩崎 仁, 鈴木 浩明, 高橋 昭光, 豊島 秀男, 曽根 博仁, 島野 仁, 山田 信博

    糖尿病   50 ( 7 )   535 - 535   2007.7

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  • The regulation of adiponectin receptors expression by acute exercise in mice

    H. Huang, K. T. Licia, H. Sone, R. Ajisaka

    EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES   115 ( 7 )   417 - 422   2007.7

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    Adiponectin is an adipocyte-derived factor that plays a pivotal role in lipid and glucose metabolism. Recently, two types of adiponectin receptors (AdipoR1 and AdipoR2) were identified. While, although physical exercise is useful for improving insulin sensitivity, the effect of physical exercise on adiponectin and adiponectin receptors are still unclear. In present study, we investigated whether acute exercise affects the plasma adiponectin concentration and expression of adiponectin receptor in skeletal muscle and liver in healthy mice C57BL/6. Following an acute exercise, plasma glucose, insulin, FFA, and adiponectin were measured. The mRNA levels of AdipR1 and AdipoR2 were also analyzed. Although acute exercise did not significantly change plasma adiponectin concentration at 2 hours or 18 hours after the exercise compared with control group, the expression levels of AdipoR1 significantly increased in both skeletal muscle (2H: 1.2-fold, p=0.0423, 18H: 1.4-fold, p=0.0006) and liver (2H: 1.3-fold, p=0.0448) compared with control group. In contrast, the level of AdipoR2 mRNA was decreased in skeletal muscle (18H: 0.8-fold, p=0.027) and liver (2H: 0.9-fold, p=0.1551) compared with control group. Additionally, the transcription factor Foxo1 mRNA expression level was also significantly increased in skeletal muscle (2H: 10-fold, p = 0.0001, 18H: 3-fold, p = 0.0424) and liver (2H: 2-fold, p=0.002, 18H: 2-fold, p=0.0014) compared with control group by the acute exercise. These findings suggest that acute exercise affects the expression level of adiponectin receptors, and an increase of Foxo1 expression might be relative to regulate adiponectin receptors.

    DOI: 10.1055/s-2007-981660

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  • The regulation of adiponectin receptors expression by acute exercise in mice

    H. Huang, K. T. Lida, H. Sone, R. Ajisaka

    Experimental and Clinical Endocrinology and Diabetes   115 ( 7 )   417 - 422   2007.7

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    Adiponectin is an adipocyte-derived factor that plays a pivotal role in lipid and glucose metabolism. Recently, two types of adiponectin receptors (AdipoR1 and AdipoR2) were identified. While, although physical exercise is useful for improving insulin sensitivity, the effect of physical exercise on adiponectin and adiponectin receptors are still unclear. In present study, we investigated whether acute exercise affects the plasma adiponectin concentration and expression of adiponectin receptor in skeletal muscle and liver in healthy mice C57BL/6. Following an acute exercise, plasma glucose, insulin, FFA, and adiponectin were measured. The mRNA levels of AdipR1 and AdipoR2 were also analyzed. Although acute exercise did not significantly change plasma adiponectin concentration at 2 hours or 18 hours after the exercise compared with control group, the expression levels of AdipoR1 significantly increased in both skeletal muscle (2H: 1.2-fold, p = 0.0423, 18H: 1.4-fold, p = 0.0006) and liver (2H: 1.3-fold, p = 0.0448) compared with control group. In contrast, the level of AdipoR2 mRNA was decreased in skeletal muscle (18H: 0.8-fold, p = 0.027) and liver (2H: 0.9-fold, p = 0.1551) compared with control group. Additionally, the transcription factor Foxo1 mRNA expression level was also significantly increased in skeletal muscle (2H: 10-fold, p = 0.0001,18H: 3-fold, p = 0.0424) and liver (2H: 2-fold, p = 0.002, 18H: 2-fold, p = 0.0014) compared with control group by the acute exercise. These findings suggest that acute exercise affects the expression level of adiponectin receptors, and an increase of Foxo1 expression might be relative to regulate adiponectin receptors. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart.

    DOI: 10.1055/s-2007-981660

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  • Both current and past smoking are dose dependent risk factors for the development of microalbuminuria in Japanese men with type 2 diabetes

    Kazumi Saito, Koichi Kawai, Shiro Tanaka, Satoru Kodama, Shu Miao, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    DIABETES   56   A604 - A604   2007.6

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  • 【メタボリックシンドロームup to date】 メタボリックシンドロームにおいて糖代謝異常、脂質代謝異常、高血圧が重積しやすい原因は何ですか?

    曽根 博仁

    日本医師会雑誌   136 ( 特別1 )   S108 - S108   2007.6

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  • 糖尿病/耐糖能障害と動脈硬化 各種高脂血症薬の糖尿病合併心血管病進展予防効果の検討 厳格な脂質及び糖代謝制御の必要性について

    林 登志雄, 井口 昭久, 井藤 英喜, 山田 信博, 曽根 博仁, 横手 幸太郎, 服部 良之, 渡邉 裕司, 川嶋 成乃亮, 吉栖 正生

    日本動脈硬化学会総会プログラム・抄録集   39回   149 - 149   2007.6

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  • にがりの脂肪細胞分化に及ぼす影響の検討

    岸本 良美, 近藤 春美, 都, 吉岡 絵理, 才田 恵美, 平田 悠美子, 田口 千恵, 澤, 谷 真理子, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    日本動脈硬化学会総会プログラム・抄録集   39回   275 - 275   2007.6

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  • 有酸素性運動によるHDLコレステロール上昇のメタアナリシス

    児玉 暁, 叔 びょう, 齋藤 和美, 島野 仁, 山田 信博, 曽根 博仁, 鈴木 恵美子, 近藤 和雄, 田中 司朗, 大橋 靖雄

    成人病と生活習慣病   37 ( 5 )   594 - 594   2007.5

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  • 喫煙の糖尿病腎症発症に及ぼす影響に関するコホート研究

    齋藤 和美, 叔 びょう, 児玉 暁, 鈴木 恵美子, 近藤 和雄, 曽根 博仁, 島野 仁, 山田 信博, 田中 司朗, 大橋 靖雄, 川井 紘一

    成人病と生活習慣病   37 ( 5 )   592 - 592   2007.5

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  • 生活習慣病の臨床エビデンス 生活習慣療法の理想と現実

    曽根 博仁, 児玉 暁, 佐藤 睦美, 菅原 歩美, 福士 亜矢子

    Q&Aでわかる肥満と糖尿病   6 ( 3 )   537 - 539   2007.5

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  • Risk imparted by various parameters of smoking in Japanese men with type 2 diabetes on their development of microalbuminuria - Analysis from the Tsukuba Kawai Diabetes Registry

    Kazumi Saito, Hirohito Sone, Koichi Kawai, Shiro Tanaka, Satoru Kodama, Miao Shu, Emiko Suzuki, Kazuo Kondo, Shigeru Yamamoto, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada

    DIABETES CARE   30 ( 5 )   1286 - 1288   2007.5

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    DOI: 10.2337/dc06-2149

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  • Risk imparted by various parameters of smoking in Japanese men with type 2 diabetes on their development of microalbuminuria - Analysis from the Tsukuba Kawai Diabetes Registry

    Kazumi Saito, Hirohito Sone, Koichi Kawai, Shiro Tanaka, Satoru Kodama, Miao Shu, Emiko Suzuki, Kazuo Kondo, Shigeru Yamamoto, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada

    DIABETES CARE   30 ( 5 )   1286 - 1288   2007.5

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    DOI: 10.2337/dc06-2149

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  • Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol - A meta-analysis

    Satoru Kodama, Shiro Tanaka, Kazumi Saito, Miao Shu, Yasuko Sone, Fumiko Onitake, Emiko Suzuki, Hitoshi Shimano, Shigeru Yamamoto, Kazuo Kondo, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    ARCHIVES OF INTERNAL MEDICINE   167 ( 10 )   999 - 1008   2007.5

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    Background: Aerobic exercise is believed to reduce the risk of cardiovascular disease partially through increasing serum levels of high-density lipoprotein cholesterol (HDL-C). However, this effect varies considerably among exercise intervention studies.
    Methods: Electronic database searches of MEDLINE (1966-2005) for randomized controlled trials that examined the effect of exercise training on HDL-C level.
    Results: Twenty-five articles were included. Mean net change in HDL-C level was statistically significant but modest (2.53 mg/dL [0.065 mmol/L]; P &lt;. 001). Minimal weekly exercise volume for increasing HDL-C level was estimated to be 900 kcal of energy expenditure per week or 120 minutes of exercise per week. Univariate regression analysis indicated that every 10-minute prolongation of exercise per session was associated with an approximately 1.4-mg/dL (0.036-mmol/L) increase in HDL-C level. In contrast, there was no significant association between exercise frequency or intensity. Multiple meta-regression analyses demonstrated that subjects with a body mass index (calculated as weight in kilograms divided by height in meters squared) less than 28 and total cholesterol level of 220 mg/dL [5.7 mmol/L] or more experienced an approximately 2.1-mg/dL (0.054-mmol/L) larger increase in HDL-C level than those with a body mass index of 28 or more and total cholesterol level less than 220 mg/dL (5.7 mmol/L).
    Conclusions: Regular aerobic exercise modestly increases HDL-C level. There appears to exist a minimum exercise volume for a significant increase in HDL-C level. Exercise duration per session was the most important element of an exercise prescription. Exercise was more effective in subjects with initially high total cholesterol levels or low body mass index.

    DOI: 10.1001/archinte.167.10.999

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  • Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol - A meta-analysis

    Satoru Kodama, Shiro Tanaka, Kazumi Saito, Miao Shu, Yasuko Sone, Fumiko Onitake, Emiko Suzuki, Hitoshi Shimano, Shigeru Yamamoto, Kazuo Kondo, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone

    ARCHIVES OF INTERNAL MEDICINE   167 ( 10 )   999 - 1008   2007.5

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    Background: Aerobic exercise is believed to reduce the risk of cardiovascular disease partially through increasing serum levels of high-density lipoprotein cholesterol (HDL-C). However, this effect varies considerably among exercise intervention studies.
    Methods: Electronic database searches of MEDLINE (1966-2005) for randomized controlled trials that examined the effect of exercise training on HDL-C level.
    Results: Twenty-five articles were included. Mean net change in HDL-C level was statistically significant but modest (2.53 mg/dL [0.065 mmol/L]; P &lt;. 001). Minimal weekly exercise volume for increasing HDL-C level was estimated to be 900 kcal of energy expenditure per week or 120 minutes of exercise per week. Univariate regression analysis indicated that every 10-minute prolongation of exercise per session was associated with an approximately 1.4-mg/dL (0.036-mmol/L) increase in HDL-C level. In contrast, there was no significant association between exercise frequency or intensity. Multiple meta-regression analyses demonstrated that subjects with a body mass index (calculated as weight in kilograms divided by height in meters squared) less than 28 and total cholesterol level of 220 mg/dL [5.7 mmol/L] or more experienced an approximately 2.1-mg/dL (0.054-mmol/L) larger increase in HDL-C level than those with a body mass index of 28 or more and total cholesterol level less than 220 mg/dL (5.7 mmol/L).
    Conclusions: Regular aerobic exercise modestly increases HDL-C level. There appears to exist a minimum exercise volume for a significant increase in HDL-C level. Exercise duration per session was the most important element of an exercise prescription. Exercise was more effective in subjects with initially high total cholesterol levels or low body mass index.

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  • 循環器病学の論点 メタボリックシンドロームは存在するか? 存在しない?

    曽根 博仁

    Therapeutic Research   28 ( 4 )   547 - 551   2007.4

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  • 全国多施設共同研究による糖尿病患者の動脈硬化性疾患罹患の追跡調査 観察開始時の特徴 JDDMスタデイー

    横山 宏樹, 川井 紘一, 杉本 英克, 平尾 紘一, 武田 浩, 大石 まり子, 南 昌江, 宮澤 一裕, 工藤 幹彦, 大河原 久子, 高村 宏, 高井 昌彦, 高橋 千恵子, 土井 邦紘, 岩崎 皓一, 福元 良英, 曽根 博仁, 松島 雅人, 高木 廣文, 小林 正

    糖尿病   50 ( Suppl.1 )   S - 193   2007.4

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  • 日本人男性2型糖尿病患者における早期腎症発症のリスクファクターの検討

    齋藤 和美, 田中 司朗, 児玉 暁, 叔 森, 鈴木 恵美子, 近藤 和雄, 高橋 昭光, 島野 仁, 大橋 靖雄, 山田 信博, 川井 紘一, 曽根 博仁

    糖尿病   50 ( Suppl.1 )   S - 174   2007.4

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  • アスコルビン酸の栄養状態の違いによるナトリウム依存性ビタミンCトランスポーター(SVCT)の発現変動

    曽根 保子, 鬼武 ふみ子, 叔 森, 齋藤 和美, 児玉 暁, 曽根 博仁, 鈴木 恵美子

    ビタミン   81 ( 4 )   180 - 180   2007.4

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  • JDCS(Japan Diabetes Complications Study)

    曽根 博仁, 山田 信博

    BIO Clinica   22 ( 4 )   353 - 360   2007.4

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    米国のDCCT(Diabetes Control and Complications Trial)や英国のUKPDS(United Kingdom Prospective Diabetes Study)に代表される欧米における大規模臨床研究は、糖尿病診療エビデンスの形成に多大な貢献をしてきた。これに対して、日本人を含む東アジア人糖尿病患者の大規模臨床研究はこれまで不十分であった。JDCSは日本全国の2型糖尿病患者2200人を前向きに追跡している前向き研究で、生活習慣介入を中心とした強化治療の有効性も検討している。JDCSのデータにより、日本人と欧米人の糖尿病患者に様々な病態の相違が明らかになった。今後始まる本格的解析により、日本人糖尿病患者に最適化された治療のための臨床エビデンスがさらに得られるものと期待される。(著者抄録)

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  • 【心・脳・末梢血管イベントにおけるリスクの違いを極める】 各危険因子の違いからみる 糖尿病

    曽根 博仁, 山田 信博

    Vascular Medicine   3 ( 2 )   125 - 134   2007.4

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    糖尿病患者には病初期から心血管疾患が多発するため(=糖尿病大血管合併症)、糖尿病は心血管疾患の予防戦略上、重要なターゲットである。大血管合併症を予防するためには、血糖、血清脂質、血圧のすべてについて厳格なコントロールを病初期からおこなう必要がある。これまでの大規模臨床研究は欧米人患者を主体としてきたが、日本人を含む東アジア人糖尿病患者は、欧米人糖尿病患者とは心血管の発症状況やリスクファクターが異なるため、東アジア人糖尿病患者の大規模前向き研究が必要である。同時に糖尿病患者における食事療法や運動療法による大血管合併症予防効果についても今後さらにエビデンスを充実させる必要がある。(著者抄録)

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  • 中高齢者における高感度CRPと運動耐容能の関連および運動トレーニング効果

    鰺坂 隆一, 村上 晴香, 前田 清司, 久野 譜也, 田中 喜代次, 渡辺 重行, 青沼 和隆, 山口 巖, 大槻 毅, 家光 素行, 曽根 博仁

    心臓   39 ( 2 )   12 - 14   2007.4

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    定期的服薬をしていない中高齢者を対象に、運動耐容能が血清高感度CRP濃度と関連を有するか、運動トレーニングが血清高感度CRP濃度を低下させ得るかについて検討した。運動耐容能は中年者182名、高齢者88名の計270名を対象に症候限界漸増自転車エルゴメータ運動負荷試験にて最高酸素摂取量またはdouble product breaking point(DPBP)時仕事率を測定した。運動トレーニング効果は中年者70名、高齢者99名の計169名を対象に自転車エルゴメータを用い、仕事率の80%強度で30分の運動を週5回の頻度で実施した。その結果、トレーニング前の血清高感度CRP濃度は高齢群が有意に高値であった。中年群において、血清高感度CRP濃度は身体活動量とは有意の関連は認めなかったが、最高酸素摂取量及びDPBP時仕事率とは有意の負の相関を認めた。一方、高齢群においては、血清高感度CRP濃度は身体活動量、最高酸素摂取量及びDPBP時仕事率のいずれとも有意の負の相関を認めた。中年群では、運動トレーニングにより身体活動量及び運動耐容能指標が有意に改善した。高齢群では、運動トレーニングにて身体活動量が有意に増加し、体格指数と血清高感度CRP濃度が有意に低下した。中年群、高齢群いずれにおいても、運動トレーニング前の血清高感度CRP濃度と運動トレーニングによるその変化量との間に有意の負の相関を認めた。

    DOI: 10.11281/shinzo1969.39.Supplement2_12

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  • 脂肪細胞分化に及ぼすにがりの影響

    岸本 良美, 近藤 春美, 都, 吉岡 絵理, 才田 恵美, 平田 悠美子, 田口 千恵, 澤, 谷 真理子, 貴堂 としみ, 曽根 博仁, 近藤 和雄

    日本栄養・食糧学会大会講演要旨集   61回   146 - 146   2007.4

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  • Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver

    Takashi Yamamoto, Hitoshi Shimano, Noriyuki Inoue, Yoshimi Nakagawa, Takashi Matsuzaka, Akimitsu Takahashi, Naoya Yahagi, Hirohito Sone, Hiroaki Suzuki, Hideo Toyoshima, Nobuhiro Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   282 ( 16 )   11687 - 11695   2007.4

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    Sterol regulatory element-binding protein ( SREBP)-1c is a transcription factor that controls synthesis of fatty acids and triglycerides in the liver and is highly regulated by nutrition and hormones. In the current studies we show that protein kinase A ( PKA), a mediator of glucagon/cAMP, a fasting signaling, suppresses SREBP-1c by modulating the activity of liver X receptor alpha( LXR alpha), a dominant activator of SREBP-1c expression. Activation of PKA repressed LXR-induced SREBP-1c expression both in rat primary hepatocytes and mouse livers. Promoter analyses revealed that the LXR alpha-binding site in the SREBP-1c promoter is responsible for PKA inhibitory effect on SREBP-1c transcription. In vitro and in vivo PKA directly phosphorylated LXR alpha, and the two consensus PKA target sites ( 195, 196 serines and 290, 291 serines) in its ligand binding/heterodimerization domain were crucial for the inhibition of LXR signaling. PKA phosphorylation of LXR alpha caused impaired DNA binding activity by preventing LXR alpha/RXR dimerization and decreased its transcription activity by inhibiting recruitment of coactivator SCR-1 and enhancing recruitment of corepressor NcoR1. These results indicate that LXR alpha is regulated not only by oxysterol derivatives but also by PKA-mediated phosphorylation, which suggests that nutritional regulation of SREBP-1c and lipogenesis could be regulated at least partially through modulation of LXR.

    DOI: 10.1074/jbc.M611911200

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  • Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver

    Takashi Yamamoto, Hitoshi Shimano, Noriyuki Inoue, Yoshimi Nakagawa, Takashi Matsuzaka, Akimitsu Takahashi, Naoya Yahagi, Hirohito Sone, Hiroaki Suzuki, Hideo Toyoshima, Nobuhiro Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   282 ( 16 )   11687 - 11695   2007.4

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    Sterol regulatory element-binding protein ( SREBP)-1c is a transcription factor that controls synthesis of fatty acids and triglycerides in the liver and is highly regulated by nutrition and hormones. In the current studies we show that protein kinase A ( PKA), a mediator of glucagon/cAMP, a fasting signaling, suppresses SREBP-1c by modulating the activity of liver X receptor alpha( LXR alpha), a dominant activator of SREBP-1c expression. Activation of PKA repressed LXR-induced SREBP-1c expression both in rat primary hepatocytes and mouse livers. Promoter analyses revealed that the LXR alpha-binding site in the SREBP-1c promoter is responsible for PKA inhibitory effect on SREBP-1c transcription. In vitro and in vivo PKA directly phosphorylated LXR alpha, and the two consensus PKA target sites ( 195, 196 serines and 290, 291 serines) in its ligand binding/heterodimerization domain were crucial for the inhibition of LXR signaling. PKA phosphorylation of LXR alpha caused impaired DNA binding activity by preventing LXR alpha/RXR dimerization and decreased its transcription activity by inhibiting recruitment of coactivator SCR-1 and enhancing recruitment of corepressor NcoR1. These results indicate that LXR alpha is regulated not only by oxysterol derivatives but also by PKA-mediated phosphorylation, which suggests that nutritional regulation of SREBP-1c and lipogenesis could be regulated at least partially through modulation of LXR.

    DOI: 10.1074/jbc.M611911200

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  • 日本人2型糖尿病患者における虚血性心疾患の頻度とリスクファクター

    曽根 博仁, 山田 信博

    糖尿病診療マスター   5 ( 2 )   116 - 117   2007.3

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  • 糖尿病性腎症4期にて妊娠し、母児とも無事に出産し得た1型糖尿病の1例

    岩崎 仁, 小俣 勝哉, 三浦 光弘, 岩崎 祐子, 鈴木 浩明, 高橋 昭光, 曽根 博仁, 豊島 秀男, 島野 仁, 山田 信博

    日本内科学会関東地方会   543回   34 - 34   2007.3

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  • 男性2型糖尿病患者の早期腎症発症に対する喫煙歴の影響 Tsukuba Kawai Diabetes Registryにおける検討

    齋藤 和美, 川井 紘一, 児玉 暁, 田中 司朗, 叔 森, 高橋 昭光, 鈴木 浩明, 島野 仁, 大橋 靖雄, 山田 信博, 曽根 博仁

    日本内分泌学会雑誌   82 ( 4 )   929 - 929   2007.3

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  • 【糖尿病治療のエビデンスを日本の臨床に活かす】 Japan Diabetes Complications Study(JDCS) 日本人2型糖尿病患者の大規模臨床研究

    曽根 博仁, 赤沼 安夫, 山田 信博

    実験治療   ( 685 )   6 - 10   2007.3

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  • 【メタボリックシンドローム時代の糖尿病研究の最前線】 組織的な糖尿病対策のあり方 JDCS 日本人を対象にしたはじめての大規模臨床介入研究

    曽根 博仁, 山田 信博, 赤沼 安夫, JDCSグループ

    医学のあゆみ   220 ( 13 )   1275 - 1281   2007.3

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    非欧米人糖尿病患者を対象にしたはじめての大規模臨床介入研究であるJDCSは、日本全国の2型糖尿病患者2,200人の現状を前向きに追跡しつつ、生活習慣介入を中心とした強化治療の有効性も検討している。本格的解析はこれからであるが、その中間データから日本人と欧米人の糖尿病患者にさまざまな病態の違いがあることが見出されている。日本人糖尿病患者の診療には日本人患者のエビデンスが必要であることが強く示唆される。また、合併症を予防するためには血糖、血圧、血清脂質のすべてを良好な状態にコントロールする必要があることも確認されつつある。(著者抄録)

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  • 大血管症の克服をめざして 大規模臨床研究からの新しいエビデンス 大血管症リスクファクターとその管理

    曽根 博仁, 山田 信博

    糖尿病学の進歩   ( 41 )   215 - 222   2007.3

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  • Cigarette smoking is associated with low glomerular filtration rate in male patients with type 2 diabetes: Response to De Cosmo et al. [2]

    Kazumi Saito, Nobuhiro Yamada, Hirohito Sone

    Diabetes Care   30 ( 3 )   e2   2007.3

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    DOI: 10.2337/dc06-2295

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  • Cigarette smoking is associated with low glomerular filtration rate in male patients with type 2 diabetes: Response to De Cosmo et al. [2]

    Kazumi Saito, Nobuhiro Yamada, Hirohito Sone

    Diabetes Care   30 ( 3 )   e2   2007.3

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    DOI: 10.2337/dc06-2295

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  • 習慣的運動のHDLコレステロール(HDL-C)への影響に関するメタ解析

    児玉 暁, 田中 司朗, 齋藤 和美, 島野 仁, 鈴木 恵美子, 近藤 和雄, 大橋 靖雄, 山田 信博, 曽根 博仁

    日本内科学会雑誌   96 ( Suppl. )   203 - 203   2007.2

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  • 健常中高齢者における運動トレーニングの血清高感度CRP濃度に対する効果

    鰺坂 隆一, 田辺 匠, 大槻 毅, 村上 晴香, 前田 清司, 田中 喜代次, 曽根 博仁, 久野 譜也

    体力科学   56 ( 1 )   179 - 189   2007.2

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    健常中高齢者169例(男59例、女110例、平均65.9±6.4歳)を対象に、自転車エルゴメーターによる運動と筋力トレーニングからなる運動プログラムを24週間行い、血清高感度C反応性タンパク質(CRP)濃度、体重、身体活動量などの経時変化を検討した。対象は運動前のCRP濃度によって正常群139例と高値群30例の2群に分けて検討した。プログラム終了後、身体活動量と最大酸素消費量は有意に増加したが、体重の有意な変化はなかった。CRP値は全体では有意な変化はなかったが、高値群では有意に減少した。血清CRP値の高い者において、血清CRP値は体重を減少させることなく運動によって減少することがわかった。

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  • 喫煙の糖尿病腎症発症に及ぼす影響に関するコホート研究

    齋藤 和美, 叔 びょう, 児玉 暁, 田中 司朗, 鈴木 恵美子, 近藤 和雄, 島野 仁, 大橋 靖雄, 山田 信博, 川井 紘一, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   33   62 - 62   2007.1

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  • 臨床研究のあたらしい潮流 わが国発の臨床研究推進に向けて アウトカム研究 Japan Diabetes Complications Study(JDCS) 日本人2型糖尿病患者の特徴と現状

    曽根 博仁, 赤沼 安夫, 山田 信博, JDCSグループ

    医学のあゆみ   220 ( 3 )   263 - 271   2007.1

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    アジア人糖尿病患者の大規模臨床研究に基づくエビデンスはこれまで不十分であった。JDCSは日本全国の2型糖尿病患者2,200人を前向きに追跡している臨床研究で、糖尿病発症後平均10年の患者において生活習慣介入を中心とした強化治療の有効性を検討している。日本人と欧米人の糖尿病患者を比較すると、肥満や合併症の頻度、合併症のリスクファクターなどさまざまな違いがみられることがJDCSのデータにより明らかになった。日本人糖尿病患者に最適化された治療のためには、多数の日本人糖尿病患者から得られた臨床エビデンスがさらに充実することが望まれる。(著者抄録)

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  • メタボリックシンドロームと糖代謝

    曽根 博仁

    機能性食品と薬理栄養   4 ( 2 )   79 - 85   2007.1

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  • 生活習慣病のための検査 検査値をどうみるか 糖尿病に関する検査

    曽根 博仁

    Life Style Medicine   1 ( 1 )   62 - 69   2007.1

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  • 有酸素性運動によるHDLコレステロール上昇のメタアナリシス

    児玉 暁, 叔 びょう, 齋藤 和美, 鈴木 恵美子, 近藤 和雄, 田中 司朗, 島野 仁, 大橋 靖雄, 山田 信博, 曽根 博仁

    日本成人病(生活習慣病)学会会誌   33   64 - 64   2007.1

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  • Even low-intensity and low-volume exercise training may improve insulin resistance in the elderly

    Satoru Kodama, Miao Shu, Kazumi Saito, Haruka Murakami, Kiyoji Tanaka, Shinya Kuno, Ryuichi Ajisaka, Yasuko Sone, Fumiko Onitake, Akimitsu Takahashi, Hitoshi Shimano, Kazuo Kondo, Nobuhiro Yamada, Hirohito Sone

    INTERNAL MEDICINE   46 ( 14 )   1071 - 1077   2007

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    Objective Moderate to high intensity exercise training is known to ameliorate the coronary risk factors in relation to an improvement in body composition. However, the benefit of low-intensity and low-volume training for these risk factors remains unclear in elderly people. Therefore, we investigated the effects of low-intensity and low-volume exercise training on blood lipid values and insulin resistance in the elderly.
    Methods A total of 56 healthy elderly individuals (42 females and 14 males) aged 64 +/- 6 years participated in a 12-week exercise program, comprising aerobic training and resistance training.
    Results After the program, there were no significant changes in high-density lipoprotein cholesterol, triglyceride serum levels, or in peak oxygen uptake on average. However, the homeostasis of minimal assessment of insulin resistance (HOMA-IR) value was significantly reduced by 21%. The participants were categorized into tertiles based on initial Body Mass Index (BMI). The Middle-BMI group (non-obese subjects) showed reduced HOMA-IR (2.0 -&gt; 1.3, P&lt;0.01), but this reduction was not associated with the reduction in BMI (r=0.08, P=0.74), whereas the two reductions were significantly associated in the High-BMI group (r=0.61, P=0.01).
    Conclusion Even low-intensity and low-volume exercise training, which would ordinarily be insufficient for improving mean lipid values or aerobic fitness, was found to be effective in improving insulin resistance in the elderly. The improvement in insulin resistance was independent of the improvement in obesity.

    DOI: 10.2169/internalmedicine.46.0096

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  • Even low-intensity and low-volume exercise training may improve insulin resistance in the elderly

    Satoru Kodama, Miao Shu, Kazumi Saito, Haruka Murakami, Kiyoji Tanaka, Shinya Kuno, Ryuichi Ajisaka, Yasuko Sone, Fumiko Onitake, Akimitsu Takahashi, Hitoshi Shimano, Kazuo Kondo, Nobuhiro Yamada, Hirohito Sone

    INTERNAL MEDICINE   46 ( 14 )   1071 - 1077   2007

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    Objective Moderate to high intensity exercise training is known to ameliorate the coronary risk factors in relation to an improvement in body composition. However, the benefit of low-intensity and low-volume training for these risk factors remains unclear in elderly people. Therefore, we investigated the effects of low-intensity and low-volume exercise training on blood lipid values and insulin resistance in the elderly.
    Methods A total of 56 healthy elderly individuals (42 females and 14 males) aged 64 +/- 6 years participated in a 12-week exercise program, comprising aerobic training and resistance training.
    Results After the program, there were no significant changes in high-density lipoprotein cholesterol, triglyceride serum levels, or in peak oxygen uptake on average. However, the homeostasis of minimal assessment of insulin resistance (HOMA-IR) value was significantly reduced by 21%. The participants were categorized into tertiles based on initial Body Mass Index (BMI). The Middle-BMI group (non-obese subjects) showed reduced HOMA-IR (2.0 -&gt; 1.3, P&lt;0.01), but this reduction was not associated with the reduction in BMI (r=0.08, P=0.74), whereas the two reductions were significantly associated in the High-BMI group (r=0.61, P=0.01).
    Conclusion Even low-intensity and low-volume exercise training, which would ordinarily be insufficient for improving mean lipid values or aerobic fitness, was found to be effective in improving insulin resistance in the elderly. The improvement in insulin resistance was independent of the improvement in obesity.

    DOI: 10.2169/internalmedicine.46.0096

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  • 【メタボリックシンドローム 病因解明と予防・治療の最新戦略】 疫学 メタボリックシンドロームに関するコホート研究 JDCS中間解析結果が示す日本人糖尿病患者におけるメタボリックシンドローム

    曽根 博仁, 赤沼 安夫, 山田 信博

    日本臨床   64 ( 増刊9 メタボリックシンドローム )   74 - 83   2006.12

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    Other Link: http://search.jamas.or.jp/link/ui/2007108096

  • 【新展開を迎えた動脈硬化危険因子の治療】 これからの動脈硬化治療とその評価

    山田 信博, 石川 雄一, 曽根 博仁, 代田 浩之

    The Lipid   17 ( 5 )   388 - 398   2006.12

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  • 【21世紀の不整脈診療】 糖尿病と不整脈

    曽根 博仁, 齋藤 和美

    成人病と生活習慣病   36 ( 11 )   1311 - 1316   2006.11

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    糖尿病患者にはさまざまな不整脈がみられ、突然死のリスクとなる可能性が指摘されている。糖尿病に多くみられる冠動脈疾患や自律神経障害などは不整脈の発生基質となる。糖尿病に合併しやすい不整脈には、QT延長症候群やQT間隔分散の増大、心房細動などがあり、特にQT間隔の異常は、torsade de pointes(トルサード・ド・ポアンツ)型を含む心室頻拍や心室細動など致死的な心室性不整脈に結びつく可能性がある。これらの機序解明にはさらなる検討が必要で、特に日本人における大規模臨床データの積み重ねが求められる。糖尿病患者には、無痛性心筋虚血のスクリーニングを兼ねて年1回は心電図検査を行い、QT延長の有無も含めて十分に精査する必要がある。(著者抄録)

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  • 【糖尿病マクロアンギオパシー 診断・予防・治療の最新動向】 糖尿病マクロアンギオパシーの疫学 糖尿病マクロアンギオパシーに関する長期介入研究 欧米と我が国のコホート研究とその特徴

    曽根 博仁, 山田 信博

    日本臨床   64 ( 11 )   2021 - 2030   2006.11

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  • 2型糖尿病患者における腎症発症のリスクファクターに関する前向き研究

    齋藤 和美, 曽根 博仁, 本橋 しのぶ, 高橋 昭光, 鈴木 浩明, 豊島 秀男, 島野 仁, 山田 信博, 川井 紘一

    Diabetes Frontier   17 ( 5 )   682 - 682   2006.10

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDC Study)における糖尿病性腎症の発症と進展について

    田中 佐智子, 田中 司朗, 横田 千津子, 守屋 達美, 矢島 義忠, 山田 研一, 大橋 靖雄, 曽根 博仁, 山田 信博, 赤沼 安夫, 片山 茂裕

    Diabetes Frontier   17 ( 5 )   683 - 684   2006.10

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  • 腎症-進展の危険因子 日本人集団における腎症発症・進展に関するケース・コントロール・スタディ

    齋藤 和美, 曽根 博仁, 山田 信博, 川井 紘一

    糖尿病合併症   20 ( Suppl.1 )   97 - 97   2006.9

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  • 糖尿病治療におけるエビデンス 心血管疾患のエビデンス JDCSからみた日本人のデータ

    曽根 博仁, 石橋 俊, 横手 幸太郎, 笈田 耕治, 及川 眞一, 井藤 英喜, 山崎 義光, 赤沼 安夫, 山田 信博

    糖尿病学の進歩   ( 40 )   102 - 108   2006.9

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  • 【糖尿病診療のエビデンス&プラクティス 欧米のエビデンスを日本でどこまで活かせるか】 2型糖尿病患者における代謝管理と大血管障害

    曽根 博仁, 山田 信博

    糖尿病診療マスター   4 ( 6 )   723 - 728   2006.9

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    DOI: 10.11477/mf.1415100303

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  • 中高齢者における血清高感度CRP濃度と運動耐容能の関連 SATプロジェクト188

    鰺坂 隆一, 大槻 毅, 前田 清司, 松田 光生, 久野 譜也, 田中 喜代次, 曽根 博仁

    日本臨床スポーツ医学会誌   14 ( 3 )   303 - 310   2006.8

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    心疾患・呼吸器疾患を有さない中高齢者270名を対象に血清高感度CRP濃度と運動耐容能の関連について検討した。その結果、血清CRP濃度は平均0.637±0.715mg/Lで、220例(81.4%)が1mg/L未満に分布していた。血清CRP濃度は年齢、体重、BMI、インスリン、HDLコレステロール、最大酸素摂取量と有意な関連を認め、ステップワイズ回帰分析では最高酸素摂取量とBMIのみが有意に選択された。以上より、運動耐容能は血清CRP濃度と独立した関連因子であることが示唆された。

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  • Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice

    Toyonori Kato, Hitoshi Shimano, Takashi Yamamoto, Tomotaka Yokoo, Yuko Endo, Mayumi Ishikawa, Takashi Matsuzaka, Yoshimi Nakagawa, Shin Kumadaki, Naoya Yahagi, Akimitsu Takahashi, Hirohito Sone, Hiroaki Suzuki, Hideo Toyoshima, Alyssa H. Hasty, Satoru Takahashi, Hiroshi Gomi, Tetsuro Izumi, Nobuhiro Yamada

    CELL METABOLISM   4 ( 2 )   143 - 154   2006.8

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    Granuphilin is a crucial component of the docking machinery of insulin-containing vesicles to the plasma membrane. Here, we show that the granuphilin promoter is a target of SREBP-1c, a transcription factor that controls fatty acid synthesis, and MafA, a beta cell differentiation factor. Potassium-stimulated insulin secretion (KSIS) was suppressed in islets with adenoviral-mediated overexpression of granuphilin and enhanced in islets with knockdown of granuphilin (in which granuphilin had been knocked down). SREBP-1c and granuphilin were activated in islets from beta cell-specific SREBP-1c transgenic mice, as well as in several diabetic mouse models and normal islets treated with palmitate, accompanied by a corresponding reduction in insulin secretion. Knockdown- or knockout-mediated ablation of granuphilin or SREBP-1c restored KSIS in these islets. Collectively, our data provide evidence that activation of the SREBP-1c/granuphilin pathway is a potential mechanism for impaired insulin secretion in diabetes, contributing to beta cell lipotoxicity.

    DOI: 10.1016/j.cmet.2006.06.009

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  • Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice

    Toyonori Kato, Hitoshi Shimano, Takashi Yamamoto, Tomotaka Yokoo, Yuko Endo, Mayumi Ishikawa, Takashi Matsuzaka, Yoshimi Nakagawa, Shin Kumadaki, Naoya Yahagi, Akimitsu Takahashi, Hirohito Sone, Hiroaki Suzuki, Hideo Toyoshima, Alyssa H. Hasty, Satoru Takahashi, Hiroshi Gomi, Tetsuro Izumi, Nobuhiro Yamada

    CELL METABOLISM   4 ( 2 )   143 - 154   2006.8

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    Granuphilin is a crucial component of the docking machinery of insulin-containing vesicles to the plasma membrane. Here, we show that the granuphilin promoter is a target of SREBP-1c, a transcription factor that controls fatty acid synthesis, and MafA, a beta cell differentiation factor. Potassium-stimulated insulin secretion (KSIS) was suppressed in islets with adenoviral-mediated overexpression of granuphilin and enhanced in islets with knockdown of granuphilin (in which granuphilin had been knocked down). SREBP-1c and granuphilin were activated in islets from beta cell-specific SREBP-1c transgenic mice, as well as in several diabetic mouse models and normal islets treated with palmitate, accompanied by a corresponding reduction in insulin secretion. Knockdown- or knockout-mediated ablation of granuphilin or SREBP-1c restored KSIS in these islets. Collectively, our data provide evidence that activation of the SREBP-1c/granuphilin pathway is a potential mechanism for impaired insulin secretion in diabetes, contributing to beta cell lipotoxicity.

    DOI: 10.1016/j.cmet.2006.06.009

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  • 各種高脂血症治療薬の糖尿病性心血管病進展予防効果の総合的検討

    林 登志雄, 井口 昭久, 野村 秀樹, 井藤 英喜, 曽根 博仁, 渡邊 裕司, 吉栖 正生, 服部 良之, 川嶋 成乃亮, 横手 幸太郎

    日本動脈硬化学会総会プログラム・抄録集   38回   263 - 263   2006.7

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  • 妊娠32週で発症した劇症1型糖尿病が疑われた1症例

    小俣 勝哉, 三浦 光弘, 鈴木 浩明, 豊島 秀男, 高橋 昭光, 曽根 博仁, 藤木 豊, 島野 仁, 山田 信博

    糖尿病   49 ( 7 )   561 - 561   2006.7

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  • 【糖尿病診療の新時代とIT】 疫学および医療情報解析からみた日本人糖尿病の現状 JDCSのデータからみた糖尿病診療の現況

    曽根 博仁

    Q&Aでわかる肥満と糖尿病   5 ( 別冊5 )   96 - 98   2006.7

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  • 【心血管疾患の危険因子としてのメタボリックシンドローム】 日本の糖尿病患者における心血管疾患とメタボリックシンドロームの現況 Japan Diabetes Complications Study(JDCS)より

    曽根 博仁, 山田 信博, JDCSグループ

    進歩する心臓研究   XXVI ( 1 )   5 - 11   2006.6

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  • The effect of exercise training on adiponectin receptor expression in KKAy obese/diabetic mice

    Hu Huang, Kaoruko Tada Iida, Hirohito Sone, Tomotaka Yokoo, Nobuhiro Yamada, Ryuichi Ajisaka

    JOURNAL OF ENDOCRINOLOGY   189 ( 3 )   643 - 653   2006.6

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    Adiponectin is an adipocyte-derived factor that plays a pivotal role in lipid and glucose metabolism. Recently, two types of adiponectin receptors (AdipoR1 and AdipoR2) were identified. We investigated whether exercise training (ET) or dietary restriction (DR) affects the expression of adiponectin receptors in skeletal muscle and liver, thereby improving glucose and lipid metabolism in KKAy mice. KKAy mice were subjected to 8 weeks of exercise training or food restriction. Following the experimental protocol, an intravenous glucose tolerance test and an intraperitoneal insulin tolerance test were performed in addition to the measurement of blood lipid and adiponectin concentrations. The mRNA levels of adiponectin, adiponectin receptors and genes that are putatively regulated by the adiponectin receptors were also analyzed. Both the 8-week exercise training and food restriction protocol improved insulin resistance in KKAy mice but did not alter plasma adiponectin concentration nor its mRNA expression. In comparison with C57BL/6 mice, AdipoR1 expression level was significantly decreased in skeletal muscle and AdipoR2 expression level was significantly increased in the liver in KKAy mice. After the 8-week experimental protocol, the expression level of AdipoR1 mRNA was approximately 1-8-fold greater in the skeletal muscle and 1(.)3-fold greater in the liver, and the level of AdipoR2 mRNA was 30% less in the liver of the ET group as compared with the control group. Additionally, in the ET group, mRNA expression of acyl coenzyme A-oxidase and carnitine palmitoyl transferase 1 (CPT1) was greater in the liver but not in skeletal muscle. In contrast, no significant changes were observed in the expression of genes encoding the adiponectin receptors in addition to other genes except for CPT1 in the DR group. These findings suggest that chronic exercise training affects the expression level of adiponectin receptors thereby improving insulin resistance in KKAy mice.

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  • The effect of exercise training on adiponectin receptor expression in KKAy obese/diabetic mice

    Hu Huang, Kaoruko Tada Iida, Hirohito Sone, Tomotaka Yokoo, Nobuhiro Yamada, Ryuichi Ajisaka

    JOURNAL OF ENDOCRINOLOGY   189 ( 3 )   643 - 653   2006.6

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    Adiponectin is an adipocyte-derived factor that plays a pivotal role in lipid and glucose metabolism. Recently, two types of adiponectin receptors (AdipoR1 and AdipoR2) were identified. We investigated whether exercise training (ET) or dietary restriction (DR) affects the expression of adiponectin receptors in skeletal muscle and liver, thereby improving glucose and lipid metabolism in KKAy mice. KKAy mice were subjected to 8 weeks of exercise training or food restriction. Following the experimental protocol, an intravenous glucose tolerance test and an intraperitoneal insulin tolerance test were performed in addition to the measurement of blood lipid and adiponectin concentrations. The mRNA levels of adiponectin, adiponectin receptors and genes that are putatively regulated by the adiponectin receptors were also analyzed. Both the 8-week exercise training and food restriction protocol improved insulin resistance in KKAy mice but did not alter plasma adiponectin concentration nor its mRNA expression. In comparison with C57BL/6 mice, AdipoR1 expression level was significantly decreased in skeletal muscle and AdipoR2 expression level was significantly increased in the liver in KKAy mice. After the 8-week experimental protocol, the expression level of AdipoR1 mRNA was approximately 1-8-fold greater in the skeletal muscle and 1(.)3-fold greater in the liver, and the level of AdipoR2 mRNA was 30% less in the liver of the ET group as compared with the control group. Additionally, in the ET group, mRNA expression of acyl coenzyme A-oxidase and carnitine palmitoyl transferase 1 (CPT1) was greater in the liver but not in skeletal muscle. In contrast, no significant changes were observed in the expression of genes encoding the adiponectin receptors in addition to other genes except for CPT1 in the DR group. These findings suggest that chronic exercise training affects the expression level of adiponectin receptors thereby improving insulin resistance in KKAy mice.

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  • 【メタボリックシンドロームの管理と今後の展望】 メタボリックシンドロームの臨床的意義 糖尿病

    曽根 博仁, 山田 信博

    動脈硬化予防   5 ( 1 )   19 - 27   2006.5

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  • Cut points of waist circumference - Response to Oda

    H Sone, S Tanaka, Y Ohashi, N Yamada

    DIABETES CARE   29 ( 5 )   1189 - 1189   2006.5

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    DOI: 10.2337/dc06-0329

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  • Cut points of waist circumference - Response to Oda

    H Sone, S Tanaka, Y Ohashi, N Yamada

    DIABETES CARE   29 ( 5 )   1189 - 1189   2006.5

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    DOI: 10.2337/dc06-0329

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  • Oligo-capping SST(Signal Sequence Trap)法による糖尿病網膜症増殖組織における分泌タンパク質の単離・同定

    渡邉 和寿, 豊島 秀男, 岡本 史樹, 横尾 友隆, 鈴木 浩明, 飯田 薫子, 大垣 聡子, 加治 優一, 高松 俊行, 高橋 昭光, 曽根 博仁, 島野 仁, 大鹿 哲郎, 山田 信博

    糖尿病   49 ( Suppl.1 )   S157 - S157   2006.4

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  • 【メタボリックシンドローム2006-2007 REVISIT】 最新治療エビデンス 糖代謝 Japan Diabetes Complications Study(JDCS)

    曽根 博仁, 山田 信博, JDCSグループ

    医学のあゆみ   217 ( 1 )   61 - 66   2006.4

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    日本人糖尿病患者の合併症や病態的特徴を明らかにするためにわが国で進行中のJapan Diabetes Complications Study(JDCS)の中間結果より,日本人と欧米人糖尿病患者の違いがいくつも明らかになってきた.そのデータによると,従来の診断基準によって日本人2型糖尿病患者でメタボリックシンドロームを診断しても,心血管疾患予測にはそれほど有用でないことが判明し,日本人糖尿病患者に適した心血管合併症のスクリーニング法をさらに検討する必要があると思われた(著者抄録)

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  • インスリン遺伝子転写因子Maf Aに変異を有する若年発症糖尿病の症例

    高橋 昭光, 島野 仁, 松坂 賢, 斉藤 和美, 平嶺 辰英, 小俣 勝哉, 加藤 豊範, 石川 まゆみ, 岡田 純代, 石垣 直美, 岩崎 仁, 遠藤 祐子, 井上 訓之, 山本 隆史, 中川 嘉, 飯田 薫子, 曽根 博仁, 鈴木 浩明, 豊島 秀男, 高橋 智, 山田 信博

    糖尿病   49 ( Suppl.1 )   S213 - S213   2006.4

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  • 脂肪細胞におけるp21WAF1/CIP1の役割

    井上 訓之, 島野 仁, 石川 まゆみ, 岡田 純代, 中川 嘉, 山本 隆史, 松坂 賢, 高橋 昭光, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 矢作 直也, 山田 信博

    糖尿病   49 ( Suppl.1 )   S207 - S207   2006.4

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDC Study)における糖尿病性腎症の発症と進展について

    田中 佐智子, 田中 司郎, 横田 千津子, 守屋 達美, 矢島 義忠, 山田 研一, 大橋 靖雄, 曽根 博仁, 山田 信博, 赤沼 安夫, 片山 茂裕

    糖尿病   49 ( Suppl.1 )   S254 - S254   2006.4

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  • インスリン分泌刺激作用を持つ新規腸管特異的分泌タンパク遺伝子の同定

    横尾 友隆, 豊島 秀男, 飯田 薫子, 鈴木 浩明, 渡邉 和寿, 高橋 昭光, 曽根 博仁, 島野 仁, 山田 信博

    糖尿病   49 ( Suppl.1 )   S249 - S249   2006.4

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  • 1 Coronary Heart Disease and Metabolic Syndrome in Japanese Patients with Diabetes(Treatment Strategy Update for Coronary Artery Disease with Diabetes Mellitus,Topic 8 (TP8) (IHD),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation Society)

    Sone Hirohito, Yamada Nobuhiro

    Circulation journal : official journal of the Japanese Circulation Society   70   70 - 70   2006.3

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  • 平成16年度 日本体育協会スポーツ医・科学研究報告 中高年者の運動プログラムに関する総合的研究 (第3報) 病態別(疾患別)運動プログラムの立案 糖尿病のための運動プログラム

    中垣内 真樹, 金山 正恵, 山中 伊津美, 曽根 博仁

    日本体育協会スポーツ科学研究報告集   2004-2005年度   28 - 34   2006.3

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  • 【日本の肥満と糖尿病】 Q&A 大規模臨床研究からみた日本人糖尿病患者の特徴は?

    曽根 博仁, 山田 信博

    Q&Aでわかる肥満と糖尿病   5 ( 2 )   256 - 259   2006.3

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  • JDCSにおける脂質代謝異常と動脈硬化疾患との関連

    曽根 博仁, 石橋 俊, 及川 眞一, 山崎 義光, 山田 信博

    内分泌・糖尿病科   22 ( 3 )   326 - 331   2006.3

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  • 【糖尿病とメタボリックシンドローム】 日本人2型糖尿病患者におけるメタボリックシンドロームの現況と臨床的意義 Japan Diabetes Complications Study(JDCS)より

    曽根 博仁, 山田 信博, JDCSグループ

    プラクティス   23 ( 2 )   165 - 170   2006.3

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  • 糖尿病合併症に関する最近の知見 糖尿病合併症とそのリスクファクターの人種・民族差

    曽根 博仁, 山田 信博

    分子糖尿病学の進歩: 基礎から臨床まで   2006   168 - 175   2006.3

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    Language:Japanese   Publisher:金原出版(株)  

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  • 小人症,小頭症および染色体異常を伴い,インスリン抵抗性改善薬が著効した若年発症糖尿病の1例

    豊島 秀男, 島野 仁, 曽根 博仁, 鈴木 浩明, 高橋 昭光, 小田原 雅人, 山田 信博

    日本内科学会関東地方会   534回   26 - 26   2006.3

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  • 日本人2型糖尿病患者の心血管疾患発症予測におけるメタボリックシンドローム診断の臨床的有用性 Japan Diabetes Complications Study(JDCS)の中間解析より

    曽根 博仁, 田中 佐智子, 石橋 俊, 井藤 英喜, 山崎 義光, 齋藤 康, 大橋 靖雄, 赤沼 安夫, 山田 信博

    日本内科学会雑誌   95 ( Suppl. )   142 - 142   2006.2

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  • 【糖代謝異常と循環器疾患合併症 ここが知りたい】 糖代謝異常と循環器診療 日本のエビデンス Japan Diabetes Complications Study(JDCS)の中間結果より

    曽根 博仁, 山田 信博

    臨床医のための循環器診療   ( 5 )   24 - 28   2006.2

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  • 【糖尿病診療のQuality of Careを向上させたい】 医師の壁・患者の壁 日本人の血糖コントロールの現状 JDCSのデータにみる日本の糖尿病患者の姿は?

    曽根 博仁, 山田 信博

    糖尿病診療マスター   4 ( 1 )   21 - 25   2006.1

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    DOI: 10.11477/mf.1415100431

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  • 【糖尿病と動脈硬化 その機序から診断と治療へ】 糖尿病における動脈硬化性疾患の疫学

    曽根 博仁, 山田 信博

    内分泌・糖尿病科   22 ( 1 )   7 - 14   2006.1

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  • 【糖尿病 1620万人の最適な治療を目指して】 日本人の糖尿病治療の前向き研究 Japan Diabetes Complications Study(JDCS)

    曽根 博仁, 山田 信博, JDCSグループ

    内科   97 ( 1 )   16 - 21   2006.1

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    アジア人糖尿病の大規模臨床試験や前向き疫学研究に基づくエビデンスは,これまで不十分であった.JDCSは,日本全国の2型糖尿病患者2,200人余を前向きに追跡している臨床研究である.JDCSのデータにより,日本人と欧米人の糖尿病患者を比較すると,肥満や合併症の頻度,合併症のリスクファクターなど,さまざまな違いがみられることが明らかになった.日本人糖尿病患者に最適化された治療のためには,多数の日本人糖尿病患者から得られた臨床エビデンスがさらに充実することが望まれる(著者抄録)

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  • The new worldwide definition of metabolic syndrome is not a better diagnostic predictor of cardiovascular disease in Japanese diabetic patients than the existing definitions: Additional analysis from the Japan Diabetes Complications Study

    H Sone, S Tanaka, S Ishibashi, Y Yamasaki, S Oikawa, H Ito, Y Saito, Y Ohashi, Y Akanuma, N Yamada

    DIABETES CARE   29 ( 1 )   145 - 147   2006.1

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  • TFE3 transcriptionally activates hepatic IRS-2, participates in insulin signaling and ameliorates diabetes

    Y Nakagawa, H Shimano, T Yoshikawa, T Ide, M Tamura, M Furusawa, T Yamamoto, N Inoue, T Matsuzaka, A Takahashi, AH Hasty, H Suzuki, H Sone, H Toyoshima, N Yahagi, N Yamada

    NATURE MEDICINE   12 ( 1 )   107 - 113   2006.1

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    Using an expression cloning strategy, we have identified TFE3, a basic helix-loop-helix protein, as a transactivator of metabolic genes that are regulated through an E-box in their promoters. Adenovirus-mediated expression of TFE3 in hepatocytes in culture and in vivo strongly activated expression of IRS-2 and Akt and enhanced phosphorylation of insulin-signaling kinases such as Akt, glycogen synthase kinase 3 beta and p70S6 kinase. TFE3 also induced hexokinase II (HK2) and insulin-induced gene 1 (INSIG1). These changes led to metabolic consequences, such as activation of glycogen and protein synthesis, but not lipogenesis, in liver. Collectively, plasma glucose levels were markedly reduced both in normal mice and in different mouse models of diabetes, including streptozotocin-treated, db/db and KK mice. Promoter analyses showed that IRS2, HK2 and INSIG1 are direct targets of TFE3. Activation of insulin signals in both insulin depletion and resistance suggests that TFE3 could be a therapeutic target for diabetes.

    DOI: 10.1038/nm1334

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  • Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy

    S Yatoh, M Mizutani, T Yokoo, T Kozawa, H Sone, H Toyoshima, S Suzuki, H Shimano, Y Kawakami, Y Okuda, N Yamada

    DIABETES-METABOLISM RESEARCH AND REVIEWS   22 ( 1 )   38 - 45   2006.1

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    Background Pericyte ghosts and acellular capillaries are well known as early histological changes resulting from diabetic retinopathy. These histological changes mean that the cell death of retinal microvessels has accelerated. It was reported that apoptosis of retinal microvascular cells (RMCs) was increased in diabetic patients. Therefore, we investigated apoptosis of RMCs in Goto-Kakizaki (GK) rats, a type 2 diabetic model, and involvement with antioxidants (a combination of vitamins C and E) or a novel inhibitor of advanced glycation, OPB-9195.
    Methods GK rats were treated with the antioxidants combination or OPB-9195 for 36 weeks. We obtained isolated preparations of the vascular network from their retinas by trypsin digestion. Apoptosis of retinal vascular cells was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.
    Results We found that apoptosis of RMCs was increased in the diabetic GK rats. Furthermore, a combination of vitamins C and E and an advanced glycation end-products inhibitor mostly inhibited this increased apoptosis.
    Conclusions We concluded that apoptosis of RMCs was a good marker that indicates the progression of diabetic retinopathy in GK rats. Both oxidative stress and the accumulation of advanced glycation end-products appears to promote the apoptosis of retinal microvascular cells, and antioxidants or advanced glycation end-products inhibitors might ameliorate diabetic retinopathy. Copyright (c) 2005 John Wiley & Sons, Ltd.

    DOI: 10.1002/dmrr.562

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  • TFE3 transcriptionally activates hepatic IRS-2, participates in insulin signaling and ameliorates diabetes

    Y Nakagawa, H Shimano, T Yoshikawa, T Ide, M Tamura, M Furusawa, T Yamamoto, N Inoue, T Matsuzaka, A Takahashi, AH Hasty, H Suzuki, H Sone, H Toyoshima, N Yahagi, N Yamada

    NATURE MEDICINE   12 ( 1 )   107 - 113   2006.1

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    Language:English   Publisher:NATURE PUBLISHING GROUP  

    Using an expression cloning strategy, we have identified TFE3, a basic helix-loop-helix protein, as a transactivator of metabolic genes that are regulated through an E-box in their promoters. Adenovirus-mediated expression of TFE3 in hepatocytes in culture and in vivo strongly activated expression of IRS-2 and Akt and enhanced phosphorylation of insulin-signaling kinases such as Akt, glycogen synthase kinase 3 beta and p70S6 kinase. TFE3 also induced hexokinase II (HK2) and insulin-induced gene 1 (INSIG1). These changes led to metabolic consequences, such as activation of glycogen and protein synthesis, but not lipogenesis, in liver. Collectively, plasma glucose levels were markedly reduced both in normal mice and in different mouse models of diabetes, including streptozotocin-treated, db/db and KK mice. Promoter analyses showed that IRS2, HK2 and INSIG1 are direct targets of TFE3. Activation of insulin signals in both insulin depletion and resistance suggests that TFE3 could be a therapeutic target for diabetes.

    DOI: 10.1038/nm1334

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  • The new worldwide definition of metabolic syndrome is not a better diagnostic predictor of cardiovascular disease in Japanese diabetic patients than the existing definitions: Additional analysis from the Japan Diabetes Complications Study

    H Sone, S Tanaka, S Ishibashi, Y Yamasaki, S Oikawa, H Ito, Y Saito, Y Ohashi, Y Akanuma, N Yamada

    DIABETES CARE   29 ( 1 )   145 - 147   2006.1

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  • Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy

    S Yatoh, M Mizutani, T Yokoo, T Kozawa, H Sone, H Toyoshima, S Suzuki, H Shimano, Y Kawakami, Y Okuda, N Yamada

    DIABETES-METABOLISM RESEARCH AND REVIEWS   22 ( 1 )   38 - 45   2006.1

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    Background Pericyte ghosts and acellular capillaries are well known as early histological changes resulting from diabetic retinopathy. These histological changes mean that the cell death of retinal microvessels has accelerated. It was reported that apoptosis of retinal microvascular cells (RMCs) was increased in diabetic patients. Therefore, we investigated apoptosis of RMCs in Goto-Kakizaki (GK) rats, a type 2 diabetic model, and involvement with antioxidants (a combination of vitamins C and E) or a novel inhibitor of advanced glycation, OPB-9195.
    Methods GK rats were treated with the antioxidants combination or OPB-9195 for 36 weeks. We obtained isolated preparations of the vascular network from their retinas by trypsin digestion. Apoptosis of retinal vascular cells was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.
    Results We found that apoptosis of RMCs was increased in the diabetic GK rats. Furthermore, a combination of vitamins C and E and an advanced glycation end-products inhibitor mostly inhibited this increased apoptosis.
    Conclusions We concluded that apoptosis of RMCs was a good marker that indicates the progression of diabetic retinopathy in GK rats. Both oxidative stress and the accumulation of advanced glycation end-products appears to promote the apoptosis of retinal microvascular cells, and antioxidants or advanced glycation end-products inhibitors might ameliorate diabetic retinopathy. Copyright (c) 2005 John Wiley & Sons, Ltd.

