Faculty Profiles - FUJIHARA Kazuya

Papers - FUJIHARA Kazuya

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Demographic and Dietary Determinants of the Association between