    DOI: 10.1002/dmrr.562

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  • 健常中高齢者における運動トレーニングの血清高感度CRP濃度に対する効果

    体力科学   56   179 - 190   2006

  • Outcome of one-year of specialist care of patients with type 2 diabetes: A multi-center prospective survey (JDDM 2)

    Hirohito Sone, Koichi Kawai, Hirofumi Takagi, Nobuhiro Yamada, Masashi Kobayashi

    INTERNAL MEDICINE   45 ( 9 )   589 - 597   2006

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    OBJECTIVE Specialist care is reportedly associated with favorable therapeutic results, although detailed outcomes of recent large-scale prospective surveys of specialist care have yet to be published. The goal of this study was to elucidate the effects of one year's specialist care on the management of type 2 diabetes.
    PATIENTS AND METHODS A multi-centered, prospective observational study was undertaken. 754 type 2 diabetes patients, who made their first visit to one of eleven participating outpatient clinics specializing in diabetes care, were enrolled. Routine structured diabetes care according to established guideline, including diabetes self-management education, was provided to all patients at each clinic visit. Parameters relating to glycemic control, serum lipids, blood pressure, patient follow-up status and others were followed for twelve months.
    RESULTS The HbA(1C) level had improved significantly from 8.4 +/- 2.2% at baseline to 6.8 +/- 1.2% after six months and was 7.0 +/- 1.3% after twelve months (mean +/- SD). The higher the baseline HbA1C level, the greater the subsequent improvement. Moreover, the most dramatic improvements in HbA1C levels were seen within the first three months. The proportion of patients satisfying all of the therapeutic goals was extremely low at baseline and remained at less than 10% after twelve months of specialist care.
    CONCLUSIONS Diabetic patients under specialist care experienced substantial improvement, especially in glycemic control, as early as a few months after the first visit. However, 35 percent of patients dropped out during the 12-month study period and this is one area that needs to be improved.

    DOI: 10.2169/internalmedicine.45.1609

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  • Outcome of one-year of specialist care of patients with type 2 diabetes: A multi-center prospective survey (JDDM 2)

    Hirohito Sone, Koichi Kawai, Hirofumi Takagi, Nobuhiro Yamada, Masashi Kobayashi

    INTERNAL MEDICINE   45 ( 9 )   589 - 597   2006

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    OBJECTIVE Specialist care is reportedly associated with favorable therapeutic results, although detailed outcomes of recent large-scale prospective surveys of specialist care have yet to be published. The goal of this study was to elucidate the effects of one year's specialist care on the management of type 2 diabetes.
    PATIENTS AND METHODS A multi-centered, prospective observational study was undertaken. 754 type 2 diabetes patients, who made their first visit to one of eleven participating outpatient clinics specializing in diabetes care, were enrolled. Routine structured diabetes care according to established guideline, including diabetes self-management education, was provided to all patients at each clinic visit. Parameters relating to glycemic control, serum lipids, blood pressure, patient follow-up status and others were followed for twelve months.
    RESULTS The HbA(1C) level had improved significantly from 8.4 +/- 2.2% at baseline to 6.8 +/- 1.2% after six months and was 7.0 +/- 1.3% after twelve months (mean +/- SD). The higher the baseline HbA1C level, the greater the subsequent improvement. Moreover, the most dramatic improvements in HbA1C levels were seen within the first three months. The proportion of patients satisfying all of the therapeutic goals was extremely low at baseline and remained at less than 10% after twelve months of specialist care.
    CONCLUSIONS Diabetic patients under specialist care experienced substantial improvement, especially in glycemic control, as early as a few months after the first visit. However, 35 percent of patients dropped out during the 12-month study period and this is one area that needs to be improved.

    DOI: 10.2169/internalmedicine.45.1609

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  • 【日本人糖尿病と虚血性心疾患】 糖尿病と虚血性心疾患 Japan Diabetes Complications Study(JDCS)の中間結果

    曽根 博仁, 山田 信博

    プラクティス   22 ( 6 )   662 - 667   2005.11

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  • 【最新の高脂血症治療とエビデンス】 高脂血症治療による糖尿病の発症ならびに動脈硬化合併症への効果

    曽根 博仁

    最新医学   60 ( 11 )   2410 - 2420   2005.11

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  • 【虚血性心疾患2006】 メタボリックシンドロームと虚血性心疾患

    曽根 博仁, 山田 信博

    成人病と生活習慣病   35 ( 10 )   1104 - 1111   2005.10

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    Language:Japanese   Publisher:(株)東京医学社  

    複数の心血管リスクファクターの重積状態であるメタボリックシンドロームは,虚血性心疾患の一次・二次予防を考えるうえで,高LDL血症や喫煙などと並ぶ重要性を有すると認識されるようになった.欧米の前向き大規模研究においては,メタボリックシンドローム患者では虚血性心疾患の発症やそれによる死亡リスクが有意に高まることが示されている.複数のリスクファクターの集合体であるメタボリックシンドロームに対処するには,各リスクを丁寧かつ粘り強くコントロールしていくことが重要である.特に糖尿病合併例のような高リスク群においては,血圧や血清脂質の十分なコントロールが求められる.また,メタボリックシンドロームの有病率や臨床的意義は,診断基準や人種によって微妙に異なることがある.最近内外で新しい診断基準が発表されたが,日本人(東アジア人)における臨床的意義や日常診療における有用性を検証するために,今後のエビデンスの蓄積が期待される(著者抄録)

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  • スポーツ医学Q&A メタボリックシンドローム患者に対する運動療法について

    児玉 暁, 叔 びょう, 曽根 博仁

    臨床スポーツ医学   22 ( 10 )   1298 - 1303   2005.10

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    Other Link: http://search.jamas.or.jp/link/ui/2006009741

  • Sterol regulatory element-binding proteins activate insulin gene promoter directly and indirectly through synergy with BETA2/E47

    M Amemiya-Kudo, J Oka, T Ide, T Matsuzaka, H Sone, T Yoshikawa, N Yahagi, S Ishibashi, J Osuga, N Yamada, T Murase, H Shimano

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 41 )   34577 - 34589   2005.10

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    Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47. Here we have demonstrated that the insulin promoter is a novel target for SREBPs established as lipid-synthetic transcription factors. Promoter analyses of rat insulin I gene in non-beta cells revealed that nuclear SREBP-1c activates the insulin promoter through three novel SREBP-binding sites (SREs), two of which overlap with E-boxes, binding sites for BETA2/ E47. SREBP-1c activation of the insulin promoter was markedly enhanced by co-expression of BETA2/ E47. This synergistic activation by SREBP-1c/ BETA2/ E47 was not mediated through SREs but through the E-boxes on which BETA2/ E47 physically interacts with SREBP-1c, suggesting a novel function of SREBP as a co-activator. These two cis-DNA regions, E1 and E2, with an appropriate distance separating them, were mandatory for the synergism, which implicates formation of SREBP-1c center dot BETA2 center dot E47 complex in a DNA looping structure for efficient recruitment of CREB- binding protein/ p300. However, in the presence of PDX1, the synergistic action of SREBP-1c with BETA2/E47 was canceled. SREBP-1c-mediated activation of the insulin promoter and expression became overt in beta cell lines and isolated islets when endogenous PDX-1 expression was low. This cryptic SREBP-1c action might play a compensatory role in insulin expression in diabetes with beta cell lipotoxicity.

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  • Sterol regulatory element-binding proteins activate insulin gene promoter directly and indirectly through synergy with BETA2/E47

    M Amemiya-Kudo, J Oka, T Ide, T Matsuzaka, H Sone, T Yoshikawa, N Yahagi, S Ishibashi, J Osuga, N Yamada, T Murase, H Shimano

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 41 )   34577 - 34589   2005.10

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    Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47. Here we have demonstrated that the insulin promoter is a novel target for SREBPs established as lipid-synthetic transcription factors. Promoter analyses of rat insulin I gene in non-beta cells revealed that nuclear SREBP-1c activates the insulin promoter through three novel SREBP-binding sites (SREs), two of which overlap with E-boxes, binding sites for BETA2/ E47. SREBP-1c activation of the insulin promoter was markedly enhanced by co-expression of BETA2/ E47. This synergistic activation by SREBP-1c/ BETA2/ E47 was not mediated through SREs but through the E-boxes on which BETA2/ E47 physically interacts with SREBP-1c, suggesting a novel function of SREBP as a co-activator. These two cis-DNA regions, E1 and E2, with an appropriate distance separating them, were mandatory for the synergism, which implicates formation of SREBP-1c center dot BETA2 center dot E47 complex in a DNA looping structure for efficient recruitment of CREB- binding protein/ p300. However, in the presence of PDX1, the synergistic action of SREBP-1c with BETA2/E47 was canceled. SREBP-1c-mediated activation of the insulin promoter and expression became overt in beta cell lines and isolated islets when endogenous PDX-1 expression was low. This cryptic SREBP-1c action might play a compensatory role in insulin expression in diabetes with beta cell lipotoxicity.

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  • Lipid synthetic transcription factor SREBP-1a activates p21(WAF1/CIP1), a universal cyclin-dependent kinase inhibitor

    N Inoue, H Shimano, M Nakakuki, T Matsuzaka, Y Nakagawa, T Yamamoto, R Sato, A Takahashi, H Sone, N Yahagi, H Suzuki, H Toyoshima, N Yamada

    MOLECULAR AND CELLULAR BIOLOGY   25 ( 20 )   8938 - 8947   2005.10

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    Sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that regulate lipid synthetic genes. In contrast to SREBP-2, which regulates cellular cholesterol level in normal cells, SREBP-1a is highly expressed in actively growing cells and activates entire programs of genes involved in lipid synthesis such as cholesterol, fatty acids, triglycerides, and phospholipids. Previously, the physiological relevance of this potent activity of SREBP-1a has been thought to regulate the supply of membrane lipids in response to cell growth. Here we show that nuclear SREBP-1a and SREBP-2 bind directly to a novel SREBP binding site in the promoter of the p21(WAF1/CIP1) gene, the major cyclin-dependent kinase inhibitor, and strongly activate its promoter activity. Only the SREBP-1a isoform consistently causes induction of p21. at both the mRNA and protein levels. Colony formation assays and polyploidy of livers from transgenic mice suggest that activation of p21. by SREBP-1a could inhibit cell growth. Activation of endogenous SREBPs in lipid deprivation conditions was associated with induction of p21 mRNA and protein. Expression of p21 was reduced in SREBP-1 null mice. These data suggest a physiological role of SREBP-1a in p21 regulation. Identification of p21 as a new SREBP target might implicate a new paradigm in the link between lipid synthesis and cell growth.

    DOI: 10.1128/MCB.25.20.8938-8947.2005

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  • Lipid synthetic transcription factor SREBP-1a activates p21(WAF1/CIP1), a universal cyclin-dependent kinase inhibitor

    N Inoue, H Shimano, M Nakakuki, T Matsuzaka, Y Nakagawa, T Yamamoto, R Sato, A Takahashi, H Sone, N Yahagi, H Suzuki, H Toyoshima, N Yamada

    MOLECULAR AND CELLULAR BIOLOGY   25 ( 20 )   8938 - 8947   2005.10

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    Sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that regulate lipid synthetic genes. In contrast to SREBP-2, which regulates cellular cholesterol level in normal cells, SREBP-1a is highly expressed in actively growing cells and activates entire programs of genes involved in lipid synthesis such as cholesterol, fatty acids, triglycerides, and phospholipids. Previously, the physiological relevance of this potent activity of SREBP-1a has been thought to regulate the supply of membrane lipids in response to cell growth. Here we show that nuclear SREBP-1a and SREBP-2 bind directly to a novel SREBP binding site in the promoter of the p21(WAF1/CIP1) gene, the major cyclin-dependent kinase inhibitor, and strongly activate its promoter activity. Only the SREBP-1a isoform consistently causes induction of p21. at both the mRNA and protein levels. Colony formation assays and polyploidy of livers from transgenic mice suggest that activation of p21. by SREBP-1a could inhibit cell growth. Activation of endogenous SREBPs in lipid deprivation conditions was associated with induction of p21 mRNA and protein. Expression of p21 was reduced in SREBP-1 null mice. These data suggest a physiological role of SREBP-1a in p21 regulation. Identification of p21 as a new SREBP target might implicate a new paradigm in the link between lipid synthesis and cell growth.

    DOI: 10.1128/MCB.25.20.8938-8947.2005

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  • 【脳卒中と認知症】 Q&A 脳梗塞予防におけるスタチンの効果は?

    曽根 博仁

    Q&Aでわかる肥満と糖尿病   4 ( 5 )   878 - 880   2005.9

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  • EBMから見た糖尿病における心血管疾患予防の重要性 Japan Diabetes Complications Study

    曽根 博仁, 水野 佐智子, 大橋 靖雄, 高橋 和男, 齋藤 康, 井藤 英喜, 山崎 義光, 石橋 俊, 赤沼 安夫, 山田 信博

    糖尿病学の進歩   ( 39 )   19 - 23   2005.9

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  • 運動トレーニングは,高齢者の中でも心血管ハイリスク者においてより有効である

    児玉 暁, 淑 びょう, 村上 晴香, 久野 譜也, 田中 喜代次, 松田 光生, 山田 信博, 曽根 博仁

    日本臨床スポーツ医学会誌   13 ( 4 )   S96 - S96   2005.9

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  • Japan Diabetes Complications Study(JDCS)における糖尿病とその合併症に関する臨床疫学的検討と国際比較

    曽根 博仁, 山田 信博

    糖尿病合併症   19 ( 2 )   114 - 122   2005.8

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  • 短期間の運動が中高齢者の内臓脂肪面積および糖代謝能に及ぼす影響

    林 容市, 田中 喜代次, 曽根 博仁, 久野 譜也

    体力科学   54 ( 4 )   305 - 313   2005.8

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    高齢者を対象にした短期間の運動介入前後における内臓脂肪(VF)とインスリン抵抗性の変化から,運動によるインスリン抵抗性の改善とVFの変化の関連について検討した.日常生活において特別な運動習慣を持たない中・高齢者26例を対象とし,健康支援プログラムに基づき,3ヵ月にわたり運動を実践した.内臓脂肪面積(VFA)の測定値100cm2を境界値として,VFAが100cm2以上を腹腔内脂肪型肥満(VFO)群,それ未満をControl群とした.有酸素性運動と自体重を負荷とした筋力トレーニングをおこなうことにより,VFO(男)においてのみHOMA-Rが改善したが,VFAには有意な減少は得られなかった.運動の実践により,VFの変化(減少)を伴わずともインスリン分泌が良好に改善される可能性が示唆された

    DOI: 10.7600/jspfsm.54.305

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  • 血糖コントロールの悪化を契機に診断された特発性間質性肺炎の症例

    三浦 光弘, 高橋 昭光, 石川 まゆみ, 石垣 直美, 飯田 薫子, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 島野 仁, 山田 信博

    糖尿病   48 ( 7 )   523 - 523   2005.7

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  • 糖尿病モデルマウスにおけるTFE3によるIRS-2の発現調節とインスリンシグナルへの影響

    中川 嘉, 島野 仁, 山本 隆史, 古沢 美香, 松坂 賢, 鈴木 宏奈, 高橋 昭光, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 山田 信博

    日本臨床分子医学会学術総会プログラム・抄録集   42回   106 - 106   2005.7

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  • 日本から発信する血管病のEBM JDCS(Japan Diabetes Complications Study)

    曽根 博仁, 田中 佐智子, 清野 弘明, 山崎 義光, 石橋 俊, 山下 英俊, 井藤 英喜, 齋藤 康, 片山 茂裕, 大橋 靖雄, 赤沼 安夫, 山田 信博, JDCSグループ

    Vascular Medicine   1 ( 1 )   86 - 94   2005.7

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  • 糖尿病合併症の疫学研究の現状と課題 Japan Diabetes Complications Study(JDCS)中間報告にみる現代日本の糖尿病合併症

    曽根 博仁, 清野 弘明, 山崎 義光, 石橋 俊, 山下 英俊, 井藤 英喜, 齋藤 康, 片山 茂裕, 松岡 健平, 大橋 靖雄, 赤沼 安夫, 山田 信博

    糖尿病合併症   19 ( 1 )   28 - 32   2005.7

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  • 劇症1型糖尿病と急性膵炎に続発した糖尿病との鑑別が困難であった一例

    平嶺 辰英, 小俣 勝哉, 曽根 博仁, 鈴木 浩明, 豊島 秀男, 島野 仁, 山田 信博

    糖尿病   18 ( 7 )   59 - 64   2005.7

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  • 全身性に動脈硬化性疾患を発症した糖尿病患者の1例

    石川 まゆみ, 大垣 聡子, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 島野 仁, 山田 信博

    日本内科学会関東地方会   527回   23 - 23   2005.6

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  • 健常者の食後血中トリグリセリド上昇における定期的運動トレーニングの有効性

    曽根 博仁, 山田 信博

    デサントスポーツ科学   26   33 - 41   2005.6

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    60歳以上の健常人28名(男13名,女15名)に3ヵ月間の有酸素運動トレーニングプログラムを提供し,その前後に経口脂肪負荷試験(OFTT)を実施した.プログラム前後で空腹時TG(トリグリセリド)値には明らかな変化がなかったにもかかわらず,OFTTでのTG上昇幅は有意に減少し(プログラム前平均96.6mg/dl,プログラム後79.4mg/dl),この減少は空腹時インスリンの低下を伴っていた

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  • 【糖尿病性細小血管症 基礎・臨床のアップデート】 糖尿病性細小血管症の定義,疫学 糖尿病性細小血管症の本邦における有病率と発症率

    曽根 博仁, 山下 英俊, 片山 茂裕, 赤沼 安夫, 山田 信博

    日本臨床   63 ( 増刊6 糖尿病性細小血管症 )   18 - 22   2005.6

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  • Is the diagnosis of metabolic syndrome useful for predicting cardiovascular disease in Asian diabetic patients? Analysis from the Japan Diabetes Complications Study

    H Sone, S Mizuno, H Fujii, Y Yoshimura, Y Yamasaki, S Ishibashi, S Katayama, Y Saito, H Ito, Y Ohashi, Y Akanuma, N Yamada

    DIABETES CARE   28 ( 6 )   1463 - 1471   2005.6

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    OBJECTIVE - The metabolic syndrome (MetS) is believed to be associated with an increased risk of cardiovascular disease (CVD). Although its prevalence is extremely high among diabetic patients, its prevalence in those with no history of CVD has not been determined. Moreover, prospective studies published on the association between MetS and cardiovascular events in diabetic populations have used only the World Health Organization (WHO) definition of MetS and included only white European subjects. The aim of this study was to determine the prevalence of MetS, as defined by both the WHO and the National Cholesterol Education Program (NCEP), and its predictive value for CVD in Asian diabetic patients in a long-term, prospective setting.
    RESEARCH DESIGN AND METHODS - The baseline characteristics and incidence/hazard ratio of cardiovascular events (coronary heart disease and stroke) were determined in 1,424 Japanese type 2 diabetic patients with and without MetS, as defined by WHO (WHO-MetS) or the NCEP.
    RESULTS - A high prevalence (38-53%, depending on sex and definition) of MetS was found among diabetic patients, even those with no history of CVD. During the 8-year study period, only WHO-MetS was a predictor for CVD in female patients. In male patients, although both definitions of MetS were significant predictors for CVD, individual components of MetS, such as hyperlipidemia or hypertension, were equivalent or better predictors.
    CONCLUSIONS - We found that MetS is relatively common in diabetic patients with no history of CVD. We suggest that the commonly used definitions of MetS, at least in their present forms, have limited clinical usefulness for Asian diabetic patients and may need some ethnic group-specific modifications for global use.

    DOI: 10.2337/diacare.28.6.1463

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  • Is the diagnosis of metabolic syndrome useful for predicting cardiovascular disease in Asian diabetic patients? Analysis from the Japan Diabetes Complications Study

    H Sone, S Mizuno, H Fujii, Y Yoshimura, Y Yamasaki, S Ishibashi, S Katayama, Y Saito, H Ito, Y Ohashi, Y Akanuma, N Yamada

    DIABETES CARE   28 ( 6 )   1463 - 1471   2005.6

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    OBJECTIVE - The metabolic syndrome (MetS) is believed to be associated with an increased risk of cardiovascular disease (CVD). Although its prevalence is extremely high among diabetic patients, its prevalence in those with no history of CVD has not been determined. Moreover, prospective studies published on the association between MetS and cardiovascular events in diabetic populations have used only the World Health Organization (WHO) definition of MetS and included only white European subjects. The aim of this study was to determine the prevalence of MetS, as defined by both the WHO and the National Cholesterol Education Program (NCEP), and its predictive value for CVD in Asian diabetic patients in a long-term, prospective setting.
    RESEARCH DESIGN AND METHODS - The baseline characteristics and incidence/hazard ratio of cardiovascular events (coronary heart disease and stroke) were determined in 1,424 Japanese type 2 diabetic patients with and without MetS, as defined by WHO (WHO-MetS) or the NCEP.
    RESULTS - A high prevalence (38-53%, depending on sex and definition) of MetS was found among diabetic patients, even those with no history of CVD. During the 8-year study period, only WHO-MetS was a predictor for CVD in female patients. In male patients, although both definitions of MetS were significant predictors for CVD, individual components of MetS, such as hyperlipidemia or hypertension, were equivalent or better predictors.
    CONCLUSIONS - We found that MetS is relatively common in diabetic patients with no history of CVD. We suggest that the commonly used definitions of MetS, at least in their present forms, have limited clinical usefulness for Asian diabetic patients and may need some ethnic group-specific modifications for global use.

    DOI: 10.2337/diacare.28.6.1463

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  • Transgenic mice overexpressing SREBP-1a under the control of the PEPCK promoter exhibit insulin resistance, but not diabetes

    A Takahashi, H Shimano, Y Nakagawa, T Yamamoto, K Motomura, T Matsuzaka, H Sone, H Suzuki, H Toyoshima, N Yamada

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE   1740 ( 3 )   427 - 433   2005.6

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    Sterol regulatory element-binding protein-1 (SREBP-1) is a transcription factor which regulates genes involved in the synthesis of fatty acids and triglycerides. The overexpression of nuclear SREBP-1a in transgenic mice under the control of the PEPCK promoter (TgSREBP-1a) caused a massively enlarged fatty liver and disappearance of peripheral white adipose tissue. In the current study, we estimated the impact of this lipid transcription factor on plasma glucose/insulin metabolism in vivo. TgSREBP-1a exhibited mild peripheral insulin resistance as evidenced by hyperinsulinemia both at fasting and after intravenous glucose loading, and retarded glucose reduction after insulin injection due to decreased plasma leptin levels. Intriguingly, hyperinsulinerma in TgSREBP-1a mice was markedly exacerbated in a fed state and sustained after intravenous glucose loading, and paradoxically decreased after the portal injection of glucose. TgSREBP-1a mice consistently showed very small plasma glucose increases after portal glucose loading because of a large capacity for hepatic glucose uptake. These data suggested that hepatic insulin resistance emerges postprandially. In addition, pancreatic islets from TgSREBP-1a were enlarged. These data demonstrate that SREBP-la activation in the liver has a strong impact on plasma insulin levels, implicating the potential role of SREBPs in hepatic insulin metabolism relating to insulin resistance. (c) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.bbadis.2004.11.006

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  • Transgenic mice overexpressing SREBP-1a under the control of the PEPCK promoter exhibit insulin resistance, but not diabetes

    A Takahashi, H Shimano, Y Nakagawa, T Yamamoto, K Motomura, T Matsuzaka, H Sone, H Suzuki, H Toyoshima, N Yamada

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE   1740 ( 3 )   427 - 433   2005.6

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    Sterol regulatory element-binding protein-1 (SREBP-1) is a transcription factor which regulates genes involved in the synthesis of fatty acids and triglycerides. The overexpression of nuclear SREBP-1a in transgenic mice under the control of the PEPCK promoter (TgSREBP-1a) caused a massively enlarged fatty liver and disappearance of peripheral white adipose tissue. In the current study, we estimated the impact of this lipid transcription factor on plasma glucose/insulin metabolism in vivo. TgSREBP-1a exhibited mild peripheral insulin resistance as evidenced by hyperinsulinemia both at fasting and after intravenous glucose loading, and retarded glucose reduction after insulin injection due to decreased plasma leptin levels. Intriguingly, hyperinsulinerma in TgSREBP-1a mice was markedly exacerbated in a fed state and sustained after intravenous glucose loading, and paradoxically decreased after the portal injection of glucose. TgSREBP-1a mice consistently showed very small plasma glucose increases after portal glucose loading because of a large capacity for hepatic glucose uptake. These data suggested that hepatic insulin resistance emerges postprandially. In addition, pancreatic islets from TgSREBP-1a were enlarged. These data demonstrate that SREBP-la activation in the liver has a strong impact on plasma insulin levels, implicating the potential role of SREBPs in hepatic insulin metabolism relating to insulin resistance. (c) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.bbadis.2004.11.006

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  • TCA回路の部分阻害がエネルギー代謝に及ぼす影響

    曽根 博仁, 島野 仁, 高橋 昭光, 鈴木 浩明, 豊島 秀男, 山田 信博

    日本臨床分子医学会記録   41   42 - 42   2005.5

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  • 糖尿病診療の現状:2型糖尿病 肥満はどこまで影響するか

    曽根 博仁, 吉村 幸雄, 井藤 英喜, 山田 信博

    Mebio   22 ( 5 )   74 - 78   2005.5

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  • Vascular risk factors and diabetic neuropathy

    H Sone, S Mizuno, N Yamada

    NEW ENGLAND JOURNAL OF MEDICINE   352 ( 18 )   1926 - 1926   2005.5

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    DOI: 10.1056/NEJM200505053521817

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  • アディポネクチン分泌およびアディポネクチン受容体発現に対する運動効果の検討

    飯田 薫子, 黄 虎, 曽根 博仁, 豊島 秀男, 鯵坂 隆一, 山田 信博

    糖尿病   48 ( Suppl.2 )   S80 - S80   2005.4

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  • 新規栄養代謝調節転写因子TFE3は糖尿病モデルマウスの病態を改善する

    中川 嘉, 島野 仁, 井出 智広, 山本 隆史, 松坂 賢, 高橋 昭光, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 山田 信博

    糖尿病   48 ( Suppl.2 )   S49 - S49   2005.4

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  • 膵β細胞にSREBP-1cを強発現させたトランスジェニックマウスの検討

    高橋 昭光, 本村 香織, 加藤 豊範, 吉川 智弘, 松坂 賢, 山本 隆史, 石川 まゆみ, 岡田 純代, 石垣 直美, 飯田 薫子, 鈴木 浩明, 豊島 秀男, 曽根 博仁, 中川 嘉, 島野 仁, 山田 信博

    日本内分泌学会雑誌   81 ( 1 )   101 - 101   2005.4

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  • PKAによるLXRのリン酸化を介したSREBP-1c遺伝子の転写抑制

    山本 隆史, 山田 信博, 島野 仁, 豊島 秀男, 曽根 博仁, 鈴木 浩明, 飯田 薫子, 高橋 昭光, 中川 嘉

    日本内分泌学会雑誌   81 ( 1 )   204 - 204   2005.4

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  • 新規脂肪酸伸長酵素Fatty acyl-elongaseの生体内における機能および病態への関与

    松坂 賢, 島野 仁, 矢作 直也, 中川 嘉, 高橋 昭光, 山本 隆史, 曽根 博仁, 豊島 秀男, 大須賀 淳一, 山田 信博

    日本内分泌学会雑誌   81 ( 1 )   101 - 101   2005.4

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  • 思春期糖尿病の症例検討

    若山 直美, 島野 仁, 曽根 博仁, 鈴木 浩明, 豊島 秀男, 山田 信博

    思春期学   23 ( 1 )   85 - 85   2005.3

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  • 【糖尿病腎症の発症と進展】 糖尿病腎症の発症と進展 JDC Study 6年次解析

    片山 茂裕, 横田 千津子, 守屋 達美, 矢島 義忠, 山田 研一, 水野 佐智子, 大橋 靖雄, 曽根 博仁, 山田 信博, 赤沼 安夫

    内分泌・糖尿病科   20 ( 3 )   261 - 266   2005.3

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    糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDCStudy)は,2000例余の2型糖尿病患者で生活習慣の改善に対する介入効果をみたわが国では初めての大規模介入試験である.JDCStudyの6年次の糖尿病腎症に関する成績を紹介した.糖尿病腎症追跡対象者1796例を解析対象者とした.介入群は,保健士・栄養士などの資格を有する専門の指導員が約2週間に1度で,電話をかけ直接患者を指導した.介入群において血糖コントロールがやや良好であるが,有意差は得られていない.また,血圧に対して,十分な介入を行っていないのが現状である

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  • 【肥満予防の科学】 内臓脂肪型肥満と皮下脂肪型肥満

    曽根 博仁, 児玉 暁, 叔 びょう

    体育の科学   55 ( 3 )   205 - 210   2005.3

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    Other Link: http://search.jamas.or.jp/link/ui/2005126277

  • 高齢女性における食後脂質上昇反応に対する有酸素運動トレーニングの影響

    曽根 博仁, 叔 びょう, 児玉 暁, 山崎 健, 村上 晴香, 飯田 薫子, 久野 譜也, 田中 喜代次, 伊藤 佐智子, 齋藤 和典, 山田 信博

    健康医科学研究助成論文集   20 ( 20 )   65 - 72   2005.3

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    平均年齢66.4±7.1歳の健常高齢者17名を対象に,3ヵ月間の有酸素運動トレーニングプログラムの前後で経口脂肪負荷試験(OFTT)を実施し,有酸素運動が食後高脂血症に与える影響と効果について検討した.総コレステロール,LDLコレステロールは有意な低下を認め,HDLコレステロールの有意な上昇を認めたが空腹時TG値の低下は認められなかった.空腹時血糖は上昇を認め,インシュリンは有意に低下し,HOMA-Rは有意は変化を示さなかった.OFTT時TG値はトレーニングにより123±67mg/dlから99±60mg/dlへと有意に低下した.すなわち,高齢女性での有酸素運動トレーニングは食後高脂血症に対する有効な治療法であることが示唆された

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  • 【糖尿病と動脈硬化症 疫学・成因・臨床における新展開】 疫学 日本の2型糖尿病患者における動脈硬化症の現状

    曽根 博仁, 水野 佐智子, 笈田 耕治, 山崎 義光, 豊永 哲至, 及川 眞一, 齋藤 康, 大橋 靖雄, 山田 信博, JDCSグループ(Japan, Diabetes Complications, Study Grou

    Angiology Frontier   4 ( 1 )   11 - 17   2005.3

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    Japan Diabetes Complications Study(JDCS)はわが国有数の2型糖尿病患者コホートである.その中間解析により,日本人2型糖尿病患者においても,高血圧や高脂血症が大血管合併症のリスクを大きく上昇させており,その予防のためには,血糖コントロールとともに脂質や血圧のコントロールも重要であることが明らかになった.また糖尿病患者では,虚血性心疾患が脳血管障害より高頻度にみられるなど,非糖尿病患者にはみられない特徴が明らかになっている.さらに日本人糖尿病患者と欧米人糖尿病患者との間には,基礎的病態から薬物の効果に至るまで多くの違いが存在していることもわかってきた(著者抄録)

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  • 日本人は、軽度の肥満でも糖尿病になりやすい (特集 肥満と糖尿病)

    曽根 博仁, 山田 信博

    食の科学   ( 325 )   8 - 12   2005.3

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  • 日本人2型糖尿病患者の病態と合併症の特徴 Japan Diabetes Complications Study(JDCS)中間解析より

    曽根 博仁, 石橋 俊, 井藤 英喜, 大橋 靖雄, 赤沼 安夫, 山田 信博, JDCSグループ

    日本内科学会雑誌   94 ( Suppl. )   141 - 141   2005.2

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  • 誌上症例検討会 「劇症1型糖尿病」と「急性膵炎に続発した糖尿病」との鑑別が困難であった一例

    平嶺 辰英, 小俣 勝哉, 曽根 博仁, 鈴木 浩明, 豊島 秀男, 島野 仁, 山田 信博, 岡田 浩介, 田中 直見

    内科専門医会誌   17 ( 1 )   59 - 64   2005.2

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  • Transgenic mice overexpressing nuclear SREBP-1c in pancreatic beta-cells

    A Takahashi, K Motomura, T Kato, T Yoshikawa, Y Nakagawa, N Yahagi, H Sone, H Suzuki, H Toyoshima, N Yamada, H Shimano

    DIABETES   54 ( 2 )   492 - 499   2005.2

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    Influx of excess fatty acids and the resultant accumulation of intracellular triglycerides are linked to impaired insulin secretion and action in the pathogenesis of type 2 diabetes. Sterol regulatory element-binding protein (SREBP)-1c is a transcription factor that controls cellular synthesis of fatty acids and triglycerides. SREBP-1c is highly expressed in high-energy and insulin-resistant states. To investigate effects of this synthetic lipid regulator on insulin secretion, we generated transgenic mice overexpressing nuclear SREBP-1c under the insulin promoter. beta-Cell-specific expression of SREBP-1c caused reduction in islet mass and impaired glucose-stimulated insulin secretion and was associated with accumulation of triglycerides, suppression of pancreas duodenal homeobox-1, and upregulation of uncoupling protein 2 gene expression. The mice presented with impaired glucose tolerance that was exacerbated by a high-energy diet. Taken together with enhanced insulin secretion from SREBP-1-null islets, these data suggest that SREBP-1c and endogenous lipogenesis could be involved in beta-cell dysfunction and diabetes.

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  • Transgenic mice overexpressing nuclear SREBP-1c in pancreatic beta-cells

    A Takahashi, K Motomura, T Kato, T Yoshikawa, Y Nakagawa, N Yahagi, H Sone, H Suzuki, H Toyoshima, N Yamada, H Shimano

    DIABETES   54 ( 2 )   492 - 499   2005.2

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    Influx of excess fatty acids and the resultant accumulation of intracellular triglycerides are linked to impaired insulin secretion and action in the pathogenesis of type 2 diabetes. Sterol regulatory element-binding protein (SREBP)-1c is a transcription factor that controls cellular synthesis of fatty acids and triglycerides. SREBP-1c is highly expressed in high-energy and insulin-resistant states. To investigate effects of this synthetic lipid regulator on insulin secretion, we generated transgenic mice overexpressing nuclear SREBP-1c under the insulin promoter. beta-Cell-specific expression of SREBP-1c caused reduction in islet mass and impaired glucose-stimulated insulin secretion and was associated with accumulation of triglycerides, suppression of pancreas duodenal homeobox-1, and upregulation of uncoupling protein 2 gene expression. The mice presented with impaired glucose tolerance that was exacerbated by a high-energy diet. Taken together with enhanced insulin secretion from SREBP-1-null islets, these data suggest that SREBP-1c and endogenous lipogenesis could be involved in beta-cell dysfunction and diabetes.

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  • Plasma chloride concentration as a new diagnostic indicator of insulin insufficiency

    H Kikuchi, Y Kawakami, K Kakihana, K Kawai, Y Murayama, Y Iizuka, S Suzuki, H Suzuki, H Sone, H Toyoshima, H Shimano, N Yamada

    DIABETES RESEARCH AND CLINICAL PRACTICE   67 ( 2 )   137 - 143   2005.2

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    The medical criteria for initiating insulin therapy, based on clinical profiles of type 2 diabetic patients, have not yet been clearly established. We explored various parameters with 48 type 2 diabetic patients who were taking oral hypoglycernic medication.
    Among parameters, body mass index (BMI), the fasting plasma glucose level (FPG), and plasma chloride concentration were identified by forward-stepwise discriminant analysis as parameters that can discriminate between patients who were and those who were not undergoing insulin therapy.
    In combination, these parameters correctly diagnosed 86.4% of the patients who were undergoing insulin therapy, and 84.6% of those who were not undergoing insulin therapy. Further, we observed significant correlations between plasma chloride concentrations and either plasma sodium or organic acid concentrations, suggesting that impaired insulin action may reduce plasma chloride concentrations through changes in plasma sodium and organic acid metabolism. Our results suggest that plasma chloride concentration is a possible new indicator of insulin insufficiency.
    (C) 2004 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2004.06.011

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  • Plasma chloride concentration as a new diagnostic indicator of insulin insufficiency

    H Kikuchi, Y Kawakami, K Kakihana, K Kawai, Y Murayama, Y Iizuka, S Suzuki, H Suzuki, H Sone, H Toyoshima, H Shimano, N Yamada

    DIABETES RESEARCH AND CLINICAL PRACTICE   67 ( 2 )   137 - 143   2005.2

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    The medical criteria for initiating insulin therapy, based on clinical profiles of type 2 diabetic patients, have not yet been clearly established. We explored various parameters with 48 type 2 diabetic patients who were taking oral hypoglycernic medication.
    Among parameters, body mass index (BMI), the fasting plasma glucose level (FPG), and plasma chloride concentration were identified by forward-stepwise discriminant analysis as parameters that can discriminate between patients who were and those who were not undergoing insulin therapy.
    In combination, these parameters correctly diagnosed 86.4% of the patients who were undergoing insulin therapy, and 84.6% of those who were not undergoing insulin therapy. Further, we observed significant correlations between plasma chloride concentrations and either plasma sodium or organic acid concentrations, suggesting that impaired insulin action may reduce plasma chloride concentrations through changes in plasma sodium and organic acid metabolism. Our results suggest that plasma chloride concentration is a possible new indicator of insulin insufficiency.
    (C) 2004 Elsevier Ireland Ltd. All rights reserved.

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  • 動脈硬化Update 2004 日本人2型糖尿病における動脈硬化合併症の解析と国際比較

    曽根 博仁, 大橋 靖雄, 赤沼 安夫, 山田 信博

    Therapeutic Research   26 ( 1 )   68 - 68   2005.1

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  • 糖尿病 治療 運動療法

    曽根 博仁, 叔 びょう, 飯田 薫子, 山田 信博

    Annual Review内分泌,代謝   2005   131 - 135   2005.1

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  • 【メタボリックシンドロームと動脈硬化】 Japan Diabetes Complications Study(JDCS)にみるメタボリックシンドローム

    曽根 博仁, 水野 佐智子, 藤井 仁美, 大橋 靖雄, 赤沼 安夫, 山田 信博

    動脈硬化予防   3 ( 4 )   34 - 41   2004.12

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  • 急性膵炎を契機にDKA・バセドウ病クリーゼを併発した一症例

    茨木 洋子, 小俣 勝哉, 平嶺 辰英, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 島野 仁, 山田 信博, 岩崎 仁, 藤田 利枝, 松島 照彦, 山下 亀次郎

    日本内分泌学会雑誌   80 ( 3 )   653 - 653   2004.12

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  • 【スポーツ医学検査測定ハンドブック】 検体検査 内分泌検査 プロラクチン,成長ホルモン,抗利尿ホルモン

    児玉 暁, 曽根 博仁

    臨床スポーツ医学   21 ( 臨増 )   374 - 377   2004.12

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  • 【スポーツ医学検査測定ハンドブック】 検体検査 生化学検査 尿酸

    児玉 暁, 曽根 博仁

    臨床スポーツ医学   21 ( 臨増 )   331 - 333   2004.12

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  • 【スポーツ医学検査測定ハンドブック】 検体検査 内分泌検査 副腎皮質刺激ホルモン,糖質コルチコイド

    児玉 暁, 曽根 博仁

    臨床スポーツ医学   21 ( 臨増 )   382 - 385   2004.12

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  • 医学と医療の最前線 糖尿病と合併症 日本人における最近の動向

    曽根 博仁, 齋藤 康, 吉村 幸雄, 石橋 俊, 井藤 英喜, 山下 英俊, 山崎 義光, 片山 茂裕, 大橋 靖雄, 赤沼 安夫, 山田 信博, JDCSグループ

    日本内科学会雑誌   93 ( 11 )   2427 - 2434   2004.11

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    DOI: 10.2169/naika.93.2427

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  • 【糖尿病と高血圧】 治療 糖尿病患者における降圧療法の心血管イベント抑制効果

    曽根 博仁, 山田 信博

    Complication: 糖尿病と血管   9 ( 2 )   139 - 144   2004.11

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  • 両側精巣腫瘍を呈した先天性副腎皮質過形成の1例

    小島 崇宏, 服部 一紀, 関戸 哲利, 河合 弘二, 島居 徹, 赤座 英之, 淡野 宏輔, 曽根 博仁, 山田 信博, 下山田 博明, 野口 雅之

    茨城県臨床医学雑誌   ( 40 )   109 - 109   2004.11

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  • WGEF is a novel RhoGEF expressed in intestine, liver, heart, and kidney

    YH Wang, H Suzuki, T Yokoo, K Tada-Iida, R Kihara, M Miura, K Watanabe, H Sone, H Shimano, H Toyoshima, N Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   324 ( 3 )   1053 - 1058   2004.11

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    Rho family GTPases regulate multiple cellular processes through their downstream effectors, where their activities are stimulated by the guanine nucleotide exchange factors. Here, we report a new member of RhoGEF, WGEF, which has the classical structure of DH-PH domain and a C-terminal SH3 domain. WGEF was shown to activate RhoA, Cdc42, and Racl by pulldown assay, and forced expression of WGEF resulted in marked rearrangement of the actin cytoskeleton, which is typically seen by the activation of RhoA, Cdc42, and Racl. WGEF was highly expressed in intestine and also in liver, heart and kidney, which may suggest the involvement of WGEF in the development and functions of these organs. The expression pattern may also suggest the possible importance of WGEF in the understanding of diseases based on metabolic disorder. (C) 2004 Elsevier Inc. All rights reserved.

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  • Requirement for hypertension and hyperlipidemia medication in US and Japanese patients with diabetes

    H Sone, N Yamada, S Mizuno, Y Ohashi, S Ishibashi

    AMERICAN JOURNAL OF MEDICINE   117 ( 9 )   711 - 712   2004.11

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    DOI: 10.1016/j.amjmed.2004.06.030

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  • Requirement for hypertension and hyperlipidemia medication in US and Japanese patients with diabetes

    H Sone, N Yamada, S Mizuno, Y Ohashi, S Ishibashi

    AMERICAN JOURNAL OF MEDICINE   117 ( 9 )   711 - 712   2004.11

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  • WGEF is a novel RhoGEF expressed in intestine, liver, heart, and kidney

    YH Wang, H Suzuki, T Yokoo, K Tada-Iida, R Kihara, M Miura, K Watanabe, H Sone, H Shimano, H Toyoshima, N Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   324 ( 3 )   1053 - 1058   2004.11

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    Rho family GTPases regulate multiple cellular processes through their downstream effectors, where their activities are stimulated by the guanine nucleotide exchange factors. Here, we report a new member of RhoGEF, WGEF, which has the classical structure of DH-PH domain and a C-terminal SH3 domain. WGEF was shown to activate RhoA, Cdc42, and Racl by pulldown assay, and forced expression of WGEF resulted in marked rearrangement of the actin cytoskeleton, which is typically seen by the activation of RhoA, Cdc42, and Racl. WGEF was highly expressed in intestine and also in liver, heart and kidney, which may suggest the involvement of WGEF in the development and functions of these organs. The expression pattern may also suggest the possible importance of WGEF in the understanding of diseases based on metabolic disorder. (C) 2004 Elsevier Inc. All rights reserved.

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  • 【糖尿病にみられる性差】 糖尿病合併症における性差

    曽根 博仁, 山田 信博

    性差と医療   1 ( 4 )   437 - 441   2004.10

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  • 日本人における新しいエビデンス 糖尿病における血管合併症の発症予防と進展抑制に関する研究(Japan Diabetes Complications Study:JDCS)

    曽根 博仁, 水野 佐智子, 大橋 靖雄, 齋藤 康, 井藤 英喜, 山下 英俊, 山崎 義光, 片山 茂裕, 赤沼 安夫, 山田 信博

    糖尿病学の進歩   ( 38 )   161 - 165   2004.9

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  • 【日本人のメタボリックシンドロームとは】 メタボリックシンドロームの治療 介入試験

    曽根 博仁, 山田 信博

    Progress in Medicine   24 ( 9 )   2235 - 2241   2004.9

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  • 糖尿病合併症の疫学研究の現状と課題 Japan Diabetes Complications Study(JDCS)中間報告にみる現代日本の糖尿病合併症

    曽根 博仁, 清野 弘明, 山崎 義光, 石橋 俊, 山下 英俊, 井藤 英喜, 齋藤 康, 片山 茂裕, 松岡 健平, 大橋 靖雄, 赤沼 安夫, 山田 信博

    糖尿病合併症   18 ( Suppl.1 )   41 - 41   2004.9

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  • Alcohol use and diabetes mellitus

    H Sone, N Yamada, S Mizuno, R Aida, Y Ohashi, L Mascitelli, F Pezzetta

    ANNALS OF INTERNAL MEDICINE   141 ( 5 )   408 - 409   2004.9

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    DOI: 10.7326/0003-4819-141-5-200409070-00026

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  • Alcohol use and diabetes mellitus

    H Sone, N Yamada, S Mizuno, R Aida, Y Ohashi, L Mascitelli, F Pezzetta

    ANNALS OF INTERNAL MEDICINE   141 ( 5 )   408 - 409   2004.9

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    DOI: 10.7326/0003-4819-141-5-200409070-00026

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  • 【食後高脂血症・高血糖と動脈硬化症】 食後高脂血症の診断法

    曽根 博仁, 齋籐 和典, 山田 信博

    Mebio   21 ( 9 )   34 - 38   2004.9

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  • 日本における2型糖尿病の現況 Japan Diabetes Complications Study(JDCS)中間結果より

    曽根 博仁, 井藤 英喜, 齋藤 康, 山下 英俊, 山崎 義光, 清野 弘明, 片山 茂裕, 大橋 靖雄, 山田 信博, JDCSグループ

    最新医学   59 ( 8 )   1826 - 1832   2004.8

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  • 食後高トリグリセリド血症モデル動物の作製と解析

    高橋 昭光, 島野 仁, 中川 嘉, 松坂 賢, 山本 隆史, 本村 香織, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 山田 信博

    Therapeutic Research   2 ( 7 )   1397 - 1400   2004.7

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    生活習慣病における動脈硬化形成と食後高トリグリセリド(TG)血症の関連が注目されているが,食後高TG血症の成因や動脈硬化形成に至るまでのメカニズムについてはいまだ不明な点が多く,これらを検討するためのモデル動物の確立が必要である.内因性TG合成亢進モデルのSREBP-1cを肝臓で強発現させたトランスジェニック(TgSREBP-1c)マウスとLDL受容体ノックアウト(LDLRKO)マウスを交配させ,そのフェノタイプについて解析した.TgSREBP-1c/LDLRKOマウスでは,肥満,過食を伴わないにもかかわらず,LDLRKOに比べて著明な食後高TG血症とHDL低下を呈し,より高度なプラークの形成を認め,動脈硬化惹起性の表現型を示した.TgSREBP-1c/LDLRKOマウスは,食後高TG血症の成因および動脈硬化惹起性病態解析に有用である可能性が示唆された

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  • TCA回路の部分阻害がエネルギー代謝に及ぼす影響

    曽根 博仁, 島野 仁, 高橋 昭光, 鈴木 浩明, 豊島 秀男, 山田 信博

    日本臨床分子医学会学術総会プログラム・抄録集   41回   45 - 45   2004.7

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  • 【プライマリーケアの実際 臨床研修マニュアル】 プライマリーケアのコツ 疾患 内分泌・代謝疾患 糖尿病

    曽根 博仁, 山田 信博

    臨床医   30 ( 増刊 )   1085 - 1086   2004.6

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  • [Prevention and therapeutic strategy of metabolic syndrome--implications from the interim results of Japan Diabetes Complications Study(JDCS)].

    Sone H, Mizuno S, Ohashi Y, Akanuma Y, Yamada N, Japan Diabetes Complications Study Group

    日本臨床   62 ( 6 )   1150 - 1157   2004.6

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  • 【プライマリーケアの実際 臨床研修マニュアル】 プライマリーケアのコツ 疾患 内分泌・代謝疾患 インスリノーマ

    曽根 博仁, 山田 信博

    臨床医   30 ( 増刊 )   1083 - 1084   2004.6

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  • Type 2 diabetes prevalence in Asian subjects

    H Sone, S Mizuno, Y Ohashi, N Yamada

    DIABETES CARE   27 ( 5 )   1251 - 1252   2004.5

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    DOI: 10.2337/diacare.27.5.1251

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  • 両側精巣腫瘍を呈した先天性副腎皮質過形成の1例

    小島 崇宏, 服部 一紀, 関戸 哲利, 河合 弘二, 島居 徹, 赤座 英之, 淡野 宏輔, 曽根 博仁, 山田 信博, 下山田 博明, 野口 雅之

    泌尿器外科   17 ( 5 )   445 - 445   2004.5

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  • わが国の2型糖尿病患者の現況-Japan Diabetes Complications Study(JDCS)6年次中間報告より

    曽根 博仁, 山田 信博, 水野 佐智子, 大橋 靖雄, 石橋 俊, 井藤 英喜, 齋藤 康, 片山 茂裕, 赤沼 安夫

    成人病と生活習慣病   34 ( 5 )   739 - 739   2004.5

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  • 糖尿病性神経障害において神経因性膀胱のみ顕著に認められた若年男性の1例

    遠藤 祐子, 淡野 宏輔, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 島野 仁, 山田 信博

    糖尿病   47 ( 5 )   423 - 423   2004.5

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  • 食後高トリグリセリド血症モデル動物の作成と解析

    高橋 昭光, 島野 仁, 中川 嘉, 松坂 賢, 山本 隆史, 本村 香織, 小林 和人, 井上 訓之, 石川 まゆみ, 岡田 純代, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 山田 信博

    糖尿病   47 ( Suppl.1 )   S258 - S258   2004.4

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  • SREBPs suppress IRS-2-mediated insulin signalling in the liver

    T Ide, H Shimano, N Yahagi, T Matsuzaka, M Nakakuki, T Yamamoto, Y Nakagawa, A Takahashi, H Suzuki, H Sone, H Toyoshima, A Fukamizu, N Yamada

    NATURE CELL BIOLOGY   6 ( 4 )   351 - 357   2004.4

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    Insulin receptor substrate 2 (IRS-2) is the main mediator of insulin signalling in the liver, controlling insulin sensitivity. Sterol regulatory element binding proteins (SREBPs) have been established as transcriptional regulators of lipid synthesis. Here, we show that SREBPs directly repress transcription of IRS-2 and inhibit hepatic insulin signalling. The IRS-2 promoter is activated by forkhead proteins through an insulin response element (IRE). Nuclear SREBPs effectively replace and interfere in the binding of these transactivators, resulting in inhibition of the downstream PI(3)K/Akt pathway, followed by decreased glycogen synthesis. These data suggest a molecular mechanism for the physiological switching from glycogen synthesis to lipogenesis and hepatic insulin resistance that is associated with hepatosteatosis.

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  • Statins downregulate ATP-binding-cassette transporter A1 gene expression in macrophages

    H Sone, H Shimano, M Shu, M Nakakuki, A Takahashi, M Sakai, Y Sakamoto, T Yokoo, K Matsuzaka, H Okazaki, Y Nakagawa, KT Iida, H Suzuki, H Toyoshima, S Horiuchi, N Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   316 ( 3 )   790 - 794   2004.4

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    The ATP-binding-cassette transporter A1 (ABCA1) plays an essential role in cellular cholesterol efflux and helps prevent macrophages from becoming foam cells. The statins are widely used as cholesterol-lowering agents and have other anti-atherogenic actions. We tested the effects of four different statins (fluvastatin, atorvastatin, simvastatin, and lovastatin) on ABCA1 expression in macrophages in vitro. The statins suppressed ABCA1 mRNA expression in RAW246.7 and THP-1 macrophage cell lines and in mouse peritoneal macrophages. The effect was time- and dose-dependent and was abolished by the addition of the post-reductase product, mevalonate. These findings imply that there is a possible modulation of the well-known beneficial effects of the statins on the reverse cholesterol transport pathway. (C) 2004 Elsevier Inc. All rights reserved.

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  • Statins downregulate ATP-binding-cassette transporter A1 gene expression in macrophages

    H Sone, H Shimano, M Shu, M Nakakuki, A Takahashi, M Sakai, Y Sakamoto, T Yokoo, K Matsuzaka, H Okazaki, Y Nakagawa, KT Iida, H Suzuki, H Toyoshima, S Horiuchi, N Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   316 ( 3 )   790 - 794   2004.4

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    The ATP-binding-cassette transporter A1 (ABCA1) plays an essential role in cellular cholesterol efflux and helps prevent macrophages from becoming foam cells. The statins are widely used as cholesterol-lowering agents and have other anti-atherogenic actions. We tested the effects of four different statins (fluvastatin, atorvastatin, simvastatin, and lovastatin) on ABCA1 expression in macrophages in vitro. The statins suppressed ABCA1 mRNA expression in RAW246.7 and THP-1 macrophage cell lines and in mouse peritoneal macrophages. The effect was time- and dose-dependent and was abolished by the addition of the post-reductase product, mevalonate. These findings imply that there is a possible modulation of the well-known beneficial effects of the statins on the reverse cholesterol transport pathway. (C) 2004 Elsevier Inc. All rights reserved.

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  • SREBPs suppress IRS-2-mediated insulin signalling in the liver

    T Ide, H Shimano, N Yahagi, T Matsuzaka, M Nakakuki, T Yamamoto, Y Nakagawa, A Takahashi, H Suzuki, H Sone, H Toyoshima, A Fukamizu, N Yamada

    NATURE CELL BIOLOGY   6 ( 4 )   351 - 357   2004.4

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    Insulin receptor substrate 2 (IRS-2) is the main mediator of insulin signalling in the liver, controlling insulin sensitivity. Sterol regulatory element binding proteins (SREBPs) have been established as transcriptional regulators of lipid synthesis. Here, we show that SREBPs directly repress transcription of IRS-2 and inhibit hepatic insulin signalling. The IRS-2 promoter is activated by forkhead proteins through an insulin response element (IRE). Nuclear SREBPs effectively replace and interfere in the binding of these transactivators, resulting in inhibition of the downstream PI(3)K/Akt pathway, followed by decreased glycogen synthesis. These data suggest a molecular mechanism for the physiological switching from glycogen synthesis to lipogenesis and hepatic insulin resistance that is associated with hepatosteatosis.

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  • SREBP-1はHNF-4αと結合し糖新生系遺伝子の発現を抑制する

    山本 隆史, 島野 仁, 中川 嘉, 井出 智広, 矢作 直也, 松坂 賢, 高橋 昭光, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 山田 信博

    糖尿病   47 ( Suppl.1 )   S259 - S259   2004.4

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  • 【わかる糖尿病網膜症のEBM】 日本の2型糖尿病患者における血管合併症とそのリスクファクター

    曽根 博仁, 川崎 良, 山下 英俊, 山田 信博

    あたらしい眼科   21 ( 4 )   449 - 453   2004.4

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  • 【Metabolic syndrome 診断と治療の進歩】 機序と病態 血管障害 冠動脈疾患のリスク

    曽根 博仁, 山田 信博

    日本内科学会雑誌   93 ( 4 )   670 - 676   2004.4

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    心血管リスクファクターの一個人における重積が,冠動脈疾患の発症率を飛躍的に上昇させることは以前から知られていた.このようなmetabolic syndromeを独立した疾患概念と捉えた診断基準が近年提唱され,その有病率や冠動脈疾患発症頻度の検討が始まった.さらに冠動脈疾患ハイリスク集団としてのmetabolic syndrome患者を対象とした臨床介入試験も行われつつある

    DOI: 10.2169/naika.93.670

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  • 【高血圧合併糖尿病 ピットフォールと対策】 2型糖尿病における肥満と高血圧

    曽根 博仁, 吉村 幸雄, 井藤 英喜, 山崎 義光, 山田 信博

    綜合臨床   53 ( 4 )   1467 - 1472   2004.4

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    耐糖能異常と肥満と高血圧はいずれもメタボリック・シンドロームの主要構成因子であり,これらの合併は,動脈硬化性疾患の素地として臨床的重要度が高い.そこで,肥満,高血圧と2型糖尿病との関連について,我が国の2型糖尿病患者の大規模臨床研究Japan Diabetes Complications Study(JDCS)を始めとする最近の研究を紹介しながら概説した

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  • STZ糖尿病マウスの肝臓におけるインスリン非依存的SREBP-1c発現誘導

    松坂 賢, 島野 仁, 矢作 直也, 高橋 昭光, 曽根 博仁, 豊島 秀男, 石橋 俊, 大須賀 淳一, 山田 信博

    糖尿病   47 ( Suppl.1 )   S269 - S269   2004.4

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  • TCA回路部分阻害がエネルギー代謝に及ぼす影響 クエン酸合成酵素(CS)遺伝子ヘテロノックアウト(KO)マウスの解析

    曽根 博仁, 島野 仁, 叔 森, 児玉 弘, 田口 美保, 高橋 昭光, 飯田 薫子, 中川 嘉, 鈴木 浩明, 豊島 秀男, 奥田 諭吉, 山田 信博

    糖尿病   47 ( Suppl.1 )   S165 - S165   2004.4

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  • 2型糖尿病と肥満

    曽根 博仁, 山田 信博, JDCSグループ

    医学のあゆみ   209 ( 4 )   241 - 242   2004.4

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  • Signal sequence trap(SST)改良法を用いた精巣上体新規分泌蛋白質の単離同定

    飯田 薫子, 豊島 秀男, 鈴木 浩明, 曽根 博仁, 島野 仁, 山田 信博

    日本内分泌学会雑誌   80 ( 1 )   116 - 116   2004.4

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  • Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice

    T Matsuzaka, H Shimano, N Yahagi, M Amemiya-Kudo, H Okazaki, Y Tamura, Y Iizuka, K Ohashi, S Tomita, M Sekiya, A Hasty, Y Nakagawa, H Sone, H Toyoshima, S Ishibashi, J Osuga, N Yamada

    DIABETES   53 ( 3 )   560 - 569   2004.3

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    Insulin and glucose together have been previously shown to regulate hepatic sterol regulatory element-binding protein (SREBP)-1c expression. We sought to explore the nutritional regulation of lipogenesis through SREBP-1c induction in a setting where effects of sugars versus insulin could be distinguished. To do so, mice were insulin depleted by streptozotocin (STZ) administration and subjected to a fasting-refeeding protocol with glucose, fructose, or sucrose. Unexpectedly, the insulin-depleted mice exhibited a marked induction of SREBP-1c on all sugars, and this increase in SREBP-1c was even more dramatic than in the non-STZ-administered controls. The time course of changes in SREBP-1 induction varied depending on the type of sugars in both control and STZ-administered mice. Glucose refeeding gave a peak of SREBP-1c induction, whereas fructose refeeding caused slow and gradual increments, and sucrose refeeding fell between these two responses. Expression of various lipogenic enzymes were also gradually increased over time, irrespective of the types of sugars, with greater intensities in STZ-administered than in nontreated mice. In contrast, induction of hepatic glucokinase and suppression of phoshoenolpyruvate carboxykinase were insulin dependent in an early refed state. These data clearly demonstrate that nutritional regulation of SREBP-1c and lipogenic genes may be completely independent of insulin as long as sufficient carbohydrates are available.

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  • Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice

    T Matsuzaka, H Shimano, N Yahagi, M Amemiya-Kudo, H Okazaki, Y Tamura, Y Iizuka, K Ohashi, S Tomita, M Sekiya, A Hasty, Y Nakagawa, H Sone, H Toyoshima, S Ishibashi, J Osuga, N Yamada

    DIABETES   53 ( 3 )   560 - 569   2004.3

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    Insulin and glucose together have been previously shown to regulate hepatic sterol regulatory element-binding protein (SREBP)-1c expression. We sought to explore the nutritional regulation of lipogenesis through SREBP-1c induction in a setting where effects of sugars versus insulin could be distinguished. To do so, mice were insulin depleted by streptozotocin (STZ) administration and subjected to a fasting-refeeding protocol with glucose, fructose, or sucrose. Unexpectedly, the insulin-depleted mice exhibited a marked induction of SREBP-1c on all sugars, and this increase in SREBP-1c was even more dramatic than in the non-STZ-administered controls. The time course of changes in SREBP-1 induction varied depending on the type of sugars in both control and STZ-administered mice. Glucose refeeding gave a peak of SREBP-1c induction, whereas fructose refeeding caused slow and gradual increments, and sucrose refeeding fell between these two responses. Expression of various lipogenic enzymes were also gradually increased over time, irrespective of the types of sugars, with greater intensities in STZ-administered than in nontreated mice. In contrast, induction of hepatic glucokinase and suppression of phoshoenolpyruvate carboxykinase were insulin dependent in an early refed state. These data clearly demonstrate that nutritional regulation of SREBP-1c and lipogenic genes may be completely independent of insulin as long as sufficient carbohydrates are available.

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  • SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes

    T Yamamoto, H Shimano, Y Nakagawa, T Ide, N Yahagi, T Matsuzaka, M Nakakuki, A Takahashi, H Suzuki, H Sone, H Toyoshima, R Sato, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 13 )   12027 - 12035   2004.3

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    The hepatocyte nuclear factor-4alpha (HNF-4alpha)/PGC-1 pathway plays a crucial role in the transcriptional regulation of hepatic gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and Glc-6-Pase, genes that are activated at fasting and suppressed in a fed state. SREBP-1c dominates the nutritional regulation of lipogenic genes inverse to gluconeogenesis. Here we show the mechanism by which SREBP-1 suppresses expression of gluconeogenic genes. A series of luciferase reporter assays demonstrated that SREBP-1a and - 1c effectively inhibited the PEPCK promoter activity that was induced by HNF-4alpha. The HNF-4alpha-binding site in the glucocorticoid-response unit was responsible for the SREBP-1 inhibition, although SREBP-1 did not bind to the PEPCK promoter as demonstrated by electrophoretic mobility shift assays. The inhibitory effect was more potent in the isoform of SREBP-1a than SREBP-1c and was eliminated by deletion of the amino-terminal transactivation domain of SREBP-1. Coimmunoprecipitation experiments demonstrated that these two transcription factors directly interact through the transactivation domain of SREBP-1 and the ligand binding/ AF2 domains of HNF-4alpha. Estimation of coactivator recruitment using HNF-4alpha-Gal4DBD fusion assay showed that SREBP-1 competitively inhibited PGC-1 recruitment, a requirement for HNF-4alpha activation. Consistent with these results, hepatic PEPCK and Glc-6-Pase mRNA levels are suppressed by overexpression of SREBP-1a and - 1c in the transgenic mice. Our data indicate that SREBP-1 has a novel role as negative regulator of gluconeogenic genes through a cross-talk with HNF-4alpha interference with PGC-1 recruitment.

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  • SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes

    T Yamamoto, H Shimano, Y Nakagawa, T Ide, N Yahagi, T Matsuzaka, M Nakakuki, A Takahashi, H Suzuki, H Sone, H Toyoshima, R Sato, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 13 )   12027 - 12035   2004.3

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    The hepatocyte nuclear factor-4alpha (HNF-4alpha)/PGC-1 pathway plays a crucial role in the transcriptional regulation of hepatic gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and Glc-6-Pase, genes that are activated at fasting and suppressed in a fed state. SREBP-1c dominates the nutritional regulation of lipogenic genes inverse to gluconeogenesis. Here we show the mechanism by which SREBP-1 suppresses expression of gluconeogenic genes. A series of luciferase reporter assays demonstrated that SREBP-1a and - 1c effectively inhibited the PEPCK promoter activity that was induced by HNF-4alpha. The HNF-4alpha-binding site in the glucocorticoid-response unit was responsible for the SREBP-1 inhibition, although SREBP-1 did not bind to the PEPCK promoter as demonstrated by electrophoretic mobility shift assays. The inhibitory effect was more potent in the isoform of SREBP-1a than SREBP-1c and was eliminated by deletion of the amino-terminal transactivation domain of SREBP-1. Coimmunoprecipitation experiments demonstrated that these two transcription factors directly interact through the transactivation domain of SREBP-1 and the ligand binding/ AF2 domains of HNF-4alpha. Estimation of coactivator recruitment using HNF-4alpha-Gal4DBD fusion assay showed that SREBP-1 competitively inhibited PGC-1 recruitment, a requirement for HNF-4alpha activation. Consistent with these results, hepatic PEPCK and Glc-6-Pase mRNA levels are suppressed by overexpression of SREBP-1a and - 1c in the transgenic mice. Our data indicate that SREBP-1 has a novel role as negative regulator of gluconeogenic genes through a cross-talk with HNF-4alpha interference with PGC-1 recruitment.

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  • Energy intake and obesity in Japanese patients with type 2 diabetes

    H Sone, Y Yoshimura, H Ito, Y Ohashi, N Yamada

    LANCET   363 ( 9404 )   248 - 249   2004.1

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    DOI: 10.1016/S0140-6736(03)15348-2

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  • わが国の2型糖尿病患者の現況 Japan Diabetes Complications Study(JDCS)6年次中間報告より

    曽根 博仁, 水野 佐智子, 石橋 俊, 井藤 英喜, 斉藤 康, 片山 茂裕, 大橋 靖雄, 赤沼 安夫, 山田 信博

    日本成人病(生活習慣病)学会会誌   30   75 - 75   2004.1

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  • Energy intake and obesity in Japanese patients with type 2 diabetes

    H Sone, Y Yoshimura, H Ito, Y Ohashi, N Yamada

    LANCET   363 ( 9404 )   248 - 249   2004.1

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  • 糖尿病 治療 運動療法

    曽根 博仁, 飯田 薫子, 山田 信博

    Annual Review内分泌,代謝   2004   161 - 165   2004.1

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  • 【糖尿病と心血管障害】 糖尿病における動脈硬化症予防のためのトータルケア Japan Diabetes Complications Study(JDCS)中間結果より

    曽根 博仁, 山田 信博, JDCSグループ

    最新医学   59 ( 1 )   99 - 105   2004.1

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    Japan Diabetes Complications Study(JDCS)は,日本全国の2型糖尿病患者2,000名余りを追跡している大規模臨床研究である.その中間結果によると,動脈硬化合併症の発症率は12.8/1,000人年で,非糖尿病者の約3倍であった.有意な危険因子としては性別,年齢のほか,HbA1C,HDLコレステロール,LDLコレステロール,収縮期血圧などが明らかになり,その予防には血糖コントールと共に脂質や血圧のコントロールも重要であることが判明した

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  • P57(Kip2) regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus

    T Yokoo, H Toyoshima, M Miura, YH Wang, KT Iida, H Suzuki, H Sone, H Shimano, T Gotoda, S Nishimori, K Tanaka, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 52 )   52919 - 52923   2003.12

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    p57(Kip2) is the only cyclin-dependent kinase (Cdk) inhibitor shown to be essential for mouse embryogenesis. The fact suggests that p57 has a specific role that cannot be compensated by other Cdk inhibitors. LIM-kinase 1 (LIMK-1) is a downstream effector of the Rho family of GTPases that phosphorylates and inactivates an actin depolymerization factor, cofilin, to induce the formation of actin fiber. Here we demonstrate that p57 regulates actin dynamics by binding and translocating LIMK-1 from the cytoplasm into the nucleus, which in turn results in a reorganization of actin fiber. The central region of p57, a unique feature among the Cdk inhibitors, and the N-terminal region of LIMK-1, which contains the LIM domains were essential for the interaction. Expression of p57, but not p27(Kip1) or a p57 mutant, with a deletion in the central region was shown to induce marked reorganization of actin filament and a translocation of LIMK-1. Our findings indicate p57 may act as a key regulator in embryogenesis by bearing two distinct functions, the regulation of cell cycle through binding to Cdks and the regulation of actin dynamics through binding to LIMK-1, both of which should be important in developmental procedure.

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  • P57(Kip2) regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus

    T Yokoo, H Toyoshima, M Miura, YH Wang, KT Iida, H Suzuki, H Sone, H Shimano, T Gotoda, S Nishimori, K Tanaka, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 52 )   52919 - 52923   2003.12

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    p57(Kip2) is the only cyclin-dependent kinase (Cdk) inhibitor shown to be essential for mouse embryogenesis. The fact suggests that p57 has a specific role that cannot be compensated by other Cdk inhibitors. LIM-kinase 1 (LIMK-1) is a downstream effector of the Rho family of GTPases that phosphorylates and inactivates an actin depolymerization factor, cofilin, to induce the formation of actin fiber. Here we demonstrate that p57 regulates actin dynamics by binding and translocating LIMK-1 from the cytoplasm into the nucleus, which in turn results in a reorganization of actin fiber. The central region of p57, a unique feature among the Cdk inhibitors, and the N-terminal region of LIMK-1, which contains the LIM domains were essential for the interaction. Expression of p57, but not p27(Kip1) or a p57 mutant, with a deletion in the central region was shown to induce marked reorganization of actin filament and a translocation of LIMK-1. Our findings indicate p57 may act as a key regulator in embryogenesis by bearing two distinct functions, the regulation of cell cycle through binding to Cdks and the regulation of actin dynamics through binding to LIMK-1, both of which should be important in developmental procedure.

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  • Mouse MafA, homologue of zebrafish somite Maf 1, contributes to the specific transcriptional activity through the insulin promoter

    M Kajihara, H Sone, M Amemiya, Y Katoh, M Isogai, H Shimano, N Yamada, S Takahashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   312 ( 3 )   831 - 842   2003.12

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    Large Maf transcription factors, which are members of the basic leucine zipper (b-Zip) superfamily, have been reported to be involved in embryonic development and cell differentiation. Previously, we isolated a novel zebrafish large Maf cDNA, somite Maf1 (SMaf1), which possesses transactivational activity within its N-terminus domain. To elucidate SMaf1 function in mammals, we tried to isolate the Mouse homologue of zebrafish SMaf1. We isolated the mouse homologue of zebrafish SMaf1, which is the same molecule as the recently reported MafA. MafA mRNA was detected in formed somites, head neural tube, and liver cells in the embryos. In the adult mouse, MafA transcript was amplified in the brain, lung, spleen, and kidney by RT-PCR. MafA mRNA was also detectable in beta-cell line. Next, we analyzed the transcriptional activity of MafA using rat insulin promoters I and II (RIPI and II), since a part of RIP sequence was similar to the Maf recognition element (MARE) and MafA was expressed in pancreatic beta-cells. MafA was able to activate transcription from RIPII, but not RIPI, in a dose dependent manner and the activity was dependent on RIPE3b/C1 sequences. In addition, the amount of MafA protein was regulated by glucose concentration. These results indicate that MafA is the homologue of zebrafish SMaf1 and acts as a transcriptional activator of the insulin gene promoter through the RIPE3b element. (C) 2003 Published by Elsevier Inc.

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  • 【糖尿病と動脈硬化症】 日本人糖尿病患者における動脈硬化性疾患の現状 JDCSより

    曽根 博仁, 赤沼 安夫, 山田 信博, JDCSグループ

    糖尿病   46 ( 12 )   903 - 906   2003.12

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    DOI: 10.11213/tonyobyo1958.46.903

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  • Mouse MafA, homologue of zebrafish somite Maf 1, contributes to the specific transcriptional activity through the insulin promoter

    M Kajihara, H Sone, M Amemiya, Y Katoh, M Isogai, H Shimano, N Yamada, S Takahashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   312 ( 3 )   831 - 842   2003.12

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    Large Maf transcription factors, which are members of the basic leucine zipper (b-Zip) superfamily, have been reported to be involved in embryonic development and cell differentiation. Previously, we isolated a novel zebrafish large Maf cDNA, somite Maf1 (SMaf1), which possesses transactivational activity within its N-terminus domain. To elucidate SMaf1 function in mammals, we tried to isolate the Mouse homologue of zebrafish SMaf1. We isolated the mouse homologue of zebrafish SMaf1, which is the same molecule as the recently reported MafA. MafA mRNA was detected in formed somites, head neural tube, and liver cells in the embryos. In the adult mouse, MafA transcript was amplified in the brain, lung, spleen, and kidney by RT-PCR. MafA mRNA was also detectable in beta-cell line. Next, we analyzed the transcriptional activity of MafA using rat insulin promoters I and II (RIPI and II), since a part of RIP sequence was similar to the Maf recognition element (MARE) and MafA was expressed in pancreatic beta-cells. MafA was able to activate transcription from RIPII, but not RIPI, in a dose dependent manner and the activity was dependent on RIPE3b/C1 sequences. In addition, the amount of MafA protein was regulated by glucose concentration. These results indicate that MafA is the homologue of zebrafish SMaf1 and acts as a transcriptional activator of the insulin gene promoter through the RIPE3b element. (C) 2003 Published by Elsevier Inc.

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  • 【体質と環境】 Q.&A. 過食が原因ですか?

    曽根 博仁, 山田 信博

    Q&Aでわかる肥満と糖尿病   2 ( 6 )   92 - 94   2003.11

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  • 強力なライフスタイル介入による2型糖尿病コントロールの試み 長期の血糖コントロールに関与する因子の解析

    曽根 博仁, 山田 信博, 水野 佐智子, 片桐 あかね, 大橋 靖雄, 赤沼 安夫

    内科専門医会誌   15 ( 4 )   582 - 588   2003.11

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    2型糖尿病患者2000名を対象にした大規模臨床介入試験Japan Diabetes Complications Study(JDCS)のデータベースを用いて,2型糖尿病患者の血糖コントロールに生活習慣介入が及ぼす影響,長期的な血糖コントロールに関与する因子の解析を行った.その結果,無作為に2群に分けられた生活習慣介入群と非介入群を比較すると,開始2年目から5年後にHbA1cはわずかながら介入群で有意な改善がみられた.長期血糖コントロールに関与する因子解析では,若年・軽症患者は高齢・重症患者と比べ,長期的にHbA1cの増悪傾向を認め,血糖コントロール改善患者は増悪患者と比べ有意に血清脂質の改善がみられた.また,同じ2型糖尿病でも,日本人と白人患者の肥満度は大きく異なり,両群の遺伝的背景に基づく病態の相違が示唆された

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  • 【糖・脂質代謝と臓器相関】 副腎髄質と糖・脂質代謝

    曽根 博仁, 山田 信博

    内分泌・糖尿病科   17 ( 5 )   450 - 454   2003.11

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  • 【糖尿病と大血管障害 心疾患を中心に】 日本の2型糖尿病患者における大血管合併症の現状について Japan Diabetes Complications Study(JDCS)の中間結果より

    曽根 博仁, 水野 佐智子, 大橋 靖雄, 齋藤 康, 井藤 英喜, 山崎 義光, 赤沼 安夫, 山田 信博

    Diabetes Frontier   14 ( 5 )   588 - 592   2003.10

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  • 長寿フロントライン 高齢者糖尿病を対象とした前向き大規模臨床介入研究

    曽根 博仁, 山田 信博, 井藤 英喜

    Aging & Health   12 ( 3 )   34 - 35   2003.10

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  • 【糖尿病診療マニュアル】 基礎から臨床のトピックス JDCS(Japan Diabetes Complications Study)

    曽根 博仁, 赤沼 安夫, 山田 信博

    日本医師会雑誌   130 ( 8 )   S95 - S95   2003.10

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  • 著明な胆汁うっ滞型肝障害を伴ったバセドウ病の一例

    大垣 聡子, 曽根 博仁, 大谷 明夫, 鈴木 浩明, 豊島 秀男, 島野 仁, 山口 高史, 山田 信博

    日本内分泌学会雑誌   79 ( Suppl. )   33 - 36   2003.9

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    59歳男.主訴は黄疸,体重減少,全身倦怠感.バセドウ病と胆汁うっ滞型肝障害を認めた.腹部超音波検査では肝内胆管の拡張は認められず,心不全も認められなかった.肝炎ウイルスマーカーは陰性であり,抗核抗体陽性であった.自己免疫性肝炎の国際診断基準は満たさなかった.発症10日後以降に脳症が出現し,亜急性型劇症肝炎と考えられた.ステロイド剤の投与は無効であり,高ビリルビン血症の治療として施行された血漿交換も一時的な効果を示したのみであった.バセドウ病については血漿交換により,症状・検査値共に改善が認められた.バセドウ病に対する治療としては,著明な肝不全のため抗甲状腺剤は使用せず,無機ヨード剤のみとした.無機ヨード剤開始後,一週間でeuthyroidに達したが,肝障害の改善は認められず,十二指腸潰瘍出血により死亡した.病理解剖所見では,門脈域の拡大,肝細胞索の不規則化,偽胆管の高度増生毛細胆管,増殖小胆管の著明な胆汁うっ滞,多核肝細胞の出現,Kupffer細胞の腫大を認め,門脈域にはCD3,CD8陽性T細胞が中等度浸潤していた.甲状腺はバセドウ病に一致するものであった

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  • Fenofibrate therapy improves postprandial responses to fat and malondialdehyde-modified low-density lipoprotein (MDA-LDL) levels in diabetic and non-diabetic patients with hypertriglyceridemia

    H Sone, K Saito, S Ito, K Kobayashi, A Takahashi, KT Iida, H Shimano, H Suzuki, H Toyoshima, Y Okuda, N Yamada

    ATHEROSCLEROSIS SUPPLEMENTS   4 ( 2 )   176 - 176   2003.9

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  • Long-term exercise improves postprandial response to fat in healthy elderly subjects

    H Sone, K Saito, H Murakami, M Shu, S Maeda, S Kuno, K Tanaka, R Ajisaka, H Suzuki, H Toyoshima, H Shimano, Y Okuda, M Matsuda, N Yamada

    ATHEROSCLEROSIS SUPPLEMENTS   4 ( 2 )   87 - 87   2003.9

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  • 2型糖尿病患者における血中D-マンノース濃度測定の臨床的意義

    川上 康, 曽根 博仁, 竹越 一博, 磯部 和正, 海老沼 宏幸, 斉藤 和典, 山田 信博

    臨床病理   51 ( 補冊 )   289 - 289   2003.9

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  • Effects of five-year lifestyle modification on patients with Type 2 diabetes: interim report of the Japan Diabetes Complications Study (JDCS).

    H Sone, S Ishibashi, H Ito, Y Saito, T Murase, H Yamashita, S Katayama, Y Ohashi, Y Akanuma, N Yamada

    DIABETOLOGIA   46   A235 - A236   2003.8

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  • Eicosapentaenoic acid suppresses basal and insulin-stimulated endothelin-1 production in human endothelial cells

    K Chisaki, Y Okuda, S Suzuki, T Miyauchi, M Soma, N Ohkoshi, H Sone, N Yamada, T Nakajima

    HYPERTENSION RESEARCH   26 ( 8 )   655 - 661   2003.8

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    cis-Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are the major fatty acids contained in fish oil, and are known to affect the various physiological properties of cell membranes in humans. The present study investigated the effects of polyunsaturated fatty acids on endothelin-1 (ET-1) production in human umbilical vein endothelial cells (HUVECs) and on insulin activity. After addition of various concentrations of EPA, docosahexaenoic acid, arachidonic acid, or linoleic acid to a culture medium, the concentration of ET-1 was measured using ELISA, and that of ET-1 mRNA was determined by RT-PCR. The results showed that EPA had the strongest inhibitory effect (p&lt;0.05) on both basal ET-1 production and ET-1 mRNA levels. In addition, insulin (1 mumol/l) markedly increased ET-1 production, and EPA also significantly decreased the effect induced by insulin. Pretreatment with Ca2+ chelator EGTA (1 mmol/l), NOS inhibitor L-NAME (300 mumol/l), or calmodulin antagonist W-7 (300 mumol/l) inhibited NO production by EPA (100 mumol/l), but these pretreatments had no effect on ET-1 production by EPA. These findings suggest that EPA reduces basal and insulin-enhanced ET-1 production by inhibiting ET-1 mRNA production. These effects of EPA may contribute to its vasorelaxant and anti-atherosclerotic effects.

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  • Physiological changes in circulating mannose levels in normal, glucose-intolerant, and diabetic subjects

    H Sone, H Shimano, H Ebinuma, A Takahashi, Y Yano, KT Iida, H Suzuki, H Toyoshima, Y Kawakami, Y Okuda, Y Noguchi, K Ushizawa, K Saito, N Yamada

    METABOLISM-CLINICAL AND EXPERIMENTAL   52 ( 8 )   1019 - 1027   2003.8

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    Mannose is an essential hexose that is required for glycoprotein synthesis. Although circulating mannose levels are known to be influenced by metabolic disorders, how physiological levels of mannose fluctuate in normal and diabetic subjects is largely unknown. We describe a new accurate and sensitive assay for determining circulating mannose levels, which we used to measure plasma mannose levels in 273 normal and diabetic (DM) subjects. Our results revealed a clear correlation (r = 0.754) between fasting plasma mannose (FPM) and fasting plasma glucose (FPG) levels. Our mannose assay showed sensitivity and specificity comparable to that seen for hemoglobin A(1c) (HbA(1c)) assay in subjects with impaired glucose tolerance (IGT) or DM whose FPG levels were normal. Mannose levels were found to increase less than glucose levels in response to an oral glucose tolerance test (OGTT). Furthermore, plasma mannose levels did not significantly change following a meal and more closely correlated with the coefficient of variation (CV) of daily glucose levels than did glucose itself. In conclusion, the close correlation between FPM and FPG levels taken together with the small fluctuations seen in plasma mannose in response to glucose suggests that the measurement of mannose using our assay could potentially play a supplementary role in the diagnosis and screening of patients with mild DM. (C) 2003 Elsevier Inc. All rights reserved.

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  • Eicosapentaenoic acid suppresses basal and insulin-stimulated endothelin-1 production in human endothelial cells

    K Chisaki, Y Okuda, S Suzuki, T Miyauchi, M Soma, N Ohkoshi, H Sone, N Yamada, T Nakajima

    HYPERTENSION RESEARCH   26 ( 8 )   655 - 661   2003.8

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    cis-Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are the major fatty acids contained in fish oil, and are known to affect the various physiological properties of cell membranes in humans. The present study investigated the effects of polyunsaturated fatty acids on endothelin-1 (ET-1) production in human umbilical vein endothelial cells (HUVECs) and on insulin activity. After addition of various concentrations of EPA, docosahexaenoic acid, arachidonic acid, or linoleic acid to a culture medium, the concentration of ET-1 was measured using ELISA, and that of ET-1 mRNA was determined by RT-PCR. The results showed that EPA had the strongest inhibitory effect (p&lt;0.05) on both basal ET-1 production and ET-1 mRNA levels. In addition, insulin (1 mumol/l) markedly increased ET-1 production, and EPA also significantly decreased the effect induced by insulin. Pretreatment with Ca2+ chelator EGTA (1 mmol/l), NOS inhibitor L-NAME (300 mumol/l), or calmodulin antagonist W-7 (300 mumol/l) inhibited NO production by EPA (100 mumol/l), but these pretreatments had no effect on ET-1 production by EPA. These findings suggest that EPA reduces basal and insulin-enhanced ET-1 production by inhibiting ET-1 mRNA production. These effects of EPA may contribute to its vasorelaxant and anti-atherosclerotic effects.

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  • Physiological changes in circulating mannose levels in normal, glucose-intolerant, and diabetic subjects

    H Sone, H Shimano, H Ebinuma, A Takahashi, Y Yano, KT Iida, H Suzuki, H Toyoshima, Y Kawakami, Y Okuda, Y Noguchi, K Ushizawa, K Saito, N Yamada

    METABOLISM-CLINICAL AND EXPERIMENTAL   52 ( 8 )   1019 - 1027   2003.8

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    Mannose is an essential hexose that is required for glycoprotein synthesis. Although circulating mannose levels are known to be influenced by metabolic disorders, how physiological levels of mannose fluctuate in normal and diabetic subjects is largely unknown. We describe a new accurate and sensitive assay for determining circulating mannose levels, which we used to measure plasma mannose levels in 273 normal and diabetic (DM) subjects. Our results revealed a clear correlation (r = 0.754) between fasting plasma mannose (FPM) and fasting plasma glucose (FPG) levels. Our mannose assay showed sensitivity and specificity comparable to that seen for hemoglobin A(1c) (HbA(1c)) assay in subjects with impaired glucose tolerance (IGT) or DM whose FPG levels were normal. Mannose levels were found to increase less than glucose levels in response to an oral glucose tolerance test (OGTT). Furthermore, plasma mannose levels did not significantly change following a meal and more closely correlated with the coefficient of variation (CV) of daily glucose levels than did glucose itself. In conclusion, the close correlation between FPM and FPG levels taken together with the small fluctuations seen in plasma mannose in response to glucose suggests that the measurement of mannose using our assay could potentially play a supplementary role in the diagnosis and screening of patients with mild DM. (C) 2003 Elsevier Inc. All rights reserved.

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  • 2型糖尿病患者における血中D-マンノース濃度測定の臨床的意義

    川上 康, 曽根 博仁, 山田 信博, 海老沼 宏幸, 齋藤 和典, 石島 道邦, 飯塚 儀明, 磯部 和正, 竹越 一博

    日本臨床検査自動化学会会誌   28 ( 4 )   601 - 601   2003.8

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  • 【糖尿病・合併症予防に関するメガスタディー】 Japan Diabetes Complications Study(JDCS)の中間結果

    曽根 博仁, 水野 佐智子, 大橋 靖雄, 齋藤 康, 井藤 英喜, 吉村 幸雄, 山下 英俊, 清野 弘明, 松岡 健平, 山崎 義光, 片山 茂裕, 赤沼 安夫, 山田 信博, JDCSグループ

    Diabetes Frontier   14 ( 4 )   445 - 450   2003.8

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  • Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling

    T Yoshikawa, T Ide, H Shimano, N Yahagi, M Amemiya-Kudo, T Matsuzaka, S Yatoh, T Kitamine, H Okazaki, Y Tamura, M Sekiya, A Takahashi, AH Hasty, R Sato, H Sone, JI Osuga, S Ishibashi, N Yamada

    MOLECULAR ENDOCRINOLOGY   17 ( 7 )   1240 - 1254   2003.7

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    Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors that form obligate heterodimers with retinoid X receptors (RXRs). These nuclear receptors play crucial roles in the regulation of fatty acid metabolism: LXRs activate expression of sterol regulatory element-binding protein 1c (SREBP-1c), a dominant lipogenic gene regulator, whereas PPARalpha promotes fatty acid beta-oxidation genes. In the current study, effects of PPARs on the LXR-SREBP-1c pathway were investigated. Luciferase assays in human embryonic kidney 293 cells showed that overexpression of PPARalpha and gamma dose-dependently inhibited SREBP-1c promoter activity induced by LXR. Deletion and mutation studies demonstrated that the two LXR response elements (LXREs) in the SREBP-1c promoter region are responsible for this inhibitory effect of PPARs. Gel shift assays indicated that PPARs reduce binding of LXR/RXR to LXRE. PPARalpha-selective agonist enhanced these inhibitory effects. Supplementation with RXR attenuated these inhibitions by PPARs in luciferase and gel shift assays, implicating receptor interaction among LXR, PPAR, and RXR as a plausible mechanism. Competition of PPARalpha ligand with LXR ligand was observed in LXR/RXR binding to LXRE in gel shift assay, in LXR/RXR formation in nuclear extracts by coimmunoprecipitation, and in gene expression of SREBP-1c by Northern blot analysis of rat primary hepatocytes and mouse liver RNA. These data suggest that PPARalpha activation can suppress LXR-SREBP-1c pathway through reduction of LXR/RXR formation, proposing a novel transcription factor cross-talk between LXR and PPARalpha in hepatic lipid homeostasis.

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  • Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling

    T Yoshikawa, T Ide, H Shimano, N Yahagi, M Amemiya-Kudo, T Matsuzaka, S Yatoh, T Kitamine, H Okazaki, Y Tamura, M Sekiya, A Takahashi, AH Hasty, R Sato, H Sone, JI Osuga, S Ishibashi, N Yamada

    MOLECULAR ENDOCRINOLOGY   17 ( 7 )   1240 - 1254   2003.7

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    Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors that form obligate heterodimers with retinoid X receptors (RXRs). These nuclear receptors play crucial roles in the regulation of fatty acid metabolism: LXRs activate expression of sterol regulatory element-binding protein 1c (SREBP-1c), a dominant lipogenic gene regulator, whereas PPARalpha promotes fatty acid beta-oxidation genes. In the current study, effects of PPARs on the LXR-SREBP-1c pathway were investigated. Luciferase assays in human embryonic kidney 293 cells showed that overexpression of PPARalpha and gamma dose-dependently inhibited SREBP-1c promoter activity induced by LXR. Deletion and mutation studies demonstrated that the two LXR response elements (LXREs) in the SREBP-1c promoter region are responsible for this inhibitory effect of PPARs. Gel shift assays indicated that PPARs reduce binding of LXR/RXR to LXRE. PPARalpha-selective agonist enhanced these inhibitory effects. Supplementation with RXR attenuated these inhibitions by PPARs in luciferase and gel shift assays, implicating receptor interaction among LXR, PPAR, and RXR as a plausible mechanism. Competition of PPARalpha ligand with LXR ligand was observed in LXR/RXR binding to LXRE in gel shift assay, in LXR/RXR formation in nuclear extracts by coimmunoprecipitation, and in gene expression of SREBP-1c by Northern blot analysis of rat primary hepatocytes and mouse liver RNA. These data suggest that PPARalpha activation can suppress LXR-SREBP-1c pathway through reduction of LXR/RXR formation, proposing a novel transcription factor cross-talk between LXR and PPARalpha in hepatic lipid homeostasis.

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  • Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. II. LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling

    T Ide, H Shimano, T Yoshikawa, N Yahagi, M Amemiya-Kudo, T Matsuzaka, M Nakakuki, S Yatoh, Y Iizuka, S Tomita, K Ohashi, A Takahashi, H Sone, T Gotoda, JI Osuga, S Ishibashi, N Yamada

    MOLECULAR ENDOCRINOLOGY   17 ( 7 )   1255 - 1267   2003.7

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    Fatty acid metabolism is transcriptionally regulated by two reciprocal systems: peroxisome proliferator-activated receptor (PPAR)alpha controls fatty acid degradation, whereas sterol regulatory element-binding protein-1c activated by liver X receptor (LXR) regulates fatty acid synthesis. To explore potential interactions between LXR and PPAR, the effect of LXR activation on PPARalpha signaling was investigated. In luciferase reporter gene assays, overexpression of LXRalpha or beta suppressed PPARalpha-induced peroxisome proliferator response element-luciferase activity in a dose-dependent manner. LXR agonists, T0901317 and 22(R)hydroxycholesterol, dose dependently enhanced the suppressive effects of LXRs. Gel shift assays demonstrated that LXR reduced binding of PPARalpha/retinoid X receptor (RXR) alpha to peroxisome proliferator response element. Addition of increasing amounts of RXRalpha restored these inhibitory effects in both luciferase and gel shift assays, suggesting the presence of RXRalpha competition. In vitro protein binding assays demonstrated that activation of LXR by an LXR agonist promoted formation of LXR/RXRalpha and, more importantly, LXR/PPARalpha heterodimers, leading to a reduction of PPARalpha/RXRalpha formation. Supportively, in vivo administration of the LXR ligand to mice and rat primary hepatocytes substantially decreased hepatic mRNA levels of PPARalpha-targeted genes in both basal and PPARalpha agonist-induced conditions. The amount of nuclear PPARalpha/RXR heterodimers in the mouse livers was induced by treatment with PPARalpha ligand, and was suppressed by superimposed LXR ligand. Taken together with data from the accompanying paper (Yoshikawa, T., T. Ide, H. Shimano, N. Yahagi, M. Amemiya-Kudo, T. Matsuzaka, S. Yatoh, T. Kitamine, H. Okazaki, Y. Tamura, M. Sekiya, A. Takahashi, A. H. Hasty, R. Sato, H. Sone, J. Osuga, S. Ishibashi, and N. Yamada, Endocrinology 144: 1240-1254) describing PPARalpha suppression of the LXR-sterol regulatory element-binding protein-1c pathway, we propose the presence of an intricate network of nutritional transcription factors with mutual interactions, resulting in efficient reciprocal regulation of lipid degradation and lipogenesis.

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  • Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. II. LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling

    T Ide, H Shimano, T Yoshikawa, N Yahagi, M Amemiya-Kudo, T Matsuzaka, M Nakakuki, S Yatoh, Y Iizuka, S Tomita, K Ohashi, A Takahashi, H Sone, T Gotoda, JI Osuga, S Ishibashi, N Yamada

    MOLECULAR ENDOCRINOLOGY   17 ( 7 )   1255 - 1267   2003.7

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    Fatty acid metabolism is transcriptionally regulated by two reciprocal systems: peroxisome proliferator-activated receptor (PPAR)alpha controls fatty acid degradation, whereas sterol regulatory element-binding protein-1c activated by liver X receptor (LXR) regulates fatty acid synthesis. To explore potential interactions between LXR and PPAR, the effect of LXR activation on PPARalpha signaling was investigated. In luciferase reporter gene assays, overexpression of LXRalpha or beta suppressed PPARalpha-induced peroxisome proliferator response element-luciferase activity in a dose-dependent manner. LXR agonists, T0901317 and 22(R)hydroxycholesterol, dose dependently enhanced the suppressive effects of LXRs. Gel shift assays demonstrated that LXR reduced binding of PPARalpha/retinoid X receptor (RXR) alpha to peroxisome proliferator response element. Addition of increasing amounts of RXRalpha restored these inhibitory effects in both luciferase and gel shift assays, suggesting the presence of RXRalpha competition. In vitro protein binding assays demonstrated that activation of LXR by an LXR agonist promoted formation of LXR/RXRalpha and, more importantly, LXR/PPARalpha heterodimers, leading to a reduction of PPARalpha/RXRalpha formation. Supportively, in vivo administration of the LXR ligand to mice and rat primary hepatocytes substantially decreased hepatic mRNA levels of PPARalpha-targeted genes in both basal and PPARalpha agonist-induced conditions. The amount of nuclear PPARalpha/RXR heterodimers in the mouse livers was induced by treatment with PPARalpha ligand, and was suppressed by superimposed LXR ligand. Taken together with data from the accompanying paper (Yoshikawa, T., T. Ide, H. Shimano, N. Yahagi, M. Amemiya-Kudo, T. Matsuzaka, S. Yatoh, T. Kitamine, H. Okazaki, Y. Tamura, M. Sekiya, A. Takahashi, A. H. Hasty, R. Sato, H. Sone, J. Osuga, S. Ishibashi, and N. Yamada, Endocrinology 144: 1240-1254) describing PPARalpha suppression of the LXR-sterol regulatory element-binding protein-1c pathway, we propose the presence of an intricate network of nutritional transcription factors with mutual interactions, resulting in efficient reciprocal regulation of lipid degradation and lipogenesis.

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  • 【高齢者の肥満と糖尿病 Q.&A.】 高齢者糖尿病の大規模研究とは? 「高齢糖尿病を対象とした前向き大規模臨床介入研究」について教えてください

    曽根 博仁, 山田 信博, 井藤 英喜

    Q&Aでわかる肥満と糖尿病   2 ( 4 )   40 - 42   2003.7

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  • マルチプルリスクファクター症候群の一部分症としての糖尿病性マクロアンギオパシー JDCSの中間解析からみた本邦の糖尿病大血管障害のリスクファクター

    曽根 博仁, 赤沼 安夫, 山田 信博

    糖尿病合併症   17 ( 1 )   55 - 60   2003.6

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  • Effect of thiazolidinediones and metformin on LDL oxidation and aortic endothelium relaxation in diabetic GK rats

    KT Iida, Y Kawakami, M Suzuki, H Shimano, H Toyoshima, H Sone, K Shimada, Y Iwama, Y Watanabe, H Mokuno, K Kamata, N Yamada

    AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM   284 ( 6 )   E1125 - E1130   2003.6

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    In this study, using GK diabetic rats, we compared the effects of three insulin sensitizers on lipid oxidation and the aortic relaxation response. Eight-week-old rats were treated for 4 wk with either troglitazone or pioglitazone, both of which are thiazolidinediones, or with metformin. Despite the fact that only troglitazone has a similarity in structure to alpha-tocopherol, a potent antioxidant, the level of thiobarbituric acid-reactive substance was lower, and the lag time of the conjugated dienes was longer, in the blood samples from the rats in both troglitazone- and pioglitazone-treated groups. In contrast, another insulin sensitizer, metformin, failed to inhibit the oxidation of blood samples. The aortic vasorelaxation response was increased in both troglitazone- and metformin-treated groups compared with the untreated group. These findings suggest that thiazolidinediones have a beneficial effect on lipid oxidation irrespective of the drug's structural similarity to alpha-tocopherol. It is also suggested that the thiazolidinediones and metformin improve vascular function in diabetes. These effects may play a role in the prevention of atherosclerosis in diabetic patients.

    DOI: 10.1152/ajpendo.00430.2002

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  • Effect of thiazolidinediones and metformin on LDL oxidation and aortic endothelium relaxation in diabetic GK rats

    KT Iida, Y Kawakami, M Suzuki, H Shimano, H Toyoshima, H Sone, K Shimada, Y Iwama, Y Watanabe, H Mokuno, K Kamata, N Yamada

    AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM   284 ( 6 )   E1125 - E1130   2003.6

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    In this study, using GK diabetic rats, we compared the effects of three insulin sensitizers on lipid oxidation and the aortic relaxation response. Eight-week-old rats were treated for 4 wk with either troglitazone or pioglitazone, both of which are thiazolidinediones, or with metformin. Despite the fact that only troglitazone has a similarity in structure to alpha-tocopherol, a potent antioxidant, the level of thiobarbituric acid-reactive substance was lower, and the lag time of the conjugated dienes was longer, in the blood samples from the rats in both troglitazone- and pioglitazone-treated groups. In contrast, another insulin sensitizer, metformin, failed to inhibit the oxidation of blood samples. The aortic vasorelaxation response was increased in both troglitazone- and metformin-treated groups compared with the untreated group. These findings suggest that thiazolidinediones have a beneficial effect on lipid oxidation irrespective of the drug's structural similarity to alpha-tocopherol. It is also suggested that the thiazolidinediones and metformin improve vascular function in diabetes. These effects may play a role in the prevention of atherosclerosis in diabetic patients.

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  • 日本の2型糖尿病患者における動脈硬化性疾患の発症頻度と危険因子 JDCSの中間結果より

    曽根 博仁, 水野 佐智子, 大橋 靖雄, 赤沼 安夫, 山田 信博

    動脈硬化予防   2 ( 2 )   74 - 78   2003.6

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  • 【高脂血症治療】 食後高脂血症の意義と評価

    曽根 博仁, 齋藤 和典, 山田 信博

    Mebio   20 ( 6 )   111 - 115   2003.6

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    血清トリグリセリド(TG)値の評価は,朝食前空腹時の値で行われることが一般的であったが,1日のうちの大部分がむしろ&quot;食後&quot;であることを考えると,朝空腹時の評価だけでは不十分ではないかと認識されるようになってきた.食後高脂血症は,食後の血清TG上昇の程度が,通常より大きく遷延している状態であり,高TG血症であると同時に,カイロミクロン,VLDLとそのレムナント代謝が遅延している状態であると言える.高TG血症は,動脈硬化性疾患の独立したリスクファクターであるが,食後高脂血症も同様にリスクファクターであることが明らかになりつつある.血中TG濃度は,食事,飲酒,運動などの影響を受けやすく,同一人においても変動しやすいため,単回の食後TG値測定では,必ずしも的確な食後高脂血症の診断ができない.したがって食後TG値による食後高脂血症の明確な診断閾値は,まだ決定されていない.食後高脂血症の診断のために,経口脂肪負荷試験の標準プロトコールの確立と,更に簡便な診断法の開発が望まれる

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(Japan Diabetes Complications Study;JDCS)の中間報告

    曽根 博仁, 赤沼 安夫, 山田 信博

    内分泌・糖尿病科   16 ( 6 )   575 - 581   2003.6

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  • The need to integrate diabetes education and treatment (multiple letters)

    Stephen Clement, B. Cockerill, E. Smith, H. Sone, Y. Akanuma, Nobuhiro Yamada

    Hormone and Metabolic Research   35 ( 5 )   333 - 335   2003.5

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    DOI: 10.1055/s-2003-41312

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  • Reply to Clement et al. Still a Chance for Diabetes Education. Reviewed

    H. Sone, Y. Akanuma, N. Yamada

    Hormone and Metabolic Research   35 ( 5 )   334 - 335   2003.5

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    DOI: 10.1055/s-2003-41313

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  • 血管内皮細胞死と細胞周期

    三浦 光弘, 豊島 秀男, 飯田 薫子, 鈴木 浩明, 曽根 博仁, 島野 仁, 山田 信博

    糖尿病   46 ( Suppl.1 )   S126 - S126   2003.4

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  • 骨芽細胞においてp57KIP2はLIM kinase 1と結合し,細胞骨格を制御する

    豊島 秀男, 飯田 薫子, 鈴木 浩明, 曽根 博仁, 島野 仁, 山田 信博

    日本内分泌学会雑誌   79 ( 1 )   131 - 131   2003.4

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  • 糖尿病加療中に下肢の疼痛・腫脹を繰り返し,糖尿病筋梗塞が疑われた1例

    岡田 純子, 斉藤 和美, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 島野 仁, 山田 信博

    糖尿病   46 ( 4 )   354 - 354   2003.4

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  • PEPCK-SREBP-1a transgenic mouseにおけるインスリン抵抗性

    高橋 昭光, 島野 仁, 中川 嘉, 飯田 薫子, 小林 和人, 豊島 秀男, 鈴木 浩明, 曽根 博仁, 山田 信博

    日本内分泌学会雑誌   79 ( 1 )   143 - 143   2003.4

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  • SREBPは肝臓のIRS-2を介するインスリンシグナルを抑制する

    井出 智広, 島野 仁, 中川 嘉, 高橋 昭光, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 山田 信博

    糖尿病   46 ( Suppl.1 )   S215 - S215   2003.4

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  • Sterol regulatory element binding protein 1(SREBP-1)トランスジェニックマウスにおけるインスリン抵抗性

    高橋 昭光, 島野 仁, 中川 嘉, 井出 智広, 飯田 薫子, 小林 和人, 鈴木 将玄, 大垣 聡子, 斉藤 和美, 石川 まゆみ, 三浦 光弘, 杉本 孝示, 鈴木 浩明, 豊島 秀男, 曽根 博仁, 山田 信博

    糖尿病   46 ( Suppl.1 )   S215 - S215   2003.4

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する調査(Japan Diabetes Complication Study;JDCS)の中間報告

    曽根 博仁, 井藤 英喜, 山下 英俊, 齋藤 康, 片山 茂裕, 矢島 義忠, 阿部 隆三, 大橋 靖雄, 赤沼 安夫, 山田 信博

    糖尿病   46 ( Suppl.1 )   S236 - S236   2003.4

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  • Acute gliclazide administration enhances glucose and ketone body utilization in the perfused hind limb of normal and streptozotocin-diabetic rats (vol 71, pg 647, 2002)

    Y Okuda, K Kobayashi, H Ohmori, H Sone, M Suzuki, J Ma, T Nakajima, N Yamada, K Yamashita

    LIFE SCIENCES   72 ( 17 )   2007 - 2007   2003.3

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    DOI: 10.1016/S0024-3205(03)00060-2

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  • 【ガイドラインに基づく生活習慣病の診療戦略 糖尿病】 JDCS(Japan Diabetes Complications Study)から学ぶもの

    曽根 博仁, 赤沼 安夫, 山田 信博

    Atherothrombosis   6 ( 1 )   12 - 18   2003.3

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  • 2型糖尿病患者の長期血糖コントロール予後におけるライフスタイル介入の影響 Japan Diabetes Complications Study(JDCS)中間報告データの解析より

    曽根 博仁, 片桐 あかね, 大橋 靖雄, 山田 信博

    健康医科学研究助成論文集   ( 18 )   55 - 62   2003.3

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    JDCSに登録された2547名をライフスタイル介入群1105名と非介入群1100名に無作為に分けて,介入群に対しては主治医と協力して毎回の外来における主治医による治療・指導強化,外来における患者教育専門家による指導及び電話による生活指導,コントロール不良患者に対する積極的な重点指導を行った.ライフスタイル介入効果は,開始後2年で僅かに認められた.又,コントロール良好群よりも不良群の方が改善度は良かった

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  • 著明な胆汁うっ滞型肝障害を伴ったバセドウ病の一例

    大垣 聡子, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 島野 仁, 山田 信博

    日本内分泌学会雑誌   79   89 - 89   2003.2

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  • 【高齢者の内分泌異常】 高齢者の内分泌体系はどうあるべきか

    曽根 博仁, 山田 信博

    綜合臨床   52 ( 2 )   251 - 253   2003.2

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  • ホルモン負荷試験の解釈が困難であった成長ホルモン高値の一例

    石川 まゆみ, 大垣 聡子, 豊島 秀男, 鈴木 浩明, 曽根 博仁, 島野 仁, 山田 信博

    日本内分泌学会雑誌   79   104 - 104   2003.2

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  • Obesity and type 2 diabetes in Japanese patients

    H Sone, H Ito, Y Ohashi, Y Akanuma, N Yamada

    LANCET   361 ( 9351 )   85 - 85   2003.1

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  • Obesity and type 2 diabetes in Japanese patients

    H Sone, H Ito, Y Ohashi, Y Akanuma, N Yamada

    LANCET   361 ( 9351 )   85 - 85   2003.1

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  • 【介入試験の企画と実際】 JDCS

    曽根 博仁, 山田 信博

    The Lipid   14 ( 1 )   76 - 82   2003.1

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    糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDCS)の目的は,現代日本の糖尿病患者の病態の特徴や,専門施設における糖尿病診療の現況を調査すると同時に,糖尿病細小・大血管合併症の発症・進展因子を明らかにし,治療手段を確立することである.1996年4月より,全国59施設の約2,000症例に介入を開始し,現在7年次に入っているが,介入群においてのみ開始時と比較して,僅かながら有意なHbA1cの低下が認められている.動脈硬化性合併症の頻度は,非糖尿病者の約3倍に上昇しており,血糖コントロールのほか,血圧やLDLコレステロールが,その独立したリスクファクターであることも明らかになった

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  • 糖尿病における高脂血症の原因遺伝子-Angiopoietin-like protein 3(Angptl3)

    曽根 博仁, 山田 信博

    BIO Clinica   18 ( 1 )   82 - 85   2003.1

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  • 2型糖尿病患者の長期血糖コントロールにおけるライフスタイル介入の影響

    明治生命厚生事業団健康医科学研究助成論文集   13   55 - 62   2003

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  • 食事指導と自覚的運動強度を用いたトレッドミル歩行の組合わせが2型糖尿病患者の健康・体力水準に及ぼす影響

    理学療法ジャーナル   37   257 - 260   2003

  • 低カルシウム血症をきたしたサルコイドーシスの症例

    大垣聡子, 曽根博仁, 鈴木浩明, 豊島秀男, 島野仁, 山田信博

    内科専門医会誌   15   313-314,482-492   2003

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  • The long-term effects of self-management education for patients with type 2 diabetes on glycemic control

    H Sone, H Ito, Y Saito, H Yamashita, S Ishibashi, S Katayama, R Abe, Y Ohashi, Y Akanuma, N Yamada

    DIABETES CARE   25 ( 11 )   2115 - 2116   2002.11

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  • The long-term effects of self-management education for patients with type 2 diabetes on glycemic control

    H Sone, H Ito, Y Saito, H Yamashita, S Ishibashi, S Katayama, R Abe, Y Ohashi, Y Akanuma, N Yamada

    DIABETES CARE   25 ( 11 )   2115 - 2116   2002.11

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    DOI: 10.2337/diacare.25.11.2115

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  • 【新時代の糖尿病学 病因・診断・治療研究の進歩】 糖尿病に起因する合併症 我が国における糖尿病合併症に関する長期介入研究

    曽根 博仁, 山田 信博, JDC Studyグループ

    日本臨床   60 ( 増刊10 新時代の糖尿病学(4) )   44 - 50   2002.10

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  • HMG-CoA reductase inhibitor decreases small dense low-density lipoprotein and remnant-like particle cholesterol in patients with type-2 diabetes

    H Sone, A Takahashi, H Shimano, S Ishibashi, G Yoshino, N Morisaki, Y Saito, S Kawazu, T Teramoto, T Fujita, T Shiba, Y Iwamoto, N Kuzuya, Y Akanuma, N Yamada

    LIFE SCIENCES   71 ( 20 )   2403 - 2412   2002.10

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    Patients with type 2 diabetes are known to have abnormalities in their remnant metabolism and low density lipoprotein (LDL) subfraction pattern, with a preponderance of small dense LDL. The effects of pitavastatin, a newly synthesized 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, on lipoprotein profiles in patients with type 2 diabetes were determined. Thirty-three patients were treated with pitavastatin with a daily dose of 2 mg for 8 weeks. After treatment, triglyceride, total and LDL cholesterol were significantly reduced by 28.7 +/- 36.7%, 25.2 +/- 14.3% and 36.1 +/- 14.3%, respectively. Remnant-like particle cholesterol (RLP-C), an independent risk factor for CAD which is known to be elevated in diabetic patients, was also significantly reduced - 30.9 +/- 30.5%) by the treatment and this decrease correlated well with the decrease in triglyceride level. The proportion of small dense LDL, which is known for its atherogenisity, decreased from 29.9 +/- 26.2% to 19.7 +/- 22.7% and the mean LDL particle size significantly increased from 26.36 +/- 1.13 nm to 27.10 +/- 1.36 nm. Pitavastatin, which is known to improve triglyceride levels and cholesterol levels, also improves RLP-C level and LDL subfraction profiles, and this in turn may reduce the cardiovascular risk in patients with type 2 diabetes and dyslipidemia. (C) 2002 Elsevier Science Inc. All rights reserved.

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  • HMG-CoA reductase inhibitor decreases small dense low-density lipoprotein and remnant-like particle cholesterol in patients with type-2 diabetes

    H Sone, A Takahashi, H Shimano, S Ishibashi, G Yoshino, N Morisaki, Y Saito, S Kawazu, T Teramoto, T Fujita, T Shiba, Y Iwamoto, N Kuzuya, Y Akanuma, N Yamada

    LIFE SCIENCES   71 ( 20 )   2403 - 2412   2002.10

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    Patients with type 2 diabetes are known to have abnormalities in their remnant metabolism and low density lipoprotein (LDL) subfraction pattern, with a preponderance of small dense LDL. The effects of pitavastatin, a newly synthesized 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, on lipoprotein profiles in patients with type 2 diabetes were determined. Thirty-three patients were treated with pitavastatin with a daily dose of 2 mg for 8 weeks. After treatment, triglyceride, total and LDL cholesterol were significantly reduced by 28.7 +/- 36.7%, 25.2 +/- 14.3% and 36.1 +/- 14.3%, respectively. Remnant-like particle cholesterol (RLP-C), an independent risk factor for CAD which is known to be elevated in diabetic patients, was also significantly reduced - 30.9 +/- 30.5%) by the treatment and this decrease correlated well with the decrease in triglyceride level. The proportion of small dense LDL, which is known for its atherogenisity, decreased from 29.9 +/- 26.2% to 19.7 +/- 22.7% and the mean LDL particle size significantly increased from 26.36 +/- 1.13 nm to 27.10 +/- 1.36 nm. Pitavastatin, which is known to improve triglyceride levels and cholesterol levels, also improves RLP-C level and LDL subfraction profiles, and this in turn may reduce the cardiovascular risk in patients with type 2 diabetes and dyslipidemia. (C) 2002 Elsevier Science Inc. All rights reserved.

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  • Cerebral hemorrhagic infarction after radiation for pituitary adenoma

    S Ogaki, S Suzuki, H Suzuki, M Suzuki, H Shimano, H Toyoshima, H Sone, Y Okuda, N Yamada

    INTERNAL MEDICINE   41 ( 10 )   834 - 838   2002.10

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    We report a case of cerebral hemorrhagic infarction after radiation for pituitary adenoma. A 55-year-old woman was hospitalized to check for aldosteronism, post-operative pituitary function, and recurrence of thyroid cancer. She had short-term memory disturbance beginning two months prior to admission. Brain MRI showed a T1 and T2 high intensity lesion of her left anterolateral thalamus. Brain MRA revealed a narrowing in her left middle cerebral artery. The abnormal brain lesion was diagnosed as cerebral hemorrhagic infarction. She had received radiation therapy for pituitary adenoma 20 years earlier. It was considered that her cerebral hemorrhagic infarction was caused by radiation therapy.

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  • Cerebral hemorrhagic infarction after radiation for pituitary adenoma

    S Ogaki, S Suzuki, H Suzuki, M Suzuki, H Shimano, H Toyoshima, H Sone, Y Okuda, N Yamada

    INTERNAL MEDICINE   41 ( 10 )   834 - 838   2002.10

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    We report a case of cerebral hemorrhagic infarction after radiation for pituitary adenoma. A 55-year-old woman was hospitalized to check for aldosteronism, post-operative pituitary function, and recurrence of thyroid cancer. She had short-term memory disturbance beginning two months prior to admission. Brain MRI showed a T1 and T2 high intensity lesion of her left anterolateral thalamus. Brain MRA revealed a narrowing in her left middle cerebral artery. The abnormal brain lesion was diagnosed as cerebral hemorrhagic infarction. She had received radiation therapy for pituitary adenoma 20 years earlier. It was considered that her cerebral hemorrhagic infarction was caused by radiation therapy.

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  • 糖尿病性心血管疾患の予防と治療 日本の2型糖尿病患者における動脈硬化合併症の現況 Japan Diabetes Complications Study(JDCS)の中間解析より

    曽根 博仁, 山田 信博, JDCStudyグループ

    循環器専門医   10 ( 2 )   309 - 313   2002.10

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    DOI: 10.1253/jjcsc.10.2_309

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  • Effects of lifestyle modifications on patients with type 2 diabetes: The Japan Diabetes Complications Study (JDCS) study design, baseline analysis and three year-interim report

    H Sone, A Katagiri, S Ishibashi, R Abe, Y Saito, T Murase, H Yamashita, Y Yajima, H Ito, Y Ohashi, Y Akanuma, N Yamada

    HORMONE AND METABOLIC RESEARCH   34 ( 9 )   509 - 515   2002.9

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    Background: Lifestyle modifications may affect the development of diabetes and prevent complications. However, there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes. Objective: The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes. This initial report on a multi-year study describes protocols and the analysis of baseline data and three-year interim results. Design: The study was a randomized, controlled, multi-centre, prospective intervention trial. The trial included patients from 59 Japanese institutes specializing in diabetes care. Patients: The study enrolled 2205 patients with previously diagnosed type 2 diabetes. Intervention: The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling. The intervention group received educational materials concerning the importance of lifestyle and behavioural changes, a diary to record progress of laboratory and other data, and a pedometer. Measurements: Parameters and indices related to glycemic control, diabetic complications, dyslipidemia, hypertension, obesity, and atherosclerosis were measured several times a year. Results: Small but significant differences in HbA1c levels between the intervention (INT) and conventional (CON) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year (CON group, 7.78 +/- 1.27 % vs. INT group, 7.62 +/- 1.20 %, the initial HbA1c level was 7.80 +/- 1.42 % for the CON group and 7.68 +/- 1.28 % for the INT group). Data on differences in occurrence of micro- or macrovascular complications are not yet available. Conclusions: The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention.

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  • Effects of lifestyle modifications on patients with type 2 diabetes: The Japan Diabetes Complications Study (JDCS) study design, baseline analysis and three year-interim report

    H Sone, A Katagiri, S Ishibashi, R Abe, Y Saito, T Murase, H Yamashita, Y Yajima, H Ito, Y Ohashi, Y Akanuma, N Yamada

    HORMONE AND METABOLIC RESEARCH   34 ( 9 )   509 - 515   2002.9

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    Background: Lifestyle modifications may affect the development of diabetes and prevent complications. However, there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes. Objective: The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes. This initial report on a multi-year study describes protocols and the analysis of baseline data and three-year interim results. Design: The study was a randomized, controlled, multi-centre, prospective intervention trial. The trial included patients from 59 Japanese institutes specializing in diabetes care. Patients: The study enrolled 2205 patients with previously diagnosed type 2 diabetes. Intervention: The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling. The intervention group received educational materials concerning the importance of lifestyle and behavioural changes, a diary to record progress of laboratory and other data, and a pedometer. Measurements: Parameters and indices related to glycemic control, diabetic complications, dyslipidemia, hypertension, obesity, and atherosclerosis were measured several times a year. Results: Small but significant differences in HbA1c levels between the intervention (INT) and conventional (CON) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year (CON group, 7.78 +/- 1.27 % vs. INT group, 7.62 +/- 1.20 %, the initial HbA1c level was 7.80 +/- 1.42 % for the CON group and 7.68 +/- 1.28 % for the INT group). Data on differences in occurrence of micro- or macrovascular complications are not yet available. Conclusions: The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention.

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  • マルチプルリスクファクター症候群の一部分症としての糖尿病性マクロアンギオパシー JDCSの中間解析からみた本邦の糖尿病大血管障害のリスクファクター

    曽根 博仁, 山田 信博

    糖尿病合併症   16 ( Suppl.1 )   50 - 50   2002.9

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  • Vascular endothelial growth factor gene expression in a retinal pigmented cell is up-regulated by glucose deprivation through 3 ' UTR

    K Iida, Y Kawakami, H Sone, H Suzuki, S Yatoh, K Isobe, K Takekoshi, N Yamada

    LIFE SCIENCES   71 ( 14 )   1607 - 1614   2002.8

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    Diabetic retinopathy is known to be worsened when hypoglycemia occurs, however the pathogenic mechanisms are not defined. Vascular endothelial growth factor (VEGF) is increased in ocular fluid with diabetic retinopathy ana linked with development of retinopathy. In this study, we examined whether glucose deficiency could upregulate VEGF levels in retinal pigmented cells. Exposure to glucose deprived medium induced 30% up-regulation of VEGF mRNA. In hypoxia, as one of the most well-known inducer of VEGF, its up-regulation mechanism is mainly due to increase of transcription of VEGF gene via hypoxia response element in 5'-untranslated region (5'-UTR). We examined the role of 5'-UTR and 3'-UTR of VEGF gene in glucose deprived conditions using luciferase assay system. 5'-UTR containing reporter vector did not show increase of activity in glucose deprived conditions in contrast to the result in oxygen deprived condition. Both 5'-UTR and 3'-UTR containing vector demonstrated significant increase of activity in glucose deficient conditions compared with 5'-UTR containing vector. These findings suggest 3'-UTR of VEGF gene is important for increasing mRNA level in glucose deprived condition. (C) 2002 Elsevier Science Inc. All rights reserved.

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  • Vascular endothelial growth factor gene expression in a retinal pigmented cell is up-regulated by glucose deprivation through 3 ' UTR

    K Iida, Y Kawakami, H Sone, H Suzuki, S Yatoh, K Isobe, K Takekoshi, N Yamada

    LIFE SCIENCES   71 ( 14 )   1607 - 1614   2002.8

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    Diabetic retinopathy is known to be worsened when hypoglycemia occurs, however the pathogenic mechanisms are not defined. Vascular endothelial growth factor (VEGF) is increased in ocular fluid with diabetic retinopathy ana linked with development of retinopathy. In this study, we examined whether glucose deficiency could upregulate VEGF levels in retinal pigmented cells. Exposure to glucose deprived medium induced 30% up-regulation of VEGF mRNA. In hypoxia, as one of the most well-known inducer of VEGF, its up-regulation mechanism is mainly due to increase of transcription of VEGF gene via hypoxia response element in 5'-untranslated region (5'-UTR). We examined the role of 5'-UTR and 3'-UTR of VEGF gene in glucose deprived conditions using luciferase assay system. 5'-UTR containing reporter vector did not show increase of activity in glucose deprived conditions in contrast to the result in oxygen deprived condition. Both 5'-UTR and 3'-UTR containing vector demonstrated significant increase of activity in glucose deficient conditions compared with 5'-UTR containing vector. These findings suggest 3'-UTR of VEGF gene is important for increasing mRNA level in glucose deprived condition. (C) 2002 Elsevier Science Inc. All rights reserved.

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  • Glucose uptake and adenoviral mediated GLUT1 infection decrease hypoxia-induced HIF-1 alpha levels in cardiac myocytes

    R Malhotra, DGW Tyson, H Sone, K Aoki, AK Kumagai, FC Brosius

    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY   34 ( 8 )   1063 - 1073   2002.8

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    Hypoxia causes a large array of adaptive and physiological responses in all cells including cardiac myocytes. In order to elucidate the molecular effects ofincreased glucose flux on hypoxic cardiac myocytes we focused on the basic helix-loop-helix transcription factor, hypoxia inducible factor 1 alpha (HIF-1alpha), which is rapidly upregulated in hypoxic cells and elicits a number of responses including augmentation of glucose uptake. Primary cultures of neonatal rat cardiac myocytes as well as embryonic rat heart-derived myogenic H9c2 cells demonstrated a significant upregulation of HIF-1alpha when subjected to hypoxia of 6-8 h in the absence of glucose. Re-addition of extracellular glucose to the medium resulted in a decrease of HIF-1alpha levels by almost 50%. This glucose effect was blocked by addition of glycolytic inhibitors. In addition, glucose uptake and glycolysis resulted in substantial decreased levels of p53, which is regulated by HIF-1alpha. Adenoviral infection of cultures of cardiac myocytes with the facilitative glucose transporter, GLUT1 followed by hypoxia of 24 h also resulted in a significant reduction in the protein expression of HIF-1alpha compared to control vector-infected cultures. GLUT1 infected cultures also demonstrated fewer apoptotic cells and a reduction in the release of cytochrome c after hypoxia. Inhibition of the ubiquitin-proteasomal pathway by a variety of 26S proteasomal inhibitors increased HIF-1alpha to similar levels under both normoxic and hypoxic conditions and in the presence or absence of glucose. This result suggested that glucose induces HIF-1alpha degradation via a proteasomal pathway. This conclusion was substantiated by immuneprecipitation experiments of total cell extracts, which demonstrated an increase of ubiquitinated HIF-1a relative to total HIF-1alpha in the presence of glucose during hypoxia. Thus, glucose as well as GLUT1 overexpression diminishes hypoxia-incluced HIF-1alpha protein via an ubiquitin-proteasomal pathway in hypoxic cardiac myocytes. This represents a novel feedback mechanism that may play an important role in adaptation of cardiac myocytes to hypoxia and ischemia. (C) 2002 Elsevier Science Ltd. All rights reserved.

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  • Glucose uptake and adenoviral mediated GLUT1 infection decrease hypoxia-induced HIF-1 alpha levels in cardiac myocytes

    R Malhotra, DGW Tyson, H Sone, K Aoki, AK Kumagai, FC Brosius

    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY   34 ( 8 )   1063 - 1073   2002.8

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    Hypoxia causes a large array of adaptive and physiological responses in all cells including cardiac myocytes. In order to elucidate the molecular effects ofincreased glucose flux on hypoxic cardiac myocytes we focused on the basic helix-loop-helix transcription factor, hypoxia inducible factor 1 alpha (HIF-1alpha), which is rapidly upregulated in hypoxic cells and elicits a number of responses including augmentation of glucose uptake. Primary cultures of neonatal rat cardiac myocytes as well as embryonic rat heart-derived myogenic H9c2 cells demonstrated a significant upregulation of HIF-1alpha when subjected to hypoxia of 6-8 h in the absence of glucose. Re-addition of extracellular glucose to the medium resulted in a decrease of HIF-1alpha levels by almost 50%. This glucose effect was blocked by addition of glycolytic inhibitors. In addition, glucose uptake and glycolysis resulted in substantial decreased levels of p53, which is regulated by HIF-1alpha. Adenoviral infection of cultures of cardiac myocytes with the facilitative glucose transporter, GLUT1 followed by hypoxia of 24 h also resulted in a significant reduction in the protein expression of HIF-1alpha compared to control vector-infected cultures. GLUT1 infected cultures also demonstrated fewer apoptotic cells and a reduction in the release of cytochrome c after hypoxia. Inhibition of the ubiquitin-proteasomal pathway by a variety of 26S proteasomal inhibitors increased HIF-1alpha to similar levels under both normoxic and hypoxic conditions and in the presence or absence of glucose. This result suggested that glucose induces HIF-1alpha degradation via a proteasomal pathway. This conclusion was substantiated by immuneprecipitation experiments of total cell extracts, which demonstrated an increase of ubiquitinated HIF-1a relative to total HIF-1alpha in the presence of glucose during hypoxia. Thus, glucose as well as GLUT1 overexpression diminishes hypoxia-incluced HIF-1alpha protein via an ubiquitin-proteasomal pathway in hypoxic cardiac myocytes. This represents a novel feedback mechanism that may play an important role in adaptation of cardiac myocytes to hypoxia and ischemia. (C) 2002 Elsevier Science Ltd. All rights reserved.

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  • Acetoacetyl-coenzyme a synthetase (AACAS) is a lipogenic enzyme modulated by sterol regulatory element-binding proteins and diabetes

    H Sone, H Shimano, A Takahashi, N Inoue, M Taguchi, H Toyoshima, Y Okuda, N Yamada

    DIABETES   51   A332 - A332   2002.6

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  • Cloning and characterization of a mammalian fatty acyl-CoA elongase as a lipogenic enzyme regulated by SREBPs

    T Matsuzaka, H Shimano, N Yahagi, T Yoshikawa, M Amemiya-Kudo, AH Hasty, H Okazaki, Y Tamura, Y Iizuka, K Ohashi, J Osuga, A Takahashi, S Yato, H Sone, S Ishibashi, N Yamada

    JOURNAL OF LIPID RESEARCH   43 ( 6 )   911 - 920   2002.6

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    The mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following the building of fatty acids to 16 carbons by fatty acid synthase has yet to be identified. In the process of searching for genes activated by sterol regulatory element-binding protein 1 (SREBP-1) by using DNA microarray, we identified and characterized a murine cDNA clone that is highly similar to a fatty acyl-CoA elongase gene family such as Cig30, Sscs, and yeast ELOs. Studies on the cells overexpressing the full length cDNA indicate that the encoded protein, designated fatty acyl-CoA ellongase (FACE), has a FACE activity specific for long-chains; C12-C16 saturated-and monosaturated-fatty acids. Hepatic expression of this identified gene was consistently activated in the livers of transgenic mice overexpressing nuclear SREBP-1a, -1c, or -2. FACE mRNA levels are markedly induced in a refed state after fasting in the liver and adipose tissue. This refeeding response is significantly reduced in SREBP-1 deficient mice. Dietary PUFAs caused a profound suppression of this gene expression, which could be restored by SREBP-1c overexpression. Hepatic FACE expression was also highly up-regulated in leptin-deficient ob/ob mice. Hepatic FACE mRNA was markedly increased by administration of a pharmacological agonist of liver X-activated receptor (LXR), a dominant activator for SREBP-1c expression. These data indicated that this elongase is a new member of mammalian lipogenic enzymes regulated by SREBP-1, playing an important role in de novo synthesis of long-chain saturated and monosaturated fatty acids in conjunction with fatty acid synthase and stearoyl-CoA desaturase.

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  • Acute gliclazide administration enhances glucose and ketone body utilization in the perfused hind limb of normal and streptozotocin-diabetic rats

    Y Okuda, K Kobayashi, H Ohmori, H Sone, S Suzuki, J Ma, T Nakajima, N Yamada, K Yamashita

    LIFE SCIENCES   71 ( 6 )   647 - 654   2002.6

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    Sulfonylureas are the most commonly used oral hypoglycemic agents. Their hypoglycemic actions are produced not only by stimulating insulin secretion but also by extrapancreatic mechanisms. Some groups have already demonstrated the extrapancreatic actions of sulfonylureas on carbohydrate metabolism in the liver, fat and muscle. In this study, we showed in an in situ perfused hind limb preparation of STZ-diabetic rats that gliclazide has an acute effect on ketone body and glucose utilization. (C) 2002 Elsevier Science Inc. All rights reserved.

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  • PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages

    KT Iida, Y Kawakami, H Suzuki, H Sone, H Shimano, H Toyoshima, Y Okuda, N Yamada

    FEBS LETTERS   520 ( 1-3 )   177 - 181   2002.6

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    Recently it has been reported that macrophages express a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma). Using a ligand of PPARgamma, troglitazone or pioglitazone, we have shown that the expression of two genes involved in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, were increased by activation of PPARgamma through a PPAR response element (PPRE) in THP-1 macrophages. In addition, treatment with troglitazone significantly increased the activity of HMG-CoA reductase and the amount of intracellular cholesterol. Thus, we conclude that PPARgamma and its agonists increase the cholesterol content of macrophages by the increased expression of genes involved in cholesterol biosynthesis. These findings suggest that PPARgamma may play a role in cholesterol metabolism in macrophages. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

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  • PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages

    KT Iida, Y Kawakami, H Suzuki, H Sone, H Shimano, H Toyoshima, Y Okuda, N Yamada

    FEBS LETTERS   520 ( 1-3 )   177 - 181   2002.6

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    Recently it has been reported that macrophages express a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma). Using a ligand of PPARgamma, troglitazone or pioglitazone, we have shown that the expression of two genes involved in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, were increased by activation of PPARgamma through a PPAR response element (PPRE) in THP-1 macrophages. In addition, treatment with troglitazone significantly increased the activity of HMG-CoA reductase and the amount of intracellular cholesterol. Thus, we conclude that PPARgamma and its agonists increase the cholesterol content of macrophages by the increased expression of genes involved in cholesterol biosynthesis. These findings suggest that PPARgamma may play a role in cholesterol metabolism in macrophages. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

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  • Cloning and characterization of a mammalian fatty acyl-CoA elongase as a lipogenic enzyme regulated by SREBPs

    T Matsuzaka, H Shimano, N Yahagi, T Yoshikawa, M Amemiya-Kudo, AH Hasty, H Okazaki, Y Tamura, Y Iizuka, K Ohashi, J Osuga, A Takahashi, S Yato, H Sone, S Ishibashi, N Yamada

    JOURNAL OF LIPID RESEARCH   43 ( 6 )   911 - 920   2002.6

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    The mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following the building of fatty acids to 16 carbons by fatty acid synthase has yet to be identified. In the process of searching for genes activated by sterol regulatory element-binding protein 1 (SREBP-1) by using DNA microarray, we identified and characterized a murine cDNA clone that is highly similar to a fatty acyl-CoA elongase gene family such as Cig30, Sscs, and yeast ELOs. Studies on the cells overexpressing the full length cDNA indicate that the encoded protein, designated fatty acyl-CoA ellongase (FACE), has a FACE activity specific for long-chains; C12-C16 saturated-and monosaturated-fatty acids. Hepatic expression of this identified gene was consistently activated in the livers of transgenic mice overexpressing nuclear SREBP-1a, -1c, or -2. FACE mRNA levels are markedly induced in a refed state after fasting in the liver and adipose tissue. This refeeding response is significantly reduced in SREBP-1 deficient mice. Dietary PUFAs caused a profound suppression of this gene expression, which could be restored by SREBP-1c overexpression. Hepatic FACE expression was also highly up-regulated in leptin-deficient ob/ob mice. Hepatic FACE mRNA was markedly increased by administration of a pharmacological agonist of liver X-activated receptor (LXR), a dominant activator for SREBP-1c expression. These data indicated that this elongase is a new member of mammalian lipogenic enzymes regulated by SREBP-1, playing an important role in de novo synthesis of long-chain saturated and monosaturated fatty acids in conjunction with fatty acid synthase and stearoyl-CoA desaturase.

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  • Acute gliclazide administration enhances glucose and ketone body utilization in the perfused hind limb of normal and streptozotocin-diabetic rats

    Y Okuda, K Kobayashi, H Ohmori, H Sone, S Suzuki, J Ma, T Nakajima, N Yamada, K Yamashita

    LIFE SCIENCES   71 ( 6 )   647 - 654   2002.6

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    Sulfonylureas are the most commonly used oral hypoglycemic agents. Their hypoglycemic actions are produced not only by stimulating insulin secretion but also by extrapancreatic mechanisms. Some groups have already demonstrated the extrapancreatic actions of sulfonylureas on carbohydrate metabolism in the liver, fat and muscle. In this study, we showed in an in situ perfused hind limb preparation of STZ-diabetic rats that gliclazide has an acute effect on ketone body and glucose utilization. (C) 2002 Elsevier Science Inc. All rights reserved.

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  • 糖尿病性血管障害の分子機構 糖尿病の動脈硬化におけるインスリン抵抗性の意義

    島野 仁, 飯田 薫子, 高橋 昭光, 曽根 博仁, 鈴木 浩明, 豊島 秀男, 矢作 直也, 大須賀 淳一, 石橋 俊, 山田 信博

    動脈硬化   ( 34回抄集 )   111 - 111   2002.6

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  • 無痛性甲状腺炎を契機にケトアシドーシスを発症したSPIDDMの症例

    若山 直美, 豊島 秀男, 矢藤 繁, 曽根 博仁, 島野 仁, 鈴木 誠司, 奥田 諭吉, 山田 信博

    糖尿病   45 ( 6 )   432 - 432   2002.6

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  • 【生活習慣病 一次予防から治療まで】 予防 糖尿病 Japan Diabetes Complications Study(JDCS)の概要と意義

    曽根 博仁, 山田 信博, JDCStudyグループ

    最新医学   57 ( 6月増刊 )   1379 - 1388   2002.6

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    JDCSは,本邦の2型糖尿病患者において,ライフスタイル修飾を中心とした介入が,血糖コントロールと合併症発症・進展に与える影響を検討するために,平成8年度より始められた大規模前向き臨床研究である.糖尿病及びその血管合併症の発症・進展因子を明らかにするという目的もある.本研究のプロトコールと,これまで明らかになった所見について述べた

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  • 塩化アンベノニウムにより低血糖をきたしたと考えられた糖尿病の一例

    矢藤 繁, 島野 仁, 若山 直美, 斉藤 和美, 曽根 博仁, 豊島 秀男, 奥田 諭吉, 山田 信博, 鈴木 誠司, 川上 康

    糖尿病   45 ( 6 )   445 - 445   2002.6

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  • SREBPにより調節されるリポジェニック酵素 Acetoacetyl CoA Synthetase(AACAS)の解析

    曽根 博仁, 島野 仁, 高橋 昭光, 田口 美保, 井上 訓之, 横尾 友隆, 飯田 薫子, 鈴木 浩明, 豊島 秀男, 山田 信博

    動脈硬化   ( 34回抄集 )   171 - 171   2002.6

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  • マルチプルリスクファクター症候群をいかに捉えるか 糖尿病 Japan Diabetes Complications Study(JDCS)から

    曽根 博仁

    動脈硬化   ( 34回抄集 )   122 - 122   2002.6

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  • 食後高脂血症(PPHL)診断マーカー確立の試み 脂肪負荷試験(OFTT)との相関(第2報)

    曽根 博仁, 島野 仁, 高橋 昭光, 鈴木 将玄, 鈴木 浩明, 奥田 諭吉, 伊藤 佐智子, 小堀 樹一郎, 齋藤 和典, 山田 信博

    動脈硬化   ( 34回抄集 )   218 - 218   2002.6

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  • 【軽症2型糖尿病の治療戦略 インスリン分泌異常と食後高血糖からのアプローチ】 大血管障害を防ぐための積極的な早期介入 境界型・軽症2型糖尿病はなぜ動脈硬化になりやすいのか? 動脈硬化からみた治療の必要性

    曽根 博仁, 山田 信博

    Mebio   19 ( 5別冊 )   63 - 68   2002.5

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  • 脂質とインスリン分泌・作用の相互関係 SREBPとインスリン

    島野 仁, 矢作 直也, 雨宮 三千代, 曽根 博仁, 高橋 照光

    糖尿病   45 ( Suppl.2 )   S27 - S27   2002.4

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  • 【内科 100年のあゆみ(内分泌・代謝)】 主要疾患の歴史 高脂血症

    曽根 博仁, 山田 信博

    日本内科学会雑誌   91 ( 4 )   1202 - 1207   2002.4

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    DOI: 10.2169/naika.91.1202

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  • クッシング症候群におけるコルチゾール値と左室肥大との関連についての検討

    大垣 聡子, 鈴木 誠司, 鈴木 浩明, 曽根 博仁, 豊島 秀男, 島野 仁, 奥田 諭吉, 山田 信博

    日本内分泌学会雑誌   78 ( 1 )   146 - 146   2002.4

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  • 経口血糖降下剤の二次無効症例へのインスリン導入判定の検討

    菊池 浩子, 鈴木 誠司, 矢藤 繁, 曽根 博仁, 豊島 秀男, 島野 仁, 川上 康, 山田 信博

    糖尿病   45 ( Suppl.2 )   S181 - S181   2002.4

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  • マクロファージ分泌TNF-αに対するインスリンの直接作用についての検討

    飯田 薫子, 島野 仁, 高橋 昭光, 曽根 博仁, 豊島 秀男, 奥田 諭吉, 山田 信博

    糖尿病   45 ( Suppl.2 )   S174 - S174   2002.4

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  • Sterol regulatory element binding protein 1(SREBP1)トランスジェニックマウスにおける耐糖能の検討

    高橋 昭光, 島野 仁, 飯田 薫子, 小林 和人, 鈴木 将玄, 豊島 秀男, 曽根 博仁, 山田 信博

    糖尿病   45 ( Suppl.2 )   S246 - S246   2002.4

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  • 2型糖尿病(DM)患者の食後高脂血症(PPHL)診断指標 経口脂肪負荷試験(OFTT)との相関

    曽根 博仁, 島野 仁, 高橋 昭光, 鈴木 将玄, 小林 和人, 飯田 薫子, 若山 直美, 大垣 聡子, 斎藤 和美, 矢藤 繁, 鈴木 浩明, 豊島 秀男, 川上 康, 奥田 諭吉, 伊藤 佐智子, 小堀 樹一郎, 齋藤 和典, 山田 信博

    糖尿病   45 ( Suppl.2 )   S237 - S237   2002.4

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  • Cardiovascular Events in Patients with Type 2 Diabetes and Effects of Lifestyle Modifications : The Japan Diabetes Complications Study (JDCS)

    Sone Hirohito, Yamada Nobuhiro, JDCStudy Group

    Circulation journal : official journal of the Japanese Circulation Society   66   49 - 49   2002.3

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  • Insulin inhibits apoptosis of macrophage cell line, THP-1 cells, via phosphatidylinositol-3-kinase-dependent pathway

    KT Iida, H Suzuki, H Sone, H Shimano, H Toyoshima, S Yatoh, T Asano, Y Okuda, N Yamada

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   22 ( 3 )   380 - 386   2002.3

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    Hyperinsulinemia has recently been reported as a risk factor for atherosclerotic diseases such as coronary heart disease; however, its precise mechanism is not well understood. To elucidate the role of insulin in the development of atherogenesis, we have investigated the effect of insulin on cell survival in macrophages, which are known to be important in the atherosclerotic process. Apoptosis was induced in macrophage cell lines derived from human monocytes or murine macrophages by serum starvation. Insulin administration retarded macrophage apoptosis by means of DNA laddering, dimethylthiazol diphenyltetrazolium bromide assay, and annexin V binding assay. Insulin also enhanced mRNA expression and protein production of the antiapoptotic Bel-XL gene in a dose-dependent manner within the range of physiological concentrations. In the exploration of the signaling pathway involved in these antiapoptotic effects of insulin, pretreatment of cells with a specific inhibitor of phosphatidylinositol-3-kinase significantly suppressed insulin-mediated cell survival and insulin-induced Bcl-XL expression in macrophages. These data indicate that the survival effect of insulin on the apoptosis of macrophages is associated with the upregulation of Bcl-XL expression, and it may be mediated through the phosphatidylinositol-3-kinase signaling pathway. These mechanisms could be involved in the possible role of insulin in the development of atherosclerosis.

    DOI: 10.1161/hq0302.105272

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  • Insulin inhibits apoptosis of macrophage cell line, THP-1 cells, via phosphatidylinositol-3-kinase-dependent pathway

    KT Iida, H Suzuki, H Sone, H Shimano, H Toyoshima, S Yatoh, T Asano, Y Okuda, N Yamada

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   22 ( 3 )   380 - 386   2002.3

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    Hyperinsulinemia has recently been reported as a risk factor for atherosclerotic diseases such as coronary heart disease; however, its precise mechanism is not well understood. To elucidate the role of insulin in the development of atherogenesis, we have investigated the effect of insulin on cell survival in macrophages, which are known to be important in the atherosclerotic process. Apoptosis was induced in macrophage cell lines derived from human monocytes or murine macrophages by serum starvation. Insulin administration retarded macrophage apoptosis by means of DNA laddering, dimethylthiazol diphenyltetrazolium bromide assay, and annexin V binding assay. Insulin also enhanced mRNA expression and protein production of the antiapoptotic Bel-XL gene in a dose-dependent manner within the range of physiological concentrations. In the exploration of the signaling pathway involved in these antiapoptotic effects of insulin, pretreatment of cells with a specific inhibitor of phosphatidylinositol-3-kinase significantly suppressed insulin-mediated cell survival and insulin-induced Bcl-XL expression in macrophages. These data indicate that the survival effect of insulin on the apoptosis of macrophages is associated with the upregulation of Bcl-XL expression, and it may be mediated through the phosphatidylinositol-3-kinase signaling pathway. These mechanisms could be involved in the possible role of insulin in the development of atherosclerosis.

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  • SREBPが制御する新たなlipogenic酵素:アセチルCoA合成酵素の解析

    曽根 博仁, 島野 仁, 井上 訓之, 坂倉 有紀, 雨宮 三千代, 高橋 昭光, 山田 信博

    日本臨床分子医学会記録   38   44 - 44   2002.2

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  • Acetyl-coenzyme A synthetase is a lipogenic enzyme controlled by SREBP-1 and energy status Reviewed

    Hirohito Sone, Hitoshi Shimano, Yuki Sakakura, Noriyuki Inoue, Michiyo Amemiya-Kudo, Naoya Yahagi, Mitsujiro Osawa, Hiroaki Suzuki, Tomotaka Yokoo, Akimitsu Takahashi, Kaoruko Iida, Hideo Toyoshima, Atsushi Iwama, Nobuhiro Yamada

    American Journal of Physiology-Endocrinology and Metabolism   282 ( 1 )   E222 - E230   2002.1

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    DNA microarray analysis on upregulated genes in the livers from transgenic mice overexpressing nuclear sterol regulatory element-binding protein (SREBP)-1a, identified an espressed sequence tag (EST) encoding a part of murine cytosolic acetyl-coenzyme A synthetase (ACAS). Northern blot analysis of the livers from transgenic mice demonstrated that this gene was highly induced by SREBP-1a, SREBP-1c, and SREBP-2. DNA sequencing of the 5′ flanking region of the murine ACAS gene identified a sterol regulatory element with an adjacent Sp1 site. This region was shown to be responsible for SREBP binding and activation of the ACAS gene by gel shift and luciferase reporter gene assays. Hepatic and adipose tissue ACAS mRNA levels in normal mice were suppressed at fasting and markedly induced by refeeding, and this dietary regulation was nearly abolished in SREBP-1 knockout mice, suggesting that the nutritional regulation of the ACAS gene is controlled by SREBP-1. The ACAS gene was downregulated in streptozotocin-induced diabetic mice and was restored after insulin replacement, suggesting that diabetic status and insulin also regulate this gene. When acetate was administered, hepatic ACAS mRNA was negatively regulated. These data on dietary regulation and SREBP-1 control of ACAS gene expression demonstrate that ACAS is a novel hepatic lipogenic enzyme, providing further evidence that SREBP-1 and insulin control the supply of acetyl-CoA directly from cellular acetate for lipogenesis. However, its high conservation among different species and the wide range of its tissue distribution suggest that this enzyme might also play an important role in basic cellular energy metabolism.

    DOI: 10.1152/ajpendo.00189.2001

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  • Dual regulation of mouse Delta(5)- and Delta(6)-desaturase gene expression by SREBP-1 and PPAR alpha

    T Matsuzaka, H Shimano, N Yahagi, M Amemiya-Kudo, T Yoshikawa, AH Hasty, Y Tamura, J Osuga, H Okazaki, Y Iizuka, A Takahashi, H Sone, T Gotoda, S Ishibashi, N Yamada

    JOURNAL OF LIPID RESEARCH   43 ( 1 )   107 - 114   2002.1

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    In the process of seeking sterol regulatory element-binding protein 1a (SREBP-1a) target genes, we identified and cloned a cDNA clone encoding mouse Delta(5)-desaturase (D5D). The hepatic expression of D5D as well as Delta(6)-desaturase (D6D) was highly activated in transgenic mice overexpressing nuclear SREBP-1a, -1c, and -2. Disruption of the SREBP-1 gene significantly reduced the expression of both desaturases in the livers of SREBP-1-deficient mice refed after fasting. The hepatic expression of both desaturases was downregulated by dietary PUFA, which were reported to suppress SREBP-1c gene expression. Sustained expression of hepatic nuclear SREBP-1c protein in the transgenic mice abolished the PUFA suppression of both desaturases. Although these data suggested that SREBP-1c regulates D5D and D6D expression, there was no difference in either the D5D or D6D mRNA level between fasted and refed normal mouse livers, indicating a mechanism for fasting induction of both desaturases. Administration of fibrate, a pharmacological ligand for peroxisome proliferator activating receptor alpha (PPARalpha), caused a significant increase in expression of both desaturases. The data suggested that D5D and D6D expression is dually regulated by SREBP-1c and PPARalpha, two reciprocal transcription factors for fatty acid metabolism, and could be involved in lipogenic gene regulation by producing PUFA.

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  • Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements

    T Yoshikawa, H Shimano, N Yahagi, T Ide, M Amemiya-Kudo, T Matsuzaka, M Nakakuki, S Tomita, H Okazaki, Y Tamura, Y Iizuka, K Ohashi, A Takahashi, H Sone, J Osuga, T Gotoda, S Ishibashi, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 3 )   1705 - 1711   2002.1

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    Previous studies have demonstrated that polyunsaturated fatty acids (PUFAs) suppress sterol regulatory element-binding protein 1c (SREBP-1c) expression and, thus, lipogenesis. In the current study, the molecular mechanism for this suppressive effect was investigated with luciferase reporter gene assays using the SREBP-1c promoter in HEK293 cells. Consistent with previous data, the addition of PUFAs to the medium in the assays robustly inhibited the SREBP-1c promoter activity. Deletion and mutation of the two liver X receptor (LXR)-responsive elements (LXREs) in the SREBP-1c promoter region eliminated this suppressive effect, indicating that both LXREs are important PUFA-suppressive elements. The luciferase activities of both SREBP-1c promoter and LXRE enhancer constructs induced by co-expression of LXRalpha or -beta were strongly suppressed by the addition of various PUFAs (arachidonic acid &gt; eicosapentaenoic acid &gt; docosahexaenoic acid &gt; linoleic acid), whereas saturated or mono-unsaturated fatty acids had minimal effects. Gel shift mobility and ligand binding domain activation assays demonstrated that PUFA suppression of SREBP-1c expression is mediated through its competition with LXR ligand in the activation of the ligand binding domain of LXR, thereby inhibiting binding of LXP/retinoid X receptor heterodimer to the LXREs in the SREBP-le promoter. These data suggest that PUFAs could be deeply involved in nutritional regulation of cellular fatty acid levels by inhibiting an LXR-SREBP-1c system crucial for lipogenesis.

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  • Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements

    T Yoshikawa, H Shimano, N Yahagi, T Ide, M Amemiya-Kudo, T Matsuzaka, M Nakakuki, S Tomita, H Okazaki, Y Tamura, Y Iizuka, K Ohashi, A Takahashi, H Sone, J Osuga, T Gotoda, S Ishibashi, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 3 )   1705 - 1711   2002.1

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    Previous studies have demonstrated that polyunsaturated fatty acids (PUFAs) suppress sterol regulatory element-binding protein 1c (SREBP-1c) expression and, thus, lipogenesis. In the current study, the molecular mechanism for this suppressive effect was investigated with luciferase reporter gene assays using the SREBP-1c promoter in HEK293 cells. Consistent with previous data, the addition of PUFAs to the medium in the assays robustly inhibited the SREBP-1c promoter activity. Deletion and mutation of the two liver X receptor (LXR)-responsive elements (LXREs) in the SREBP-1c promoter region eliminated this suppressive effect, indicating that both LXREs are important PUFA-suppressive elements. The luciferase activities of both SREBP-1c promoter and LXRE enhancer constructs induced by co-expression of LXRalpha or -beta were strongly suppressed by the addition of various PUFAs (arachidonic acid &gt; eicosapentaenoic acid &gt; docosahexaenoic acid &gt; linoleic acid), whereas saturated or mono-unsaturated fatty acids had minimal effects. Gel shift mobility and ligand binding domain activation assays demonstrated that PUFA suppression of SREBP-1c expression is mediated through its competition with LXR ligand in the activation of the ligand binding domain of LXR, thereby inhibiting binding of LXP/retinoid X receptor heterodimer to the LXREs in the SREBP-le promoter. These data suggest that PUFAs could be deeply involved in nutritional regulation of cellular fatty acid levels by inhibiting an LXR-SREBP-1c system crucial for lipogenesis.

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  • Dual regulation of mouse Delta(5)- and Delta(6)-desaturase gene expression by SREBP-1 and PPAR alpha

    T Matsuzaka, H Shimano, N Yahagi, M Amemiya-Kudo, T Yoshikawa, AH Hasty, Y Tamura, J Osuga, H Okazaki, Y Iizuka, A Takahashi, H Sone, T Gotoda, S Ishibashi, N Yamada

    JOURNAL OF LIPID RESEARCH   43 ( 1 )   107 - 114   2002.1

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    In the process of seeking sterol regulatory element-binding protein 1a (SREBP-1a) target genes, we identified and cloned a cDNA clone encoding mouse Delta(5)-desaturase (D5D). The hepatic expression of D5D as well as Delta(6)-desaturase (D6D) was highly activated in transgenic mice overexpressing nuclear SREBP-1a, -1c, and -2. Disruption of the SREBP-1 gene significantly reduced the expression of both desaturases in the livers of SREBP-1-deficient mice refed after fasting. The hepatic expression of both desaturases was downregulated by dietary PUFA, which were reported to suppress SREBP-1c gene expression. Sustained expression of hepatic nuclear SREBP-1c protein in the transgenic mice abolished the PUFA suppression of both desaturases. Although these data suggested that SREBP-1c regulates D5D and D6D expression, there was no difference in either the D5D or D6D mRNA level between fasted and refed normal mouse livers, indicating a mechanism for fasting induction of both desaturases. Administration of fibrate, a pharmacological ligand for peroxisome proliferator activating receptor alpha (PPARalpha), caused a significant increase in expression of both desaturases. The data suggested that D5D and D6D expression is dually regulated by SREBP-1c and PPARalpha, two reciprocal transcription factors for fatty acid metabolism, and could be involved in lipogenic gene regulation by producing PUFA.

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  • A Case of Diabetic Patient with Intramuscular Abscess, Cholecystitis, and Erythroderma

    KOBAYASHI K., SUZUKI S., MIURA M., TAKAHASHI A., MIZUTANI M., SHIMANO H., SONE H., TOYOSHIMA H., KAWAKAMI Y., OKUDA Y., YAMADA N.

    Journal of the Japan Diabetes Society   45 ( 11 )   797 - 802   2002

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  • 誌上討論 症例再提示 頭部打撲後に低ナトリウム血症をきたした1例

    山田 浩, 角 誠二郎, 佐藤 正, 狩野 孝之, 佐原 正起, 高橋 昭光, 曽根 博仁, 佐藤 一俊, 左川 均, 松田 彰

    内科専門医会誌   13 ( 4 )   737 - 757   2001.11

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  • つくば健康科学フォーラム2000

    曽根 博仁, 奥田 諭吉

    臨床スポーツ医学 = The journal of clinical sports medicine   18 ( 10 )   1191 - 1192   2001.10

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  • Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor

    AH Hasty, H Shimano, J Osuga, Namatame, I, A Takahashi, N Yahagi, S Perrey, Y Iizuka, Y Tamura, M Amemiya-Kudo, T Yoshikawa, H Okazaki, K Ohashi, K Harada, T Matsuzaka, H Sone, T Gotoda, R Nagai, S Ishibashi, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 40 )   37402 - 37408   2001.10

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    Leptin-deficient mice (ob/ob) are an excellent murine model for obesity, insulin resistance, and diabetes, all of which are components of a multiple risk factor syndrome that, along with hypercholesterolemia, precipitates a potential high risk for atherosclerosis. In the current study, we show an unexpectedly severe hyperlipidemia in ob/ob mice on a background of low density lipoprotein receptor (LDLR) deficiency (-/-). Doubly mutant mice (LDLR-/-; ob/ob) exhibited striking elevations in both total plasma cholesterol (TC) and triglyceride (TG) levels (1715 +/- 87 and 1016 +/- 172 mg/dl, respectively), at age 3-4 months, resulting in extensive atherosclerotic lesions throughout the aorta by 6 months. Lipoprotein analyses revealed the elevated TC and TG levels to be due to a large increase in an apoB-containing broad-beta remnant lipoprotein fraction. While fasting, diet restriction, and low level leptin treatment significantly lowered TG levels, they caused only slight changes in TC levels. Hepatic cholesterol and triglyceride contents as well as mRNA levels of cholesterologenic and lipogenic enzymes suggest that leptin deficiency increased hepatic triglyceride production but did not change cholesterol production in ob/ob mice regardless of their LDLR genotype. These data provide evidence that the hypertriglyceridemia and hypercholesterolemia in the doubly mutant mice are caused by distinct mechanisms and point to the possibility that leptin might have some impact on plasma cholesterol metabolism, possibly through an LDLR-independent pathway. This model will be an excellent tool for future studies on the relationship between impaired fuel metabolism, increased plasma remnant lipoproteins, diabetes, and atherosclerosis.

    DOI: 10.1074/jbc.M010176200

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  • Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor

    AH Hasty, H Shimano, J Osuga, Namatame, I, A Takahashi, N Yahagi, S Perrey, Y Iizuka, Y Tamura, M Amemiya-Kudo, T Yoshikawa, H Okazaki, K Ohashi, K Harada, T Matsuzaka, H Sone, T Gotoda, R Nagai, S Ishibashi, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 40 )   37402 - 37408   2001.10

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    Leptin-deficient mice (ob/ob) are an excellent murine model for obesity, insulin resistance, and diabetes, all of which are components of a multiple risk factor syndrome that, along with hypercholesterolemia, precipitates a potential high risk for atherosclerosis. In the current study, we show an unexpectedly severe hyperlipidemia in ob/ob mice on a background of low density lipoprotein receptor (LDLR) deficiency (-/-). Doubly mutant mice (LDLR-/-; ob/ob) exhibited striking elevations in both total plasma cholesterol (TC) and triglyceride (TG) levels (1715 +/- 87 and 1016 +/- 172 mg/dl, respectively), at age 3-4 months, resulting in extensive atherosclerotic lesions throughout the aorta by 6 months. Lipoprotein analyses revealed the elevated TC and TG levels to be due to a large increase in an apoB-containing broad-beta remnant lipoprotein fraction. While fasting, diet restriction, and low level leptin treatment significantly lowered TG levels, they caused only slight changes in TC levels. Hepatic cholesterol and triglyceride contents as well as mRNA levels of cholesterologenic and lipogenic enzymes suggest that leptin deficiency increased hepatic triglyceride production but did not change cholesterol production in ob/ob mice regardless of their LDLR genotype. These data provide evidence that the hypertriglyceridemia and hypercholesterolemia in the doubly mutant mice are caused by distinct mechanisms and point to the possibility that leptin might have some impact on plasma cholesterol metabolism, possibly through an LDLR-independent pathway. This model will be an excellent tool for future studies on the relationship between impaired fuel metabolism, increased plasma remnant lipoproteins, diabetes, and atherosclerosis.

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  • Elevated levels of vascular endothelial growth factor in the sera of patients with rheumatoid arthritis - Correlation with disease activity

    H Sone, M Sakauchi, A Takahashi, H Suzuki, N Inoue, K Iida, H Shimano, H Toyoshima, Y Kawakami, Y Okuda, K Matsuo, N Yamada

    LIFE SCIENCES   69 ( 16 )   1861 - 1869   2001.9

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    To evaluate vascular endothelial growth factor (VEGF) levels in relation to disease activity in rheumatoid arthritis (RA), VEGF in the serum of 155 patients with RA and 75 healthy control subjects was quantified by our highly sensitive enzyme-linked immunosorbent assay. VEGF levels were found to correlate with the articular index (AI) and Lansbury's activity index (LI). Patients with RA had a mean serum VEGF concentration of 153.5 +/- 111.8 pg/ml, which was significantly higher than control subjects (104.8 +/- 65.7 pg/ml; P&lt;0.01). VEGF concentration was elevated significantly according to disease progression as expressed by stages I to IV and correlated with AI (r=0.530, P&lt;0.0001) and LI (r=0.688, P&lt;0.0001) in stages I and II as well as with the conventional erythrocyte sedimentation rate or serum C-reactive protein concentration. Serum VEGF levels may therefore be valuable as a marker of disease activity in patients with early RA, and this cytokine may play a significant role in the pathophysiology of RA. (C) 2001 Elsevier Science Inc. All rights reserved.

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  • Elevated levels of vascular endothelial growth factor in the sera of patients with rheumatoid arthritis - Correlation with disease activity

    H Sone, M Sakauchi, A Takahashi, H Suzuki, N Inoue, K Iida, H Shimano, H Toyoshima, Y Kawakami, Y Okuda, K Matsuo, N Yamada

    LIFE SCIENCES   69 ( 16 )   1861 - 1869   2001.9

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    To evaluate vascular endothelial growth factor (VEGF) levels in relation to disease activity in rheumatoid arthritis (RA), VEGF in the serum of 155 patients with RA and 75 healthy control subjects was quantified by our highly sensitive enzyme-linked immunosorbent assay. VEGF levels were found to correlate with the articular index (AI) and Lansbury's activity index (LI). Patients with RA had a mean serum VEGF concentration of 153.5 +/- 111.8 pg/ml, which was significantly higher than control subjects (104.8 +/- 65.7 pg/ml; P&lt;0.01). VEGF concentration was elevated significantly according to disease progression as expressed by stages I to IV and correlated with AI (r=0.530, P&lt;0.0001) and LI (r=0.688, P&lt;0.0001) in stages I and II as well as with the conventional erythrocyte sedimentation rate or serum C-reactive protein concentration. Serum VEGF levels may therefore be valuable as a marker of disease activity in patients with early RA, and this cytokine may play a significant role in the pathophysiology of RA. (C) 2001 Elsevier Science Inc. All rights reserved.

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  • Thrombospondin-1によるグリオーマ血管新生の制御

    高野 晋吾, 曽根 博仁, 坪井 康次, 松村 明, 能勢 忠男, 三井 洋司

    日本癌学会総会記事   60回   456 - 456   2001.9

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  • Sterol regulatory element-binding proteins induce an entire pathway of cholesterol synthesis

    Y Sakakura, H Shimano, H Sone, A Takahashi, K Inoue, H Toyoshima, S Suzuki, N Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   286 ( 1 )   176 - 183   2001.8

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    To evaluate the effects of sterol regulatory element-binding proteins (SREBPs) on the expression of the individual enzymes in the cholesterol synthetic pathway, we examined expression of these genes in the livers from wild-type and transgenic mice overexpressing nuclear SREBP-1a or -2. As estimated by a Northern blot analysis, overexpression of nuclear SREBP-1a or -2 caused marked increases in mRNA levels of the whole battery of cholesterogenic genes. This SREBP activation covers not only rate-limiting enzymes such as HMG CoA synthase and reductase that have been well established as SREBP targets, but also all the enzyme genes in the cholesterol synthetic pathway tested here. The activated genes include mevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl phosphate isomerase, geranylgeranyl pyrophosphate synthase, farnesyl pyrophosphate synthase, squalene synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and 7-dehydro-cholesterol reductase. These results demonstrate that SREBPs activate every step of cholesterol synthetic pathway, contributing to an efficient cholesterol synthesis. (C) 2001 Academic Press.

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  • Sterol regulatory element-binding proteins induce an entire pathway of cholesterol synthesis

    Y Sakakura, H Shimano, H Sone, A Takahashi, K Inoue, H Toyoshima, S Suzuki, N Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   286 ( 1 )   176 - 183   2001.8

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    To evaluate the effects of sterol regulatory element-binding proteins (SREBPs) on the expression of the individual enzymes in the cholesterol synthetic pathway, we examined expression of these genes in the livers from wild-type and transgenic mice overexpressing nuclear SREBP-1a or -2. As estimated by a Northern blot analysis, overexpression of nuclear SREBP-1a or -2 caused marked increases in mRNA levels of the whole battery of cholesterogenic genes. This SREBP activation covers not only rate-limiting enzymes such as HMG CoA synthase and reductase that have been well established as SREBP targets, but also all the enzyme genes in the cholesterol synthetic pathway tested here. The activated genes include mevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl phosphate isomerase, geranylgeranyl pyrophosphate synthase, farnesyl pyrophosphate synthase, squalene synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and 7-dehydro-cholesterol reductase. These results demonstrate that SREBPs activate every step of cholesterol synthetic pathway, contributing to an efficient cholesterol synthesis. (C) 2001 Academic Press.

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  • Insulin up-regulates tumor necrosis factor-alpha production in macrophages through an extracellular-regulated kinase-dependent pathway

    KT Iida, H Shimano, Y Kawakami, H Sone, H Toyoshima, S Suzuki, T Asano, Y Okuda, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 35 )   32531 - 32537   2001.8

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    Hyperinsulinemia has recently been reported as a risk factor for atherosclerotic diseases such as coronary heart disease; however, the effect of insulin on the development of atherosclerosis is not well understood. Here we have investigated the direct effect of insulin on macrophages, which are known to be important in the atherosclerotic process. We treated THP-1 macrophages with insulin (10(-7) M) and examined the gene expression using nucleic acid array systems. The results of array analysis showed that insulin stimulated gene expression of tumor necrosis factor-alpha (TNF-alpha) the most among all genes in the analysis. In addition, insulin administration to macrophages enhanced both mRNA expression and protein secretion of TNF-alpha in a dose-dependent manner. To determine the signaling pathway involved in this TNF-alpha response to insulin, we pretreated. the cells with three distinct protein kinase inhibitors: wortmannin, PD98059, and SB203580. Only PD98059, which inhibits extracellular signal-regulated kinases, suppressed insulin-induced production of TNF-alpha mRNA and protein in THP-1 macrophages. These observations indicate that insulin stimulates TNF-alpha production in macrophages by regulating the expression of TNF-alpha mRNA and that the extracellular signal-regulated kinase signaling pathway may have a critical role in stimulating the production of TNF-alpha in response to insulin in macrophages.

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  • Insulin up-regulates tumor necrosis factor-alpha production in macrophages through an extracellular-regulated kinase-dependent pathway

    KT Iida, H Shimano, Y Kawakami, H Sone, H Toyoshima, S Suzuki, T Asano, Y Okuda, N Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 35 )   32531 - 32537   2001.8

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    Hyperinsulinemia has recently been reported as a risk factor for atherosclerotic diseases such as coronary heart disease; however, the effect of insulin on the development of atherosclerosis is not well understood. Here we have investigated the direct effect of insulin on macrophages, which are known to be important in the atherosclerotic process. We treated THP-1 macrophages with insulin (10(-7) M) and examined the gene expression using nucleic acid array systems. The results of array analysis showed that insulin stimulated gene expression of tumor necrosis factor-alpha (TNF-alpha) the most among all genes in the analysis. In addition, insulin administration to macrophages enhanced both mRNA expression and protein secretion of TNF-alpha in a dose-dependent manner. To determine the signaling pathway involved in this TNF-alpha response to insulin, we pretreated. the cells with three distinct protein kinase inhibitors: wortmannin, PD98059, and SB203580. Only PD98059, which inhibits extracellular signal-regulated kinases, suppressed insulin-induced production of TNF-alpha mRNA and protein in THP-1 macrophages. These observations indicate that insulin stimulates TNF-alpha production in macrophages by regulating the expression of TNF-alpha mRNA and that the extracellular signal-regulated kinase signaling pathway may have a critical role in stimulating the production of TNF-alpha in response to insulin in macrophages.

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  • SREBPが制御する新たなlipogenic酵素:Acetyl CoA合成酵素の解析

    曽根 博仁, 島野 仁, 井上 訓之, 坂倉 有紀, 雨宮 三千代, 高橋 昭光, 山田 信博

    日本臨床分子医学会学術総会プログラム・抄録集   38回   48 - 48   2001.8

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  • Disease model: hyperinsulinemia and insulin resistance - Part A - targeted disruption of insulin signaling or glucose transport

    H Sone, H Suzuki, A Takahashi, N Yamada

    TRENDS IN MOLECULAR MEDICINE   7 ( 7 )   320 - 322   2001.7

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    Insulin resistance and hyperinsulinemia are common pathophysiological features of several metabolic diseases, obesity and diabetes being two notable examples. In this article we review how the use of animal models has increased our understanding of insulin resistance and hyperinsulinemia, with a particular emphasis on the use of mice with targeted disruptions of the insulin signaling pathway.

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  • 多彩な症状を呈するpost-treatment neuropathyをきたした1型糖尿病の一例

    鈴木 將玄, 鈴木 誠司, 大垣 聡子, 曽根 博仁, 豊島 秀男, 島野 仁, 奥田 諭吉, 山田 信博

    糖尿病   44 ( 7 )   594 - 594   2001.7

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  • 骨髄炎をきたした糖尿病壊疽を画像評価し,保存的療法で改善をみた一例

    大垣 聡子, 鈴木 誠司, 鈴木 將玄, 曽根 博仁, 豊島 秀男, 島野 仁, 奥田 諭吉, 山田 信博

    糖尿病   44 ( 7 )   595 - 595   2001.7

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  • Plasma mannose levels in patients with diabetes mellitus and their clinical significance

    H Sone, H Shimano, A Takahashi, Y Kawakami, Y Okuda, H Ebinuma, K Saitoh, N Yamada

    DIABETES   50   A426 - A426   2001.6

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  • Acetyl-coenzyme a synthetase is a new lipogenic enzyme controlled by sterol regulatory element-finding proteins and influenced by diabetes

    H Sone, L Shimano, N Inoue, Y Sakakura, M Amemiya, A Takahashi, M Osawa, A Iwama, N Yamada

    DIABETES   50   A407 - A407   2001.6

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  • Gastric distension-induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat

    T Ishiguchi, M Nakajima, H Sone, H Tada, AK Kumagai, T Takahashi

    JOURNAL OF PHYSIOLOGY-LONDON   533 ( 3 )   801 - 813   2001.6

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    1. The pylorus plays an important role in the regulation of gastric emptying. In addition to the autonomic neuropathy associated with long-standing diabetes, acute hyperglycaemia per se has effects on gastric emptying. In this study, the role of the central nervous system in modulating the effects of hyperglycaemia on gastric distension-induced pyloric relaxation was investigated.
    2. Gastric distension-induced pyloric relaxation was significantly reduced by subdiaphragmatic vagotomy, hexamethonium (20 mg kg(-1)) and N-G-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1)), a nitric oxide synthase (NOX) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanchnectomy nor guanethidine (5 mg kg(-1)) had an effect.
    3. An intravenous (I.V.) infusion of D-glucose (20 %) for 30 min, which increased blood glucose concentrations from 5.4 to 12.8 mM, significantly inhibited gastric distension-induced pyloric relaxation.
    4. An intracerebroventricular (I.C.V.) injection of D-glucose (3 mu mol) also significantly inhibited gastric distension-induced pyloric relaxation without affecting peripheral blood glucose concentrations.
    5. I.V. infusion of D-glucose significantly elevated hypothalamic neuropeptide Y (NPY) concentrations.
    6. Intracerebroventricular (I.C.V.) administration of NPY (0.03-3 nmol) and a Y1 receptor agonist, [leu(31), pro(34)] Npy (0.03-3 nmol), significantly inhibited gastric distension-induced pyloric relaxation in a dose-dependent manner.
    7. I.C.V. administration of a Y1 receptor antagonist, BIBP 3226 (30 nmol), and of a NPY antibody (titre 1:24 000, 3 mul) abolished the inhibitory effects of hyperglycaemia on gastric distension-induced pyloric relaxation.
    8. Taken together, these findings suggest that gastric distension-induced pyloric relaxation is mediated via a vago-vagal reflex and NO release. Acute hyperglycaemia stimulates hypothalamic NPY release, which, acting through the Y1 receptor, inhibits gastric distension-induced pyloric relaxation in rats exposed to acute elevations in blood glucose concentrations.

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  • Gastric distension-induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat

    T Ishiguchi, M Nakajima, H Sone, H Tada, AK Kumagai, T Takahashi

    JOURNAL OF PHYSIOLOGY-LONDON   533 ( 3 )   801 - 813   2001.6

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    1. The pylorus plays an important role in the regulation of gastric emptying. In addition to the autonomic neuropathy associated with long-standing diabetes, acute hyperglycaemia per se has effects on gastric emptying. In this study, the role of the central nervous system in modulating the effects of hyperglycaemia on gastric distension-induced pyloric relaxation was investigated.
    2. Gastric distension-induced pyloric relaxation was significantly reduced by subdiaphragmatic vagotomy, hexamethonium (20 mg kg(-1)) and N-G-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1)), a nitric oxide synthase (NOX) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanchnectomy nor guanethidine (5 mg kg(-1)) had an effect.
    3. An intravenous (I.V.) infusion of D-glucose (20 %) for 30 min, which increased blood glucose concentrations from 5.4 to 12.8 mM, significantly inhibited gastric distension-induced pyloric relaxation.
    4. An intracerebroventricular (I.C.V.) injection of D-glucose (3 mu mol) also significantly inhibited gastric distension-induced pyloric relaxation without affecting peripheral blood glucose concentrations.
    5. I.V. infusion of D-glucose significantly elevated hypothalamic neuropeptide Y (NPY) concentrations.
    6. Intracerebroventricular (I.C.V.) administration of NPY (0.03-3 nmol) and a Y1 receptor agonist, [leu(31), pro(34)] Npy (0.03-3 nmol), significantly inhibited gastric distension-induced pyloric relaxation in a dose-dependent manner.
    7. I.C.V. administration of a Y1 receptor antagonist, BIBP 3226 (30 nmol), and of a NPY antibody (titre 1:24 000, 3 mul) abolished the inhibitory effects of hyperglycaemia on gastric distension-induced pyloric relaxation.
    8. Taken together, these findings suggest that gastric distension-induced pyloric relaxation is mediated via a vago-vagal reflex and NO release. Acute hyperglycaemia stimulates hypothalamic NPY release, which, acting through the Y1 receptor, inhibits gastric distension-induced pyloric relaxation in rats exposed to acute elevations in blood glucose concentrations.

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  • ヒト血管内皮細胞のNitric oxide,ET-1産生に対するEicosapentaenoic acidの影響

    知崎 圭吾, 奥田 諭吉, 曽根 博仁, 鈴木 誠司, 山田 信博

    動脈硬化   29 ( Suppl. )   254 - 254   2001.5

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  • 【高脂血症診療のエビデンス】 糖・脂質・エネルギー代謝の転写調節

    曽根 博仁, 山田 信博

    カレントテラピー   19 ( 6 )   749 - 753   2001.5

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    糖・脂質・エネルギー代謝関連の遺伝子は主に転写調節により,mRNAレベルで調節を受けており,MODYにおける転写因子異常のように代謝疾患とも深く関与している.SREBP,PPAR,C/EBP等の転写因子を介した糖代謝と脂質代謝の相互関連,特に糖尿病,肥満,高脂血症や高血圧等の背景的病態ともいえるインスリン抵抗性と脂肪細胞分化との関係などが,近年徐々に解明されつつある.将来的には,転写調節によるエネルギー代謝の包括的調節機構の全容把握,及びこのシステムの破綻である糖尿病,肥満,高脂血症や高血圧等の病態解明,更には代謝関連遺伝子の転写調節に直接介入する治療法の開発などが期待される

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  • 【内分泌代謝 糖尿病合併症の治療 動脈硬化予防のためのABC】 脳血管障害のマネージメント

    曽根 博仁, 山田 信博

    Mebio   18 ( 5 )   13 - 18   2001.5

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  • SREBPにより調節される新たなlipogenic enzyme Acetyl CoA Synthetaseの解析

    曽根 博仁, 島野 仁, 井上 訓之, 坂倉 有紀, 雨宮 三千代, 高橋 昭光, 飯田 薫子, 豊島 秀男, 鈴木 誠司, 山田 信博

    動脈硬化   29 ( Suppl. )   260 - 260   2001.5

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  • ヒト血管内皮細胞のNitric oxide,ET-1産生に対する多価不飽和脂肪酸の新しい薬理活性

    知崎 圭吾, 奥田 諭吉, 浅野 道子, 高橋 昭光, 矢藤 繁, 曽根 博仁, 鈴木 誠司, 山田 信博

    日本内分泌学会雑誌   77 ( 1 )   150 - 150   2001.4

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  • 糖尿病患者における血中D-マンノース値の臨床的意義

    曽根 博仁, 島野 仁, 高橋 昭光, 三浦 光弘, 小林 和人, 飯田 薫子, 若山 直美, 斎藤 和美, 大垣 聡子, 豊島 秀男

    日本内分泌学会雑誌   77 ( 1 )   80 - 80   2001.4

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  • 異所性ACTH症候群との鑑別が困難であったCushing病の一例

    鈴木 將玄, 鈴木 誠司, 大垣 聡子, 曽根 博仁, 豊島 秀男, 島野 仁, 奥田 諭吉, 山田 信博

    日本内分泌学会雑誌   77 ( 1 )   144 - 144   2001.4

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  • マクロファージに対するインスリンの作用についての基礎的検討

    飯田 薫子, 川上 康, 島野 仁, 曽根 博仁, 豊島 秀男, 鈴木 誠司, 奥田 諭吉, 山田 信博

    日本内分泌学会雑誌   77 ( 1 )   134 - 134   2001.4

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  • 食後高脂血症マーカー確立の試み 脂肪負荷試験との相関

    曽根 博仁, 山田 信博

    健康医科学研究助成論文集   16 ( 16 )   102 - 107   2001.3

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    空腹時アポCII,CIIIは,食後TGレベルやRLP-Cレベルと比較べた時,試験食を必要とせず空腹時の濃度から脂肪負荷後のTGレベルを推測できる可能性が示された.単回採血のみでもOFTTにおけるTG/AUCをかなり高い精度で予測しうることが判明した.今回得られた正脂血症者における結果を高脂血症患者の成績と比べて,より簡便な食後高脂血症のマーカーについて検討する予定である

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  • 血中D-マンノース濃度に関する基礎的検討と糖尿病臨床への応用

    高橋 昭光, 曽根 博仁, 島野 仁, 鈴木 将玄, 鈴木 誠司, 川上 康, 奥田 諭吉, 海老沼 宏幸, 齋藤 和典, 山田 信博

    糖尿病   44 ( Suppl.1 )   S127 - S127   2001.3

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  • 難消化性オリゴ糖の2型糖尿病患者における有用性の検討

    井上 由加利, 奥田 諭吉, 飯田 薫子, 鶴嶋 陽子, 曽根 博仁, 浅野 道子, 佐藤 栄子, 鈴木 誠司, 山田 信博, 山下 亀次郎

    糖尿病   44 ( Suppl.1 )   S207 - S207   2001.3

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  • 糖尿病性神経障害におけるモノフィラメントの有用性の検討

    鈴木 將玄, 鈴木 誠司, 大垣 聡子, 曽根 博仁, 豊島 秀男, 島野 仁, 奥田 諭吉, 山田 信博

    糖尿病   44 ( Suppl.1 )   S176 - S176   2001.3

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  • 新しいlipogenic enzyme Acetyl CoA Synthetase(ACAS)の糖尿病における発現調節

    曽根 博仁, 島野 仁, 井上 訓之, 板倉 有紀, 雨宮 三千代, 高橋 昭光, 飯田 薫子, 豊島 秀男, 奥田 諭吉, 山田 信博

    糖尿病   44 ( Suppl.1 )   S110 - S110   2001.3

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  • Insulinのヒト血管内皮細胞におけるNitric oxide,ET-1産生に対する多価不飽和脂肪酸の作用

    知崎 圭吾, 奥田 諭吉, 浅野 道子, 高橋 昭光, 矢藤 繁, 曽根 博仁, 鈴木 誠司, 山田 信博

    糖尿病   44 ( Suppl.1 )   S94 - S94   2001.3

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  • 糖尿病モデル動物におけるインスリン抵抗性改善薬の血中脂質及び血中過酸化脂質に対する効果

    飯田 薫子, 多田, 川上 康, 曽根 博仁, 島野 仁, 豊島 秀男, 鈴木 誠司, 奥田 諭吉, 山田 信博

    糖尿病   44 ( Suppl.1 )   S163 - S163   2001.3

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  • Kinematic approach to gait analysis in patients with rheumatoid arthritis involving the knee joint

    M Sakauchi, K Narushima, H Sone, Y Kamimaki, Y Yamazaki, S Kato, T Takita, N Suzuki, K Moro

    ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH   45 ( 1 )   35 - 41   2001.2

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    Objective. To analyze abnormal gait patterns in patients with rheumatoid arthritis involving the knee joint,
    Methods. In 2 patient groups with rheumatoid arthritis, changes in relevant angular parameters in the sagittal plane were analyzed by an electromagnetic tracking instrument. One group consisted of patients with knee joint involvement and severe inflammation without progressive destruction; the other group had knee joint involvement with progressive destruction and low disease activity. Knee angle was measured as the projected angle in the sagittal plane formed by 3 sensors (hip-knee-ankle); the changing mean angle, angular velocity, and angular acceleration were displayed. Furthermore, the angle formed by the vector element's endpoints for each sensor's displacement (designated alpha angle) was measured continuously.
    Results, Compared with age-matched controls, patients with severe inflammatory knee joint involvement showed limitation of alpha angle change in the stance phase, and patients with knee joint destruction had shortened swing phase duration and decreased alpha angle change in the swing phase. A sharpened alpha angular velocity change curve was observed in the latter. Characteristic differences between groups with inflammation and destruction were more clearly evident from the alpha angle than from the knee angle itself.
    Conclusion. We observed gait differences between rheumatoid arthritis patients with active inflammatory arthritic knee joint involvement without progressive destruction and those with joint destruction and minimal inflammation. Features of gait disturbance in rheumatoid arthritis were not simple, even with a single major site. Therefore, techniques such as biokinetic gait analysis can provide practical information about functional joint integrity in this patient population that could aid in therapeutic decision making.

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  • Kinematic approach to gait analysis in patients with rheumatoid arthritis involving the knee joint

    M Sakauchi, K Narushima, H Sone, Y Kamimaki, Y Yamazaki, S Kato, T Takita, N Suzuki, K Moro

    ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH   45 ( 1 )   35 - 41   2001.2

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    Objective. To analyze abnormal gait patterns in patients with rheumatoid arthritis involving the knee joint,
    Methods. In 2 patient groups with rheumatoid arthritis, changes in relevant angular parameters in the sagittal plane were analyzed by an electromagnetic tracking instrument. One group consisted of patients with knee joint involvement and severe inflammation without progressive destruction; the other group had knee joint involvement with progressive destruction and low disease activity. Knee angle was measured as the projected angle in the sagittal plane formed by 3 sensors (hip-knee-ankle); the changing mean angle, angular velocity, and angular acceleration were displayed. Furthermore, the angle formed by the vector element's endpoints for each sensor's displacement (designated alpha angle) was measured continuously.
    Results, Compared with age-matched controls, patients with severe inflammatory knee joint involvement showed limitation of alpha angle change in the stance phase, and patients with knee joint destruction had shortened swing phase duration and decreased alpha angle change in the swing phase. A sharpened alpha angular velocity change curve was observed in the latter. Characteristic differences between groups with inflammation and destruction were more clearly evident from the alpha angle than from the knee angle itself.
    Conclusion. We observed gait differences between rheumatoid arthritis patients with active inflammatory arthritic knee joint involvement without progressive destruction and those with joint destruction and minimal inflammation. Features of gait disturbance in rheumatoid arthritis were not simple, even with a single major site. Therefore, techniques such as biokinetic gait analysis can provide practical information about functional joint integrity in this patient population that could aid in therapeutic decision making.

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  • Ibuprofen-related hypoglycemia in a patient receiving sulfonylurea

    H Sone, A Takahashi, N Yamada

    ANNALS OF INTERNAL MEDICINE   134 ( 4 )   344 - 344   2001.2

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    DOI: 10.7326/0003-4819-134-4-200102200-00027

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  • Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice

    H Sone, Y Kawakami, M Sakauchi, Y Nakamura, A Takahashi, H Shimano, Y Okuda, T Segawa, H Suzuki, N Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   281 ( 2 )   562 - 568   2001.2

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    Vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of inflammatory joint diseases, including rheumatoid arthritis (RA), To determine the importance of this cytokine in vivo, the effect of administering VEGF-neutralizing antibodies to mice with collagen-induced arthritis (CIA), which has many immunological and pathological similarities to human RA, has been investigated. Either saline, normal rabbit immunoglobulin or anti-human VEGF121 rabbit polyclonal antibody was administered to mice subcutaneously either before the onset of arthritis or after the establishment of clinical disease. Anti-VEGF antibody administered prior to disease onset significantly delayed the development of arthritis and decreased clinical score and paw thickness as well as histological severity. On the other hand, the frequency of occurrence of disease compared to either the control group administered saline or normal rabbit immunoglobulin was not altered. Anti-VEGF antibody also significantly ameliorated clinical and histological parameters even when administered after disease onset. These results indicate a possible therapeutical potential for anti-VEGF treatment in human arthritis. (C) 2001 Academic Press.

    DOI: 10.1006/bbrc.2001.4395

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  • Ibuprofen-related hypoglycemia in a patient receiving sulfonylurea

    H Sone, A Takahashi, N Yamada

    ANNALS OF INTERNAL MEDICINE   134 ( 4 )   344 - 344   2001.2

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    DOI: 10.7326/0003-4819-134-4-200102200-00027

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  • Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice

    H Sone, Y Kawakami, M Sakauchi, Y Nakamura, A Takahashi, H Shimano, Y Okuda, T Segawa, H Suzuki, N Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   281 ( 2 )   562 - 568   2001.2

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    Vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of inflammatory joint diseases, including rheumatoid arthritis (RA), To determine the importance of this cytokine in vivo, the effect of administering VEGF-neutralizing antibodies to mice with collagen-induced arthritis (CIA), which has many immunological and pathological similarities to human RA, has been investigated. Either saline, normal rabbit immunoglobulin or anti-human VEGF121 rabbit polyclonal antibody was administered to mice subcutaneously either before the onset of arthritis or after the establishment of clinical disease. Anti-VEGF antibody administered prior to disease onset significantly delayed the development of arthritis and decreased clinical score and paw thickness as well as histological severity. On the other hand, the frequency of occurrence of disease compared to either the control group administered saline or normal rabbit immunoglobulin was not altered. Anti-VEGF antibody also significantly ameliorated clinical and histological parameters even when administered after disease onset. These results indicate a possible therapeutical potential for anti-VEGF treatment in human arthritis. (C) 2001 Academic Press.

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  • 下垂体腺腫,甲状腺癌,原発性アルドステロン症を発症し多彩な臨床症状を呈した一例

    原口 典博, 大垣 聡子, 鈴木 將玄, 鈴木 誠司, 島野 仁, 豊島 秀男, 曽根 博仁, 奥田 諭吉, 山田 信博

    日本内科学会関東地方会   488回   30 - 30   2001.2

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  • 糖尿病 日本人における糖尿病合併症の長期介入研究(JDC Study)の中間解析

    曽根 博仁, 山田 信博

    Annual Review内分泌,代謝   2001   29 - 34   2001.1

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  • Disease model: Hyperinsulinemia and insulin resistance. Part A - Targeted disruption of insulin signaling or glucose transport

    Hirohito Sone, Hiroaki Suzuki, Akimitsu Takahashi, Nobuhiro Yamada

    Trends in Molecular Medicine   7 ( 7 )   320 - 322   2001

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    Insulin resistance and hyperinsulinemia are common pathophysiological features of several metabolic diseases, obesity and diabetes being two notable examples. In this article we review how the use of animal models has increased our understanding of insulin resistance and hyperinsulinemia, with a particular emphasis on the use of mice with targeted disruptions of the insulin signaling pathway.

    DOI: 10.1016/S1471-4914(01)02041-X

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  • Disease model: hyperinsulinemia and insulin resistance. Part B--polygenic and other animal models

    Hirohito Sone, Akimitsu Takahashi, Kaoruko Iida, Nobuhiro Yamada

    Trends Mol Med   7 ( 8 )   373 - 376   2001

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    Deficiency of leptin or its receptor produces hyperinsulinemia with marked obesity. Paradoxically, severe insulin resistance also accompanies lipodystrophy. Animal models of these contrasting conditions have enabled us to observe the profound and complicated aspects of the underlying pathologies. In addition, conventional polygenic rodents with known genetic backgrounds, such as the spontaneously hypertensive rat and the Goto-Kakisaki rat, have also been used to investigate these abnormalities.

    DOI: 10.1016/S1471-4914(01)02072-X

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  • 【内科 この1年の進歩】 脂質代謝

    曽根 博仁, 山田 信博

    内科   86 ( 6 )   1144 - 1149   2000.12

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  • 一過性心不全を契機に診断されたCushing's diseaseの1例

    大垣 聡子, 鈴木 將玄, 鈴木 誠司, 島野 仁, 豊島 秀男, 曽根 博仁, 奥田 諭吉, 山田 信博

    日本内分泌学会雑誌   76   129 - 129   2000.12

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  • SREBPによるコレステロール合成系遺伝子の調節

    坂倉 有紀, 島野 仁, 曽根 博仁, 山田 信博

    日本臨床分子医学会記録   37   47 - 47   2000.11

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  • 脂肪細胞内PPARδ作用と脂肪細胞分化・ob遺伝子発現

    川上 康, 新井 健夫, 飯田 薫子, 曽根 博仁, 中井 利昭, 山田 信博

    日本臨床分子医学会記録   37   42 - 42   2000.11

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  • Refractive changes in diabetic patients during intensive glycaemic control

    F Okamoto, H Sone, T Nonoyama, S Hommura

    BRITISH JOURNAL OF OPHTHALMOLOGY   84 ( 10 )   1097 - 1102   2000.10

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    Aims-To evaluate the clinical course and the characteristics of transient refractive error occurring during intensive glycaemic control of severe hyperglycaemia.
    Methods-28 eyes of patients with persistent diabetes were included in this prospective study. During the observation period, patients underwent general ophthalmological examination and A-mode scan ultrasonography was performed at each examination-at days 1, 3, and 7, and then once every week or every other week until recovery of hyperopia.
    Results-A transient hyperopic change occurred in all patients receiving improved control after hyperglycaemia. Hyperopic change developed a mean of 3.4 (SD 2.0) days after the onset of treatment, and reached a peak at 10.3 (6.1) days, where the maximum hyperopic change in an eye was 1.47 (0.87) D (range 0.50-3.75 D). Recovery of the previous refraction occurred between 14 and 84 days after the initial assessment. There was a positive correlation between the magnitude of the maximum hyperopic change and (1) the plasma glucose concentration on admission (p&lt;0.01), (2) the HbA(1c) level on admission (p&lt;0.005), (3) the daily rate of plasma glucose reduction over the first 7 days of treatment (p&lt;0.001), (4) the number of days required for hyperopia to reach its peak (p&lt;0.001), and (5) the number of days required for the development and resolution of hyperopic changes (p&lt;0.0001). There was a negative correlation between the maximum hyperopic change of an eye and baseline value of refraction (p&lt;0.01). During transient hyperopia, no significant changes were observed in the radius of the anterior corneal curvature, axial length, lens thickness, or depth of anterior chamber.
    Conclusions-The degree of transient hyperopia associated with rapid correction of hyperglycaemia is highly dependent on the rate of reduction of the plasma glucose level. A reduction of refractive index in intraocular tissues, especially in lens, appears to be responsible for this hyperopic change.

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  • Refractive changes in diabetic patients during intensive glycaemic control

    F Okamoto, H Sone, T Nonoyama, S Hommura

    BRITISH JOURNAL OF OPHTHALMOLOGY   84 ( 10 )   1097 - 1102   2000.10

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    Aims-To evaluate the clinical course and the characteristics of transient refractive error occurring during intensive glycaemic control of severe hyperglycaemia.
    Methods-28 eyes of patients with persistent diabetes were included in this prospective study. During the observation period, patients underwent general ophthalmological examination and A-mode scan ultrasonography was performed at each examination-at days 1, 3, and 7, and then once every week or every other week until recovery of hyperopia.
    Results-A transient hyperopic change occurred in all patients receiving improved control after hyperglycaemia. Hyperopic change developed a mean of 3.4 (SD 2.0) days after the onset of treatment, and reached a peak at 10.3 (6.1) days, where the maximum hyperopic change in an eye was 1.47 (0.87) D (range 0.50-3.75 D). Recovery of the previous refraction occurred between 14 and 84 days after the initial assessment. There was a positive correlation between the magnitude of the maximum hyperopic change and (1) the plasma glucose concentration on admission (p&lt;0.01), (2) the HbA(1c) level on admission (p&lt;0.005), (3) the daily rate of plasma glucose reduction over the first 7 days of treatment (p&lt;0.001), (4) the number of days required for hyperopia to reach its peak (p&lt;0.001), and (5) the number of days required for the development and resolution of hyperopic changes (p&lt;0.0001). There was a negative correlation between the maximum hyperopic change of an eye and baseline value of refraction (p&lt;0.01). During transient hyperopia, no significant changes were observed in the radius of the anterior corneal curvature, axial length, lens thickness, or depth of anterior chamber.
    Conclusions-The degree of transient hyperopia associated with rapid correction of hyperglycaemia is highly dependent on the rate of reduction of the plasma glucose level. A reduction of refractive index in intraocular tissues, especially in lens, appears to be responsible for this hyperopic change.

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  • 拡張型心筋症の治療により著しい高ナトリウム血症をきたした尿崩症合併,2型糖尿病の1例

    鈴木 浩明, 片根 由美子, 清水 郁子, 川上 康, 小田原 雅人, 鈴木 誠司, 水谷 正一, 曽根 博仁, 奥田 諭吉, 飯田 啓治

    糖尿病   43 ( 10 )   914 - 914   2000.10

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  • Enhancement of glucose transport by vascular endothelial growth factor in retinal endothelial cells

    H Sone, BK Deo, AK Kumagai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   41 ( 7 )   1876 - 1884   2000.6

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    PURPOSE. To investigate effects of vascular endothelial growth factor (VEGF) on glucose transport and GLUT1 glucose transporter expression in primary bovine retinal endothelial cell (BREC) cultures.
    METHODS. Glucose transport in control and VEGF-treated BREC cultures was determined by measurement of [C-14]-3-O-methylglucose (3MG) uptake. GLUT1 protein and mRNA was determined by Western and Northern blot analyses, respectively. Protein kinase C (PKC) activity was measured in control and VEGF-treated cultures, and glucose transport was determined with and without prior PKC depletion and PKC inhibition.
    RESULTS. Dose-dependent increases in 3MG uptake were seen in the VEGF-treated cultures, with an increase of 69% after a 24-hour exposure to 50 ng/ml VEGF (P &lt; 0.001). Total cellular GLUT1 mRNA or protein, however, was unchanged. Western blot analysis of plasma membrane fractions revealed a 75% increase in plasma membrane GLUT1 in VEGF-treated cultures (P = 0.02), suggesting that the VEGF-stimulated increase in glucose transport was due to a translocation of GLUT1 to the cell membrane. VEGF stimulated a 90% increase in PK activity in membrane fractions from cultures treated with VEGF, and VEGF-stimulated enhancement of glucose transport was abolished by cellular PKC depletion and by general and PKC beta inhibition.
    CONCLUSIONS. The present study demonstrates VEGF-mediated enhancement of retinal endothelial cell glucose transport and suggests that this increase is due to PKC beta-mediated translocation of cytosolic GLUT1 to the plasma membrane surface. Upregulation of retinal endothelial cell glucose transport by various factors associated with the development of retinopathy may be responsible for the metabolic derangements observed in the diabetic inner blood-retinal barrier in vivo.

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  • Enhancement of glucose transport by vascular endothelial growth factor in retinal endothelial cells

    H Sone, BK Deo, AK Kumagai

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   41 ( 7 )   1876 - 1884   2000.6

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    PURPOSE. To investigate effects of vascular endothelial growth factor (VEGF) on glucose transport and GLUT1 glucose transporter expression in primary bovine retinal endothelial cell (BREC) cultures.
    METHODS. Glucose transport in control and VEGF-treated BREC cultures was determined by measurement of [C-14]-3-O-methylglucose (3MG) uptake. GLUT1 protein and mRNA was determined by Western and Northern blot analyses, respectively. Protein kinase C (PKC) activity was measured in control and VEGF-treated cultures, and glucose transport was determined with and without prior PKC depletion and PKC inhibition.
    RESULTS. Dose-dependent increases in 3MG uptake were seen in the VEGF-treated cultures, with an increase of 69% after a 24-hour exposure to 50 ng/ml VEGF (P &lt; 0.001). Total cellular GLUT1 mRNA or protein, however, was unchanged. Western blot analysis of plasma membrane fractions revealed a 75% increase in plasma membrane GLUT1 in VEGF-treated cultures (P = 0.02), suggesting that the VEGF-stimulated increase in glucose transport was due to a translocation of GLUT1 to the cell membrane. VEGF stimulated a 90% increase in PK activity in membrane fractions from cultures treated with VEGF, and VEGF-stimulated enhancement of glucose transport was abolished by cellular PKC depletion and by general and PKC beta inhibition.
    CONCLUSIONS. The present study demonstrates VEGF-mediated enhancement of retinal endothelial cell glucose transport and suggests that this increase is due to PKC beta-mediated translocation of cytosolic GLUT1 to the plasma membrane surface. Upregulation of retinal endothelial cell glucose transport by various factors associated with the development of retinopathy may be responsible for the metabolic derangements observed in the diabetic inner blood-retinal barrier in vivo.

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  • 【生活習慣病の患者指導】 生活習慣病のコンセプト どんな疾患をさしているのか?なぜ成人病でなく生活習慣病なのか?

    曽根 博仁, 山田 信博

    臨床医   26 ( 6 )   1472 - 1476   2000.6

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  • 【Sports Medicine】 Life Style Modificationと疾患の予防に向けて 各種疾患の予防と治療のために 肥満と運動

    曽根 博仁, 坂倉 有紀, 川上 康

    Mebio   17 ( 5 )   70 - 76   2000.5

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  • 食後高脂血症マーカー確立の試み 脂肪負荷試験との相関

    曽根 博仁, 齋藤 和典, 坂倉 有紀, 鈴木 浩明, 小林 和人, 高橋 昭光, 鈴木 誠司, 川上 康, 山田 信博

    動脈硬化   28 ( Suppl. )   124 - 124   2000.5

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  • 急速血糖降下による一過性遠視化の原因解析

    岡本 史樹, 本村 幸子, 曽根 博仁, 野々山 智仁

    眼科臨床医報   94 ( 2 )   250 - 251   2000.2

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する調査(JDCStudy)について(第1報)

    曽根 博仁, 山田 信博, 赤沼 安夫

    日本内科学会雑誌   89 ( 臨増 )   141 - 141   2000.2

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  • Japan Diabetes Complication Study (JDCS) における糖尿病とその合併症に関する臨床疫学的検討と国際比較

    曽根博仁

    糖尿病合併症   14   80 - 84   2000

  • Effects of intraocular or systemic administration of neutralizing antibody against vascular endothelial growth factor on the murine experimental model of retinopathy

    H Sone, Y Kawakami, AK Kumagai, Y Oduka, Y Sekine, S Honmura, T Segawa, H Suzuki, K Yamashita, N Yamada

    LIFE SCIENCES   65 ( 24 )   2573 - 2580   1999.11

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    Vascular endothelial growth factor (VEGF), the strongest known angiogenic cytokine and also a potent enhancer of vascular permeability, is closely associated with diabetic ocular complications and other intraocular neovascular diseases. The therapeutic effect of VEGF-neutralizing antibody on oxygen-induced retinopathy in an experimental murine model of proliferative retinopathy was investigated. Intraocular and systemic injection of the antibody resulted in 46% and 18% reductions in the number of nuclei of newly formed vessels of this model, respectively. The results demonstrated that a neutralizing antibody against VEGF was highly effective in the treatment of intraocular neovascularization and suggested possible modes of therapy in human intraocular neovascular diseases, including diabetic proliferative retinopathy.

    DOI: 10.1016/S0024-3205(99)00526-3

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  • Effects of intraocular or systemic administration of neutralizing antibody against vascular endothelial growth factor on the murine experimental model of retinopathy

    H Sone, Y Kawakami, AK Kumagai, Y Oduka, Y Sekine, S Honmura, T Segawa, H Suzuki, K Yamashita, N Yamada

    LIFE SCIENCES   65 ( 24 )   2573 - 2580   1999.11

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    Vascular endothelial growth factor (VEGF), the strongest known angiogenic cytokine and also a potent enhancer of vascular permeability, is closely associated with diabetic ocular complications and other intraocular neovascular diseases. The therapeutic effect of VEGF-neutralizing antibody on oxygen-induced retinopathy in an experimental murine model of proliferative retinopathy was investigated. Intraocular and systemic injection of the antibody resulted in 46% and 18% reductions in the number of nuclei of newly formed vessels of this model, respectively. The results demonstrated that a neutralizing antibody against VEGF was highly effective in the treatment of intraocular neovascularization and suggested possible modes of therapy in human intraocular neovascular diseases, including diabetic proliferative retinopathy.

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  • 【Vascular biology 分子生物学と病態・治療】 血管病の分子病態 リポ蛋白代謝と動脈硬化

    曽根 博仁, 山田 信博

    医学のあゆみ   191 ( 5 )   485 - 488   1999.10

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  • 糖尿病網膜症と糖尿病血管新生緑内障における前房水と血中の血管内皮増殖因子/血管透過性因子濃度

    小沢 忠彦, 曽根 博仁, 奥田 諭吉, 川上 康, 関根 康夫, 今井 正之, 本村 幸子, 稲富 誠, 谷口 重雄, 松尾 克彦, 瀬川 俊章, 鈴木 日出夫, 山下 亀次郎

    日本眼科学会雑誌   102 ( 11 )   731 - 738   1998.11

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    インスリン非依存型糖尿病患者の前房水・血清中血管内皮増殖因子/血管透過性因子(VEGF/VPF)濃度を検討した.増殖網膜症患者群(n=12),血管新生緑内障患者群(n=11)の前房水VEGF/VPF濃度は,網膜症非合併患者群(n=10)に対して有意に高値を示した.血管新生緑内障患者群では著しい高値を示し,VEGF/VPFが網膜症のみならず同血管新生緑内障の発症,進展にも重要な役割を演じている可能性が強く推定された.血清VEGF/VPF濃度は網膜症の進行度とは相関がなかった.健常人のデータとも有意差はなかった.本研究の結果は血管新生緑内障に対する抗VEGF/VPF療法の可能性を示唆する

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  • Vascular endothelial growth factor in angiosarcoma

    M Fujimoto, T Kiyosawa, S Murata, K Matsuo, H Suzuki, H Sone, Y Okuda, Y Nakayama, H Yaoita

    ANTICANCER RESEARCH   18 ( 5B )   3725 - 3729   1998.9

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    Angiosarcoma(AS) is a malignant tumour of the endothelium of lymphatic or blood vessels. Vascular endothelial growth factor (VEGF) a specific mitogen of endothelial cells, is considered essential for the growth of many tumours including AS. We have recently treated several patients with AS; in two of them, using a newly developed enzyme-linked immunosorbant assay (ELISA) for VEGF, we sequentially measured serum VEGF concentrations. While serial serum VEGF levels reflected tumour burden, the various VEGF concentrations were within the normal range we reported previously. Furthermore, the VEGF; concentrations were not remarkably elevated in PIS tumour tissue compared with benign vascular lesions and hypervascular tumours.

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  • Vascular endothelial growth factor in angiosarcoma

    M Fujimoto, T Kiyosawa, S Murata, K Matsuo, H Suzuki, H Sone, Y Okuda, Y Nakayama, H Yaoita

    ANTICANCER RESEARCH   18 ( 5B )   3725 - 3729   1998.9

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    Angiosarcoma(AS) is a malignant tumour of the endothelium of lymphatic or blood vessels. Vascular endothelial growth factor (VEGF) a specific mitogen of endothelial cells, is considered essential for the growth of many tumours including AS. We have recently treated several patients with AS; in two of them, using a newly developed enzyme-linked immunosorbant assay (ELISA) for VEGF, we sequentially measured serum VEGF concentrations. While serial serum VEGF levels reflected tumour burden, the various VEGF concentrations were within the normal range we reported previously. Furthermore, the VEGF; concentrations were not remarkably elevated in PIS tumour tissue compared with benign vascular lesions and hypervascular tumours.

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  • Hypoxia and endothelin-1 induce VEGF production in human vascular smooth muscle cells

    Y Okuda, K Tsurumaru, S Suzuki, T Miyauchi, M Asano, Y Hong, H Sone, R Fujita, M Mizutani, Y Kawakami, T Nakajima, M Soma, K Matsuo, H Suzuki, K Yamashita

    LIFE SCIENCES   63 ( 6 )   477 - 484   1998.7

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    Vascular endothelial growth factor /vascular permeability factor (VEGF/VPF) is a secreted mitogen for vascular endothelial cells, and it promotes vascular permeability and neovascularization in vivo. We investigated the mechanisms by which low oxygen tension modulates the expression of VEGF in human aortic vascular smooth muscle cells (h-SMC) in vitro. Moreover, we measured VEGF levels in the cultured medium with or without endothelin-1 (ET-1) using a newly developed, highly sensitive, enzyme-linked immunosorbent assay. Hypoxia resulted in a substantial induction of VEGF transcripts at 3 and 24 hr. VEGF levels were significantly higher when h-SMC were cultured in medium containing ET-1 than when cultured in medium without ET-1. In conclusion, hypoxia and ET-1 constitute potent stimuli for VEGF production in h-SMC.

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  • Hypoxia and endothelin-1 induce VEGF production in human vascular smooth muscle cells

    Y Okuda, K Tsurumaru, S Suzuki, T Miyauchi, M Asano, Y Hong, H Sone, R Fujita, M Mizutani, Y Kawakami, T Nakajima, M Soma, K Matsuo, H Suzuki, K Yamashita

    LIFE SCIENCES   63 ( 6 )   477 - 484   1998.7

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    Vascular endothelial growth factor /vascular permeability factor (VEGF/VPF) is a secreted mitogen for vascular endothelial cells, and it promotes vascular permeability and neovascularization in vivo. We investigated the mechanisms by which low oxygen tension modulates the expression of VEGF in human aortic vascular smooth muscle cells (h-SMC) in vitro. Moreover, we measured VEGF levels in the cultured medium with or without endothelin-1 (ET-1) using a newly developed, highly sensitive, enzyme-linked immunosorbent assay. Hypoxia resulted in a substantial induction of VEGF transcripts at 3 and 24 hr. VEGF levels were significantly higher when h-SMC were cultured in medium containing ET-1 than when cultured in medium without ET-1. In conclusion, hypoxia and ET-1 constitute potent stimuli for VEGF production in h-SMC.

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  • Increase in serum vascular endothelial growth factor levels during altitude training

    M Asano, K Kaneoka, T Nomura, K Asano, H Sone, K Tsurumaru, K Yamashita, K Matsuo, H Suzuki, Y Okuda

    ACTA PHYSIOLOGICA SCANDINAVICA   162 ( 4 )   455 - 459   1998.4

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    The present study was performed to evaluate the effects of physical exercise at altitudes on serum vascular endothelial growth factor (VEGF) levels. Eight subjects underwent intensive swimming training for 21 days at 1886 m. After altitude training commenced, red blood cell (RBC) counts and erythropoietin levels increased, but both haemoglobin and haematocrit levels did not change significantly. The serum level of VEGF, measured by means of a highly sensitive chemiluminescence (ELISA), showed a transient decrease 10 days after start of the altitude training, thereafter increasing significantly to reach a peak level 19 days later, rising from 23.0 +/- 5.3 to 46.0 +/- 14.6 pg mL(-1) (P &lt; 0.05 vs. before). On return to low altitude in japan,the level of VEGF decreased, and 1 month later had returned to initial levels. Endurance training at altitudes increases serum VEGF levels, this could be an adaptive reaction to hypoxic conditions. This result suggests that VEGF may provide a new physiological parameter for hypoxic stress imposed by high altitude training.

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  • Increase in serum vascular endothelial growth factor levels during altitude training

    M Asano, K Kaneoka, T Nomura, K Asano, H Sone, K Tsurumaru, K Yamashita, K Matsuo, H Suzuki, Y Okuda

    ACTA PHYSIOLOGICA SCANDINAVICA   162 ( 4 )   455 - 459   1998.4

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    The present study was performed to evaluate the effects of physical exercise at altitudes on serum vascular endothelial growth factor (VEGF) levels. Eight subjects underwent intensive swimming training for 21 days at 1886 m. After altitude training commenced, red blood cell (RBC) counts and erythropoietin levels increased, but both haemoglobin and haematocrit levels did not change significantly. The serum level of VEGF, measured by means of a highly sensitive chemiluminescence (ELISA), showed a transient decrease 10 days after start of the altitude training, thereafter increasing significantly to reach a peak level 19 days later, rising from 23.0 +/- 5.3 to 46.0 +/- 14.6 pg mL(-1) (P &lt; 0.05 vs. before). On return to low altitude in japan,the level of VEGF decreased, and 1 month later had returned to initial levels. Endurance training at altitudes increases serum VEGF levels, this could be an adaptive reaction to hypoxic conditions. This result suggests that VEGF may provide a new physiological parameter for hypoxic stress imposed by high altitude training.

    DOI: 10.1046/j.1365-201X.1998.0318e.x

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  • 糖尿病網膜症と糖尿病血管新生緑内障における前房水と血中の血管内皮細胞増殖因子/血管透過性因子濃度.

    日本眼科学会雑誌   102   731 - 738   1998

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  • Serum vascular endothelial growth factor levels are elevated in diabetic patients with hyperglycemia

    S Yatoh, Y Okuda, M Asano, H Sone, Y Asakura, S Suzuki, Y Kawakami, H Suzuki, K Yamashita

    DIABETOLOGIA   40   1575 - 1575   1997.6

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  • Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes

    H Sone, Y Kawakami, Y Okuda, Y Sekine, S Honmura, K Matsuo, T Segawa, H Suzuki, K Yamashita

    DIABETOLOGIA   40 ( 6 )   726 - 730   1997.6

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    Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF levels in ocular tissue of 6-, 12-, 18- and 28-week-old Goto-Kakizaki (GK) rats, a well-known model of non-insulin-dependent diabetes, were evaluated by highly sensitive ELISA. VEGF concentrations in the GK rat as well as in non-diabetic Wistar rat significantly decreased from the age of 6 weeks to 18 weeks. However, although VEGF concentrations in the Wistar rat continued to fall significantly from 18 to 28 weeks of age, the levels were maintained between 18 and 28 weeks of age in GK rats. Levels were significantly different between the GK and Wistar rats at 28 weeks of age. Results of immunohistochemical studies of the eyes of Wistar and GK rats at 28 weeks of age suggest diffuse distribution of this cytokine in cells of neural origin. Weak to moderate VEGF immunoreactivity was exhibited mainly in the ganglion cell layer, inner plexiform layer and inner/outer nuclear layers in rats with and without diabetes. However, in the retinal optic nerve fiber layer, retinal pigment epithelium and choroid, strong VEGF immunoreactivity was noted only in the GK rat. In conclusion, increased VEGF production in certain ocular tissue, similar to that in humans, is observed quite early, at least before the appearance of observable retinal changes in the diabetic GK rat. This also suggests that the GI( rat can be used as a model of initial or latent phase diabetic retinopathy.

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  • Acute effects of thromboxane dual blocker (KDI-792) on different portions of lower limb blood flow - A study using Doppler ultrasonography and laser Doppler flowmetry in type 2 diabetic patients

    H Sone, Y Okuda, Y Tsurushima, M Asano, S Suzuki, Y Kawakami, K Yamashita

    PROSTAGLANDINS   53 ( 6 )   395 - 409   1997.6

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    The acute effects of a newly synthesized thromboxane dual blocker (KDI-792), a combined thromboxane synthase inhibitor and receptor antagonist, on lower limb circulation were examined using twodimensional color and pulse Doppler ultrasonography and laser Doppler flowmetry. A randomized single-masked, placebo-controlled trial was performed on 36 type 2 diabetic patients with minimally impaired baseline flow. The anatomical cross-sectional area (CSA), maximum flow velocity (MFV) and flow volume index (FVI) in the right dorsal pedis artery (DPA) and right femoral artery (FA) were determined by Doppler ultrasonography before and 45 and 90 minutes after the administration of either 100 or 200 mg of KDI-792 to the dose groups or placebo to the control group. Periflux blood flow (PBF) in the right foot was determined simultaneously by laser Doppler flowmetry. Both CSA and MFV in the dose groups were significantly increased in both the FA and DPA. FVI was markedly increased from 21.4 +/- 3.7 to 68.3 +/- 26.8 in the DPA (M +/- SD, P &lt; 0.01) and from 365.4 +/- 35.3 to 771.7 +/- 75.7 in the FA (P &lt; 0.01) in the 200 mg dose group. In the 100 mg dose group, FVI was markedly increased from 20.0 +/- 8.7 to 68.3 +/- 26.8 (P &lt; 0.02) in the DPA rind from 372.5 +/- 130.0 to 677.5 +/- 187.8 (P &lt; 0.01) in the FA. PBF was also increased in both dose groups (from 4.15 +/- 1.4 to 7.0 +/- 4.0 ml/min/100 g tissue in the 200 mg dose group, P &lt; 0.01), whereas there were no significant changes in either measurement in the control group. There were no significant changes in pulse rate or blood pressure after administration in either the dosage group or the placebo group. These and previous findings indicate that a single administration of KDI-792 markedly increases lower limb blood flow and might have a more potent vasodilating effect than that of prostaglandin I-2 derivatives.

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  • Acute effects of thromboxane dual blocker (KDI-792) on different portions of lower limb blood flow - A study using Doppler ultrasonography and laser Doppler flowmetry in type 2 diabetic patients

    H Sone, Y Okuda, Y Tsurushima, M Asano, S Suzuki, Y Kawakami, K Yamashita

    PROSTAGLANDINS   53 ( 6 )   395 - 409   1997.6

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    The acute effects of a newly synthesized thromboxane dual blocker (KDI-792), a combined thromboxane synthase inhibitor and receptor antagonist, on lower limb circulation were examined using twodimensional color and pulse Doppler ultrasonography and laser Doppler flowmetry. A randomized single-masked, placebo-controlled trial was performed on 36 type 2 diabetic patients with minimally impaired baseline flow. The anatomical cross-sectional area (CSA), maximum flow velocity (MFV) and flow volume index (FVI) in the right dorsal pedis artery (DPA) and right femoral artery (FA) were determined by Doppler ultrasonography before and 45 and 90 minutes after the administration of either 100 or 200 mg of KDI-792 to the dose groups or placebo to the control group. Periflux blood flow (PBF) in the right foot was determined simultaneously by laser Doppler flowmetry. Both CSA and MFV in the dose groups were significantly increased in both the FA and DPA. FVI was markedly increased from 21.4 +/- 3.7 to 68.3 +/- 26.8 in the DPA (M +/- SD, P &lt; 0.01) and from 365.4 +/- 35.3 to 771.7 +/- 75.7 in the FA (P &lt; 0.01) in the 200 mg dose group. In the 100 mg dose group, FVI was markedly increased from 20.0 +/- 8.7 to 68.3 +/- 26.8 (P &lt; 0.02) in the DPA rind from 372.5 +/- 130.0 to 677.5 +/- 187.8 (P &lt; 0.01) in the FA. PBF was also increased in both dose groups (from 4.15 +/- 1.4 to 7.0 +/- 4.0 ml/min/100 g tissue in the 200 mg dose group, P &lt; 0.01), whereas there were no significant changes in either measurement in the control group. There were no significant changes in pulse rate or blood pressure after administration in either the dosage group or the placebo group. These and previous findings indicate that a single administration of KDI-792 markedly increases lower limb blood flow and might have a more potent vasodilating effect than that of prostaglandin I-2 derivatives.

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  • Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes

    H Sone, Y Kawakami, Y Okuda, Y Sekine, S Honmura, K Matsuo, T Segawa, H Suzuki, K Yamashita

    DIABETOLOGIA   40 ( 6 )   726 - 730   1997.6

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    Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF levels in ocular tissue of 6-, 12-, 18- and 28-week-old Goto-Kakizaki (GK) rats, a well-known model of non-insulin-dependent diabetes, were evaluated by highly sensitive ELISA. VEGF concentrations in the GK rat as well as in non-diabetic Wistar rat significantly decreased from the age of 6 weeks to 18 weeks. However, although VEGF concentrations in the Wistar rat continued to fall significantly from 18 to 28 weeks of age, the levels were maintained between 18 and 28 weeks of age in GK rats. Levels were significantly different between the GK and Wistar rats at 28 weeks of age. Results of immunohistochemical studies of the eyes of Wistar and GK rats at 28 weeks of age suggest diffuse distribution of this cytokine in cells of neural origin. Weak to moderate VEGF immunoreactivity was exhibited mainly in the ganglion cell layer, inner plexiform layer and inner/outer nuclear layers in rats with and without diabetes. However, in the retinal optic nerve fiber layer, retinal pigment epithelium and choroid, strong VEGF immunoreactivity was noted only in the GK rat. In conclusion, increased VEGF production in certain ocular tissue, similar to that in humans, is observed quite early, at least before the appearance of observable retinal changes in the diabetic GK rat. This also suggests that the GI( rat can be used as a model of initial or latent phase diabetic retinopathy.

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  • 糖尿病患者について

    曾根 博仁, 奥田 諭吉, 山下 亀次郎, 田中 喜代次, 浅野 勝己

    臨床スポーツ医学 = The journal of clinical sports medicine   14 ( 2 )   170 - 174   1997.2

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    Other Link: http://search.jamas.or.jp/link/ui/1997160645

  • Effects of high glucose concentration and a thromboxane synthase inhibitor on the production of thromboxane A2 and prostaglandin I2 and E2 by cultured retinal endothelial cells

    Hirohito Sone, Yukichi Okuda, Yasushi Kawakami, Kamejiro Yamashita

    Life Sciences   58 ( 3 )   239 - 243   1996.12

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    To clarify the involvement of the prostaglandin (PG)-thromboxane (TX) system in diabetic retinopathy, the production of thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and prostaglandin E2 (PGE2), and the effects of a thromboxane synthase inhibitor (TXSI
    KDI-792
    5Z-6-[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridylmethyl)-2 pyrrolidinyl]-5-hexenoic acid hydrochloride) were examined under high glucose concentration using bovine retinal endothelial cells. TXB2 was used as an index of TXA2, and 6-keto-PGF1α as an index of PGI2. The levels of TXA2 and PGI2 were 182.3±34.3 pg/mg and 336.7±36.1 pg/mg protein at 5.5 mM of glucose, and both increased linearly with the glucose concentration to reach 430.1±29.7 pg/mg and 511.4±65.8 pg/mg protein at 33 mM glucose (mean±SD, P&lt
    0.01). Neither TXA2 nor PGI2 changed significantly under elevated osmolarity. The production of PGE2 was affected only slightly by high glucose concentrations or by TXSI. Normalization of the PGI2/TXA2 ratio by TXSI at high glucose concentrations was marked.

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  • Effects of high glucose concentration and a thromboxane synthase inhibitor on the production of thromboxane A2 and prostaglandin I2 and E2 by cultured retinal endothelial cells

    Hirohito Sone, Yukichi Okuda, Yasushi Kawakami, Kamejiro Yamashita

    Life Sciences   58 ( 3 )   239 - 243   1996.12

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    To clarify the involvement of the prostaglandin (PG)-thromboxane (TX) system in diabetic retinopathy, the production of thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and prostaglandin E2 (PGE2), and the effects of a thromboxane synthase inhibitor (TXSI
    KDI-792
    5Z-6-[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridylmethyl)-2 pyrrolidinyl]-5-hexenoic acid hydrochloride) were examined under high glucose concentration using bovine retinal endothelial cells. TXB2 was used as an index of TXA2, and 6-keto-PGF1α as an index of PGI2. The levels of TXA2 and PGI2 were 182.3±34.3 pg/mg and 336.7±36.1 pg/mg protein at 5.5 mM of glucose, and both increased linearly with the glucose concentration to reach 430.1±29.7 pg/mg and 511.4±65.8 pg/mg protein at 33 mM glucose (mean±SD, P&lt
    0.01). Neither TXA2 nor PGI2 changed significantly under elevated osmolarity. The production of PGE2 was affected only slightly by high glucose concentrations or by TXSI. Normalization of the PGI2/TXA2 ratio by TXSI at high glucose concentrations was marked.

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  • Vascular endothelial growth factor level in aqueous humor of diabetic patients with rubeotic glaucoma is markedly elevated

    H Sone, Y Okuda, Y Kawakami, M Hanatani, H Suzuki, T Kozawa, S Honmura, K Yamashita

    DIABETES CARE   19 ( 11 )   1306 - 1307   1996.11

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  • Acute effect of beraprost sodium on lower limb circulation in patients with non-insulin-dependent diabetes mellitus-evaluation by color Doppler ultrasonography and laser cutaneous blood flowmetry

    Y Okuda, H Sone, S Mizutani, M Asano, Y Tsurushima, M Ogawa, K Tada, Y Asakura, Y Kawakami, S Suzuki, K Yamashita

    PROSTAGLANDINS   52 ( 5 )   375 - 384   1996.11

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    The acute effects of beraprost sodium (sodium (+/-)-(1R*, 2R, 3aS*, 8bS*)-2, 3, 3a 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-I-octen-6-ynyl]-1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I-2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner(R) 40 mu g) and elastase (Elaszym(R) 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BM and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.

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  • Vascular endothelial growth factor level in aqueous humor of diabetic patients with rubeotic glaucoma is markedly elevated

    H Sone, Y Okuda, Y Kawakami, M Hanatani, H Suzuki, T Kozawa, S Honmura, K Yamashita

    DIABETES CARE   19 ( 11 )   1306 - 1307   1996.11

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  • Acute effect of beraprost sodium on lower limb circulation in patients with non-insulin-dependent diabetes mellitus-evaluation by color Doppler ultrasonography and laser cutaneous blood flowmetry

    Y Okuda, H Sone, S Mizutani, M Asano, Y Tsurushima, M Ogawa, K Tada, Y Asakura, Y Kawakami, S Suzuki, K Yamashita

    PROSTAGLANDINS   52 ( 5 )   375 - 384   1996.11

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    The acute effects of beraprost sodium (sodium (+/-)-(1R*, 2R, 3aS*, 8bS*)-2, 3, 3a 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-I-octen-6-ynyl]-1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I-2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner(R) 40 mu g) and elastase (Elaszym(R) 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BM and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.

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  • Predicting long-term glycemic control of post-educational type II diabetic patients by evaluating serum 1,5-anhydroglucitol levels

    H Sone, Y Okuda, T Yamaoka, Y Kawakami, M Odawara, T Matsushima, K Kawai, K Yamashita

    DIABETES RESEARCH AND CLINICAL PRACTICE   34 ( 2 )   83 - 88   1996.10

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    1,5-Anhydroglucitol (1,5-AG) is known to closely reflect diabetic control within several days. The possibility of predicting long-term glycemic control after an educational hospitalization of type II diabetic patients was investigated by examining the relationship between changes in serum 1,5-AG levels after a short-term trial home stay following an educational program and long-term changes in glycosylated hemoglobin A(1C) (HbA(1C)) levels after discharge. After 22 patients with type II diabetes had successfully completed the educational hospitalization program, they returned as outpatients for 5 nights in a row. Changes in serum 1,5-AG levels were determined during this period. The HbA(1C) levels were then determined over a period of 3 months after discharge, and the relationship between changes in 1,5-AG and HbA(1C) levels was examined. Changes in serum 1,5-AG levels during the 5-day trial home stay and the changes in HbA(1C) levels during the 3 months after discharge from the hospital were found to be significantly correlated (r = 0.70, P &lt; 0.01). A comparison of the decreased group, which exhibited a decrease in I,5-AG levels of 5.0 mu mol/l or more during the trial home stay, and the unchanged group, revealed that increases in body mass index 3 months after discharge were significantly higher in the decreased group (1.2 +/- 0.4%) than in the unchanged group (0.2 +/- 0.5%) (P &lt; 0.05). Determination of serum 1,5-AG levels of patients with type II diabetes before and after a trial home stay following educational hospitalization was found to be useful in identifying patients at high risk of recurrence of poor glycemic control in the future. Copyright (C) 1996 EIsevier Science Ireland Ltd.

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  • Predicting long-term glycemic control of post-educational type II diabetic patients by evaluating serum 1,5-anhydroglucitol levels

    H Sone, Y Okuda, T Yamaoka, Y Kawakami, M Odawara, T Matsushima, K Kawai, K Yamashita

    DIABETES RESEARCH AND CLINICAL PRACTICE   34 ( 2 )   83 - 88   1996.10

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    1,5-Anhydroglucitol (1,5-AG) is known to closely reflect diabetic control within several days. The possibility of predicting long-term glycemic control after an educational hospitalization of type II diabetic patients was investigated by examining the relationship between changes in serum 1,5-AG levels after a short-term trial home stay following an educational program and long-term changes in glycosylated hemoglobin A(1C) (HbA(1C)) levels after discharge. After 22 patients with type II diabetes had successfully completed the educational hospitalization program, they returned as outpatients for 5 nights in a row. Changes in serum 1,5-AG levels were determined during this period. The HbA(1C) levels were then determined over a period of 3 months after discharge, and the relationship between changes in 1,5-AG and HbA(1C) levels was examined. Changes in serum 1,5-AG levels during the 5-day trial home stay and the changes in HbA(1C) levels during the 3 months after discharge from the hospital were found to be significantly correlated (r = 0.70, P &lt; 0.01). A comparison of the decreased group, which exhibited a decrease in I,5-AG levels of 5.0 mu mol/l or more during the trial home stay, and the unchanged group, revealed that increases in body mass index 3 months after discharge were significantly higher in the decreased group (1.2 +/- 0.4%) than in the unchanged group (0.2 +/- 0.5%) (P &lt; 0.05). Determination of serum 1,5-AG levels of patients with type II diabetes before and after a trial home stay following educational hospitalization was found to be useful in identifying patients at high risk of recurrence of poor glycemic control in the future. Copyright (C) 1996 EIsevier Science Ireland Ltd.

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  • Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus

    Y Okuda, M Mizutani, M Ogawa, H Sone, M Asano, Y Asakura, M Isaka, S Suzuki, Y Kawakami, JB Field, K Yamashita

    JOURNAL OF DIABETES AND ITS COMPLICATIONS   10 ( 5 )   280 - 287   1996.9

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    The present study was undertaken to investigate the efficacy of a new, highly purified (purity greater than 91%), ethyl esterification product from natural eicosapentaenoic acid (EPA-E, C20:5 omega 3) in patients with type II diabetes mellitus (NIDDM). Hemodynamic changes were assessed at the level of the dorsalis pedis artery using an ultrasonic color Doppler duplex system before and after oral administration of EPA-E at a dose of 1800 mg/day for 48 weeks. The cross-sectional area of the dorsalis pedis artery increased significantly from 2.5 +/- 0.2 to 3.9 +/- 0.4 mm(2) (48 weeks, mean +/- SE, p &lt; 0.05). Moreover, EPA-E improved the clinical symptom (coldness, numbness) as well as the vibration perception threshold sense of the lower extremities [from 32.1 +/- 8.5 to 16.1 +/- 4.8 (48 weeks) mu m]. A significant decrease of serum triglycerides was also noted by EPA-E administration. Furthermore, significant decrease of the excretion of albumin in urine [from 24.4 +/- 3.3 to 13.9 +/- 1.8 (48 weeks) mg/g . Cr, p &lt; 0.05]. The results of this study suggest that EPA-E has significant beneficial effects on diabetic neuropathy and serum lipids as well as other diabetic complications such as nephropathy and macroangiopathy.

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  • Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus

    Y Okuda, M Mizutani, M Ogawa, H Sone, M Asano, Y Asakura, M Isaka, S Suzuki, Y Kawakami, JB Field, K Yamashita

    JOURNAL OF DIABETES AND ITS COMPLICATIONS   10 ( 5 )   280 - 287   1996.9

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    The present study was undertaken to investigate the efficacy of a new, highly purified (purity greater than 91%), ethyl esterification product from natural eicosapentaenoic acid (EPA-E, C20:5 omega 3) in patients with type II diabetes mellitus (NIDDM). Hemodynamic changes were assessed at the level of the dorsalis pedis artery using an ultrasonic color Doppler duplex system before and after oral administration of EPA-E at a dose of 1800 mg/day for 48 weeks. The cross-sectional area of the dorsalis pedis artery increased significantly from 2.5 +/- 0.2 to 3.9 +/- 0.4 mm(2) (48 weeks, mean +/- SE, p &lt; 0.05). Moreover, EPA-E improved the clinical symptom (coldness, numbness) as well as the vibration perception threshold sense of the lower extremities [from 32.1 +/- 8.5 to 16.1 +/- 4.8 (48 weeks) mu m]. A significant decrease of serum triglycerides was also noted by EPA-E administration. Furthermore, significant decrease of the excretion of albumin in urine [from 24.4 +/- 3.3 to 13.9 +/- 1.8 (48 weeks) mg/g . Cr, p &lt; 0.05]. The results of this study suggest that EPA-E has significant beneficial effects on diabetic neuropathy and serum lipids as well as other diabetic complications such as nephropathy and macroangiopathy.

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  • Radioiodinated metaiodobenzylguanidine scintigraphy for pheochromocytoma - A false-positive case of adrenocortical adenoma and literature review

    H Sone, Y Okuda, Y Nakamura, N Ishikawa, T Yamaoka, Y Kawakami, M Odawara, T Matsushima, K Kawai, K Yamashita

    HORMONE RESEARCH   46 ( 3 )   138 - 142   1996.8

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    Radioiodinated metaiodobenzylguanidine (MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. We describe herein the first case of a definite adrenocortical adenoma that demonstrated false-positive uptake on MIBG scintigraphy. In addition, we reviewed all 13 reported cases showing false-positive uptake, and suggest that careful evaluation is needed before diagnosing a 'silent' or 'asymptomatic' pheochromocytoma.

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  • Radioiodinated metaiodobenzylguanidine scintigraphy for pheochromocytoma - A false-positive case of adrenocortical adenoma and literature review

    H Sone, Y Okuda, Y Nakamura, N Ishikawa, T Yamaoka, Y Kawakami, M Odawara, T Matsushima, K Kawai, K Yamashita

    HORMONE RESEARCH   46 ( 3 )   138 - 142   1996.8

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    Radioiodinated metaiodobenzylguanidine (MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. We describe herein the first case of a definite adrenocortical adenoma that demonstrated false-positive uptake on MIBG scintigraphy. In addition, we reviewed all 13 reported cases showing false-positive uptake, and suggest that careful evaluation is needed before diagnosing a 'silent' or 'asymptomatic' pheochromocytoma.

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  • Progesterone induces vascular endothelial growth factor on retinal pigment epithelial cells in culture

    H Sone, Y Okuda, Y Kawakami, S Kondo, M Hanatani, K Matsuo, H Suzuki, K Yamashita

    LIFE SCIENCES   59 ( 1 )   21 - 25   1996.5

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    Diabetic retinopathy is known to frequently deteriorate during pregnancy but the cause remains obscure. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a potent vascular endothelial cell mitogen which is mainly up-regulated by hypoxia, and is closely associated with the development and progression of diabetic retinopathy. To examine the influence of the drastic hormonal alterations during pregnancy on the worsening of diabetic retinopathy, we examined the effects of estradiol (E(2)) and progesterone (P-4) on the production of VEGF/VPF in bovine retinal pigment epithelial cells in culture. The VEGF/VPF production was significantly elevated (214.5+/-28.3 ng/g protein, P&lt;0.01) by 48 h of exposure to a high concentration of P-4(10 mu M), which is still within the physiological range during pregnancy, compared to that of the control group (147.7+/-17.9 ng/g protein). However, E(2) significantly stimulated the production of VEGF/VPF only at concentrations (100 mu M) much higher than normally encountered during pregnancy. These two hormones were not observed to have a synergistic effect, at least at physiological concentrations. As the increase in serum P-4 levels during pregnancy is reported to be greater in pregnant diabetic patients with progressive retinopathy, our findings suggest that P-4 may contribute to the worsening of diabetic retinopathy during pregnancy by up-regulating intraocular VEGF levels.

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  • Progesterone induces vascular endothelial growth factor on retinal pigment epithelial cells in culture

    H Sone, Y Okuda, Y Kawakami, S Kondo, M Hanatani, K Matsuo, H Suzuki, K Yamashita

    LIFE SCIENCES   59 ( 1 )   21 - 25   1996.5

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    Diabetic retinopathy is known to frequently deteriorate during pregnancy but the cause remains obscure. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a potent vascular endothelial cell mitogen which is mainly up-regulated by hypoxia, and is closely associated with the development and progression of diabetic retinopathy. To examine the influence of the drastic hormonal alterations during pregnancy on the worsening of diabetic retinopathy, we examined the effects of estradiol (E(2)) and progesterone (P-4) on the production of VEGF/VPF in bovine retinal pigment epithelial cells in culture. The VEGF/VPF production was significantly elevated (214.5+/-28.3 ng/g protein, P&lt;0.01) by 48 h of exposure to a high concentration of P-4(10 mu M), which is still within the physiological range during pregnancy, compared to that of the control group (147.7+/-17.9 ng/g protein). However, E(2) significantly stimulated the production of VEGF/VPF only at concentrations (100 mu M) much higher than normally encountered during pregnancy. These two hormones were not observed to have a synergistic effect, at least at physiological concentrations. As the increase in serum P-4 levels during pregnancy is reported to be greater in pregnant diabetic patients with progressive retinopathy, our findings suggest that P-4 may contribute to the worsening of diabetic retinopathy during pregnancy by up-regulating intraocular VEGF levels.

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  • Vascular endothelial growth factor is induced by long-term high glucose concentration and up-regulated by acute glucose deprivation in cultured bovine retinal pigmented epithelial cells

    H Sone, Y Kawakami, Y Okuda, S Kondo, M Hanatani, H Suzuki, K Yamashita

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   221 ( 1 )   193 - 198   1996.4

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    Vascular endothelial growth factor (VEGF) is closely correlated to diabetic retinopathy. Its basal production in three types of cultured retinal cells (endothelial cells, pericytes and retinal pigment epithelial cells; RPE) was examined. RPE production of VEGF was markedly higher than the rest of the cells. VEGF production in RPE was significantly elevated by 10-day, but not by 1- or 3-day exposure to 16.5 mM glucose compared to a 5.5 mM glucose group. Transient deterioration of diabetic retinopathy is frequently observed during rapid correction of glycemic control. To determine whether VEGF is up-regulated following a sharp drop in the glucose concentration or not, we examined the changes in VEGF production in RPE before and after a sudden drop in the glucose concentration. VEGF production was significantly increased by a glucose concentration decrease from 5.5 to 0.5 mM, but not by a decrease from 33 or 16.5 to 5.5 mM. These findings suggest that up-regulation of VEGF may contribute to the development of diabetic retinopathy and its worsening by hypoglycemia. (C) 1996 Academic Press, Inc.

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  • Vascular endothelial growth factor is induced by long-term high glucose concentration and up-regulated by acute glucose deprivation in cultured bovine retinal pigmented epithelial cells

    H Sone, Y Kawakami, Y Okuda, S Kondo, M Hanatani, H Suzuki, K Yamashita

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   221 ( 1 )   193 - 198   1996.4

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    Vascular endothelial growth factor (VEGF) is closely correlated to diabetic retinopathy. Its basal production in three types of cultured retinal cells (endothelial cells, pericytes and retinal pigment epithelial cells; RPE) was examined. RPE production of VEGF was markedly higher than the rest of the cells. VEGF production in RPE was significantly elevated by 10-day, but not by 1- or 3-day exposure to 16.5 mM glucose compared to a 5.5 mM glucose group. Transient deterioration of diabetic retinopathy is frequently observed during rapid correction of glycemic control. To determine whether VEGF is up-regulated following a sharp drop in the glucose concentration or not, we examined the changes in VEGF production in RPE before and after a sudden drop in the glucose concentration. VEGF production was significantly increased by a glucose concentration decrease from 5.5 to 0.5 mM, but not by a decrease from 33 or 16.5 to 5.5 mM. These findings suggest that up-regulation of VEGF may contribute to the development of diabetic retinopathy and its worsening by hypoglycemia. (C) 1996 Academic Press, Inc.

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  • 培養ウシ網膜色素上皮細胞のVEGF産生に及ぼすプロゲステロン及びグルコース濃度変化の影響

    曽根 博仁

    糖尿病   39 ( Suppl.1 )   494 - 494   1996.4

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  • Primary adrenal lymphoma presenting as Addisonian crisis. Pitfalls in the diagnosis of bilateral adrenal swelling

    H Sone, Y Okuda, Y Nakamura, M Asano, Y Kawakami, K Kawai, K Yamashita

    HORMONE AND METABOLIC RESEARCH   28 ( 2 )   116 - 116   1996.2

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  • Primary adrenal lymphoma presenting as Addisonian crisis. Pitfalls in the diagnosis of bilateral adrenal swelling

    H Sone, Y Okuda, Y Nakamura, M Asano, Y Kawakami, K Kawai, K Yamashita

    HORMONE AND METABOLIC RESEARCH   28 ( 2 )   116 - 116   1996.2

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  • Bisphosphonate投与によりCacrisisを回避しえた副甲状腺癌再発転移の1例

    ホルモンと臨床44増刊号「興味ある症例 第28集」   150 - 154   1996

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  • トリロスタンの術前投与が有用であった巨大副腎皮質癌の1症例

    ホルモンと臨床   44   189 - 193   1996

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  • ウシ培養網膜血管内皮細胞のTXA2, PGI2, PGE2産生に対する高グルコースおよびTX合成酵素阻害薬の影響

    曽根 博仁

    日本臨床代謝学会記録   XXXII   24 - 25   1995.12

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  • THE EFFECT OF NILVADIPINE ON BLOODFLOW IN THE DORSAL PEDIS ARTERY IN TYPE-2 DIABETIC-PATIENTS - A STUDY USING DUPLEX-DOPPLER ULTRASONOGRAPHY

    H SONE, Y OKUDA, M MIZUTANI, Y KAWAKAMI, C BANNAI, K YAMASHITA

    POSTGRADUATE MEDICAL JOURNAL   71 ( 840 )   613 - 616   1995.10

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    The effects of nilvadipine on the peripheral circulation in the lower extremities using a duplex system of two-dimensional colour and pulse Doppler ultrasonography were studied in 32 patients with type 2 diabetes mellitus and mild essential hypertension. The patients (19 men and 13 women) were randomly divided into treatment and control groups. The anatomical cross-sectional area and blood flow index of the dorsal pedis artery were determined by colour and pulse Doppler ultrasonography before and 60 min after administration of 4 mg nilvadipine or placebo. Pulse rate and blood pressure were measured simultaneously. There were no significant changes in pulse rate or blood pressure after administration of either drug. Both cross-sectional areas (from 4.3 +/- 0.4 to 5.2 +/- 0.5 mm(2), p &lt; 0.05) and blood flow index (from 40.3 +/- 4.3 to 58.8 +/- 9.0, p &lt; 0.05) were significantly increased in the treatment group, whereas there were no significant changes in either measurement in the control group. The findings showed that a single administration of nilvadipine increases blood flow in the dorsal pedis arteries of diabetic patients.

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  • TRANSIENT NEPHROGENIC DIABETES-INSIPIDUS ACCOMPANIED BY POSSIBLE PSYCHOGENIC POLYDIPSIA

    H SONE, K KAWAI, M NISHI, S SHIMAKURA, C BANNAI, Y KAWAKAMI, M ODAWARA, T MATSUSHIMA, Y OKUDA, K YAMASHITA

    HORMONE RESEARCH   44 ( 4 )   193 - 196   1995.10

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    A 50-year-old Japanese man had been suffering from polydipsia and polyuria for 2 months without any other specific symptoms, His daily urinary output reached 5 liters. On admission, no abnormalities of the kidneys, heart, thyroid, adrenals, pituitary or hypothalamus were detected by laboratory tests and MRI of the head, Pure psychogenic polydipsia was ruled out because his urine volume did not decrease sufficiently with 18 h of water deprivation and the subsequent injection of aqueous vasopressin. Plasma arginine vasopressin (AVP) levels against plasma osmolality remained within the normal range during the test. These results indicated that diabetes insipidus in this case was caused by renal insensitivity to AVP, The symptoms disappeared spontaneously, and marked improvement was observed in a second water deprivation test 1 month later, although the maximum urine concentration was still subnormal. The combination of both latent insufficiency of AVP secretion and impairment of the renal countercurrent system induced by psychogenic polydipsia was speculated as a possible mechanism for the transient nephrogenic diabetes insipidus in this case.

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  • THE EFFECT OF NILVADIPINE ON BLOODFLOW IN THE DORSAL PEDIS ARTERY IN TYPE-2 DIABETIC-PATIENTS - A STUDY USING DUPLEX-DOPPLER ULTRASONOGRAPHY

    H SONE, Y OKUDA, M MIZUTANI, Y KAWAKAMI, C BANNAI, K YAMASHITA

    POSTGRADUATE MEDICAL JOURNAL   71 ( 840 )   613 - 616   1995.10

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    Language:English   Publisher:BRITISH MED JOURNAL PUBL GROUP  

    The effects of nilvadipine on the peripheral circulation in the lower extremities using a duplex system of two-dimensional colour and pulse Doppler ultrasonography were studied in 32 patients with type 2 diabetes mellitus and mild essential hypertension. The patients (19 men and 13 women) were randomly divided into treatment and control groups. The anatomical cross-sectional area and blood flow index of the dorsal pedis artery were determined by colour and pulse Doppler ultrasonography before and 60 min after administration of 4 mg nilvadipine or placebo. Pulse rate and blood pressure were measured simultaneously. There were no significant changes in pulse rate or blood pressure after administration of either drug. Both cross-sectional areas (from 4.3 +/- 0.4 to 5.2 +/- 0.5 mm(2), p &lt; 0.05) and blood flow index (from 40.3 +/- 4.3 to 58.8 +/- 9.0, p &lt; 0.05) were significantly increased in the treatment group, whereas there were no significant changes in either measurement in the control group. The findings showed that a single administration of nilvadipine increases blood flow in the dorsal pedis arteries of diabetic patients.

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  • TRANSIENT NEPHROGENIC DIABETES-INSIPIDUS ACCOMPANIED BY POSSIBLE PSYCHOGENIC POLYDIPSIA

    H SONE, K KAWAI, M NISHI, S SHIMAKURA, C BANNAI, Y KAWAKAMI, M ODAWARA, T MATSUSHIMA, Y OKUDA, K YAMASHITA

    HORMONE RESEARCH   44 ( 4 )   193 - 196   1995.10

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    A 50-year-old Japanese man had been suffering from polydipsia and polyuria for 2 months without any other specific symptoms, His daily urinary output reached 5 liters. On admission, no abnormalities of the kidneys, heart, thyroid, adrenals, pituitary or hypothalamus were detected by laboratory tests and MRI of the head, Pure psychogenic polydipsia was ruled out because his urine volume did not decrease sufficiently with 18 h of water deprivation and the subsequent injection of aqueous vasopressin. Plasma arginine vasopressin (AVP) levels against plasma osmolality remained within the normal range during the test. These results indicated that diabetes insipidus in this case was caused by renal insensitivity to AVP, The symptoms disappeared spontaneously, and marked improvement was observed in a second water deprivation test 1 month later, although the maximum urine concentration was still subnormal. The combination of both latent insufficiency of AVP secretion and impairment of the renal countercurrent system induced by psychogenic polydipsia was speculated as a possible mechanism for the transient nephrogenic diabetes insipidus in this case.

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  • Diabetes Care in Emergency Settings Reviewed

    H. Sone, Y. Kawakami, Y. Okuda, K. Yamashita

    Diabetes Care   18 ( 9 )   1310 - 1311   1995.9

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    Authorship:Lead author   Language:English   Publisher:American Diabetes Association  

    DOI: 10.2337/diacare.18.9.1310

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  • DIABETES CARE IN EMERGENCY SETTINGS

    H SONE, Y KAWAKAMI, Y OKUDA, K YAMASHITA

    DIABETES CARE   18 ( 9 )   1310 - 1310   1995.9

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  • 糖尿病性腎症

    曽根 博仁

    臨牀と研究   72 ( 9 )   2297 - 2298   1995.9

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  • 両側性副腎Incidentalomaの一例

    曽根 博仁

    日本内分泌学会雑誌   71 ( 6 )   787 - 787   1995.9

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  • EFFICACY OF IBUDILAST ON LOWER-LIMB CIRCULATION OF DIABETIC-PATIENTS WITH MINIMALLY IMPAIRED BASE-LINE FLOW - A STUDY USING COLOR DOPPLER ULTRASONOGRAPHY AND LASER-DOPPLER FLOWMETRY

    H SONE, Y OKUDA, Y ASAKURA, M ASANO, M MIZUTANI, C BANNAI, K YAMASHITA

    ANGIOLOGY   46 ( 8 )   699 - 703   1995.8

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    Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The hemodynamic effects of ibudilast were evaluated in 41 patients with nan-insulin-dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography and laser Doppler blood flowmetry. Before and one hour after oral administration of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal microcirculatory blood volume (MBV) were measured, In the ibudilast group, all of the parameters (CSA, BFI, and MBV) significantly increased as compared with the elastase group. These data suggest that ibudilast is effective in ameliorating diabetic macroangiopathy and microangiopathy of the lower limbs.

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  • EFFICACY OF IBUDILAST ON LOWER-LIMB CIRCULATION OF DIABETIC-PATIENTS WITH MINIMALLY IMPAIRED BASE-LINE FLOW - A STUDY USING COLOR DOPPLER ULTRASONOGRAPHY AND LASER-DOPPLER FLOWMETRY

    H SONE, Y OKUDA, Y ASAKURA, M ASANO, M MIZUTANI, C BANNAI, K YAMASHITA

    ANGIOLOGY   46 ( 8 )   699 - 703   1995.8

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    Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The hemodynamic effects of ibudilast were evaluated in 41 patients with nan-insulin-dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography and laser Doppler blood flowmetry. Before and one hour after oral administration of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal microcirculatory blood volume (MBV) were measured, In the ibudilast group, all of the parameters (CSA, BFI, and MBV) significantly increased as compared with the elastase group. These data suggest that ibudilast is effective in ameliorating diabetic macroangiopathy and microangiopathy of the lower limbs.

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  • RESTORATION OF MYOINOSITOL UPTAKE BY EICOSAPENTAENOIC ACID IN HUMAN SKIN FIBROBLASTS CULTURED IN HIGH-GLUCOSE MEDIUM

    Y OKUDA, T SAWADA, M MIZUTANI, H SONE, S SUZUKI, Y KAWAKAMI, M SOMA, M SUZUKI, H YAOITA, K YAMASHITA

    LIFE SCIENCES   57 ( 5 )   PL71 - PL74   1995.6

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    The effects of elevated glucose and eicosapentaenoic acid (EPA, C20:5 omega 3) an myo-inositol uptake in human skin fibroblasts (HSF) were evaluated. Myo-inositol incorporation into HSF was dependent on an active transport system via Na+-K+ ATPase activity based on the results with Na+ deprivation and ouabain (5 mM). Although glucose (27.5, 55 mM) inhibited 2-[H-3] myo-inositol uptake, the addition of EPA (3x10(-4) M) prevented glucose-mediated inhibition. Since EPA decreased glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate some of the devastating functions associated with diabetes.

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  • RESTORATION OF MYOINOSITOL UPTAKE BY EICOSAPENTAENOIC ACID IN HUMAN SKIN FIBROBLASTS CULTURED IN HIGH-GLUCOSE MEDIUM

    Y OKUDA, T SAWADA, M MIZUTANI, H SONE, S SUZUKI, Y KAWAKAMI, M SOMA, M SUZUKI, H YAOITA, K YAMASHITA

    LIFE SCIENCES   57 ( 5 )   PL71 - PL74   1995.6

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    The effects of elevated glucose and eicosapentaenoic acid (EPA, C20:5 omega 3) an myo-inositol uptake in human skin fibroblasts (HSF) were evaluated. Myo-inositol incorporation into HSF was dependent on an active transport system via Na+-K+ ATPase activity based on the results with Na+ deprivation and ouabain (5 mM). Although glucose (27.5, 55 mM) inhibited 2-[H-3] myo-inositol uptake, the addition of EPA (3x10(-4) M) prevented glucose-mediated inhibition. Since EPA decreased glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate some of the devastating functions associated with diabetes.

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  • 糖尿病網膜症・腎症の発症および進展におけるVEGF(Vascular Endothelial Growth Factor)の関与

    曽根 博仁

    糖尿病   38 ( Suppl.1 )   257 - 257   1995.4

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  • 糖尿病患者の下肢血流におけるThromboxane (TX) dual blocker (KDI-792)の影響

    曽根 博仁

    日本内分泌学会雑誌   71 ( 3 )   496 - 496   1995.4

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  • Comparative Analysis of Diabetes Mellitus Associated with Endocrine Diseases

    Takashi Yamaoka, Hirohito Sone, Yukichi Okuda, Mitsuo Itakura, Kamejiro Yamashita

    Journal of the Japan Diabetes Society   38 ( 6 )   421 - 429   1995

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    Clinical data obtained from diabetic patients associated with acromegaly, Cushing's syndrome, pheochromocytoma, or primary aldosteronism were analyzed. In acromegaly, the incidence of accompanying diabetes (39.6%) and the plasma glucose level in 75 g OGTT were the highest among the four diseases. Although 38.5% of patients with Cushing's syndrome had accompanying diabetes, their fasting plasma glucose concentrations were almost normal. Hyperinsulinemia was observed in these two diseases, and age, family history of diabetes, degree of hormonal abnormality, and weight gain in these patients were regarded as pathognomonic for diabetes. In pheochromocytoma and primary aldosteronism, diabetes was observed in 27.8 and 17.9%, respectively, with relatively high fasting plasma glucose concentrations. The suppression of insulin secretion, degree of hormonal abnormality, and weight loss in these patients, in addition to abnormalities of electrolytes in patients with primary aldosteronism, were considered pathognomonic for diabetes in these diseases. © 1995, THE JAPAN DIABETES SOCIETY. All rights reserved.

    DOI: 10.11213/tonyobyo1958.38.421

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  • 原発性色素結節性副腎皮質過形成と心臓粘液腫,拡張型心筋症様心不全を認めたCarney症候群の一例

    朝倉 由加利, 奥田 諭吉, 瀧澤 盛和, 曽根 博仁, 鈴木 誠司, 小田原 雅人, 川上 康, 松島 照彦, 坂内 千恵子, 川井 紘一, 山下 亀次郎

    ホルモンと臨床   43   172 - 175   1995

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  • インスリン非依存型糖尿病患者の高脂血症および血糖コントロールに及ぼすBezafibrateの効果

    プラクティス   12   75 - 80   1995

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  • Report of a Case of Pancreatic Diabetes with Severe Zinc Deficiency

    Michiko Asano, Yukichi Okuda, Kunimi Hirano, Takashi Yamaoka, Yoko Tsurushima, Hirohito Sone, Masashi Ogawa, Masaaki Isaka, Masakazu Mizutani, Yukari Asakura, Seiji Suzuki, Chieko Bannai, Yasushi Kawakami, Masato Odawara, Teruhito Matsushima, Koichi Kawai, Takashi Yamaguchi, Kamejiro Yamashita

    Journal of the Japan Diabetes Society   38 ( 7 )   517 - 522   1995

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    We encountered a 50-year-old man with pancreatic diabetes who had a long history of heavy alcohol consumption. His serum glucose level was elevated, and he had previously been treated with insulin by another physician. About one year previously he developed erythema of the toes, watery diarrhea, a recurrent aphthous ulcer, glossitis and a taste disorder. His serum zinc level was found to be low, 39μg/dl (normal range: 50-140). A diagnosis of acrodermatitis due to zinc deficiency was made, and the patient was treated with oral ZnS04, 600 mg daily. After a few weeks of zinc therapy, serum zinc levels increased and most of the symptoms were resolved. After zinc treatment his glucose intolerance improved, and a slight increase in his plasma C-peptide responce to arginine infusion was observed. © 1995, THE JAPAN DIABETES SOCIETY. All rights reserved.

    DOI: 10.11213/tonyobyo1958.38.517

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  • 糖尿病患者における脳血栓症へのTXA2合成酵素阻害剤の使用経験

    現代医療   27   1 - 3   1995

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  • インスリン非依存型糖尿病患者の体力・活力年齢からみた運動療法の効果

    いばらき健康・スポーツ科学   13   1 - 9   1995

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  • イコサペント酸の糖尿病性神経障害を有するインスリン非依存型糖尿病患者における効果について

    プラクティス   12   607 - 612   1995

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  • 糖尿病患者における難消化性オリゴ糖の有用性についての検討

    Peptide Hormone in Pancreas   15   197 - 200   1995

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  • 大規模震災時における糖尿病患者ケアーの重要性-阪神大震災医療援護班における経験

    糖尿病   38   238 - 239   1995

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  • SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC-HORMONE (SIADH) AND GERHARDT SYNDROME-ASSOCIATED WITH SHY-DRAGER SYNDROME

    H SONE, Y OKUDA, C BANNAI, S SUZUKI, T YAMAOKA, Y ASAKURA, Y KAWAKAMI, M ODAWARA, T MATSUSHIMA, K KAWAI, T YOSHIZAWA, H MIZUSAWA, K YAMASHITA

    INTERNAL MEDICINE   33 ( 12 )   773 - 778   1994.12

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    This is the first report on a case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with Gerhardt syndrome (paralysis of bilateral vocal cords). A 67-year-old Japanese man suffering from progressive autonomic failure was diagnosed as having Shy-Drager syndrome (SDS) with hyponatremia due to SIADH and severe sleep apnea caused by a bilateral recurrent nerve palsy. Water load test showed alteration in diuresis which was corrected by phengtoin. Arginine vasopressin secretion was not suppressed by plasma osmolality below 280 mOsm/kgH(2)O. Impairment of the afferent pathways of baroreceptors, or impairment of the osmoreceptors could be speculated as the etiological factor of the SIADH observed in this case.

    DOI: 10.2169/internalmedicine.33.773

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  • SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC-HORMONE (SIADH) AND GERHARDT SYNDROME-ASSOCIATED WITH SHY-DRAGER SYNDROME

    H SONE, Y OKUDA, C BANNAI, S SUZUKI, T YAMAOKA, Y ASAKURA, Y KAWAKAMI, M ODAWARA, T MATSUSHIMA, K KAWAI, T YOSHIZAWA, H MIZUSAWA, K YAMASHITA

    INTERNAL MEDICINE   33 ( 12 )   773 - 778   1994.12

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:JAPAN SOC INTERNAL MEDICINE  

    This is the first report on a case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with Gerhardt syndrome (paralysis of bilateral vocal cords). A 67-year-old Japanese man suffering from progressive autonomic failure was diagnosed as having Shy-Drager syndrome (SDS) with hyponatremia due to SIADH and severe sleep apnea caused by a bilateral recurrent nerve palsy. Water load test showed alteration in diuresis which was corrected by phengtoin. Arginine vasopressin secretion was not suppressed by plasma osmolality below 280 mOsm/kgH(2)O. Impairment of the afferent pathways of baroreceptors, or impairment of the osmoreceptors could be speculated as the etiological factor of the SIADH observed in this case.

    DOI: 10.2169/internalmedicine.33.773

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  • 123I-MIBG scintigraphyにてfalse positiveを呈した副腎皮質非機能性腺腫の一例

    曽根 博仁

    日本内分泌学会雑誌   70 ( 7 )   705 - 705   1994.9

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  • 各種非侵襲的手法によるインスリン非依存型糖尿病患者の下肢循環についての総合的検討

    曽根 博仁

    脈管学   34 ( 9 )   794 - 794   1994.9

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  • PITFALLS IN SCANNING FOR PHEOCHROMOCYTOMA

    H SONE, Y OKUDA, Y NAKAMURA, H ISHIKAWA, T YAMAOKA, Y KAWAKAMI, K YAMASHITA

    LANCET   344 ( 8920 )   476 - 477   1994.8

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  • インスリン非依存型糖尿病患者におけるnilvadipineの足背動脈血流に対する効果

    曽根 博仁, 奥田 諭吉, 水谷 正一

    臨牀と研究   71 ( 8 )   2193 - 2196   1994.8

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    1) nilvadipine 4mgおよび対照薬elastase 1,800単位単回投与の前後における足背動脈断面積,同血流量指数を超音波カラーおよびパルスドプラ法を用いて,測定した。2)血圧・脈拍は,両群とも有意な変化を示さなかった。断面積,血流量指数はnilvadipine投与群では,投与60分後に両者とも有意な上昇を示したのに対し,対照のelastase投与群では有意な変化を認めなかった

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  • PITFALLS IN SCANNING FOR PHEOCHROMOCYTOMA

    H SONE, Y OKUDA, Y NAKAMURA, H ISHIKAWA, T YAMAOKA, Y KAWAKAMI, K YAMASHITA

    LANCET   344 ( 8920 )   476 - 477   1994.8

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  • インスリン非依存型糖尿病患者の各種下肢循環指標とその有用性についての検討

    曽根 博仁

    糖尿病   37 ( Suppl.1 )   398 - 398   1994.4

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  • 抗利尿ホルモン分泌異常症候群と両側声帯不全麻痺を合併したShy-Drager症候群の一例

    曽根 博仁, 奥田 諭吉, 坂内 千恵子

    日本内分泌学会雑誌   70 ( 2 )   75 - 84   1994.3

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    A 67-year-old man with SIADH complicated by slowly progressing autonomic failure was described. The patient noticed constipation at the age of 57. In the following years, he suffered from urinary incontinence, depletion of sweating, impotence, sleeplessness with snore, and dizziness while walking. Physical examination revealed a masked oily face with slight cerebellar disturbance.<BR>Abnormality of autonomic function tests was recognized and he was diagnosed as Shy-Drager syndrome with gradually progressing, diffuse autonomic failure accompanied by slight cerebellar ataxia and Parkinsonism. Both serum sodium level and plasma osmotic pressure were reduced, whereas daily sodium excretion was more than 100mEq and urinary osmolality was about 500mOsm/kgH<SUB>2</SUB>O. His renal function was intact, and the adreno-cortical and thyroid hormone levels were normal, then criteria of SIADH was fulfilled. SIADH was thought to have occurred on the basis of Shy-Drager syndrome.<BR>Water load test showed failure of adequate water diuresis, but intravenous phenytoin administration following the water load test ameliorated the diuresis to normal. The relationship between plasma osmolality and the ADH response indicates that ADH was adequately secreted in response to the increase in plasma osmolality but not suppressed in response to the decrease in plasma osmolality below 280mOsm/kgH<SUB>2</SUB>O. These results suggest that ADH synthesis in the hypothalamus and its secretion from the pituitary gland were both intact.<BR>The response of ADH secretion to the orthostatic hypotension induced by head-up tilt was quite blunted, being compatible with Shy-Drager Syndrome. Sleep disturbance was studied by polysomnography and laryngoscopy, and was revealed to be based upon severe sleep apnea due to incomplete paralysis of the bilateral vocal cords. Sleep apnea due to vocal cord paralysis is sometimes found to be complicated in patients with multiple system atrophy (MSA) including Shy-Drager syndrome, and is known as Gerhardt syndrome.<BR>This is the first report on a case of Shy-Drager syndrome complicated with SIADH and bilateral vocal cord paralysis. In this case, SIADH is caused by impaired afferent pathways from baroreceptors to the hypothalamus, which transfer inhibitory stimuli on ADH secretion. It is suggested that Shy-Drager syndrome should be considered one of the causes of SIADH.

    DOI: 10.1507/endocrine1927.70.2_75

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  • 抗利尿ホルモン分泌異常症候群(SIADH)と両側声帯不全麻痺を合併したShy-Drager症候群の1例

    曽根 博仁

    日本内科学会関東地方会抄録集   ( 5 )   87 - 87   1994.3

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  • 糖尿病性神経障害に対しアルガトロバン製剤が著効した症例

    Therapeutic Research   15   535 - 538   1994

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  • Effects of Beraprost Sodium on Lower Limb Circulation in NIDDM Patients-Evaluated by Doppler Echography and Laser Blood Flowmetry

    Michiko Asano, Yukichi Okuda, Masakazu Mizutani, Hirohito Sone, Yoko Trushima, Masashi Ogawa, Yukari Asakura, Takashi Yamaoka, Seiji Suzuki, Masaaki Isaka, Chieko Bannnai, Yasushi Kawakami, Masato Odawara, Teruhiko Matsushima, Koichi Kawai, Kamejiro Yamashita

    Journal of the Japan Diabetes Society   37 ( 5 )   379 - 382   1994

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    Non-insulin dependent diabetic patients were studied to evaluate the effects of Beraprost sodium (sodium (±)-(1R∗, 2R∗, 3aS∗, 8bS∗)-2, 3, 3a 8b-tetrahydro-2-hydroxy-1-[(E)-(3S∗) -3-hydroxy-4 -methyl-I-octen-6-ynyl] -1H-cyclopenta [b] benzofuran-5-butyrate) which is a stable analogue of PGI2, as a vasodilater and anti-platelet agent. Hemodynamic effects of this durg on the dorsal pedis artery were examined using a new real-time two-dimensional Doppoler echography technc-que and laser blood flowmetry. Before, and 60 min and 90 min after, oral administration of Beraprost sodium (Dolner® 40 μg) and Elastase (Elaszym® 1800 U), the cross-sectional area (Area) of the dorsal pedis artery and its blood flow index (BFI), calculated from maximum flow velocity and area, were determined. Dermal microcirulatory blood vloume (MCBV) was also measured using the laser blood flowmeter. In the Beraprost sodium group, the area and the BFI were significantly increased. MCBV was also significantly increased. In the Elastase group, no significant changes were observed. (Talbe2) From these results, it is suggested that Berarost sodium has beneficial effects on diabetic macro-and microangiopathy. © 1994, THE JAPAN DIABETES SOCIETY. All rights reserved.

    DOI: 10.11213/tonyobyo1958.37.379

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  • Effect of Ibudilast on Lower Limb Circulation in NïDDM Patients'Evaluated by Doppler Echography and Laser Blood Flowmetry-

    Hirohito Sone, Yukichi Okuda, Masakazu Mizutani, Yukari Asakura, Michiko Asano, Yoko Tsurushima, Masashi Ogawa, Takashi Yaniaoka, Seiji Suzuki, Masaaki Isaka, Chieko Bannai, Yasushi Kawakami, Masato Odawara, Teruhiko Matsushima, Koichi Kawai, Kamejiro Yamashita

    Journal of the Japan Diabetes Society   37 ( 4 )   307 - 310   1994

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    Ibudilast (3-isobutyryl-2-isopropylpyrazolo-[1,5a] pyridine) is a prostacyclin mediated vasodilator and anti-platelet agent that has a relatively long duration of action and is orally active. Non-insulin dependent diabetic patients were studied to evaluate the effects of ibudilast on hemodynamic changes in the circulation by two dimensional Doppler echography and laser blood flowmetry. Before and 1 h after administration of ibudilast (10 mg) or elastase (1800 U), the cross -sectional area (Area) of the dorsal pedis artery and its Blood Flow Index (BFI), calculated from maximum flow velocity and Area, were determined. Dermal microcirculatory blood volume (MCBV) was also measured with the laser blood flowmeter. In the ibudilast group, the Area was significantly increased from 2.72±0.32 to 3.21 ±0.35 mm2 (Mean SE, p &lt
    0.05). The BFI was also siginificantly increased from 28.3±3.7 to 37.0±5.2 (p &lt
    0.01)In the ibudilast group. MCBV was also significantly increased from 3.82±0.70 to 4.96±0.71 ml/min/100g tissue (p&lt
    0.01). No significant changes were observed in the data of the elastase group, and no side effects were observed in any of the patients in either of group. The results of this study suggest that ibudilast may be useful in ameliorating diabetic macro and microangiopathy of the lower limbs. © 1994, THE JAPAN DIABETES SOCIETY. All rights reserved.

    DOI: 10.11213/tonyobyo1958.37.307

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  • 糖尿病性神経障害患者におけるBeraprost Sodiumの下肢血流に及ぼす効果の検討

    臨床と研究   71   228 - 230   1994

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  • 抗利尿ホルモン不適切分泌症候群と両側声帯不全麻痺を合併したShy-Drager症候群の一例

    曽根 博仁

    日本内分泌学会雑誌   69 ( 8 )   726 - 726   1993.9

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  • 糖尿病コントロールの悪化に伴い遅発性初期悪化を来した肺結核症の1例

    曽根 博仁

    茨城県臨床医学雑誌   ( 29 )   16 - 16   1993.8

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  • Hemodynamic effects of lipo-PGE<sub>1</sub> on peripheral artery in patients with diabetic neuropathy : evaluated by two-dimentional color Doppler echography. Reviewed

    Okuda Y, Mizutani M, Ogawa M, Sone H, Asano M, Tsurushima Y, Morishima Y, Asakura Y, Suzuki S, Isaka M, Sakakibara M, Yamashita K, Hori M

    Diabetes Research   22   87 - 95   1993

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  • 学生として体験したオーストラリアでの心臓・肝臓移植実習について

    曽根 博仁

    医学教育   21 ( 6 )   421 - 425   1990

  • Experiences of medical education which can never be seen in Japan: Our own experiences in the university of newcastle, faculty of medicine, Australia.:Our Own Experiences in the University of Newcastle, Faculty of Medicine, Australia

    Inoue Manami, Sone Hirohito

    Igaku Kyoiku / Medical Education (Japan)   21 ( 4 )   287 - 290   1990

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    We visited the University of Newcastle to take clinical clerkships from April to June 1989. We tried to experience what we had not had in our medical educational system; for example, geriatrics or medical ethics. We also compared the difference of medical educational program between Japan and Australia, especially, the way of examining students.

    DOI: 10.11307/mededjapan1970.21.287

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Presentations

  • 内科から見た糖尿病網膜症診療ガイドラインの意義

    曽根 博仁

    第25回日本糖尿病眼学会総会  2019.9 

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    Event date: 2019.9

    Presentation type:Symposium, workshop panel (nominated)  

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  • 「これからの糖尿病食事療法における課題と展望」大規模データサイエンスから見た新食事ガイドラインに残された課題と解決案―患者さんと指導現場の疑問に答えるには―

    曽根 博仁

    第64回日本糖尿病学会年次学術集会  2021.5 

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  • 「ビッグデータで切り開く糖尿病診療」リアルワールドデータを駆使した糖尿病診療・療養指導のエビデンス確立

    曽根 博仁

    第64回日本糖尿病学会年次学術集会  2021.5 

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  • 大規模医療データサイエンスに基づく臨床栄養学ービッグデータが変える食事栄養療法の未来ー

    曽根 博仁

    第42回日本臨床栄養学会総会・第41回日本臨床栄養協会総会 第18回大連合大会  2020.10 

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  • 三条市の食育と介護の現状を踏まえた健康寿命延伸策―新潟大学との共同研究結果が示す未来への提言

    曽根 博仁

    令和2年度三条市と新潟大学の共同研究事業講演会  2020.10 

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  • 「糖尿病診療現場に活かせる日本人大規模医療データ解析」JDCSから大規模医療データサイエンスへ

    曽根 博仁

    第63回日本糖尿病学会年次学術集会  2020.10 

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  • 「慢性疾患治療のための運動療法 Up-to-date」糖尿病の予防と治療のための身体活動と運動療法

    曽根 博仁

    第39回日本臨床運動療法学会学術集会  2020.9 

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  • 「糖尿病大血管症に対する多面的アプローチ」リアルワールド・ビッグデータから見た糖尿病大血管症のリスクと管理

    曽根 博仁

    第52回日本動脈硬化学会総会・学術集会  2020.7 

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  • 日本人ビッグデータのエビデンスに基づく糖尿病生活習慣療法

    曽根 博仁

    神奈川県保険医協会第36回糖尿病セミナー  2020.2 

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  • 「診療ガイドラインの動向」糖尿病患者における動脈硬化疾患の予防

    曽根 博仁

    日本動脈硬化学会第20回 動脈硬化教育フォーラム  2020.2 

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  • 臨床研究の進め方とその成果―既存のデータを活用した研究

    曽根 博仁

    第57回 日本糖尿病学会関東甲信越地方会 教育セミナー  2020.1 

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  • 働く世代の糖尿病とその合併症の予防・治療―職域における介入のポイント

    曽根 博仁

    新潟産業保健総合支援センター 産業保健セミナー  2019.12 

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  • 新潟のビッグデータを活用した健康長寿日本一への挑戦

    曽根 博仁

    新潟大学産学交流フェスタ2019  2019.11 

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  • 大規模臨床研究・ビッグデータから見た糖尿病診療

    曽根 博仁

    日本内科学会北海道支部 第62回生涯教育講演会  2019.11 

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  • ビッグデータ解析が示すこれからの糖尿病診療

    曽根 博仁

    2019.10 

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  • 糖尿病患者の心血管イベントに対する薬物介入研究

    曽根 博仁

    第34回日本糖尿病合併症学会総会  2019.9 

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  • From Cohorts to Real-World Big Data for Prevention of Type 2 Diabetes and Its complications International conference

    SONE, Hirohito

    The 1st International Symposium on Integrated Medicine in Endocrinology and Diabetes  2019.9 

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  • 日本人若年女性におけるやせの実態と課題:エビデンスとこれからの対策

    曽根 博仁

    第20回日本内分泌学会関東甲信越支部学術集会  2019.9 

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  • これからの栄養・生活習慣病学関連の研究開発に求められる視点

    曽根 博仁

    米及び加工食品の新市場創出に向けたマッチングフォーラム in にいがた  2019.9 

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  • ビッグデータ時代の臨床エビデンスに基づく運動療法

    曽根 博仁

    第38回日本臨床運動療法学会学術集会  2019.8 

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  • ビッグデータ解析で見えてくる新たな糖尿病臨床エビデンス.大規模医療データサイエンスは日常診療をどう変えるか?

    曽根 博仁

    第19回日本糖尿病情報学会年次学術集会  2019.8 

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  • 食事療法指導に役立つ大規模臨床エビデンス

    曽根 博仁

    第18回栃木県臨床糖尿病セミナー  2019.7 

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  • 昭和・平成から令和につなげる生活習慣改善への道-2022年ガイドライン改訂に向けて「生活習慣教育・介入の効果」

    曽根 博仁

    第51回動脈硬化学会総会  2019.7 

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  • ビッグデータ解析から見た2型糖尿病の動脈硬化合併症

    曽根 博仁

    第51回動脈硬化学会総会  2019.7 

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  • ビッグデータ解析のエビデンスが示す糖尿病医療の方向性

    曽根 博仁

    第41回埼玉内分泌代謝研究会  2019.6 

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  • 新潟県における糖尿病腎症重症化予防プログラムの展開

    曽根 博仁

    新潟県糖尿病性腎症重症化予防対策担当者研修会  2019.6 

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  • From Patient Cohorts to Real-World Big Data: Seeking the Asian phenotype of type 2 diabetes International conference

    SONE, Hirohito

    The 11th Asian Association for the Study of Diabetes(AASD)  2019.5 

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    Presentation type:Oral presentation (invited, special)  

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  • 医療・保健ビッグデータを活用した糖尿病とその合併症予防のエビデンス

    曽根 博仁

    第62回日本糖尿病学会年次学術集会  2019.5 

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    Presentation type:Symposium, workshop panel (nominated)  

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  • 機能性食品と栄養学の将来を考える

    曽根 博仁

    第73回日本栄養・食糧学会総会  2019.5 

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    Presentation type:Symposium, workshop panel (nominated)  

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  • 糖尿病患者における運動療法の有効性に関する大規模臨床エビデンス

    曽根 博仁

    第92回日本内分泌学会総会  2019.5 

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  • 糖尿病の発症・重症化予防のための生活習慣療法エビデンス

    曽根 博仁

    第20回埼玉心臓リハビリテーションセミナー  2019.4 

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  • 糖尿病の疫学・大規模臨床研究-過去と未来-

    曽根 博仁

    第53回日本糖尿病学会「糖尿病学の進歩」  2019.3 

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  • 医療ビッグデータと大規模臨床データを用いた糖尿病研究 進め方の重要点とコツ

    曽根 博仁

    第53回日本糖尿病学会「糖尿病学の進歩」  2019.3 

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    Presentation type:Oral presentation (invited, special)  

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  • 全国をリードする「食育と健康長寿の街」への挑戦. 新潟県NGTプロジェクトとの連動も含めて

    曽根 博仁

    三条市役所職員研修会  2019.2 

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  • 新潟のビッグデータを活用した健康長寿日本一への挑戦シンポジウム

    曽根 博仁

    新潟県「にいがた新世代ヘルスケア情報基盤」シンポジウム  2019.1 

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  • 日本人2型糖尿病患者における食事と合併症との関連-最近20年間の食事変化も含めて-

    曽根 博仁

    第22回日本病態栄養学会総会  2019.1 

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    Presentation type:Symposium, workshop panel (nominated)  

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  • 医療との共存共栄を目指した機能性食品への期待

    曽根 博仁

    第16回日本機能性食品医用学会総会  2018.12 

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  • ビッグデータ解析が教えるわが国の糖尿病合併症の現状と課題

    曽根 博仁

    第3回 日本糖尿病・生活習慣病ヒューマンデータ学会総会  2018.12 

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    Presentation type:Symposium, workshop panel (nominated)  

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  • 食べることは元気のもと

    曽根 博仁

    新潟大学公開講座「食と糖尿病」  2018.11 

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  • 糖尿病とその重症化の予防-地域と家族と自分のために-

    曽根 博仁

    ライオンズクラブ国際協会講演会  2018.11 

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  • 肥満と2型糖尿病 ビッグデータが示すリアルワールド・エビデンス

    曽根 博仁

    日本内分泌学会 生涯教育講演会  2018.11 

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  • 大規模臨床エビデンスに基づく糖尿病の運動療法指導

    曽根 博仁

    全日本民医連糖尿病シンポジウム  2018.10 

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  • 糖尿病網膜症と大血管合併症のビッグデータ解析によるエビデンス

    曽根 博仁

    第24回日本糖尿病眼学会総会  2018.10 

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  • 糖尿病とその合併症予防を通じた県民の健康寿命延伸-特に腎症による透析予防を中心に-

    曽根 博仁

    新潟県平成30年度慢性腎臓病糖尿病対策研修会  2018.9 

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  • ビッグデータ解析に基づく2型糖尿病とその合併症の予防と治療

    曽根 博仁

    動脈硬化UpDate  2018.9 

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  • 特別講演「人間ドックのビッグデータが教える健康長寿エビデンス」

    曽根 博仁

    第59回日本人間ドック学会学術総会  2018.8 

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  • 糖尿病とその重症化予防のための食生活

    曽根 博仁

    新潟栄養・食生活学会 市民公開講演会  2018.7 

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  • 地域における糖尿病とその合併症の予防

    曽根 博仁

    村上総合病院集談会  2018.7 

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  • 臨床の現場から見た糖質制限食 (低炭水化物食) の課題

    曽根 博仁

    新潟県新たな米産業創出技術研究会  2018.7 

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  • 子どもから大人までの糖尿病・生活習慣病の予防と治療

    曽根 博仁

    第1回うおぬま市民大学講演会  2018.6 

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  • シンポジウムJDCP研究が示す我が国の糖尿病診療の現状. 日本人2型糖尿病患者における栄養摂取と身体活動の現状

    曽根 博仁

    第61 回日本糖尿病学会年次学術集会  2018.5 

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  • 教育講演「糖尿病における栄養疫学のエビデンス」

    曽根 博仁

    第61回日本糖尿病学会年次学術集会  2018.5 

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  • 糖尿病にならない、そして負けないために

    曽根 博仁

    ライオンズクラブ糖尿病フェスタ  2018.4 

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  • 医療ビッグデータ解析が開く次世代の糖尿病・生活習慣病診療

    曽根 博仁

    新潟市内科医会総会  2018.4 

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  • ビッグデータ解析が示す糖尿病とその合併症の予防

    曽根 博仁

    愛知県医師会・愛知県糖尿病対策推進会議  2018.3 

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  • 三条市と新潟大学との共同研究による小児から高齢者までの健康増進プロジェクト

    曽根 博仁

    三条市役所職員研修会  2018.3 

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  • 臨床ビッグデータから見た2型糖尿病における高トリグリセリド血症の意義

    曽根 博仁

    第52回日本糖尿病学会「糖尿病学の進歩」  2018.3 

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  • 地域・職場における糖尿病管理

    曽根 博仁

    第18回日本動脈硬化学会「動脈硬化教育フォーラム」  2018.2 

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  • 教育講演「産業保健と総合健診ー脳心血管病予防に関する包括的リスク管理チャートの活用ー糖尿病管理」

    曽根 博仁

    第46回日本総合健診医学会総会  2018.1 

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  • シンポジウム 動脈硬化予防と脂質代謝「糖尿病患者における脂質異常症と動脈硬化疾患ー日本人ビッグデータからのエビデンスー」

    曽根 博仁

    第21回日本病態栄養学会年次学術集会  2018.1 

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  • 医療ビッグデータ解析が開く新しい糖尿病診療の視点ー生活習慣療法の重要性ー

    曽根 博仁

    山梨心血管疾患診療セミナー  2017.12 

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  • 子供世代から始める生活習慣病 健康長寿の取り組み一阿賀野市と新潟大学医学部の共同研究

    曽根 博仁

    阿賀野市健康講座  2017.12 

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  • ビッグデータ解析による糖尿病合併症の予測と予防

    曽根 博仁

    日本糖尿病合併症学会・日本糖尿病眼学会  2017.11 

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  • 大規模臨床研究が教える糖尿病の新しい診療エビデンス

    曽根 博仁

    第13回知多半島医療圏糖尿病治療研究会  2017.11 

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  • シンポジウム 日本臨床疫学会と各臨床専門学会の連携「日本臨床疫学会への期待-臨床専門学会との連携によるビッグデータ時代の新しい予防・診療EBM構築を目指してー」

    曽根 博仁

    日本臨床疫学会第1回年次学術大会  2017.11 

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  • 脳・心血管疾患予防を通じた科学的根拠に基づく介護予防

    曽根 博仁

    新潟市医師会在宅医療講座  2017.11 

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  • 医療ビッグデータ解析が開く新しい糖尿病診療の視点ー生活習慣療法の重要性ー

    曽根 博仁

    第14回糖尿病病診連携懇話会  2017.11 

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  • 2型糖尿病患者における炭水化物摂取の実態と糖尿病合併症との関連

    曽根 博仁

    第2回糖尿病・生活習慣病ヒューマンデータ研究会  2017.11 

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  • 基調講演「ビッグデータ解析を活かした糖尿病の予防と治療の新しい戦略」

    曽根 博仁

    日本先進糖尿病研究会  2017.10 

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  • 糖尿病に負けず健やかに過ごすために

    曽根 博仁

    ライオンズクラブ国際協会講演会  2017.10 

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  • 日本人ビッグデータから見た糖尿病予防と治療の戦略

    曽根 博仁

    新庄市糖尿病予防研修会  2017.10 

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  • 特別講演「医療ビッグデータ解析に基づく糖尿病診療と生活習慣指導」

    曽根 博仁

    全国済生会糖尿病セミナー  2017.8 

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  • 特別講演「新しい生活習慣病臨床研究の展開ー現場に活かせるエビデンスを生み出すにはー」

    曽根 博仁

    .第4回愛知臨床研究懇話会  2017.6 

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  • シンポジウム19 生活習慣病の運動療法 「糖尿病・脂質異常を中心とした生活習慣病に対する運動の効果」

    曽根 博仁

    第17回抗加齢学会総会  2017.6 

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  • シンポジウム27 世界と日本の大規模臨床研究の現在. 日本人糖尿病の予防と治療に関するビッグデータ解析の可能性

    曽根 博仁

    第60回日本糖尿病学会年次学術集会  2017.5 

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  • 特別講演「日常診療における臨床研究の重要性―大規模現場データ解析に基づく新しい糖尿病診療」

    曽根 博仁

    神奈川県保険医協会研究会  2017.4 

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  • 教育講演「糖尿病の概念と疫学―大規模医療データから学ぶこと」

    曽根 博仁

    第51回日本糖尿病学会 糖尿病学の進歩  2017.2 

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  • 特別講演「医療ビッグデータとしての臨床検査データの利活用―糖尿病を中心とした生活習慣病分野を例に」

    曽根 博仁

    第27回 生物試料分析科学会年次学術集会  2017.2 

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  • シンポジウム17 臨床研究の進め方‐ビッグデータの活用と解析‐ 「医療ビッグデータの病態栄養学研究への活用」

    曽根 博仁

    第20回日本病態栄養学会年次学術集会  2017.1 

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  • Symposium: An international project on harmonized accumulation of reference values and clinical case records for EBLM. The Utility of Well-Defined Clinical Case Bank (CCB) for Early Detection of Endocrine, Hematological and Immune Disorders International conference

    SONE, Hirohito

    Asia-Pacific Federation for Clinical Biochemistry And Laboratory Medicine (APFCB)  2016.11 

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  • 特別講演 大規模臨床データ解析が開く新しい糖尿病合併症学-網膜症を中心に-

    曽根 博仁

    第31回日本糖尿病合併症学会/第22回日本糖尿病眼学会総会  2016.10 

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  • 糖尿病・脂質異常症を中心とした生活習慣病に対する運動の効果 シンポジウム「生活習慣病の運動療法」

    曽根 博仁

    第35回日本臨床運動療法学会学術集会  2016.9 

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  • Symposium : Diabetes care using information technology. Effects of lifestyle modification on cardiovascular complications in Japanese patients with type 2 diabetes International conference

    SONE, Hirohito

    The 10th Congress of Asian-Pacific Society of Atherosclerosis and Vascular Disease (APSAVD)  2016.7 

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  • シンポジウム「包括的リスク管理とJASガイドライン」脳心血管疾患高リスク者としての糖尿病患者への対応

    曽根 博仁

    第48回動脈硬化学会総会  2016.7 

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  • Symposium “Clinical Evidences in Macrovascular Complications” Prediction and risk assessment of diabetic macrovascular complications in Japan

    SONE, Hirohito

    2016.5 

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  • 特別講演 臨床研究のすすめ-現場に役立つ臨床研究エビデンスを現場から生み出すには-

    曽根 博仁

    臨床糖尿病医会  2016.4 

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  • シンポジウム わが国の臨床研究から何を学べばよいか JDCS

    曽根 博仁

    第50回糖尿病学の進歩  2016.2 

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  • 糖尿病とその重症化予防の視点から. パネルディスカッション「日本人の食事摂取基準2015」

    曽根 博仁

    第19回日本病態栄養学会年次学術集会  2016.1 

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  • 生活習慣病を疫学・大規模臨床データから考える「体質から生活までを考える代謝内科学」

    曽根 博仁

    日本内科学会学術集会第43回内科学の展望  2015.11 

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  • セミナー EBMに立脚した生活習慣病の患者教育と医学教育-日本の医学教育に足りないもの

    曽根 博仁

    第47回日本医学教育学会総会  2015.7 

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  • 大規模データからみた日本人糖尿病患者の動脈硬化疾患とその対策. シンポジウム6 糖尿病と動脈硬化-わが国発の臨床研究と基礎研究-

    曽根 博仁

    第47回日本動脈硬化学会総会・学術集会  2015.7 

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  • 運動療法で伸ばす健康寿命ー科学的エビデンスに基づく運動指導

    曽根 博仁

    日本医師会生涯教育講座セミナー  2015.6 

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  • 特別講演. 日本人の大規模臨床エビデンスに基づく2型糖尿病の予防と治療

    曽根 博仁

    日本内科学会信越地方会  2015.6 

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  • シンポジウム15 「日本人の食事摂取基準(2015年版)」は健康長寿社会の基盤となるか. 糖尿病とその重症化予防の観点から

    曽根 博仁

    第15回日本抗加齢医学会総会  2015.5 

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  • シンポジウム(S24) 大規模スタディから学ぶ. 医療ビッグデータを活用した糖尿病予防研究

    曽根 博仁

    第58回日本糖尿病学会年次学術集会  2015.5 

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  • シンポジウムEBMで最も高い根拠となる系統的レビュー、その最前線

    曽根 博仁

    日本医学会総会  2015.4 

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  • Symposium “Diabetes and related eye diseases in Asia-Pacific countries ” Characteristics of diabetes and its eye complications in Japan: The Japan Diabetes Complications Study International conference

    SONE, Hirohito

    The 30th Asia-Pacific Academy of Ophthalmology Congress  2015.4 

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  • 科学的エビデンスに基づく糖尿病対策-発症と合併症予防の両面から

    曽根 博仁

    第1回新潟県糖尿病対策推進会議総会  2014.12 

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  • East-West Symposium. Characteristics of diabetic complications in Japanese patients International conference

    SONE, Hirohito

    50th European Association for the Study of Diabetes (EASD)  2014.9 

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  • シンポジウム 新医学へと展開する.疫学・統計学. 抗加齢医学における実例と今後. 運動による健康長寿の可能性ー臨床疫学の視点からー

    曽根 博仁

    日本抗加齢医学会  2014.6 

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  • セミナー 日本人の大規模臨床エビデンスに基づく糖尿病の治療と予防~特に食事・運動療法を中心に~

    曽根 博仁

    第57回日本糖尿病学会年次学術集会  2014.5 

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  • Prediction and risk assessment of diabetes and its complications in Japan International conference

    SONE, Hirohito

    2013 International Conference on Diabetes and Metabolism & 5th Asian Association for the Study of Diabetes  2013.11 

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  • シンポジウム 運動と脂質代謝. 運動と糖尿病・脂質代謝異常・高血圧に対する運動療法の効果と意義

    曽根 博仁

    第68回日本体力医学会大会  2013.9 

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  • シンポジウム 医学における栄養学の最新研究-生活習慣病の食事療法に関する大規模臨床エビデンス

    曽根 博仁

    第67回日本栄養・食糧学会大会  2013.5 

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  • 細小・大血管合併症の両方を視野に入れた日本人患者に適した血糖コントロールを

    曽根 博仁

    第56回日本糖尿病学会年次学術集会  2013.5 

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  • Debate; Target HbA1c : Associations between HbA1c Level and Diabetic Complications in Japanese Patients with Type 2 Diabetes International conference

    SONE, Hirohito

    9th International Diabetes Federation Western Pacific Region Congress (9th IDF-WPR) & 4th Scientific Meeting of Asian Association for Study of Diabetes (4th AASD Scientific Meeting)  2012.11 

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  • シンポジウム JDCS: 実地臨床へのメッセージ-最近の解析結果より

    曽根 博仁

    第49回日本糖尿病学会 近畿地方会  2012.11 

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  • シンポジウム 地域医療における糖尿病の予防と治療 –未病システム学における糖尿病の意義-

    曽根 博仁

    第19回日本未病システム学会  2012.10 

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  • シンポジウム:大規模試験からのメッセージ JDCS

    曽根 博仁

    第55回日本糖尿病学会年次学術集会  2012.5 

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  • HbA1c variability as a risk of microvascular complication in diabetes International conference

    SONE, Hirohito

    2011 International Conference on Diabetes and Metabolism  2011.11 

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  • シンポジウム6 Atherosclerosis in Diabetes –Serch for Ner Therapeutic Strategies-糖尿病と動脈硬化―新しい治療戦略を探る- 「Messages from the Japan Diabetes Complications Study (JDCS)」

    曽根 博仁

    第43回日本動脈硬化学会総会・学術集会  2011.7 

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  • 動脈硬化の予防と治療―糖尿病

    曽根 博仁

    第52回日本老年医学会学術集会・総会  2010.6 

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  • The Japan Diabetes Complications Study (JDCS)

    SONE, Hirohito

    2010.5 

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  • クリニカルクエスチョンから論文出版へ

    曽根 博仁

    日本メディカルライター協会 臨床研究セミナー5  2010.3 

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  • Blood Glucose Control and Cardiovascular Disease in Japan Diabetes Complications Study(JDCS)

    SONE, Hirohito

    2010.3 

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  • 2型糖尿病患者のQOL、血管合併症及び長期予後改善のための前向き研究

    曽根 博仁

    循環器疾患等生活習慣病対策総合研究・糖尿病戦略等研究 研究成果発表会  2010.2 

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  • Obesty, Metabolic Risk Factors and Lifestyle in Patients with Type 2 Diabetes in Japan International conference

    SONE, Hirohito

    The 15th Korea-Japan Symposium on Diabetes Mellitus  2009.11 

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  • シンポジウム「動脈硬化性疾患ガイドライン-残された問題点」糖尿病と脂質異常症

    曽根 博仁

    第41回日本動脈硬化学会総会・学術集会  2009.7 

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  • シンポジウム「糖尿病と脳卒中の疫学:日本の研究から」

    曽根 博仁

    第52回日本糖尿病学会年次学術集会  2009.5 

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  • シンポジウム「糖尿病の血管合併症のトータルケア:早期診断、そして予防へ」わが国の血管合併症の実態:JDCSより

    曽根 博仁

    第106回日本内科学会講演会  2009.4 

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  • シンポジウム「生活習慣病と動脈硬化、リスクとその管理」糖尿病における動脈硬化症とそのリスクファクター管理

    曽根 博仁

    第42回日本生活習慣病学会  2008.1 

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  • シンポジウム「生活習慣病と動脈硬化、リスクとその管理」糖尿病における動脈硬化症とそのリスクファクター管理

    曽根 博仁

    第42回日本生活習慣病学会  2007.12 

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  • ワークショップ「大血管合併症」

    第22回糖尿病合併症学会  2007 

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  • アスコルビン酸の栄養状態の違いによるナトリウム依存性ビタミンCトランスポーター(SVCT)の発現変動

    日本ビタミン学会第59回大会  2007 

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  • 糖尿病網膜症の発症予防と進展抑制に関する多施設研究(Japan Diabetes Complications Study)の報告

    第61回日本臨床眼科学会  2007 

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  • 有酸素性運動によるHDLコレステロール(HDL-C)上昇のメタアナリシス

    日本内科学会講演会  2007 

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  • 日本人2型糖尿病患者における早期腎症発症のリスクファクターの検討.

    第50回日本糖尿病学会年次学術集会  2007 

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  • 全国多施設共同研究による糖尿病患者の動脈硬化性疾患の追跡調査:観察開始時の特徴-JDDMスタディー-.

    第50回日本糖尿病学会年次学術集会  2007 

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  • 脂肪酸伸長酵素Fatty acyl-CoA elongase (FACE)の生体内における機能ならびに病態への関与.

    第50回日本糖尿病学会年次学術集会  2007 

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  • 喫煙の糖尿病腎症に及ぼす影響に関するコホート研究

    日本内分泌学会関東甲信越地方会  2007 

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  • Metabolic syndrome in Japanese Type 2 Diabetic Patients. From the results of Japan Diabetes Complications Study (JDCS)

    14th Japan-Korea Symposium on Diabetes Mellitus  2007 

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  • No effect from low-carbohydrate diet on glycemic control in diabetic patients:Meta-analysis.

    14th Japan-Korea Symposium on Diabetes Mellitus  2007 

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  • Low-fat diet may improve glycemic control in diabetic patients:Meta-analysis

    14th Japan-Korea Symposium on Diabetes Mellitus  2007 

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  • Factors affecting remission of microalbuminuria in patients with type 2 diabetes: Tsukuba Kawai Diabetes Registry (TKDR) 2.

    14th Japan-Korea Symposium on Diabetes Mellitus  2007 

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  • Both current and past smoking are dose dependent risk factors for the development of microalbuminuria in Japanese men with type 2 diabetes.

    67nd Annual Meeting and Scientific Sessions, American Diabetes Association.  2007 

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  • 一般演題:栄養学的研究

    第39回日本動脈硬化学会・学術集会  2007 

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  • 喫煙の糖尿病腎症発症に及ぼす影響に関するコホート研究

    第41回日本成人病(生活習慣病)学会 学術集会  2007 

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  • 有酸素性運動によるHDLコレステロール(HDL-C)上昇のメタアナリシス

    第41回日本成人病(生活習慣病)学会 学術集会  2007 

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  • 日本人糖尿病患者における動脈硬化合併症.

    臨床疫学研究会  2007 

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  • 「元気で長生き」をめざす新しい生活科学

    お茶の水女子大学第一回ホームカミングデイ生活科学部記念講演会  2007 

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  • 臨床疫学の最近の進歩―日本人のエビデンス―Japan Diabetes Complications Study (JDCS) .

    糖尿病と生活習慣病治療研究会  2007 

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  • メタボリックシンドロームと運動

    「志賀高原で語る自然と健康」講演会  2007 

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  • 日本人2型糖尿病患者の病態と合併症

    第15回北摂糖尿病フォーラム  2007 

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  • ランチョンセミナー 日本人の血管合併症―JDCS― 第50回日本糖尿病学会年次学術集会

    第50回日本糖尿病学会年次学術集会  2007 

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  • Symposium of the Committee on the Treatment of Diabetes Mellitus. Clinical Features of Japanese Patients with Type 2 Diabetes From the results of the JDCS and other large-scale clinical studies in Japan.

    20th Spring Congress of Korea Diabetes Association  2007 

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  • 日本人の血管合併症―JDCS―

    第50回日本糖尿病学会年次学術集会  2007 

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  • 日本人における2型糖尿病とメタボリックシンドローム

    第2回上越メタボリックシンドローム懇話  2007 

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  • 日本人糖尿病患者のメタボリックシンドロームと動脈硬化性疾患について~JDCSを中心に~

    第4回広島糖尿病研究会学術講演会  2007 

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  • シンポジウム「メタボリックシンドロームと機能性食品」 糖尿病専門医の立場からみた機能性食品への期待

    第5回日本機能性食品医用学会総会  2007 

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  • 食べ物は病気を予防できるのか ―生活習慣病への挑戦― .

    お茶の水女子大学文京アカデミー公開講座  2007 

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  • シンポジウム「糖尿病網膜症-病態研究および治療の最前線-」糖尿病合併症における網膜症の位置づけ

    第22回 日本糖尿病合併症学会  2007 

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  • 日本の大規模臨床研究からみた糖尿病とその合併症

    長野医学会  2007 

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  • Type 2 diabetes and its management in Japan

    Seoul Diabetes Forum 2007  2007 

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  • Japan Diabetes Complications Study (JDCS)

    Diabetes in Metabolic Syndorome研究会  2007 

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  • 日本人2型糖尿病患者の病態と生活習慣.

    第10回志太榛原臨床栄養研究会  2007 

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  • 日本人2型糖尿病患者における高脂血症と動脈硬化イベント

    第45回東京脂質代謝研究会.  2007 

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  • Factors affecting remission of microalbuminuria in patients with type 2 diabetes: Tsukuba Kawai Diabetes Registry (TKDR) 2.

    14th Japan-Korea Symposium on Diabetes Mellitus  2007 

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  • Low-fat diet may improve glycemic control in diabetic patients:Meta-analysis.

    14th Japan-Korea Symposium on Diabetes Mellitus  2007 

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  • Both current and past smoking are dose dependent risk factors for the development of microalbuminuria in Japanese men with type 2 diabetes.

    67nd Annual Meeting and Scientific Sessions, American Diabetes Association  2007 

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  • Metabolic syndrome in Japanese Type 2 Diabetic Patients. From the results of Japan Diabetes Complications Study (JDCS)

    14th Japan-Korea Symposium on Diabetes Mellitus  2007 

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  • No effect from low-carbohydrate diet on glycemic control in diabetic patients:Meta-analysis.

    14th Japan-Korea Symposium on Diabetes Mellitus  2007 

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  • Symposium of the Committee on the Treatment of Diabetes Mellitus. Clinical Features of Japanese Patients with Type 2 Diabetes From the results of the JDCS and other large-scale clinical studies in Japan.

    20th Spring Congress of Korea Diabetes Association  2007 

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  • Type 2 diabetes and its management in Japan

    Seoul Diabetes Forum 2007  2007 

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  • 一般演題:栄養学的研究(1)

    第38回日本動脈硬化学会・学術集会  2006 

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  • 日本人2型糖尿病患者の心血管疾患発症予測におけるメタボリックシンドローム診断の臨床的有用性-Japan Diabetes Complications Study (JDCS)中間解析より

    第103回日本内科学会講演会 プレナリーセッション  2006 

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  • 2型糖尿病患者における腎症発症のリスクファクターに関する前向き研究.

    第17回日本糖尿病性腎症研究会  2006 

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  • 妊娠32週で発症した劇症1型糖尿病が疑われた一例.

    第42回日本糖尿病学会関東甲信越地方会  2006 

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  • 井村臨床研究奨励賞受賞講演「2型糖尿病患者の血管合併症に関する国際臨床疫学的研究」

    平成18年度京都成人血管病シンポジウム  2006 

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  • セミナー1 糖尿病対策を生活習慣病からアプローチ 高脂血症から見た糖尿病とガイドラインの効果的活用

    第23回糖尿病Update 賢島セミナー  2006 

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  • 日本人の糖尿病合併症の前向き大規模臨床研究:JDCSから学ぶわが国の糖尿病

    第25回東京女子医科大学糖尿病センターとの医療連携の会  2006 

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  • 糖尿病大血管障害を予防するための治療戦略

    筑波メディカルセンター公開カンファレンス  2006 

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  • 日本人における2型糖尿病とメタボリックシンドロームの現況 –JDCSの中間成績より-

    第1回Cardiovascular Update Forum (宇和島フォーラム)  2006 

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  • 教育セッション 日本発信のメガスタディーから学ぶもの JDCSから学ぶもの

    第6回糖尿病教育資源共有機構学術集会  2006 

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  • Symposium III-Metabolic Syndrome A ‘Clinical Aspect of Metabolic Syndrome’ Metabolic syndrome in Japanese patients with diabetes – From the results of Japan Diabetes Complications Study (JDCS)

    19th Spring Congress of Korea Diabetes Association  2006 

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  • 日本人2型糖尿病の現況とメタボリックシンドローム – JDCSの中間報告より 第3回静岡メタボリックシンドローム研究会

    第3回静岡メタボリックシンドローム研究会  2006 

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  • 日本人2型糖尿病における血管合併症とそのリスクファクター

    第9回京都糖尿病医会学術講演会  2006 

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  • 日本における2型糖尿病の現況と課題 -JDCSのデータから-

    福島市医師会学術講演会  2006 

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  • 「2型糖尿病の病態と診療-JDCSのデータからみた日本人患者の姿」

    第663回松本市医師会生涯教育講座  2006 

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  • Main Symposium I. Pathogenesis of metabolic syndrome. Clinical features of Japanese patients with diabetes and metabolic syndrome

    The 13th Korea-Japan Symposium on Diabetes Mellitus.  2006 

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  • 日本人2型糖尿病患者の病態と合併症-JDCSの中間結果から-

    第37回 長野県糖尿病懇話会  2006 

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  • 早期糖尿病のリスクとコントロール

    第5回「経口糖尿病薬フォーラム」  2006 

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  • メタボリックシンドロームは存在するか

    循環器病学の論点  2006 

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  • 臨床疫学研究と生活習慣病診療のエビデンス-2型糖尿病の心血管合併症を中心に-

    十日町市中魚沼郡医師会学術講演会  2006 

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  • 血管合併症予防のための糖尿病診療

    第16回 生活習慣病地域医療フォーラム  2006 

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  • 生活習慣病の改善を目指した運動療法の開発

    筑波大学COEシンポジウム 新たな身体運動科学の創生  2006 

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  • 糖尿病診療における降圧療法の意義-日本の大規模臨床研究エビデンスより.

    オルメテック学術講演会.  2006 

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  • 志賀高原で語る自然と健康 血糖が高いと言われたら

    志賀高原健康増進プログラム  2006 

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  • シンポジウム 大血管症の克服を目指して 大規模研究からの新しいエビデンス

    日本糖尿病学会第41回糖尿病学の進歩  2006 

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  • 糖尿病における動脈硬化症-日本の大規模臨床JDCSにおけるエビデンス-

    札幌生活習慣病懇話会  2006 

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  • Main Symposium I. Pathogenesis of metabolic syndrome. Clinical features of Japanese patients with diabetes and metabolic syndrome

    The 13th Korea-Japan Symposium on Diabetes Mellitus  2006 

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  • Symposium III-Metabolic Syndrome A ‘Clinical Aspect of Metabolic Syndrome’ Metabolic syndrome in Japanese patients with diabetes – From the results of Japan Diabetes Complications Study (JDCS)

    19th Spring Congress of Korea Diabetes Association  2006 

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  • 日本における糖尿病の現状と課題-動脈硬化合併症を中心に-

    北海道医師会認定生涯教育講座第10回循環・代謝セミナー  2006 

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  • 特別セッション. 糖尿病を合併した冠動脈疾患の治療戦略. わが国の糖尿病患者における冠動脈疾患の現状と課題.

    日本循環器学会総会・学術集会  2006 

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  • 大血管障害予防の観点からみた今後の糖尿病治療ーJDCSにみる日本人患者のエビデンスならびにPROactiveの結果を踏まえてー

    武田薬品学術担当者教育会  2006 

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  • 日本人糖尿病の大規模臨床エビデンス

    いわき市医師会学術講演会  2006 

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  • レクチャー 糖尿病治療におけるエビデンス-心血管疾患へのエビデンス.

    日本糖尿病学会第40回糖尿病学の進歩  2006 

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  • 日本人2型糖尿病患者の大規模臨床研究エビデンス-JDCSのこれまでの成績より-

    第11回山形糖尿病研究会  2006 

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  • 新規脂肪酸伸長酵素Fatty acyl-elongaseの生体内における機能および病態への関与.

    第78回日本内分泌学会学術総会  2005 

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  • シンポジウム. 冠動脈疾患のリスク-Metabolic Syndromeと高脂血症

    第69回日本循環器学会総会・学術集会ファイアーサイドセミナー第66回冠循環談話会  2005 

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  • 食後高脂血症治療の試み

    県南地区医師会学術講演会  2005 

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  • Symposium. Health risk of obesity and weight management with exercise.

    The 8th Asian Federation of Sports Medicine Congress.  2005 

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  • 日本の大規模臨床研究エビデンスからみた糖尿病治療-糖尿病の脂質・血圧管理は万全か

    第48回日本糖尿病学会年次学術集会ランチョンセミナー  2005 

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  • レクチャー. EBMからみた糖尿病における心血管疾患予防の重要性.

    日本糖尿病学会第39回糖尿病学の進歩  2005 

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  • シンポジウム. JDCSが示す日本人患者の心血管危険因子とその国際比較

    第9回軽症糖尿病研究会  2005 

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  • 最新の日本人データに基づく糖尿病とメタボリックシンドロームの管理

    日本医師会生涯教育講座 北多摩医学講座  2005 

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  • 生活習慣病とは

    第8回県民のための健康講座  2005 

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  • シンポジウム. 臨床試験の計画から実施まで

    第15回日本疫学会学術総会  2005 

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  • 日本における糖尿病の現状と国際比較

    日本糖尿病学会第42回関東甲信越地方会市民講座  2005 

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  • シンポジウム. 疫学および医療情報解析からみた日本人糖尿病の現況-日本の大規模臨床研究のエビデンス

    第5回糖尿病教育資源共有機構年次学術集会  2005 

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  • 日本の糖尿病患者における心血管疾患とメタボリックシンドロームの現況

    第62回東京心臓の会  2005 

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  • JDCSの結果を踏まえた糖尿病血管合併症の予防と治療.

    第42回日本糖尿病学会近畿地方会ランチョンセミナー  2005 

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  • 日本人2型糖尿病の大規模臨床研究エビデンス-Japan Diabetes Complications Study (JDCS) の最新結果より.

    第21回県北糖尿病懇話会  2005 

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  • 日本の2型糖尿病患者とその治療の現況.

    第4回沖縄糖尿病・脂質代謝研究会学術講演会  2005 

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  • メタボリックシンドロームのリスク-糖尿病とメタボリックシンドローム.

    日本心臓財団メディアワークショップ.  2005 

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  • メタボリックシンドローム「日本人糖尿病患者の大規模臨床研究から得られた知見-メタボリックシンドロームを含めて」

    東京ベイ心臓カンファレンス  2005 

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  • 日本人2型糖尿病患者のエビデンス-Japan Diabetes Complications Study (JDCS) の最新結果より

    第9回旭川軽症糖尿病研究会  2005 

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  • 糖尿病患者の治療現状-「日本の現状」

    第6回「脂質低下療法の意義」研究会  2005 

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  • パネルディスカッション. マルチプルリスクマネージメント.

    第6回「脂質低下療法の意義」研究会  2005 

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  • 日本人2型糖尿病患者の病態と合併症の特徴-Japan Diabetes Complications Study (JDCS)中間解析より

    第102回日本内科学会講演会  2005 

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  • 新規栄養代謝転写因子TFE3は糖尿病モデルマウスの病態を改善する.

    第48回日本糖尿病学会年次学術集会  2005 

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  • アディポネクチン分泌およびアディポネクチン受容体発現に対する運動効果の検討.

    第48回日本糖尿病学会年次学術集会  2005 

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  • 血糖コントロールの悪化を景気に診断された特発性間質性肺炎の症例.

    第42回日本糖尿病学会関東甲信越地方会  2005 

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  • 劇症1型糖尿病と急性膵炎に続発した糖尿病との鑑別が困難であった一例.

    第42回日本糖尿病学会関東甲信越地方会  2005 

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  • JDCSにおける腎症

    第17回日本糖尿病性腎症研究会  2005 

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  • 高齢者糖尿病のmetabolic syndromeに対する食事療法、および運動療法の介入効果に関する研究.

    公益信託日本動脈硬化予防研究基金平成16年度研究報告会  2005 

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  • PKAによるLXRのリン酸化を介したSREBP-1c遺伝子の転写抑制.

    第78回日本内分泌学会学術総会  2005 

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  • 膵β細胞にSREBP-1cを強発現させたトランスジェニックマウスの検討.

    第78回日本内分泌学会学術総会  2005 

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  • 糖尿病における動脈硬化合併症とメタボリックシンドローム

    Proactive 発表記念講演会  2005 

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  • ymposium. Health risk of obesity and weight management with exercise

    The 8th Asian Federation of Sports Medicine Congress.  2005 

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  • 心血管疾患と糖尿病・メタボリックシンドローム

    第6回Heart Care Net古河・総和・三和研究会  2005 

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  • 2型糖尿病とその治療の現況-日本の大規模臨床研究エビデンス.

    第4回神戸生活習慣病フォーラム  2005 

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  • TCA回路の部分阻害がエネルギー代謝に及ぼす影響 クエン酸合成酵素遺伝子ヘテロノックアウトマウスの解析.

    第3回北関東心血管内分泌Research Meeting  2004 

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  • わが国の2型糖尿病患者の現況-Japan Diabetes Complications Study (JDCS) 6年次中間報告より.

    第38回日本成人病(生活習慣病)学会  2004 

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  • SREBP-1はHNF-4aと結合し糖新生系遺伝子の発現を抑制する.

    第47回日本糖尿病学会年次学術集会  2004 

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  • 食後高トリグリセリド血症モデル動物の作成と解析.

    第47回日本糖尿病学会年次学術集会  2004 

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  • Signal sequence trap (SST) 改良法を用いた精巣上体新規分泌蛋白質の単離同定.

    第77回日本内分泌学会学術総会  2004 

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  • STZマウスの肝臓におけるインスリン非依存的SREBP-1発現誘導.

    第47回日本糖尿病学会年次学術集会  2004 

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  • JDCSにおける心血管イベントのリスク解析.

    代謝異常研究基金「動脈硬化による心血管イベントのリスク層別化に関する研究」第2回班会議  2004 

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  • 糖尿病神経障害において神経因性膀胱のみ顕著に認められた症例.

    第41回日本糖尿病学会関東甲信越地方会  2004 

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  • TCA回路部分阻害がエネルギー代謝に及ぼす影響-クエン酸合成酵素(CS)遺伝子ヘテロノックアウト(KO)マウスの解析-.

    第47回日本糖尿病学会年次学術集会  2004 

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(JDCS).

    公益信託日本動脈硬化予防研究基金平成15年度研究報告会  2004 

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  • 糖負荷試験において著明な高インスリン血症を呈した若年女性の一例.

    第41回日本糖尿病学会関東甲信越地方会  2004 

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  • 日本人2型糖尿病における肥満.

    県南DM治療研究会  2004 

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  • 日本の2型糖尿病患者における動脈硬化合併症-Japan Diabetes Complications Studyの中間報告より-

    関東Lipid Artery研究会  2004 

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  • 21世紀COEシンポジウム. 身体と運動の多元的関連性をめぐる新たな身体運動科学の構築に向けて

    つくばCOEの歩みと将来への展望-健康・スポーツ科学の推進  2004 

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  • 日本人2型糖尿病における肥満

    県南DM治療研究会  2004 

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  • シンポジウム. 糖尿病合併症の疫学研究の現状と課題- Japan Diabetes Complications Study (JDCS) 中間報告にみる現代日本の糖尿病合併症

    日本糖尿病合併症学会  2004 

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  • 受賞講演. Japan Diabetes Complications Study (JDCS)における糖尿病とその合併症に関する臨床疫学的検討と国際比較

    日本糖尿病合併症学会  2004 

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  • Clinical characteristics of patients with type 2 diabetes in Japan.Interim report of the Japan Diabetes Complications Study (JDCS).

    Tsukuba Lifestyle Related Disease Forum  2004 

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  • 日本人における2型糖尿病のエビデンス-Japan Diabetes Complications Study (JDCS)中間報告より.

    糖尿病セミナー  2004 

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  • 文部科学省科学技術調整費シンポジウム「地域の中高齢者における生活機能増進法の具体策」. 運動すれば生活習慣病はこわくない?

    日本人における生活習慣病と運動  2004 

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  • 2型糖尿病患者の動脈硬化合併症の現況と生活習慣介入の影響.

    木村記念循環器財団第5回臨床血管機能研究助成研究発表会  2004 

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  • 日本人2型糖尿病の心血管疾患の特徴と国際比較

    第3回糖尿病と心血管病研究会  2004 

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  • TCA回路の部分阻害がエネルギー代謝に及ぼす影響.

    第41回日本臨床分子医学会学術集会  2004 

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  • 日本人2型糖尿病患者における動脈硬化合併症の解析と国際比較.

    日本心臓財団「動脈硬化Update」研究助成研究発表会  2004 

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  • Clinical characteristics of patients with type 2 diabetes in Japan.Interim report of the Japan Diabetes Complications Study (JDCS)

    Tsukuba Lifestyle Related Disease Forum 2004  2004 

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(Japan Diabetes Complications Study; JDCS)

    公益信託日本動脈硬化予防研究基金平成15年度研究報告会  2003 

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  • 糖尿病患者における虚血性心疾患,脳血管疾患発症について

    財団法人代謝異常治療研究基金「動脈硬化による心血管イベントのリスク層別化に関する研究」研究班会議  2003 

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  • 日本の2型糖尿病における心・血管イベントの解析-JDCSの中間結果より-

    関東心・血管フォーラム  2003 

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  • 骨芽細胞においてp57KIP2はLIM kinase 1と結合し、細胞骨格を制御する

    第76回内分泌学会学術総会  2003 

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  • 糖尿病加療中に下肢の疼痛・腫脹を繰り返し糖尿病性筋梗塞が疑われた一例

    第40回日本糖尿病学会関東甲信越地方会  2003 

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(Japan Diabetes Complications Study; JDCS)

    公益信託日本動脈硬化予防研究基金 平成14年度研究報告会  2003 

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  • PEPCK-SREBP-1a transgenic mouseにおけるインスリン抵抗性.

    第76回内分泌学会学術総会  2003 

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  • アポCII欠損症の一例

    第1回茨城県膵病態治療研究会  2003 

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究 Japan Diabetes Complications Study

    公益信託日本動脈硬化予防研究基金 平成14年度研究報告会  2003 

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  • 胆汁うっ滞型肝障害を伴ったバセドウ病の一例.

    臨床内分泌Update  2003 

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  • 脳梗塞、心筋梗塞 足壊疽を合併した糖尿病患者の一例

    第2回糖尿病と心血管病研究会  2003 

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  • 2型糖尿病における血中D-マンノース濃度測定の臨床的意義

    第43回臨床化学会年会・第50回臨床検査医学会総会連合大会  2003 

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  • Sterol regulatory element binding protein 1 (SREBP-1) トランスジェニックマウスにおけるインスリン抵抗性.

    第46回日本糖尿病学会年次学術集会  2003 

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  • 血管内皮細胞死と細胞周期.

    第46回日本糖尿病学会年次学術集会  2003 

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する調査 (Japan Diabetes Complication Study ; JDCS) の中間報告.

    第46回日本糖尿病学会年次学術集会  2003 

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  • SREBPは肝臓のIRS-2を介するインスリンシグナルを抑制する

    第46回日本糖尿病学会年次学術集会  2003 

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  • Long-Term Exercise Improves Postprandial Response to Fat in Healthy Elderly Subjects.

    The 13th International Symposium on Atherosclerosis.  2003 

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  • Fenofibrate Therapy Improves Postprandial Responses to Fat and Malondialdehyde-modified Low-density Lipoprotein (MDA-LDL) levels in Diabetic and Non-diabetic Patients with Hypertriglyceridemia.

    The 13th International Symposium on Atherosclerosis  2003 

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  • Substrate Oxidation And Endocrine Hormone During A Cycling Exercise In Beta3-Ar Gene Polymorphism.

    2003 Daegu Universiade Conference.  2003 

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  • Effects of Five-Year Lifestyle Modification on Patients With Type 2 Diabetes: Interim Report of The Japan Diabetes Complications Study (JDCS).

    The 18th International Diabetes Federation Congress  2003 

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  • 21世紀COEプログラム公開ワークショップ. 健康スポーツ科学の推進. 体育科学とスポーツ医学との連携による学際的エクセレンスを目指して

    運動効果を規定する遺伝子のゲノムワイド探索  2003 

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  • ‘Type 2 Diabetes and Insulin Resistance’

    Young-Nam Endocrine Society  2003 

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  • 2型糖尿病とマルチプルリスクファクター症候群-JDCSにおける日本人患者のエビデンス

    第46回日本糖尿病学会年次学術集会ランチョンセミナー  2003 

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  • 本邦の2型糖尿病患者における血管合併症とそのリスクファクター-JDCS中間データより

    第4回茨城県糖尿病合併症治療研究会  2003 

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  • 糖尿病外来診療の実際

    茨城県医師会真壁支部学術講演会  2003 

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  • 糖尿病の恐ろしい合併症を防ぐには

    第2回県民のための健康管理講座  2003 

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  • 生活習慣と糖尿病

    新治村環境保健課健康づくり事業講演会  2003 

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  • 糖尿病の薬物治療

    第9回鹿行地区地域薬剤師勉強会  2003 

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  • ‘Type 2 Diabetes and Insulin Resistance’

    Young-Nam Endocrine Society.  2003 

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  • Effects of Five-Year Lifestyle Modification on Patients With Type 2 Diabetes: Interim Report of The Japan Diabetes Complications Study (JDCS).

    The 18th International Diabetes Federation Congress  2003 

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  • Long-Term Exercise Improves Postprandial Response to Fat in Healthy Elderly Subjects.

    The 13th International Symposium on Atherosclerosis.  2003 

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  • Fenofibrate Therapy Improves Postprandial Responses to Fat and Malondialdehyde-modified Low-density Lipoprotein (MDA-LDL) levels in Diabetic and Non-diabetic Patients with Hypertriglyceridemia.

    The 13th International Symposium on Atherosclerosis.  2003 

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  • Substrate Oxidation And Endocrine Hormone During A Cycling Exercise In Beta3-Ar Gene Polymorphism.

    2003 Daegu Universiade Conference  2003 

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  • 糖尿病性皮膚科医用に対する治療の検討

    第8回糖尿病フットケア研究会  2002 

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  • クッシング症候群におけるコルチゾール値と差室肥大との関連についての検討

    第75回日本内分泌学会学術総会  2002 

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  • マクロファージにおけるインスリン作用-動脈硬化発症機構に関する検討-

    第6回北関東糖尿病フォーラム  2002 

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  • 食後高脂血症 (PPHL) 診断マーカー確立の試み-脂肪負荷試験(OFTT)との相関 (第2報)

    第34回日本動脈硬化学会  2002 

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  • マクロファージ分泌TNF-aに対するインスリンの直接作用についての検討

    第45回日本糖尿病学会年次学術集会  2002 

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  • 経口血糖降下剤の二次無効症例へのインスリン導入判定の検討

    第45回日本糖尿病学会年次学術集会  2002 

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  • Sterol regulatory element binding protein 1 (SREBP 1) トランスジェニックマウスにおける耐糖能の検討

    第45回日本糖尿病学会年次学術集会  2002 

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  • 2型糖尿病(DM)患者の食後高脂血症(PPHL)診断指標-経口脂肪負荷試験(OFTT)との相関

    第45回日本糖尿病学会年次学術集会  2002 

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  • 本邦の2型糖尿病患者における血管合併症の現況-Japan Diabetes Complications Study (JDCStudy)の結果より

    第20回関東・甲信越Macro and Micro Circulation 研究会  2002 

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  • 糖尿病における血管合併症の発症の発症予防と進展抑制に関する研究 (JDCS)

    公益信託日本動脈硬化予防研究基金2002年研究報告会  2002 

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  • マクロファージにおけるインスリン作用についての基礎的検討

    第3回糖尿病とVascular Biology研究会  2002 

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  • 糖尿病の動脈硬化におけるインスリン抵抗性の意義

    第34回日本動脈硬化学会  2002 

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  • SREBPにより調節されるリポジェニック酵素;Acetoacetyl CoA Synthetase(AACAS)の解析

    第34回日本動脈硬化学会  2002 

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  • 原発性副腎不全を来したAIDSの一例

    日本内分泌学会学会関東甲信越地方会  2002 

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  • Insulin upregulates tumor necrosis factor –alpha production in macrophages through an extracellular-regulated kinases-dependent pathways.

    12th International Vascular Biology Meeting.  2002 

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  • Acetoacetyl-coenzyme A Synthetase (AACAS) is a Lipogenic Enzyme Modulated by Sterol Regulatory Element-binding Proteins and Diabetes.

    62nd Annual Meeting and Scientific Sessions, American Diabetes Association.  2002 

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  • Effect of eicosapentaenoic acid on production of nitric oxide and endothelin-1 in human vascular endothelial cells.

    The 5th European Congress of Endocrinology.  2002 

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  • Symposium. Prevention and treatment of diabetic cardiovascular diseases: progress at the turn of the century. Cardiovascular Events in Patients with Type 2 Diabetes and Effects of Lifestyle Modifications

    The 66th Annual Scientific Meeting of the Japanese Circulation Society  2002 

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  • パネルディスカッション. マルチプルリスクファクター症候群をいかに捉えるか

    第34回日本動脈硬化学会  2002 

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  • 糖尿病合併症について

    筑波大学付属病院市民公開健康講座  2002 

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  • 塩化アンベノニウムにより低血糖を来したと考えられる糖尿病の一例

    第39回日本糖尿病学会関東甲信越地方会  2002 

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  • 無痛性甲状腺炎を契機にケトアシドーシスを発症したSPIDDMの症例

    第39回日本糖尿病学会関東甲信越地方会  2002 

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  • 糖尿病における動脈硬化症の発症予防と進展抑制に関する研究

    厚生労働省特定疾患対策研究事業原発性高脂血症に関する調査研究平成13年度班会議  2002 

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  • 2型糖尿病における血管合併症と日本の現況

    群馬県医師会学術講演会  2002 

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  • 糖尿病薬物治療の実際

    第70回鹿島北部臨床医家懇話会  2002 

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  • シンポジウム. マルチプルリスクファクター症候群の一部分症としての糖尿病性マクロアンギオパシー

    第17回日本糖尿病合併症学会  2002 

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  • Panel Discussion. The Metabolic Syndrome-Pathogenesis and Clinical Feature. “Type 2 Diabetes in Japan”

    The Meeting of US-Japan Panel on Nutrition and Metabolism  2002 

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  • Effect of eicosapentaenoic acid on production of nitric oxide and endothelin-1 in human vascular endothelial cells.

    The 5th European Congress of Endocrinology.  2002 

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  • Symposium. Prevention and treatment of diabetic cardiovascular diseases: progress at the turn of the century. Cardiovascular Events in Patients with Type 2 Diabetes and Effects of Lifestyle Modifications.

    The 66th Annual Scientific Meeting of the Japanese Circulation Society  2002 

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  • Acetoacetyl-coenzyme A Synthetase (AACAS) is a Lipogenic Enzyme Modulated by Sterol Regulatory Element-binding Proteins and Diabetes.

    62nd Annual Meeting and Scientific Sessions, American Diabetes Association.  2002 

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  • Insulin upregulates tumor necrosis factor –alpha production in macrophages through an extracellular-regulated kinases-dependent pathways.

    12th International Vascular Biology Meeting.  2002 

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  • Panel Discussion. The Metabolic Syndrome-Pathogenesis and Clinical Feature. “Type 2 Diabetes in Japan”.

    The Meeting of US-Japan Panel on Nutrition and Metabolism  2002 

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  • 新しいlipogenic enzyme: Acetyl CoA Synthetase (ACAS)の糖尿病における発現調節

    第44回日本糖尿病学会年次学術集会  2001 

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  • 過性心不全を契機に診断されたCushing's diseaseの一例

    日本内分泌学会第11回臨床内分泌代謝:Update  2001 

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  • 下垂体腺種、甲状腺癌、原発性アルドステロン症を発症し多彩な臨床症状を呈した一例

    第448回日本内科学会関東地方会  2001 

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  • 骨髄炎をきたした糖尿病壊疽を画像評価し、保存的療法で改善をみた一例

    第38回日本糖尿病学会関東甲信越地方会  2001 

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  • 多彩な症状を呈するpost-treatment neuropathyを来した1型糖尿病の一例

    第38回日本糖尿病学会関東甲信越地方会  2001 

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  • 異所性ACTH症候群との鑑別が困難であったCushing症候群の一例

    第74回日本内分泌学会学会総会  2001 

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する研究(Japan Diabetes Complications Study: JDCS)

    公益信託日本動脈硬化予防研究基金平成12年度研究報告会  2001 

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  • 糖尿病モデル動物におけるインスリン抵抗性改善薬の血中脂質および血中過酸化脂質に対する効果

    第44回日本糖尿病学会年次学術集会  2001 

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  • ヒト血管内皮細胞のNitric oxide,ET-1産生に対するEicosapentaenoic acidの影響

    第33回日本動脈硬化学会  2001 

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  • SREBPにより調節される新たなlipogenic enzyme;Acetyl CoA Synthetaseの解析

    第33回日本動脈硬化学会  2001 

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  • Insulinのヒト血管内皮細胞におけるNitric oxide,ET-1産生に対する多価不飽和脂肪酸の作用

    第44回日本糖尿病学会年次学術集会  2001 

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  • 血中D-マンノース濃度の基礎的検討と糖尿病臨床への応用

    第44回日本糖尿病学会年次学術集会  2001 

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  • 難消化性オリゴ糖の2型糖尿病患者における有用性の検討

    第44回日本糖尿病学会年次学術集会  2001 

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  • 糖尿病神経障害におけるモノフィラメントの有効性の検討

    第44回日本糖尿病学会年次学術集会  2001 

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  • マクロファージに対するインスリンの作用についての基礎的検討

    第74回日本内分泌学会学会総会  2001 

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  • 糖尿病患者における血中D-マンノース値の臨床的意義

    第74回日本内分泌学会総会  2001 

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  • 糖尿病神経障害におけるモノフィラメントの有効性の検討

    第7回糖尿病フットケア研究会  2001 

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  • Thrombospondin-1によるグリオーマ血管新生の抑制

    第60回日本癌学会  2001 

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  • ヒト血管内皮細胞のNitric oxide,ET-1産生に対する多価不飽和脂肪酸の新しい薬理活性

    第74回日本内分泌学会学会総会  2001 

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  • SREBPが制御する新たなlipogenic 酵素:アセチル CoA 合成酵素の解析

    第38回日本臨床分子医学会  2001 

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  • Acetyl-coenzyme A Synthetase is a New Lipogenic Enzyme Controlled by Sterol Regulatory Element-binding Proteins and Influenced by Diabetes.

    61st Annual Meeting and Scientific Sessions, American Diabetes Association  2001 

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  • Plasma Mannose Levels in Patients with Diabetes Mellitus and Their Clinical Significance.

    61st Annual Meeting and Scientific Sessions, American Diabetes Association.  2001 

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  • Influences of polyunsaturated fatty acids and insulin on NO production and ET-1 production in human vascular endothelial cells.

    61h Annual Meeting and Scientific Sessions, American Diabetes Association.  2001 

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  • Effects of Lifestyle Modifications on Patients with Type 2 Diabetes: The Japan Diabetes Complications Study (JDCS).

    Japan-US Medical Cooperative Medical Science Program, Symposium on Nutrition  2001 

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  • Thrombospondin-1 inhibits glioma angiogenesis

    World Federation of Neuro-Oncology First Quadrennial Meeting  2001 

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  • 糖尿病におけるライフスタイル介入の意義 -The Japan Diabetes Complications Study (JDCS) の中間報告より

    第1回群馬血管疫学研究会  2001 

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  • Acetyl-coenzyme A Synthetase is a New Lipogenic Enzyme Controlled by Sterol Regulatory Element-binding Proteins and Influenced by Diabetes.

    61st Annual Meeting and Scientific Sessions, American Diabetes Association  2001 

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  • Thrombospondin-1 inhibits glioma angiogenesis.

    World Federation of Neuro-Oncology First Quadrennial Meeting.  2001 

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  • Effects of Lifestyle Modifications on Patients with Type 2 Diabetes: The Japan Diabetes Complications Study (JDCS).

    Japan-US Medical Cooperative Medical Science Program, Symposium on Nutrition.  2001 

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  • Plasma Mannose Levels in Patients with Diabetes Mellitus and Their Clinical Significance.

    61st Annual Meeting and Scientific Sessions, American Diabetes Association.  2001 

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  • Influences of polyunsaturated fatty acids and insulin on NO production and ET-1 production in human vascular endothelial cells.

    61h Annual Meeting and Scientific Sessions, American Diabetes Association.  2001 

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  • 心不全に陥った2次性甲状腺機能亢進症の症例

    北関東内分泌懇話会  2000 

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  • 脂肪細胞内PPARδ作用と脂肪細胞分化・ob遺伝子発現

    第37回臨床分子医学会学術総会  2000 

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  • SREBPによるコレステロール合成系遺伝子の調節

    第37回臨床分子医学会学術総会  2000 

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  • 血管内皮細胞におけるVEGFとGLUTを介するMAPK活性化経路

    第1回糖尿病とVascular Biology研究会  2000 

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  • 拡張型心筋症の治療により著しい高ナトリウム血症を来した尿崩症合併, 2型糖尿病の一例

    第37回日本糖尿病学会関東甲信越地方会  2000 

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  • 距骨壊死で発症したCharcot関節の一症例-糖尿病性Charcot関節に関する考察-

    第37回日本糖尿病学会関東甲信越地方会  2000 

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  • 糖尿病眼における血管内皮細胞増殖因子(VEGF)の産生および抗VEGF抗体療法の有効性に関する検討

    第8回日本血管細胞生物学会  2000 

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  • 血管内皮細胞におけるVEGFとGLUT1を介するERK活性化

    第8回日本血管細胞生物学会  2000 

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  • VEGFの糖尿病網膜症の発症・進展における役割とGLUT1を介するMAPK活性化経路についての基礎的研究

    第4回シンポジウム糖尿病  2000 

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  • 糖尿病における血管合併症の発症予防と進展抑制に関する調査 (JDCStudy) について (第1報)

    第97回日本内科学会講演会  2000 

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  • Extracellular-regulated kinaseの活性化における血管内皮細胞増殖因子と糖輸送担体の役割

    第4回北関東糖尿病フォーラム  2000 

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  • VEGFと血管合併症

    第11回血管内皮細胞からみた糖尿病合併症研究会  2000 

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  • Effects of lifestyle modification on patients with type 2 diabetes: the Japan diabetes complications study (JDCS).

    60th Annual Meeting and Scientific Sessions, American Diabetes Association  2000 

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  • Thiazolidines inhibit voltage-dependent calcium currents in vascular smooth muscle cells and cardiac myocytes.

    International Conference of Endocrinology  2000 

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  • Vascular endothelial growth factor (VEGF) levels in the sera of patients with rheumatoid arthritis and the effects of anti-VEGF therapy on arthritis animal model.

    The 13th Naito Conference on Molecular Biological Approaches for Intractable Diseases.  2000 

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  • パネルディスカッション. 日常生活におけるリスクファクターの管理

    第1回茨城生活習慣病フォーラム  2000 

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  • Thiazolidines inhibit voltage-dependent calcium currents in vascular smooth muscle cells and cardiac myocytes.

    International Conference of Endocrinology,  2000 

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  • Effects of lifestyle modification on patients with type 2 diabetes: the Japan diabetes complications study (JDCS).

    60th Annual Meeting and Scientific Sessions, American Diabetes Association.  2000 

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  • Vascular endothelial growth factor (VEGF) levels in the sera of patients with rheumatoid arthritis and the effects of anti-VEGF therapy on arthritis animal model.

    The 13th Naito Conference on Molecular Biological Approaches for Intractable Diseases.  2000 

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  • 糖尿病合併症発症の分子機構-VEGFと網膜症

    第36回日本臨床生理学会総会  1999 

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  • 糖尿病の外来診療−新しい経口糖尿病薬を中心に

    筑波メディカルセンター公開カンファレンス  1999 

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  • Vascular Endothelial GLUT1 Overexpression Activates Multiple Signal Transduction Pathways

    59th Annual Meeting and Scientific Sessions, American Diabetes Association  1999 

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  • GLUT1 overexpression differentially regulates MAP kinase activity in endothelial cell lines.

    Michigan Diabetes Research and Training Center Winter Symposium.  1999 

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  • 糖尿病網膜症の細胞生物学的背景-VEGFとGLUT1によるMAPK活性化経路-

    つくば糖尿病眼研究会  1999 

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  • GLUT1 overexpression differentially regulates MAP kinase activity in endothelial cell lines.

    Michigan Diabetes Research and Training Center Winter Symposium  1999 

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  • Vascular Endothelial GLUT1 Overexpression Activates Multiple Signal Transduction Pathways

    59th Annual Meeting and Scientific Sessions, American Diabetes Association.  1999 

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  • Vascular endothelial growth factor (VEGF) enhances glucose transport in retinal endothelial cells through upregulation of GLUT1 glucose transporter.

    58th Annual Meeting and Scientific Sessions, American Diabetes Association.  1998 

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  • Change in the expression of vascular endothelial growth factor (VEGF) by swimming.

    58th Annual Meeting and Scientific Sessions, American Diabetes Association.  1998 

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  • Vascular endothelial growth factor (VEGF) enhances glucose transport in retinal endothelial cells through upregulation of GLUT1 glucose transporter.

    58th Annual Meeting and Scientific Sessions, American Diabetes Association.  1998 

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  • Change in the expression of vascular endothelial growth factor (VEGF) by swimming.

    58th Annual Meeting and Scientific Sessions, American Diabetes Association.  1998 

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  • 超音波カラードプラ法による糖尿病患者における下肢動脈硬化症の検討

    第40回日本糖尿病学会年次学術集会  1997 

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  • ヒト血管平滑筋細胞における血管内皮細胞増殖因子(VEGF)の産生に及ぼすインスリンおよび脈管作動性物質の影響について

    第40回日本糖尿病学会年次学術集会  1997 

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  • ハンドグリップテストは糖尿病自律神経障害の判定に有効か

    第40回日本糖尿病学会年次学術集会  1997 

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  • 糖尿病患者における血清中血管内皮細胞増殖因子(VEGF)と高血糖,HbA1cとの関連についての検討

    第40回日本糖尿病学会年次学術集会  1997 

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  • 慢性関節リウマチにおける血管内皮細胞増殖因子(VEGF) の関与とその活動性判定・治療への応用

    第94回日本内科学会講演会  1997 

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  • 糖尿病血管新生緑内障における房水中血管内皮細胞増殖因子(VEGF)濃度の検討

    第3回日本糖尿病眼学会総会  1997 

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  • 糖尿病眼合併症における血管内皮細胞増殖因子(VEGF) の関与と抗VEGF療法の有効性に関する検討

    第40回日本糖尿病学会年次学術集会  1997 

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  • Serum vascular endotherial growth factor levels are elevated in diabetic patients with hyperglycemia.

    16th International Diabetes Federation (IDF) Congress  1997 

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  • Is sustained handgrip test useful for assessment of autonomic diabetic neuropathy?

    10th International Congress of Endocrinology.  1997 

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  • Insulin and vasopressin induce vascular endothelial growth factor on human vascular smooth muscle cells.

    16th International Diabetes Federation (IDF) Congress.  1997 

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  • Vascular endothelial growth factor (VEGF) in animal models of diabetic retinopathy.

    Oxford Workshop on Diabetic Retinopathy, JDF/EASD Meeting.  1997 

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  • Non-invasive ultrasonic analysis of femoral artery wall in patients with NIDDM: Evaluation of early arteriosclerotic lesions and relationship between diabetic neuropathy.

    57th Annual Meeting and Scientific Sessions, American Diabetes Association  1997 

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  • Effects of pancreatic hormones and vasoactivators on vascular endotherial growth factor production of human vascular smooth muscle cells.

    57th Annual Meeting and Scientific Sessions, American Diabetes Association  1997 

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  • Modulation of vascular endothelial growth factor (VEGF) in animal models of diabetic retinopathy: future implications.

    57th Annual Meeting and Scientific Sessions, American Diabetes Association.  1997 

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  • Vascular endothelial growth factor (VEGF) in animal models of diabetic retinopathy.

    Oxford Workshop on Diabetic Retinopathy, JDF/EASD Meeting  1997 

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  • Non-invasive ultrasonic analysis of femoral artery wall in patients with NIDDM: Evaluation of early arteriosclerotic lesions and relationship between diabetic neuropathy.

    57th Annual Meeting and Scientific Sessions, American Diabetes Association.  1997 

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  • Effects of pancreatic hormones and vasoactivators on vascular endotherial growth factor production of human vascular smooth muscle cells.

    57th Annual Meeting and Scientific Sessions, American Diabetes Association.  1997 

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  • Serum vascular endotherial growth factor levels are elevated in diabetic patients with hyperglycemia.

    16th International Diabetes Federation (IDF) Congress.  1997 

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  • Insulin and vasopressin induce vascular endothelial growth factor on human vascular smooth muscle cells.

    16th International Diabetes Federation (IDF) Congress.  1997 

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  • TRH負荷試験にて低反応を示したacromegaly例の検討

    第22回北関東内分泌懇話会  1996 

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  • 高酸素負荷網膜症における血管増殖因子の経時的変化

    第6回糖尿病と血管内皮細胞異常研究会  1996 

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  • 保存的治療にて軽快した化膿性椎体炎の一例

    第33回日本糖尿病学会関東甲信越地方会  1996 

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  • 糖尿病眼合併症における血管内皮細胞増殖因子 (VEGF) の関与

    第24回内分泌代謝研究会  1996 

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  • ヒト血管平滑筋細胞における血管内皮増殖因子 (VEGF) の発現調節に及ぼす高グルコース, hypoxiaの影響について

    第39回日本糖尿病学会年次学術集会  1996 

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  • 培養ウシ網膜色素上皮細胞のVEGF産生に及ぼすプロゲステロンおよびグルコース濃度変化の影響

    第39回日本糖尿病学会年次学術集会  1996 

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  • 糖尿病性血管新生緑内障における血管内皮細胞増殖因子(VEGF)の関与

    第14回富士ホルモンカンファレンス  1996 

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  • AGEレセプター(RAGE)の発現調節因子に関する検討

    第35回日本糖尿病学会年次学術集会  1996 

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  • 先天性水腎症により著明な二次性高血圧を来した一例

    第22回北関東内分泌懇話会  1996 

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  • Modulation of vascular endothelial growth factor (VEGF) in animal models of diabetic retinopathy: future implications.

    57th Annual Meeting and Scientific Sessions, American Diabetes Association  1996 

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  • Acute glucose deprivation and progesterone induce vascular endothelial growth factor on retinal pigment epithelial cells.

    56th Annual Meeting and Scientific Sessions, American Diabetes Association.  1996 

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  • Regulation of VEGF expression in human vascular smooth muscle cells and its clinical significance.

    10th International Congress of Endocrinology.  1996 

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  • Is sustained handgrip test useful for assessment of autonomic diabetic neuropathy?

    10th International Congress of Endocrinology  1996 

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  • Regulation of VEGF expression in human vascular smooth muscle cells and its clinical significance.

    10th International Congress of Endocrinology.  1996 

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  • Acute glucose deprivation and progesterone induce vascular endothelial growth factor on retinal pigment epithelial cells.

    56th Annual Meeting and Scientific Sessions, American Diabetes Association  1996 

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  • 糖尿病患者の下肢血流におけるThromboxane (TX) dual blocker (KDIー792) の影響

    第68回日本内分泌学会学術集会  1995 

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  • 糖尿病性腎不全による腎性貧血に対するヒトエリスロポエチン製剤の使用経験

    第2回糖尿病治療研究会  1995 

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  • 下垂体機能低下症を伴った慢性トルエン中毒の症例

    第68回日本内分泌学会秋期学術集会  1995 

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  • 網膜血管増殖モデルにおける血管増殖因子の同定

    第18回日本分子生物学会年会  1995 

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  • 両側性副腎Incidentalomaの一例

    第68回日本内分泌学会秋期学術集会  1995 

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  • 網膜色素上皮細胞における長期高グルコースおよび急性低グルコースのVEGF/VPF分泌に及ぼす影響

    日本血管細胞生物学研究会第3回大会  1995 

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  • Bisphosphanate投与によりCa crisisを回避しえた副甲状腺癌再発転移の一例

    第68回日本内分泌学会秋期学術集会  1995 

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  • 術前にTrilostaneが有効であった副腎癌の症例

    第68回日本内分泌学会秋期学術集会  1995 

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  • Cerebral hypoaccumulation in the single photon emission tomography (SPECT) of patients with glucose intoleranceassociated with mitochondrial gene abnormalities

    8th Japan-Korea Symposium on Diabetes Mellitus.  1995 

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  • Study of VEGF / VPF Levels in diabetic proliferative retinopathy and nephropathy.

    55th Annual Meeting and Scientific Sessions, American Diabetes Association  1995 

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  • Progesterone induces vascular endothelial growth factor (VEGF) on retinal pigment epithelial cells.

    8th Japan-Korea Symposium on Diabetes Mellitus.  1995 

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  • Cerebral hypoaccumulation in the single photon emission tomography (SPECT) of patients with glucose intoleranceassociated with mitochondrial gene abnormalities.

    8th Japan-Korea Symposium on Diabetes Mellitus  1995 

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  • Study of VEGF / VPF Levels in diabetic proliferative retinopathy and nephropathy.

    55th Annual Meeting and Scientific Sessions, American Diabetes Association.  1995 

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  • Progesterone induces vascular endothelial growth factor (VEGF) on retinal pigment epithelial cells.

    8th Japan-Korea Symposium on Diabetes Mellitus  1995 

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  • Bisphophonateの高カルシウム血症に対する本院及び海外における臨床成績

    第5回筑波大学内科集談会プログラム  1995 

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  • 繊維性乳腺症を併発したIDDM症例

    第32回日本糖尿病学会関東甲信越地方会  1995 

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  • 1,5-AGによる糖尿病教育入院患者の長期血糖予後予想の試み

    第32回日本糖尿病学会関東甲信越地方会  1995 

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  • イコサペント酸の糖尿病患者における耐糖能および糖尿病合併症に及ぼす影響について

    第38回日本糖尿病学会年次学術集会  1995 

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  • ヒト大動脈由来血管平滑筋細胞に対するイコサペント酸の効果についての検討

    第38回日本糖尿病学会年次学術集会  1995 

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  • 下垂体細胞株におけるGLUT2, Glucokinase遺伝子過剰発現によるインスリン産生変化の検討

    第38回日本糖尿病学会年次学術集会  1995 

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  • ウシ培養網膜血管内皮細胞のTXA2,PGI2,PGE2産生に対する高グルコースおよびTX合成酵素阻害薬の影響

    第32回日本臨床代謝学会  1995 

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  • CVDによる化学療法とDEMSERの併用治療を行った悪性褐色細胞腫の症例

    第21回北関東内分泌懇話会  1995 

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  • 高酸素負荷網膜症ラットモデル網膜組織における網膜血管新生因子産生の検討

    第38回日本糖尿病学会年次学術集会  1995 

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  • 糖尿病網膜症・腎症の発症および進展におけるVEGF (Vascular Endothelial Growth Factor)の関与

    第38回日本糖尿病学会年次学術集会  1995 

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  • NK活性,IL2産生能低下の認められた反復性膿瘍に罹患した糖尿病の一例

    第32回日本糖尿病学会関東甲信越地方会  1995 

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  • 一過性にADH不応になった中枢性尿崩症の症例

    第21回北関東内分泌懇話会  1995 

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  • Hemodynamic effects of nisordipine and nicardipine on lower limb circulation in NIDDM patients.

    The15th International Diabetes Federation Congress (IDF).  1994 

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  • Efficacy of beraprost sodium on subjective symptoms and nerve functions in diabetic neuropathy.

    The15th International Diabetes Federation Congress (IDF).  1994 

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  • Ultrsonographic evaluation of lower limb circulation and arteriosclerosis.

    The7th Congress of World Federation for Ultrasound in Medicine and Biology (WFUMB)  1994 

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  • Efficacy of nilvadipine on blood flow of dorsal pedis artery in non-insulin dependent diabetic patients evaluated by two-dimensional Doppler ultrasonography.

    The15th International Diabetes Federation Congress (IDF).  1994 

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  • Non-invasive evaluation of lower limb circulation in non-insulin dependent diabetic patients.

    The15th International Diabetes Federation (IDF) Satellite Symposium on "Diabetes and Macrovasucular Complication"  1994 

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  • Effects of beraprost sodium on lower limb circulation in NIDDM patients evaluated by two-dimentional doppler ultrasonography.

    The15th International Diabetes Federation Congress (IDF).  1994 

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  • . Efficacy of nilvadipine on blood flow of dorsal pedis artery in non-insulin dependent diabetic patients evaluated by two-dimensional Doppler ultrasonography.

    The15th International Diabetes Federation Congress (IDF).  1994 

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  • Ultrsonographic evaluation of lower limb circulation and arteriosclerosis.

    The7th Congress of World Federation for Ultrasound in Medicine and Biology (WFUMB).  1994 

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  • Efficacy of beraprost sodium on subjective symptoms and nerve functions in diabetic neuropathy.

    The15th International Diabetes Federation Congress (IDF).  1994 

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  • . Effects of beraprost sodium on lower limb circulation in NIDDM patients evaluated by two-dimentional doppler ultrasonography.

    The15th International Diabetes Federation Congress (IDF).  1994 

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  • Hemodynamic effects of nisordipine and nicardipine on lower limb circulation in NIDDM patients.

    The15th International Diabetes Federation Congress (IDF).  1994 

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  • Non-invasive evaluation of lower limb circulation in non-insulin dependent diabetic patients.

    The15th International Diabetes Federation (IDF) Satellite Symposium on "Diabetes and Macrovasucular Complication".  1994 

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  • インスリン非依存型糖尿病(NIDDM)患者の各種下肢循環指標とその有用性についての検討

    第37回日本糖尿病学会年次学術集会  1994 

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  • 色素沈着とGHの奇異性上昇を認めたACTH単独欠損症の一例-本院自験例の検討を含めて

    第20回北関東内分泌懇話会  1994 

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  • ACTH単独欠損症におけるTRH負荷試験の奇異性GH上昇反応について本院自験例の検討

    第5回ACTH研究会  1994 

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  • Beraprost SodiumとTocoretinateの併用が著効した糖尿病性壊疽の一症例

    第20回北関東内分泌懇話会  1994 

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  • 特発性に抗利尿ホルモン感受性の低下を認めた一例

    第20回北関東内分泌懇話会  1994 

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  • 重篤な亜鉛欠乏症を来した膵性糖尿病の一症例

    第31回日本糖尿病学関東甲信越地方会  1994 

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  • 原発性色素結節性副腎皮質過形成と心臓粘液腫,拡張型心筋症用心拡大を認めたCarney症候群の一例

    第67回日本内分泌学会秋期学術集会  1994 

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  • 睡眠時無呼吸症候群を呈した末端肥大症の一例

    第67回日本内分泌学会秋期学術集会  1994 

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  • Beraprost sodiumのNIDDM患者の下肢血流に及ぼす効果

    第67回日本内分泌学会学術総会  1994 

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  • 糖尿病神経障害におけるBeraprost sodiumの自覚症状および神経機能に及ぼす効果の検討

    第37回日本糖尿病学会年次学術集会  1994 

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  • IーMIBG scintigraphyにてfalseーpositiveを呈した副腎皮質非機能性腺腫の一例

    第67回日本内分泌学会秋期学術集会  1994 

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  • 各種非侵襲的手法によるインスリン非依存型糖尿病患者の下肢循環についての総合的検討

    第35回日本脈管学会  1994 

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  • 糖尿病神経障害患者におけるBeraprost sodiumの下肢血流における効果の検討

    第37回日本糖尿病学会年次学術集会  1994 

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  • 睡眠時無呼吸症候群を呈した末端肥大症の一例

    第20回北関東内分泌懇話会  1994 

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  • レムナント停滞のみられた糖尿病合併高脂血症の一例

    第13回脂質代謝異常症例検討会  1994 

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  • 抗利尿ホルモン不適切分泌症候群と両側声帯不全麻痺を合併したShyーDrager症候群の一例

    第419回日本内科学会関東地方会  1993 

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  • Ibudilastの下肢血流に対する効果-超音波カラードプラを用いたNIDDM患者での検討-

    糖尿病大血管障害研究会第3回シンポジウム  1993 

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  • 抗利尿ホルモン不適切分泌症候群と両側声帯不全麻痺を合併したShyーDrager症候群の一例

    第66回日本内分泌学会秋期学術集会  1993 

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  • 心不全を伴った原発性色素性結節性副腎皮質病変(PPNAD) によるCushing症候群の一例

    第3回筑波大学内科集談会  1993 

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  • 原発性副甲状腺機能亢進症の超音波カラードプラ法による評価の検討

    日本超音波学会第4回乳房・甲状腺研究部会  1993 

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  • SIADHを契機に診断された両側反回神経麻痺を合併したShyーDrager症候群の一例

    第19回北関東内分泌懇話会  1993 

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  • 心不全症状を伴った両側副腎結節性過形成(PPNAD)の一例

    第19回北関東内分泌懇話会  1993 

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Industrial property rights

  • 前糖尿病状態のスクリーニング方法及びスクリーニング試薬

    曽根 博仁

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    Application no:特願2001-73332  Date applied:2001.3

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  • 前糖尿病状態のスクリーニング方法及びスクリーニング用試薬

    海老沼 宏幸, 齋藤 和典, 曽根 博仁, 山田 信博

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    Applicant:第一化学薬品株式会社

    Application no:特願2001-073332  Date applied:2001.3

    Announcement no:特開2002-277473  Date announced:2002.9

    J-GLOBAL

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  • 前糖尿病状態のスクリーニング方法及びスクリーニング用試薬

    海老沼 宏幸, 齋藤 和典, 曽根 博仁, 山田 信博

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    Applicant:積水メディカル株式会社

    Application no:特願2001-073332  Date applied:2001.3

    Announcement no:特開2002-277473  Date announced:2002.9

    Patent/Registration no:特許第4602577号  Date registered:2010.10  Date issued:2010.10

    J-GLOBAL

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  • 眼内血管申請性疾患治療薬

    曽根 博仁

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    Application no:特願平9-9526  Date applied:1997.3

    Announcement no:特開平10-273456  Date announced:1998.10

    Patent/Registration no:特許平09-095286  Date issued:1997.3

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  • 慢性関節リウマチ治療薬

    曽根 博仁

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    Application no:特願平9-32799  Date applied:1997.1

    Announcement no:特開平10-218791  Date announced:1998.8

    Patent/Registration no:特許平09-032799  Date issued:1997.1

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  • 糖尿病性腎症診断剤

    奥田 諭吉, 曽根 博仁, 近藤 伸一, 松本 友恵

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    Applicant:東亞合成株式会社

    Application no:特願平7-045459  Date applied:1995.3

    Announcement no:特開平8-245424  Date announced:1996.9

    J-GLOBAL

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Awards

  • Expert Investigator Award

    2023.10   Japan Society for Diabetic Complications  

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  • The Xiaoren Pan Distinguished Research Award for Epidemiology of Diabetes

    2019.5   Asian Association for the Study of Diabetes(AASD)  

    Hirohito Sone

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  • 医学研究奨励賞

    2012   日本医師会  

    曽根 博仁

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

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  • 学会賞(リリー賞)

    2010   日本糖尿病学会  

    曽根 博仁

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

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  • 臨床血管機能研究助成 優秀研究賞

    2008   木村記念財団  

    曽根 博仁

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:Japan

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  • 動脈硬化Update優秀賞

    2008   日本心臓財団  

    曽根 博仁

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    Award type:International academic award (Japan or overseas)  Country:Japan

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  • 井村臨床研究奨励賞

    2006   (公財)健康加齢医学振興財団  

    曽根 博仁

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

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  • 研究奨励賞

    2002   長寿科学振興財団  

    曽根 博仁

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

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  • 認定内科専門医会 研究奨励賞

    2001   日本内科学会  

    曽根 博仁

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    Award type:International academic award (Japan or overseas)  Country:Japan

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  • Travel Grant Award

    1997   American Diabetes Association  

    SONE, Hirohito

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Research Projects

  • 日本人糖尿病患者における環境因子と遺伝因子を考慮した食事療法のエビデンス構築

    Grant number:23K10873

    2023.4 - 2026.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    堀川 千嘉, 藤原 和哉, 森川 咲子, 曽根 博仁

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

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  • Development of a comprehensive self-care system utilizing big data/AI to cure non-communicable diseases and validation of its effectiveness

    Grant number:22H03529

    2022.4 - 2026.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

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  • ウェアラブルデバイスを用いた咀嚼行動変容と歯周病改善による糖尿病コントロール

    Grant number:21H03129

    2021.4 - 2025.3

    System name:科学研究費助成事業 基盤研究(B)

    Research category:基盤研究(B)

    Awarding organization:日本学術振興会

    堀 一浩, 多部田 康一, 小野 高裕, 曽根 博仁, 高橋 直紀

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    Grant amount:\17290000 ( Direct Cost: \13300000 、 Indirect Cost:\3990000 )

    近年,咀嚼と全身の健康との関連が報告されているが,咀嚼能力と咀嚼行動(咀嚼回数やスピード)のいずれが全身の健康と関連するのかは不明瞭なままである.特に,医科で注目されている咀嚼行動に関しては,これまでアンケートによる主観的な評価にとどまっており,実効的なツールが無いことから,効果的な咀嚼行動変容を促すことができずにいた.そこで,我々は耳に掛けるだけで客観的に咀嚼行動のモニタリングが可能なウェアラブルデバイスの開発に携わってきた.本検討課題では,このデバイスを使用して成人期におけるにおける咀嚼能率と咀嚼回数,および全身との関連を明らかとし,行動変容アルゴリズムを用いて効果的な咀嚼行動変容を促すことにより,その改善効果を検討する.
    本年は,72名の対象者におにぎり1つ(100g)を摂取してもらい,その際の咀嚼回数,食事時間・咀嚼スピード・一口当たり咀嚼回数などを測定し,その後の経時的血糖値を計測した.さらに,対象者の身長体重測定,血液検査,口腔機能測定を行い,その関連について検討した.その結果,咀嚼回数は体重やBMI・腹囲と負の相関がみられ,経時的血糖変化曲線下面積(AUC)とは正の相関がみられた.また,摂取時間は咀嚼回数との相関が高く,体重・BMIとの負の相関がみられた.さらに,取り込み回数は体重・BMI・空腹時血糖と負の相関がみられた.一方で,一口当たりの咀嚼回数や咀嚼能率は体重やBMIとは相関を認めなかったが,経時血糖AUCとは正の相関を認めた.また,おにぎり咀嚼回数の中央値(234.5回)で被験者をよく噛む群とあまり咬まない群の2群に分けて比較したところ,体重,BMIには有意に差が見られ,あまり咬まない群は肥満の傾向が認められた.また,経時的血糖曲線におけるAUCの比較では,よく咬む群の方が有意に高い値となった.

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  • リアルワールドデータ分析と機械学習による健康寿命延伸/介護予防エビデンスの確立

    Grant number:21K11569

    2021.4 - 2024.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    藤原 和哉, 曽根 博仁, 児玉 暁

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    健康寿命(自立して健康に暮らせる期間)の短縮は、QOLの低下だけでなく、社会経済的影響においても深刻な問題である。要介護状態は、健康寿命の終焉を示す指標の一つであり、リスク因子の解明と個人レベルでの予防は急務である。成人ではリアルワールドデータを活用した科学的エビデンスの創出が進む一方で、高齢者領域では研究実施に多くの障害があり、データ構築/分析が大きく遅れている。今回、独自の手法により、1万人の健診及び10年分の介護データを統合し、実際の現場診療実務者の医学的評価に基づいた、正確なアウトカム判定と組み合わせることで、介護分析に特化したリアルワールドデータベースを構築する。同データを長期縦断的に解析することで、従来の断面データや個別コホートの検討では得られない、介護未発症者から介護発症/重症化へ至るリスク要因を明らかとする。
    本研究は、以下に示す研究計画の通り、以下の1で構築したデータベースを基に2のプロジェクトを実施する。
    1. 健診・健康保険レセプト・介護発生/重症化を一体化したデータベースの構築
    匿名化した上で収集された薬剤/歯科情報を含む膨大なレセプト情報、臨床指標(血液検査/生活習慣調査)、介護要因並びに増悪の情報を含む介護保険情報を連結可能匿名化し、約1万人を個人突合する
    2. 介護発生の誘因となるアウトカムの発生及び介護発生/重症化リスクの解析
    95%以上の正確性をもつ独自システムを用いた診療内容の医学的評価を基盤とした手法から、イベントと介護保険情報と照らし合わせ、介護発生/増悪のリスク因子を分析する。

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  • Factors associated with inappropriate weight loss attempts by young women in Japan.

    Grant number:21K11627

    2021.4 - 2024.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

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  • 科学的エビデンスに基づく「フィジカルエイジR」(体力年齢)の確立ならびに社会実装に向けた製品化

    2020 - 2021

    System name:産学が連携した研究開発成果の展開 研究成果展開事業 研究成果最適展開支援プログラム(A-STEP) トライアウト トライアウト

    Awarding organization:科学技術振興機構

    曽根 博仁

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    Authorship:Principal investigator 

    体力は健康寿命延伸に大きな役割を果たす。体力は、持久力、筋力、柔軟性など多要素を含み、いずれも加齢と共に低下する。各個人が、同年齢の日本人集団の中でどの程度の総合体力を有するかを数値化し、暦年齢とは別に、それより何歳若い、あるいは老いているかがわかるような指標を、科学的データに基づいて示せば、運動実施のモチベーション向上のみならず、健康診断や健康経営、イベント等の現場などに幅広く活用可能な世界標準の健康指標となりうる。我々が持つ3万人×20年分の体力テストのビッグデータにより、この体力指標(「フィジカルエイジR」として商標登録済)を確立し、システム化、製品化を通じた社会実装を行う。

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  • 本邦CLLの病態解明に基づく簡便な新規診断法の確立

    Grant number:19K07863

    2019.4 - 2024.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    瀧澤 淳, 曽根 博仁, 大島 孝一, 河本 啓介

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    慢性リンパ性白血病(CLL)は西欧諸国で最も頻度の高い成人白血病であるが、本邦を含めた東アジアでは極めて希少な疾患で、その理由は不明のままである。その原因を解明するために本邦CLLの本態を明確にすることが本研究の目的である。2020年3月まで行ってきた国内前方視登録研究(CLLRSG-01)の登録症例を対象にして研究を行っている。
    登録症例に対してフローサイトメトリー(FCM)解析により免疫表現形を解析したが、免疫表現形が典型的(CD5陽性かつCD23陽性のB細胞腫瘍)なCLLと非典型的なCLL-like LPDに分類し、免疫組織化学(IHC)を用いてLEF1発現を検討した。Matutes score 4または5のCLL27例は全例LEF1陽性であったが、score 3のCLLは33例中LEF1陽性は20例(61%)のみで1/3以上がLEF1陰性であることが判明した。CLL-like LPDは21例中8例(38%)がLEF1陽性であり、これらが本当にCLLと異なる疾患であるか更なる検討が必要と考えられた。この検討結果は2019年9月に行われたinternational workshop on CLL (iwCLL2019)に採用され発表を行った。
    さらにCLL-like LPDの本態を明らかにするために濾胞辺縁帯B細胞に特徴的な分子と考えられるIRTA1とMNDAの発現についてIHCで検討を行った。陽性コントロールとして用いた濾胞辺縁帯B細胞由来リンパ腫(節性濾胞辺縁帯リンパ腫:NMZL、脾辺縁帯リンパ腫:SMZL、節外性脾辺縁帯MALT型リンパ腫)に発現が認められIHCが機能することが確認され、染色結果を集計している。現在、FISH解析による染色体異常や免疫グロブリン重鎖可変領域(IGHV)の体細胞突然変異(SHM)の有無を含め臨床的および細胞遺伝学的解析結果との比較検討を進めている。

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  • Health life extension and QOL improvement through integrated analysis of health and medical big data

    Grant number:19H04028

    2019.4 - 2022.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Sone Hirohito

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    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    This study aims to establish a large number of scientific evidences to prevent the incidence and aggravation of lifestyle-related diseases that are directly linked to healthy life expectancy and quality of life. We constructed and analyzed a database that combines healthcare big data accumulated in the community, including health checkups, receipts, and long-term care insurance.
    As a result, we were able to establish a number of world-class evidences that are useful for healthy longevity and contribute to prevention, treatment, and planning of countermeasures through the big data sleeping in local communities. These results included the three major determinants of healthy life expectancy, risk factors for severe diabetic complications, new evidence related to diet and exercise therapy, relationship between physical fitness and various diseases, significance of medication adherence, and relationship between lifestyle and lifestyle-related diseases in school children and young adults.

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  • Examination of cross-sectional and longitudinal relationships between physical examination data including physical fitness results and bone density

    Grant number:17K09104

    2017.4 - 2020.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Kato Kiminori

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    Grant type:Competitive

    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Bone density data of about 90,000 people in total was analyzed. In a cross-sectional analysis with physical fitness measurements, the only factors independently associated with bone density were sex, age, weight, grip strength, standing forward bending, and whole-body reaction time. In a longitudinal analysis, the only factors independently associated with changes in bone density were gender, grip strength, and vertical jump. In addition, we are conducting a “Questionnaire survey on bone fracture events among osteoporosis screening examinees” for 17,000 people with osteoporosis screening, and we are aiming to publish the results.

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  • Development of a web-system for promotion of EBLM by building a clinical case bank with harmonized recording of lab data.

    Grant number:16H02771

    2016.4 - 2020.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (A)

    Awarding organization:Japan Society for the Promotion of Science

    ICHIHARA Kiyoshi

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    Grant type:Competitive

    Grant amount:\41340000 ( Direct Cost: \31800000 、 Indirect Cost:\9540000 )

    As source data for use in the practice of evidence-based laboratory medicine (EBLM), healthy reference values (RVs) of major laboratory tests and clinical and laboratory information for major diseases were accumulated by international collaboration. For the former, 18,000 healthy volunteers were recruited since 2011 through a global study on RVs by collaboration of 19 countries. Standardized test results for 50 major lab tests were put into database (DB) together with personal information obtained from a common health-status questionnaire. For the latter, as a model DB, collagen diseases and hematological malignancies were targeted. By international collaboration, clinical and laboratory findings of well-defined cases (dermatomyositis 358, systemic sclerosis 416, multiple myeloma 456, malignant lymphoma 599) were accumulated. Both DBs were placed in a newly created EBLM web system so that evidence for laboratory diagnosis can be explored by specifying various conditions.

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  • Differential diagnosis of Japanese patients with CLL and related disorders

    Grant number:16K08963

    2016.4 - 2019.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    TAKIZAWA JUN, Suzumiya Junji

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    Grant type:Competitive

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western countries, is rare in Japan. To clarify the characteristics of Japanese patients with CLL, we conducted a nationwide registry study (CLLRSG-01). The WHO classification was used to establish a central diagnosis in all cases. Analyses of flow cytometry, FISH, and the mutational status of IGHV were performed. Morphologically 162 cases were classified as CLL and 59 as other B-cell neoplasms. Immunophenotypically, 109 of the 162 cases were confirmed as CLL (classic CLL), but the other 53 patients could not be attributed to a diagnosis of CLL (CLL-like LPD). The frequency of morphologically atypical CLL in the CLL-like LPD group was higher than that in the classic CLL group. Our analyses indicate that the proportion of Japanese patients with classic CLL is much lower among those with small mature B-cell neoplasms.

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  • Establishment of clinical evidences for healthy life via integrated analysis of medical big data

    Grant number:16H03260

    2016.4 - 2019.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Sone Hirohito

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

    In order to establish scientific evidence which is useful for practical medical care and/or health activities by utilizing medical and/or health-related ‘big data’, and to contribute to the comprehensive extension of healthy life through that, the big data accumulated in the local area such as medical claim or health check-up huge database were analyzed by individually collating them in a longitudinal manner. As a result, a wide range of clinical evidences could be established, mainly regarding on the risk and pathophysiology of diabetes and its complications, obesity, hypertension and arteriosclerotic disease.

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  • 米の新規需要拡大のための輸出を目指した湿熱処理技術による保存性と生理的機能性の優れた玄米米粉開発

    2016.4 - 2019.3

    System name:革新的技術開発・緊急展開事業(うち地域戦略プロジェクト)

    Awarding organization:独立行政法人農業・食品産業技術総合研究機構

    菅原 正義

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    Grant type:Competitive

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  • 女性の出産後メタボリックシンドローム発症のリスク因子同定と予防研究

    2015.11 - 2016.3

    System name:日本医療研究開発機構研究費

    Awarding organization:厚生労働省

    平松 祐司

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    Grant type:Competitive

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  • 大規模検診データベースの縦断解析エビデンスに基づく基準範囲設定と重大イベント発症確率精密予測のフィードバックによる検診要精検者の医療機関受診率向上戦略

    2015.4 - 2017.3

    System name:日本医療研究開発機構研究費

    Awarding organization:厚生労働省

    曽根 博仁

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\22300000 ( Direct Cost: \17155001 、 Indirect Cost:\5144999 )

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  • The prevention and treatment of obesity and diabetes with BDNF, a myokine derived from skeletal muscle

    Grant number:26350885

    2014.4 - 2017.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    HANYU Osamu, NAWA Hiroyuki, FURUKAWA Kazuo

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    Grant type:Competitive

    Grant amount:\4940000 ( Direct Cost: \3800000 、 Indirect Cost:\1140000 )

    Brain-derived neurotrophic factor (BDNF) is a possible anti-obesity and anti-diabetes agent with its anorectic and hypoglycemic effect. Recently BDNF is considered as one of myokines which is produced in skeletal muscle. We demonstrated that BDNF reduces blood glucose level via suppression of glucagon secretion from pancreas. In addition, advanced glycation end products (AGEs) induces BDNF release from human platelets through the activation of the Src family kinase pathway (Furukawa, K. et al. Cardiovasc Diabetol. 2017;16(1):20). Considering the toxic action of AGEs and the protective roles of BDNF, it can be hypothesized that AGE-induced BDNF release is a biological defense system in the early phase of diabetes. Chronic elevation of AGEs may induce depletion or downregulation of BDNF in platelets during the progression of diabetes mellitus.

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  • IgG4-related disease can cause MALT lymphoma

    Grant number:25461496

    2013.4 - 2017.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Takizawa Jun

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    Grant type:Competitive

    Grant amount:\4940000 ( Direct Cost: \3800000 、 Indirect Cost:\1140000 )

    Recently some cases with MALT lymphoma arising from IgG4-related disease (IgG4-RD) were reported. To assess the association between MALT lymphoma and IgG4-RD, 69 patients with MALT lymphoma diagnosed in our hospital were examined. Of the 69 cases of MALT lymphoma, 11 (16 %) had IgG4-related disease by comprehensive diagnostic criteria for IgG4-RD. Orbita was the most frequently involved site (10 cases), followed by lung (one case). Three cases with orbital MALT lymphoma associated with IgG4-RD occurred second lymphoid neoplasms with different sites and clones, suggesting chronic inflammation produced by IgG4-RD can promote the development of lymphoid malignancies such as MALT lymphoma.

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  • 患者データベースに基づく糖尿病の新規合併症マーカーの探索と均てん化に関する研究-合併症予防と受診中断抑止の視点から

    2013.4 - 2016.3

    System name:厚生労働科学研究費補助金

    Awarding organization:厚生労働省

    野田 光彦

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    Grant type:Competitive

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  • Searching for predictors of non-communicable diseases in Japanese by integrating health and clinical sciences

    Grant number:24300233

    2012.4 - 2016.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Sone Hirohito

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\17290000 ( Direct Cost: \13300000 、 Indirect Cost:\3990000 )

    Projects regarding (1)Quantitative meta-analysis regarding risk factors of non-communicable disease (2) Effects of exercise in young adults (3) Effects of diet in young adults (4) Efficient screening of non-communicable disease (5) Clarifying predictors of complication in diabetes and other non-communicable disease (6) Assessment of health-related web information regarding non-communicable disease were promoted and many original articles have been published international journals. Clinical evidences established by these projects were employed by many clinical guidelines and contributed daily clinical care and management.

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  • 糖尿病診療均てん化のための標準的診療マニュアル作成とその有効性の検証-ガイドラインを実用化するためのシステム・体制整備の視点から

    2012.4 - 2015.3

    System name:厚生労働科学研究費補助金

    Awarding organization:厚生労働省

    野田 光彦

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    Grant type:Competitive

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  • 日本人2型糖尿病患者における生活習慣介入の長期予後効果ならびに死亡率とその危険因子に関する前向き研究(JDCS)

    2010.4 - 2015.3

    System name:厚生労働科学研究費補助金

    Awarding organization:厚生労働省

    曽根 博仁

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    Authorship:Principal investigator  Grant type:Competitive

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  • 糖尿病患者における心血管イベント発症に関する後ろ向きコホートに関する研究

    2010.4 - 2011.3

    System name:厚生労働科学研究費補助金

    Awarding organization:厚生労働省

    林 登志男

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    Grant type:Competitive

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  • 2型糖尿病患者のQOL、血管合併症及び長期予後改善のための前向き研究

    2009 - 2010.3

    System name:厚生労働科学研究費補助金

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    Grant type:Competitive

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  • 生活習慣病克服と健康寿命延伸のための生活習慣改善に関する総合的エビデンス確立事業

    2008.4 - 2012.3

    System name:科学研究費助成事業 基盤研究(B)

    Research category:基盤研究(B)

    Awarding organization:日本学術振興会

    曽根 博仁

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    Authorship:Principal investigator  Grant type:Competitive

    糖尿病やメタボリックシンドロームなど生活習慣病のリスクファクターとその予防と治療に不可欠な生活習慣療法の意義と効果を検討するために、医学・栄養学・運動科学・統計学を統合した臨床疫学的手法を駆使して、保健・医療現場で役立つ臨床エビデンスを多数確立した。

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  • 原発性高脂血症に関する調査研究

    2008 - 2011.3

    System name:厚生労働科学研究費補助金

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    Grant type:Competitive

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  • Establishing clinical evidence for prevention of lifestyle-related disease and lifestyle intervention

    Grant number:20300227

    2008 - 2011

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    SONE Hirohito, YAMADA Nobuhiro, OHASHI Yasuo

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    Grant amount:\18850000 ( Direct Cost: \14500000 、 Indirect Cost:\4350000 )

    To investigate effects and significance of lifestyles and their modification on management and prevention of life-style related diseases such as type 2 diabetes or metabolic syndrome, we integrated various related scientific fields involving medicine, nutritional and exercise sciences, statistics and established enormous number of clinical evidences including 54 original articles in international quality journals.

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  • 2型糖尿病患者のQOL、血管合併症及び長期予後改善のための前向き研究

    2008 - 2010.3

    System name:厚生労働科学研究費補助金

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    Grant type:Competitive

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  • 2型糖尿病患者のQOL、血管合併症及び長期予後改善のための前向き研究

    2007 - 2010.3

    System name:厚生労働科学研究費補助金

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    Grant type:Competitive

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  • CDKインヒビターp21の脂肪細胞分化、肥大化における役割の検討

    2006.4 - 2008.3

    System name:科学研究費助成事業 特定領域研究

    Research category:特定領域研究

    Awarding organization:日本学術振興会

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    Grant type:Competitive

    目的:細胞増殖、周期制御因子p21の脂肪細胞正常分化における生理的役割、脂肪細胞の肥大化における病的役割を明らかにしその分子的基盤を解明する事により、細胞周期制御因子の脂肪分化、肥満、インスリン抵抗性病態への関与を解明する。
    結果:3T3-L1前駆脂肪細胞における分化過程におけるp21タンパクの発現を確認したところ分化に伴い誘導されることがわかった。そこで、p21RNAiアデノウイルスを感染させ誘導されるp21をノックダウンして、脂肪細胞分化及び脂質の蓄積を評価したところp21遺伝子抑制群においては脂肪細胞分化及び脂質の蓄積が抑制されていた。また、脂肪細胞分化マーカーであるPPARγ、C/EBPα等はp21遺伝子抑制効果に伴い減少し、脂肪細胞分化初期に発現が亢進するC/EBPβがp21遺伝子抑制に畔い上昇していた。これらのことからp21遺伝子を抑制することにより脂肪細胞分化が抑制されp21は脂肪細胞分化に重要な役割を持つと考えられた。一方、p21ノックアウトマウス

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  • 糖尿病の予防治療における生活習慣因子の臨床的アウトカムに及ぼす影響の検討

    2006.4 - 2008.3

    System name:科学研究費助成事業 基盤研究(C)

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    曽根 博仁

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    Authorship:Principal investigator  Grant type:Competitive

    わが国の40歳以上の国民の1/3が糖尿病またはその疑いが強いことからもわかるように、生活習慣病の予防と治療は、将来の国民保健上の大問題である。同時に国民医療費も逼迫しており、効率的な生活習慣病対策確立のためにも、確固たる臨床エビデンスの必要性がますます高まっている。本研究は、糖尿病を中心とした生活習慣病の予防治療に関する臨床的・基礎的検討を行うことにより、将来のわが国の生活習慣指導に活かしうる科学的エビデンスを得ることを目的とした。特に糖尿病を含む生活習慣病の予防治療において重要因子である食事・運動・喫煙・飲酒などの生活習慣因子について解析した。具体的には、糖尿病患者の運動の効用や喫煙の弊害について、これまでの報告で曖昧にされていた交絡因子を、丁寧に調整または層化して解析したところ、定説とは異なる事実が多く明らかになった。たとえば喫煙を例に取ると、現に喫煙している患者のみならず、すでに禁煙した過

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  • CDKインヒビターp21の脂肪細胞分化、肥大化における役割の検討

    Grant number:18052001

    2006 - 2007

    System name:科学研究費助成事業

    Research category:特定領域研究

    Awarding organization:日本学術振興会

    島野 仁, 曽根 博仁, 松坂 賢

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    Grant amount:\8300000 ( Direct Cost: \8300000 )

    目的:細胞増殖、周期制御因子p21の脂肪細胞正常分化における生理的役割、脂肪細胞の肥大化における病的役割を明らかにしその分子的基盤を解明する事により、細胞周期制御因子の脂肪分化、肥満、インスリン抵抗性病態への関与を解明する。
    結果:3T3-L1前駆脂肪細胞における分化過程におけるp21タンパクの発現を確認したところ分化に伴い誘導されることがわかった。そこで、p21RNAiアデノウイルスを感染させ誘導されるp21をノックダウンして、脂肪細胞分化及び脂質の蓄積を評価したところp21遺伝子抑制群においては脂肪細胞分化及び脂質の蓄積が抑制されていた。また、脂肪細胞分化マーカーであるPPARγ、C/EBPα等はp21遺伝子抑制効果に伴い減少し、脂肪細胞分化初期に発現が亢進するC/EBPβがp21遺伝子抑制に畔い上昇していた。これらのことからp21遺伝子を抑制することにより脂肪細胞分化が抑制されp21は脂肪細胞分化に重要な役割を持つと考えられた。一方、p21ノックアウトマウスは、通常食ではほとんど正常マウスと差はないが、DIOにおいては、肥満の程度が軽減していた。脂肪細胞のサイズが減少していた。肥満の軽減に伴い、耐糖能、インスリン抵抗性が改善していた。アディポサイトカインの変化も減弱していた。3T3L1細胞の脂肪分化が進んだ6日後においてp21をRNAiアデノウイルスを用いて、分化後に急性欠失させたところ意外なことに急激なアポトーシスを呈し、脂肪蓄積は激減した。
    結論:p21遺伝子は脂肪細胞分化において一定の役割を担っている一方、肥満においても脂肪組織において誘導され、肥満脂肪細胞の維持とそれに伴うインスリン抵抗性の維持に重要な働きをしていることが示唆された。脂肪細胞の肥満化、脂肪の蓄積に伴う細胞ストレスの増加に対して、p21の抗アポトーシス作用に基づいているのかもしれない。肥満におけるp53/p21経路の活性化の分子メカニズムの解明が必要である。

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  • Effects of Lifestyle Factors on Clinical Outcomes of Prevention and Care of Diabetes

    Grant number:18500534

    2006 - 2007

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    SONE Hirohito

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    Grant amount:\3690000 ( Direct Cost: \3600000 、 Indirect Cost:\90000 )

    Diabetes mellitus and other lifestyle-related diseases are one of main health issues in most industrialized countries including Japan. Necessity and importance of their clinical evidences, which is useful in establishing strategies and for their prevention and care, are more and more increasing in these days. In this project, we evaluated effects of lifestyle factors such as diet, exercise, smoking, alcohol intake, etc. on various clinical parameters related to prevention and care of diabetes and other lifestyle-related diseases. By utilizing historical cohort design, meta-analysis and other methods, we could establish many important clinical evidences that could be applied in clinical settings. For example, we could find that smoking is a very important and dose-dependent risk factor for Japanese patients with diabetes to develop diabetic nephropathy. We could also clarify appropriate and suitable way of exercise for efficiently increasing HDL-cholesterol. Such results were reported in many international journals like Diabetes Care, Annals of Internal Medicine, and so on.

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  • 個体差が減量幅に与える影響を考慮したオーダーメイド減量プログラムの開発

    2004.4 - 2007.3

    System name:科学研究費助成事業 挑戦的萌芽研究

    Research category:挑戦的萌芽研究

    Awarding organization:日本学術振興会

    田中 喜代次

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    Grant type:Competitive

    本研究の目的は以下の2つの課題を遂行することであった。
    A.遺伝情報などのパラメータが減量の個体差に与える影響力を数値化する。
    B.個体差を考慮したオーダーメイド減量プログラムの有効性を検討する。
    本研究課題を達成するために,今年度だけで175名に対する減量介入を実施した。この3年間で構築したデータベースは,男性123名,女性467名,合計590名に達した。このうち350名については,140個の遺伝子に含まれる742個の一塩基遺伝子多型(SNP)の解析が終了している。さらに,性別,年齢,閉経の前後,形態,体組成,体脂肪分布,体力レベル等の減量前後の測定結果がデータベースに組み込まれている。
    このデータベースを用いて解析を進めた結果,以下のような新たな知見が得られた。
    1.体重減少によりメタボリックシンドローム構成因子は確実に改善する。体重の減少方法は,食事療法+運動療法,食事療法,運動療法の順に効果が大きい。減量目標の目安は初期体重の5%程度と言われているが,10%以

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  • メタボリックシンドロームの病態モデル動物の作成とその分子基盤の網羅的解析

    2004.4 - 2006.3

    System name:科学研究費助成事業 基盤研究(B)

    Research category:基盤研究(B)

    Awarding organization:日本学術振興会

    山田 信博

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    Grant type:Competitive

    糖尿病、高脂血症、高血圧などの生活習慣病は、終局的には虚血性心疾患や脳卒中などの動脈硬化性疾患を生じて、日本人のQOLおよび生命予後を著しく悪化させている。高カロリー、高脂肪、高単純糖質さらに運動不足の欧米型の生活習慣では、インスリン抵抗性や肥満を基軸として、加齢とともにいつの間にか、糖尿病のみならず高脂血症、高血圧などの動脈硬化危険因子を重積する場合が多い。メタボリックシンドロームの共通の病態として、肥満やインスリン抵抗性が注目されているが、その病態は単一ではなく、特定の遺伝子変異というよりは倹約遺伝子などの関連遺伝子機能の調節ないしは発現異常として捉えるべきであり、私達は遺伝子転写調節の視点、すなわち糖脂質代謝におけるエネルギー過剰あるいは消費不足に対する病的破綻状態という視点からエネルギー代謝制御機構の研究を展開してきた。メタボリックシンドロームの共通病態のひとつとして注目されているイ

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  • 腫瘍抑制因子p53活性化によるインスリン抵抗性発症の新しい分子機構の解明

    2004.4 - 2006.3

    System name:科学研究費助成事業 挑戦的萌芽研究

    Research category:挑戦的萌芽研究

    Awarding organization:日本学術振興会

    山田 信博

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    Grant type:Competitive

    肥満は先進国における主要な健康課題であり、その対策が望まれている。脂肪肝についても肥満との関連やインスリン抵抗性との関連から、その分子基盤が探索されている。DNAチップによりObマウスなどの肥満脂肪組織において腫瘍抑制因子であるp53の発現が亢進していることを見い出し、さらにp53がsterol regulatory element-binding Protein-1 (SREBP-1)や脂肪合成系諸酵素の抑制に関与していることをp53欠損マウスを用いて明らかにした。すなわち、p53が脂肪細胞における脂肪蓄積の抑制機構として重要な役割を果たしていることを見出した。
    p53が肥満時に脂肪細胞で活性化を受ける機序については現段階では不明であるが、p53はDNA障害以外にも低酸素や熱ショックなど幅広いストレスにより誘導されることが知られていることから考えると、肥満も広い意味で脂肪細胞にとってのストレスであり、インスリン抵抗性は一種のストレス応答であると見ることが可能かもしれない。このように、我々は

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  • TCA回路の部分阻害がエネルギー代謝に及ぼす影響の検討

    2004.4 - 2006.3

    System name:科学研究費助成事業 基盤研究(C)

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    曽根 博仁

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    Authorship:Principal investigator  Grant type:Competitive

    現代のエネルギー代謝疾患の増加は、ヒトのエネルギー代謝システムが近代のエネルギー需給バランスの急激な逆転に適応できなかった結果である。TCA回路は高い効率を有する洗練されたシステムではあるが、細菌などの下等生物細胞ではこれに依存しないエネルギー産生経路も発達している。クエン酸合成酵素(CS)遺伝子ノックアウト(KO)マウスを作成・解析し、同回路阻害による各エネルギー代謝経路への影響の検討し、同回路を補佐する代替エネルギー供給経路の検索、代謝疾患の病態生理との関係の検討を行った。本KOマウスはホモ欠損マウスが胎生致死であったが、ヘテロ欠損マウスについてはCS酵素活性が半分であることが判明した。エネルギー産生の低下したマウスにおいて基礎代謝、代謝性疾患の感受性、危険因子の発生、動脈硬化惹起性にもたらされる影響は、ライフスタイルと生活習慣病において重要な知見をもたらすと期待される。ヘテロマウスを基礎状態ならびに高

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  • 個体差が減量幅に与える影響を考慮したオーダーメイド減量プログラムの開発

    Grant number:16650161

    2004 - 2006

    System name:科学研究費助成事業

    Research category:萌芽研究

    Awarding organization:日本学術振興会

    田中 喜代次, 吉田 俊秀, 徳山 薫平, 曽根 博仁, 徳山 薫平

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    Grant amount:\3300000 ( Direct Cost: \3300000 )

    本研究の目的は以下の2つの課題を遂行することであった。
    A.遺伝情報などのパラメータが減量の個体差に与える影響力を数値化する。
    B.個体差を考慮したオーダーメイド減量プログラムの有効性を検討する。
    本研究課題を達成するために,今年度だけで175名に対する減量介入を実施した。この3年間で構築したデータベースは,男性123名,女性467名,合計590名に達した。このうち350名については,140個の遺伝子に含まれる742個の一塩基遺伝子多型(SNP)の解析が終了している。さらに,性別,年齢,閉経の前後,形態,体組成,体脂肪分布,体力レベル等の減量前後の測定結果がデータベースに組み込まれている。
    このデータベースを用いて解析を進めた結果,以下のような新たな知見が得られた。
    1.体重減少によりメタボリックシンドローム構成因子は確実に改善する。体重の減少方法は,食事療法+運動療法,食事療法,運動療法の順に効果が大きい。減量目標の目安は初期体重の5%程度と言われているが,10%以上の体重減少で効果が拡大する。
    2.決定木分析(データを様々な条件を基準に木の枝葉のように分類していく分析手法)を用いることにより,メタボリックシンドローム構成因子改善のための体重減少率は8.4%以上であることを明らかにした。
    3.体重減少率の個体差を減量前の各指標(性,年齢,閉経の前か後か,形態,体組成,体脂肪分布,体力レベル)の個体差から予測することは困難である,との結論を導いた。
    4.肥満関連遺伝子のSNP情報によって,体重減少率の個体差を予測することは可能である,と考えられた。その具体的なSNPの特定については,今後のさらなる研究成果が待たれるところである。
    5.食事群と食事+運動群の体重減少率の差は,SNPの組み合わせによっては,4〜5%に達することが示唆された。

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  • The effects of partial disruption of tricarboxylic acid cycle on energy metabolism. The analysis of expression forms of citrate synthetase gene-disrupted mice

    Grant number:16590864

    2004 - 2005

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    SONE Hirohito, SHIMANO Hitoshi

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    Grant amount:\3400000 ( Direct Cost: \3400000 )

    To find out solution over lifestyle-related metabolic disorders like obesity, diabetes and dyslipidemia, it is necessary to re-evaluate the significance of tricarboxylic acid (TCA) cycle, an important metabolic pathway with very high efficiency. To investigate the effects of inhibiting the cycle, the gene encoding citrate synthase (CS), one of rate-limiting enzymes of the cycle, was disrupted in mice. Homozygous (CS-/-) mice showed early embryonic lethality but heterozygous mice (CS+/-) showed partial expression of the CS gene in each of the mRNA, protein, and enzyme activity levels. Whereas there were no differences in weight, basal metabolic rate, blood pressure, fasting plasma glucose/insulin levels, serum lipid levels between wild-type and CS+/- mice, it is clarified that respiratory quotient (respiratory exchange ratio) was significantly lower and serum acetoacetate levels were significantly higher in CS+/- mice. High-fat high-sugar diet of one or two months for both wild-type and CS+/- mice resulted in marked blunted plasma response after intravenous glucose load without any differences in glucose responses in CS+/- mice compared with wild-type mice. It is thought that the mouse could be a useful model to investigate the mechanisms of insulin resistance underlying energy metabolism disorders.

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  • 腫瘍抑制因子p53活性化によるインスリン抵抗性発症の新しい分子機構の解明

    Grant number:16659237

    2004 - 2005

    System name:科学研究費助成事業

    Research category:萌芽研究

    Awarding organization:日本学術振興会

    山田 信博, 島野 仁, 曽根 博仁

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    Grant amount:\3800000 ( Direct Cost: \3800000 )

    肥満は先進国における主要な健康課題であり、その対策が望まれている。脂肪肝についても肥満との関連やインスリン抵抗性との関連から、その分子基盤が探索されている。DNAチップによりObマウスなどの肥満脂肪組織において腫瘍抑制因子であるp53の発現が亢進していることを見い出し、さらにp53がsterol regulatory element-binding Protein-1 (SREBP-1)や脂肪合成系諸酵素の抑制に関与していることをp53欠損マウスを用いて明らかにした。すなわち、p53が脂肪細胞における脂肪蓄積の抑制機構として重要な役割を果たしていることを見出した。
    p53が肥満時に脂肪細胞で活性化を受ける機序については現段階では不明であるが、p53はDNA障害以外にも低酸素や熱ショックなど幅広いストレスにより誘導されることが知られていることから考えると、肥満も広い意味で脂肪細胞にとってのストレスであり、インスリン抵抗性は一種のストレス応答であると見ることが可能かもしれない。このように、我々は、肥満に伴うインスリン抵抗性の病態は、おそらく脂肪細胞でのネガティブフィードバック機構の発動に端を発する生理/病理現象であろうという仮説を立て、検証を続けている。p53経路もその機序のひとつと位置付けて、インスリン抵抗性とp53の活性化について、検討を加えてきた。今回、2つの動物モデルを用いることにより、p53がp21発現亢進を介して脂肪肝の発症機序に関与していることを見出した。脂肪肝のモデルとして肥満を伴うObマウスおよび肥満を伴わないSREBP-1過剰発現マウスを用い、これらのモデル動物の脂肪肝においてp53発現が誘導されていることを明らかにし、p53が脂肪肝の病態において重要な役割を果たしていることが明らかとなった。

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  • Animal model for metabolic syndrome and its molecular basis.

    Grant number:16390260

    2004 - 2005

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    YAMADA Nobuhiro, SHIMANO Hitoshi, TOYOSHIMA Hideo, SONE Hirohito

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    Grant amount:\14400000 ( Direct Cost: \14400000 )

    Insulin receptor substrate 2 (IRS-2) is the main mediator of insulin signalling in the liver, controlling insulin sensitivity. Sterol regulatory element binding proteins (SREBPs) have been established as transcriptional regulators of lipid synthesis. Here, we show that SREBPs directly repress transcription of IRS-2 and inhibit hepatic insulin signalling. The IRS-2 promoter is activated by forkhead proteins through an insulin response element (IRE). Nuclear SREBPs effectively replace and interfere in the binding of these transactivators, resulting in inhibition of the downstream PI(3)K/Akt pathway, followed by decreased glycogen synthesis. These data suggest a molecular mechanism for the physiological switching from glycogen synthesis to lipogenesis and hepatic insulin resistance that is associated with hepatosteatosis.

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  • 活力寿命を評価する客観的指標作成のためのデータベースの構築

    2003.4 - 2006.4

    System name:科学研究費助成事業 基盤研究(B)

    Research category:基盤研究(B)

    Awarding organization:日本学術振興会

    田中 喜代次

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    Grant type:Competitive

    本研究の目的は以下の2つである.
    1.10〜20年前に測定対象とした中高齢者の活力年齢を再度測定し,活力寿命を評価する指標を作成するためのデータベースを構築する.
    2.ADL (activities of daily living)やQoL (quality of life)が顕著に低下した集団を擬似死亡群と定義し,活力寿命を評価する指標を提案する.
    研究期間中に測定依頼および生存確認をおこなった対象者のうち,232名(男性78名,女性157名)の者のデータが分析可能であったことから全対象者と位置づけた.全対象者のうち,調査開始から2005年の時点で死亡の確認された者は,男性9名,女性3名,計12名であった.
    本研究では"Lifespan Prediction Model"(寿命予測モデル:個人のからだ年齢と暦年齢の差から余命期間を推し量ろうとする考え方)が確立できることを研究仮説とし分析を進めた.主要な知見は以下の通りである.
    1.心疾患や糖尿病などを保有していた場合,16年間で死亡した者は初期の段階ですでに活力度の劣ることが明らかとなった.さらに,貧血傾向でありHD

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  • 遺伝子改変マウスを用いた新規脂肪酸組成調節酵素のエネルギー代謝に及ぼす影響の検討

    2003.4 - 2004.3

    System name:科学研究費助成事業 挑戦的萌芽研究

    Research category:挑戦的萌芽研究

    Awarding organization:日本学術振興会

    島野 仁

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    Grant type:Competitive

    生体内での脂肪酸合成の最終段階の反応を担い、脂肪酸組成比を制御する活性を有する脂肪酸延長酵素FACEのノックアウトマウスを作製、解析し、1.この新規脂肪酸伸長酵素の生体内での機能を解明すること、2.脂肪酸合成、組成の変化がもたらす糖脂質代謝、インスリン感受性、動脈硬化症など生活習慣病に関連する病態への影響を個体で評価することを目的として、本研究は進行中である。本年度はFACEノックアウトマウスの確立とその初期解析を行った。本マウスは、当初欠損遺伝子のホモが得られず胎生致死が疑われたが、その後の交配の進行とともに部分胎生致死であり、生存マウスを解析に供した。肝臓における脂肪酸延長酵素活性を測定したところ、対照野生群に比べほとんど消失しており、遺伝子欠損の確認と本遺伝子がその酵素活性において必須であることが確認された。本ノックアウトマウスは、性別により程度の差があるが、対照群よりもやせており、また食事の内容

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  • Construction of physiological, hematological and biochemical databases for the "Lifespan Prediction Model"

    Grant number:15300230

    2003 - 2005

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    TANAKA Kiyoji, SONE Hirohito, SHIGEMATSU Ryosuke, NAKAGAICHI Masaki, NAKADOMO Fumio

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    Grant amount:\16000000 ( Direct Cost: \16000000 )

    The purposes of this study were 1)to examine the relationship between lifespan and physical vitality (vital age) based on physiological, hematological and biochemical cross-sectional data, and 2)to evaluate the validity of estimating lifespan using the <Lifespan Prediction Model> by comparing middle-aged and older adults with lower physical vitality to those with higher physical vitality. Physical vitality was based on a combination of health/fitness information for anemia, serum cholesterol level, agility and aerobic work capacity. Participants in this study were 232 Japanese people (78 men and 157 women, aged 27-91 years) who underwent the physical vitality assessment. During the follow-up study period from 1991 to 2005,twelve people (9 men and 3 women) died. This study attempted to test the hypothesis that lifespan can be predicted from the difference between chronological age and vital age (based on physical vitality scores).
    The following results were obtained : 1.Patients with cardiovascular disease and diabetes mellitus who died during the follow-up period had relatively lower physical vitality as evidenced by anemia, lower HDLC, and lower physical fitness level at baseline. 2.Vital age for regularlyexercising coronary patients was significantly younger than patients who stopped exercising.
    These results indicate that exercise habituation for an extended period of time (5 years or more) favorably affects the physical vitality of coronary patients, supporting a model of lifespan prediction using physical vitality consisting of anemia, serum cholesterol level, agility and oxygen uptake.

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  • 遺伝子改変マウスを用いた新規脂肪酸組成調節酵素のエネルギー代謝に及ぼす影響の検討

    Grant number:15659215

    2003

    System name:科学研究費助成事業

    Research category:萌芽研究

    Awarding organization:日本学術振興会

    島野 仁, 中川 嘉, 高橋 照光, 曽根 博仁

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    Grant amount:\3300000 ( Direct Cost: \3300000 )

    生体内での脂肪酸合成の最終段階の反応を担い、脂肪酸組成比を制御する活性を有する脂肪酸延長酵素FACEのノックアウトマウスを作製、解析し、1.この新規脂肪酸伸長酵素の生体内での機能を解明すること、2.脂肪酸合成、組成の変化がもたらす糖脂質代謝、インスリン感受性、動脈硬化症など生活習慣病に関連する病態への影響を個体で評価することを目的として、本研究は進行中である。本年度はFACEノックアウトマウスの確立とその初期解析を行った。本マウスは、当初欠損遺伝子のホモが得られず胎生致死が疑われたが、その後の交配の進行とともに部分胎生致死であり、生存マウスを解析に供した。肝臓における脂肪酸延長酵素活性を測定したところ、対照野生群に比べほとんど消失しており、遺伝子欠損の確認と本遺伝子がその酵素活性において必須であることが確認された。本ノックアウトマウスは、性別により程度の差があるが、対照群よりもやせており、また食事の内容や年齢により明かに食欲の変化を認め、本酵素と肥満や食行動との関連が示唆された。現在ob/obマウスの交配ならびに高脂肪食負荷を施行中である。高脂肪食負荷における予備実験では、血糖ならびにインスリン値が野生群よりも低く、インスリン感受性が高いことが示唆され、現在さらに詳細に検討中である。生体内脂肪酸組成を改変することがエネルギー代謝やインスリン抵抗性など生活習慣病感受性に影響を与える仮説の実証が得られつつある。

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  • 低酸素反応性・可溶性VEGFレセプターを用いた悪性グリオーマの抗血管新生療法

    2002.4 - 2005.3

    System name:科学研究費助成事業 基盤研究(C)

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    高野 晋吾

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    Grant type:Competitive

    悪性グリオーマの抗血管新生療法の標的としてVEGFレセプターFlt1のうち細胞外の可溶性成分であるsoluble Flt1(sFlt1)および低酸素のマーカーであるhypoxia inducible factor 1α(HIF)に注目し、これらを用いた血管新生療法の基礎的研究を行い、臨床応用への展開を目的とした。
    1.グリオーマにおけるsFlt1およびHIFの意義:グリオーマ組織のsFlt1,HIF,VEGFの発現量を定量した。VEGF/sFlt1が1以上、HIFの高発現は予後不良因子であった。
    2.sFlt-1過剰発現の効果:sFlt1の遺伝子導入でsFltを過剰発現したグリオーマ細胞のマウスでの腫瘍増殖は、遺伝子導入していない腫瘍に比べて30%の抑制効果がみられた。
    3.HIFを抑制するCPT-11の血管新生抑制効果:CPT-11は血管内皮細胞の増殖を選択的に抑制するとともに、グリオーマ細胞のHIFの遺伝子・蛋白発現それに続くVEGFの遺伝子・蛋白発現を著明に抑制した。
    4.CPT-11の血管新生抑制スケジュールの開発:マウス皮下腫瘍モデルでCPT-11の投与方法の検討を行った。中等量短期間投与

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  • 遺伝子改変動物を用いたTCA回路遮断がもたらすエネルギー代謝への影響の検討

    2002.4 - 2004.3

    System name:科学研究費助成事業 基盤研究(C)

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    曽根 博仁

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    Authorship:Principal investigator  Grant type:Competitive

    糖尿病を初めとするエネルギー代謝異常症に対する根本的解決策を探るためには、糖・脂質・タンパク代謝を含む最も基本的なエネルギー産生経路であり、極めて高いエネルギー産生効率を有するTCA回路の意義を再検討する必要がある。最も確実かつ効率的にTCA回路を阻害する標的として、回路開始点でアセチルCoAとオキサロ酢酸からクエン酸を産生する不可逆反応の律速酵素、クエン酸合成酵素(Citrate Synthetase ; CS)遺伝子を選択し、そのノックアウト(KO)マウスを作成した。
    その結果ホモ欠損マウス(-/-)は胎生致死であることが確認された。ヘテロ欠損マウス(+/-)については、CS遺伝子発現は、RNA・タンパク・酵素活性の各レベルで+/+の約1/2であることが判明し、TCA回路の効率に大きな修飾が加わっていることが確認されたので、ヘテロ欠損マウス(+/-)と野生型(+/+)の比較を行った。
    両者は、通常食飼育では生後一年間、生存率、体重・血圧・空腹時血糖・空腹時インスリン(IRI)値・血清脂質

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  • Anti-angiogenic therapy for malignant gliomas using hypoxia-responsive soluble VEGF receptor

    Grant number:14571299

    2002 - 2004

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    TAKANO Shingo, SONE Hirohito, TSUBOI Koji, MITSUI Yoji

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    Grant amount:\2900000 ( Direct Cost: \2900000 )

    Soluble form of VEGF receptor, sFlt1 and hypoxia indutible factor(HIF) were focused on the key molecules of antiangiogenic therapy for malignant gliomas.
    1.The role of sFlt1 and HIF in glioma tissues : The VEGF/sFlt1 ration over than 1 and high expression of HIF were bad prognostic factors in the patients with gliomas.
    2.Anti-glioma effect of over expression of sFlt1 : sFlt1 gene transfection into U87 human malignant glioma cell lines resulted in 30% decrease of tumor volume compared to control.
    3.Anti-angiogenic effect of CPT-11 : CPT-11 had potent angiosuppressive agent by inhibiting HIF and VEGF expression of glioma cells and inhibiting endothelial cell proliferation and tube formation.
    4.The effect of metronomic schedule of CPT-11 for glioma growth : Low dose (1mg/kg) and long term (77 days) administration of CPT-11 resulted in glioma growth which was similar to moderate dose (40mg/kg) and short term (10 days) administration without systemic side effect.
    5.JTT treatment caused to not only enhance immune function but also inhibit angiogenesis in mouse bearing glioma.
    Metronomic chemotherapy using CPT-11 is effective for glioma growth by inhibiting HIF and VEGF expression and by inhibiting endothelial cell proliferation and tube formation. sFlt1 and JTT are also candidates as angiosuppressive agent for glioma.

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  • The effects of targeted disruption of a gene encoding rate-limiting enzyme of the TCA Cycle on mice

    Grant number:14571084

    2002 - 2003

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    SONE Hirohito, SHIMANO Hitoshi, TOYOSHIMA Hideo

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    Grant amount:\3500000 ( Direct Cost: \3500000 )

    In order to explore the fundamental solution over metabolic disorders like diabetes, it is necessary to re-evaluate the significance of tricarboxylic acid (TCA) cycle, the most important metabolic pathway with very high efficiency. To investigate the effects of inhibiting the cycle, the gene encoding citrate synthase (CS), one of rate-limiting enzymes of the cycle, was disrupted in mice. Homozygous (CS-/-) mice showed early embryonic lethality but heterozygous mice (CS+/-) showed partial expression of the CS gene in each of the mRNA, protein, and enzyme activity levels. Whereas there were no differences in weight, basal metabolic rate, blood pressure, fasting plasma glucose/insulin levels, serum lipid levels between wild-type and CS+/-mice, it is clarified that respiratory quotient (respiratory exchange ratio) was significantly lower and serum acetoacetate levels were significantly higher in CS+/-mice. High-fat high-sugar diet of one or two months for both wild-type and CS+/-mice resulted in marked blunted plasma response after intravenous glucose load without any differences in glucose responses in CS+/-mice compared with wild-type mice. It is thought that the mouse could be a useful model to investigate the mechanisms of insulin resistance underlying energy metabolism disorders.

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  • 動脈硬化惹起性リポタンパクモデル動物の作製と動脈硬化症への影響の検討

    2001.4 - 2003.3

    System name:科学研究費助成事業 基盤研究(C)

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    島野 仁

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    Grant type:Competitive

    肝臓におけるトリグリセリド(TG)の合成亢進がもたらす動脈硬化性リポタンパク形成への影響を検討するために、SREBP-1cトランスジェニクマウスとLDL受容体欠損マウス(LDLRKO)のダプルミュータントマウス(BP1c/LDLRKO)を作製し、そのリポタンパクの性状を検討した。BP1c/LDLRKOは、LDLRKOに比べ、血中トリグリセリドの著明な増加とコレステロールの軽度の増加を認めた。この傾向は空腹時採血よりも食後採血において著明であった。アガロース電気泳動では、β位(LDL分画)が増加しているLDLRKOに比べ、BP1c/LDLRKOではpreβからβにかけてbroadβバンドの増加が認められいわゆるレムナントリポタンパクの増加が示された。さらにレムナントの増加との連動がしたHDLの減少を認めた。
    肝臓のノーザンブロット解析によれば、TG合成制御転写因子であるSREBP-1cの過剰発現により、FAS, ACC, SCD1,FACEをはじめ脂肪酸合成、中性脂肪合成酵素の発現が増加しており、肝臓でのTG合成がたかまっている。それが肝臓におい

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  • Studies on a model animal for atherogenic lipoproteins and atherosclerosis

    Grant number:13671172

    2001 - 2002

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    SHIMAO Hitoshi, TAKAHASHI Akimitsu, SONE Hrohito

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    Grant amount:\3700000 ( Direct Cost: \3700000 )

    To investigate effects of enhanced hepatic trigylcerides synthesis on production of atherogenic lipoproteins, SREBP-lc transgeni and LDL receptor-deficient doubly mutant mice (BP1c/LDLRKO). were generated and their plasma lipoproteins were studied BP1c/LDLRKO showed incrases in plasma triglycerides and cholesterol especially at feeding. On agarose electrophoresis, broa beta band, suggesting presence of remnant lipoproteins was increased and LIDL cholesterol was inversely decreased as compared to controls of LDLR KO mice. Northern blot analysis of livers showed that over-expression of SREBP-lc induced expression of lipogenic enzyme genes such as FAS, ACC, and SCO. Activation of lipogenic gene expression could incrase hepatic postprandia synthesis of triglycerides and production of TG rich lipoproteins, which were accumulated in the absence of LDLR converting to remnant lipoproteins in plasma. Due to the accumulation of these atherogenic lipoproteins, BP1c/LDLRKO exhibited atherorm formation around aortic sinus at age of 8 months even on a regular diet. These mice are a good model for postprandial hyperlipidemia and metabolic syndrome.

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  • 高齢者のサクセスフル・エイジングに繋がる生物学的活力の評価

    2000.4 - 2003.3

    System name:科学研究費助成事業 基盤研究(B)

    Research category:基盤研究(B)

    Awarding organization:日本学術振興会

    田中 喜代次

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    Grant type:Competitive

    本研究では,申請者らが提案した老化尺度のひとつである活力年齢を用い,10年間にわたる長期縦断データから,運動を習慣化した中高齢者の老化が遅延する,という仮説を検証することを第一の目的とした。対象者は46〜68歳の女性16名と43〜69歳の男性10名であり,週2回の院内監視型運動教室への参加者である。教室開始前の活力年齢は,男女ともに暦年齢よりも有意に高かったが,教室開始から3ヵ月後,1年後で有意に若齢化し,暦年齢よりも有意に低くなった。その後の9年間で,女性の活力年齢は7.6歳(男性では8.6歳)しか増加せず,運動の習慣化が老化速度を遅延するという仮説が支持された。
    本研究における第二の目的は,活力年齢をベースとしながらも,加齢とともに罹患率の高まる骨粗鬆症に関する情報を含めながら,より高い年齢層のデータを収集し,高齢者の老化度を評価する新しい活力年齢を提案することであった。対象者は,32〜77歳の女性134名と35〜79歳の男性91名である。形態,血圧,肺機能,

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  • 動脈硬化症特に糖尿病大血管障害の病態におけるVEGFの役割と抗VEGF療法の効果

    2000.4 - 2002.3

    System name:科学研究費助成事業 奨励研究

    Research category:奨励研究

    Awarding organization:日本学術振興会

    曽根 博仁

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    Authorship:Principal investigator  Grant type:Competitive

    血管内皮増殖因子(VEGF)は糖尿病網膜症(DR)の血管新生・浸出性病変の発症・進展に主要な役割を果たす。一方、高血糖による血管内皮細胞障害の第一段階として、多量の血中グルコース(Glu)が同細胞内に取込まれることが重要である。同細胞のGlu取込みは専ら糖輸送担体1(GLUT1)により行われるため、GLUT1発現量は細胞内Glu取込み量を規定する重要因子である。そこでDRの病態におけるVEGFとGLUT1の、血管内皮細胞への相互作用について検討した。培養ウシ網膜血管内皮細胞(BREC)の培地中にVEGFを添加した際の、細胞内へのGlu取込みとGLUT1の発現を検討した。次に血管内皮由来のGLUT1安定強発現細胞株を作成し、そのMAPK活性について検討した。BRECにおいて、VEGF用量依存的にGlu取込みの有意な上昇(VEGF濃度50ng/mlにおいて1.6倍)を認めた。その機序として、VEGFがPKC-β1を介してGLUT1を細胞表面にtranslocateさせていることが示唆された。またGLUT1強発現細胞において、活性型ERK(p42/44 MAPK)は有意に上昇(1.8倍)して

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  • 病態モデル動物を用いた動脈硬化及びインスリン抵抗性遺伝子マップの作成

    2000.4 - 2001.3

    System name:科学研究費助成事業 特定領域研究

    Research category:特定領域研究

    Awarding organization:文部科学省

    山田 信博

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    Grant type:Competitive

    日本人の疾病構造は急激な変化をとげ、社会文明の発展、生活習慣の欧米化とともに虚血性心疾患や脳血管障害などの動脈硬化性疾患が増加している。我々は従来より発生工学的手法を用いて、インスリン抵抗性や高脂血症、耐糖能異常、高血圧を示す病態モデル動物を作成しているが、これらのモデル動物を交配する事により種々のレベルや組み合わせの高脂血症、耐糖能異常、高血圧を共有するMutliple Risk Factor(MRF)マウス作成を試みた。現在、MRFマウスとして、1.レプチン欠損(Ob/Ob)・LDLレセプター(あるいはアポE)欠損ダブルノックアウトマウスにウエスタンダイエット(少量のコレステロールおよび飽和脂肪酸を含有)を負荷、2.SREBP-1aトランスジェニックマウス(あるいはリポタンパクリパーゼランスジェニックマウスやホルモン感受性リパーゼノックアウトマウス)・LDLレセプター欠損ダブルミュータントマウスを作成している。特にレプチン欠損(Ob/Ob)・LDLレセプター(あるいはアポE)欠損

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  • Assessment of physical health status for successful aging in elderly

    Grant number:12480005

    2000 - 2002

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    TANAKA Kiyoji, SONE Hirohito, KIM Hunkyung, NAKAMURA Eitaro, NAKADOMO Fumio, TAKESHIMA Nobuo

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    Grant amount:\15900000 ( Direct Cost: \15900000 )

    The first purpose of this study was to test the hypothesis that a habitual exercise prevents functional decline in accordance with aging. For this examination, we used our current vital age (VA) equation as an indicator of the health and fitness. The subjects were 16 women and 10 men who had participated in our exercise program of two times a week for 10 years. Although the VA prior to the exercise program was significantly higher than the chronological age (CA) in women and men, the VA significantly lowered after 3-month and 1-year exercise. As a result, the VA became younger than the CA in women and men. For the following 9 years, the VA in women had increased by only 7.6 yr (8.6 yr in men). These results support the hypothesis of our first study.
    The second purpose of this study was to develop a new VA equation, which can be applicable to older adults. In the present study, correlation analysis and principal component analysis were applied to the data for 56 biomedical variables. The subjects were 134 women and 91 men. The following 12 variables in women and 10 variables in men were found suitable for the new assessment of VA.
    (For women)
    New VS = 0.021X_1 + 0.010.X_2 - 0.044X_3 - 0.008X_4 + 0.004X_5 + 0.004X_6 + 0.003X_7 + 0.043X_8 - 0.039X_9 - 0.011X_<10> - 0.419X_<11> - 0.007X_<12> + 9.64
    New VA = 8.98new VS + 0.295CA + 40.75
    (For men)
    New VS = 0.011X_2 - 0.044X_3 - 0.013X_4 - 0.005X_5 + 0.004X_7 - 0.032X_9 - 0.012X_<10> - 0.400X_<11> - 0.007X_<12> + 0.023X_<13> + 14.28
    New VA = - 8.58new VS + 0.367CA + 40.00VA = 8.98 VS - 0.295age - 40.75,
    VS = 0.021X1+0.010X2-0.044X3-0.008X4+0.004X5+0.004X6+0.003X7+0.043X8-0.039X9-0.011X10-0.0419X11-0.007X12+9.64
    where X_1 = abdominal girth, X_2 = systolic blood pressure, X_3 = oxygen uptake at lactate threshold, X_4 = heart rate at lactate threshold, X_5 = cholesterol, X_6 = LDLC, X_7 = TG, X_8 = Hct, X_9 = side stepping, X_<10> = single leg balance with eyes closed, X_<11> = FEV_<1.0>, X_<12> = calcaneal speed of sound, X_<13> = subscapular skinfold.

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  • 動脈硬化症特に糖尿病大血管障害の病態におけるVEGFの役割と抗VEGF療法の効果

    Grant number:12770632

    2000 - 2001

    System name:科学研究費助成事業

    Research category:奨励研究(A)

    Awarding organization:日本学術振興会

    曽根 博仁

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    Grant amount:\2200000 ( Direct Cost: \2200000 )

    血管内皮増殖因子(VEGF)は糖尿病網膜症(DR)の血管新生・浸出性病変の発症・進展に主要な役割を果たす。一方、高血糖による血管内皮細胞障害の第一段階として、多量の血中グルコース(Glu)が同細胞内に取込まれることが重要である。同細胞のGlu取込みは専ら糖輸送担体1(GLUT1)により行われるため、GLUT1発現量は細胞内Glu取込み量を規定する重要因子である。そこでDRの病態におけるVEGFとGLUT1の、血管内皮細胞への相互作用について検討した。培養ウシ網膜血管内皮細胞(BREC)の培地中にVEGFを添加した際の、細胞内へのGlu取込みとGLUT1の発現を検討した。次に血管内皮由来のGLUT1安定強発現細胞株を作成し、そのMAPK活性について検討した。BRECにおいて、VEGF用量依存的にGlu取込みの有意な上昇(VEGF濃度50ng/mlにおいて1.6倍)を認めた。その機序として、VEGFがPKC-β1を介してGLUT1を細胞表面にtranslocateさせていることが示唆された。またGLUT1強発現細胞において、活性型ERK(p42/44 MAPK)は有意に上昇(1.8倍)していることが明らかになった。他のMAPKファミリーであるJNK,p38活性の上昇は認めなかった。ERKは強力な細胞増殖シグナルであることから、VEGFは、GLUT1を介してERKを活性化する機序を通じて、DR増悪に関与していることが示唆された。その他、今回の結果を応用して、VEGFの自己免疫疾患における関与も検討し、本因子が、慢性関節リウマチの発症・進展に深く関与していることなどを、動物モデルおよび臨床検体を用いた検討にて示した。

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  • 病態モデル動物を用いた動脈硬化及びインスリン抵抗性遺伝子マップの作成

    Grant number:12204023

    2000

    System name:科学研究費助成事業

    Research category:特定領域研究(C)

    Awarding organization:日本学術振興会

    山田 信博, 島野 仁, 曽根 博仁

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    日本人の疾病構造は急激な変化をとげ、社会文明の発展、生活習慣の欧米化とともに虚血性心疾患や脳血管障害などの動脈硬化性疾患が増加している。我々は従来より発生工学的手法を用いて、インスリン抵抗性や高脂血症、耐糖能異常、高血圧を示す病態モデル動物を作成しているが、これらのモデル動物を交配する事により種々のレベルや組み合わせの高脂血症、耐糖能異常、高血圧を共有するMutliple Risk Factor(MRF)マウス作成を試みた。現在、MRFマウスとして、1.レプチン欠損(Ob/Ob)・LDLレセプター(あるいはアポE)欠損ダブルノックアウトマウスにウエスタンダイエット(少量のコレステロールおよび飽和脂肪酸を含有)を負荷、2.SREBP-1aトランスジェニックマウス(あるいはリポタンパクリパーゼランスジェニックマウスやホルモン感受性リパーゼノックアウトマウス)・LDLレセプター欠損ダブルミュータントマウスを作成している。特にレプチン欠損(Ob/Ob)・LDLレセプター(あるいはアポE)欠損ダブルノックアウトマウスの解析が進行しており、単独のモデルではMRFとはならないが、交配することによりMRFとなることを確認し、動脈硬化の早期進展を確認した。今後、このMRFマウスを用いて、動脈硬化症の発症進展に関与する遺伝子発現の時間、空間的変化および治療や栄養、運動による修飾の過程を定量的にとらえることにより、動脈硬化症やインスリン抵抗性の発症遺伝子のデーターベース、遺伝子情報マップを作製したいと考えている。

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  • Roles of fatty acids in pathogenesis of insulin resisitance and atherosclerosis

    Grant number:11470231

    1999 - 2000

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B).

    Awarding organization:Japan Society for the Promotion of Science

    YAMADA Nobuhiro, SONE Hirohito, TOYOSHIMA Hideo

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    Grant type:Competitive

    Grant amount:\14600000 ( Direct Cost: \14600000 )

    The main purpose of this project is to manipulate the fatty acid synthesis in a tissue specific manner and to investigate the effects of changes in fatty acids on glucose-lipid metabolism, insulin resistance, and atherosclerosis. In the previous fiscal year, we showed that SREBP-1 plays a crucial role in regulation of synthesis of fatty acids and triglycerides through the analyses of SREBP-1 transgenic and knockout mice. It is also suggested that this transcription factor regulates lipid synthesis by changing its own amount and mediates the action of insulin and glucose. This year, we performed analysis of SREBP-1 expression in a hepatic cell line, and reported that increasing concentrations of glucose in the media can induce the expression of SREBP-1 in the cells showing that glucose can be a signal to SREBP-1 induction as well as a substrate for lipid synthesis (reference 1). To elucidate the mechanism by which excess amount of energy induces SREBP-1 expression as a lipogenic signal, we sequenced and analyzed the SREBP-1c promoter (reference 2). We found a sterol regulatory element (SRE) near upsream of the transcription start site. The presence of SRE in the SREBP-1c gene promoter can explain for the overshooting phenomenon in physiological regulations of SREBP-1c and target lipogenic genes in a context of autoloop regulation. We also found an oxysterol-inducible element upsream of the SRE.This element suggests that a new link between fatty acid and cholesterol metabolism and we are in the middle of analyzing this element.

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Teaching Experience (researchmap)

  • 医科学総合演習

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  • 医科学研究特論

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  • 「臨床・疫学研究の実例」

    Institution name:東京大学大学院医学系研究科

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  • 内分泌代謝系

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  • 食と健康

    Institution name:放送大学大学院

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  • 食健康科学

    Institution name:放送大学大学院

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Teaching Experience

  • 臨床実習IIA(clinical clerkship)

    2022
    Institution name:新潟大学

  • 医学序説 I

    2022
    Institution name:新潟大学

  • 人体の構造と機能II(生理学)

    2021
    Institution name:新潟大学

  • 医学序説 II

    2021
    Institution name:新潟大学

  • 臓器別講義・演習Ⅰ

    2020
    Institution name:新潟大学

  • 臨床医学講義(集中)

    2020
    Institution name:新潟大学

  • 医学序説 I

    2020
    Institution name:新潟大学

  • 医科学研究特論

    2015
    Institution name:新潟大学

  • 医科学総合演習

    2014
    Institution name:新潟大学

  • 血液系

    2013
    -
    2017
    Institution name:新潟大学

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Social Activities

  • 新潟県糖尿病協会

    Role(s): Advisor, Organizing member

    2012

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  • 厚生労働省薬事・食品衛生審議会​ 委員

    Role(s): Advisor

    2011.1 - 2014.1

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  • 新潟市糖尿病対策推進会議

    Role(s): Advisor, Organizing member

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  • 日本糖尿病対策推進会議

    Role(s): Advisor, Organizing member

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  • 新潟県「にいがた新世代ヘルスケア情報基盤プロジェクト」

    Role(s): Advisor, Organizing member

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  • 新潟市「健幸づくり応援食品」認定制度推進委員会

    Role(s): Advisor

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  • 新潟県糖尿病対策推進会議

    Role(s): Advisor, Planner, Organizing member

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  • 新潟県スポーツドクター協会

    Role(s): Advisor, Organizing member

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  • 日本糖尿病協会

    Role(s): Advisor, Planner, Organizing member

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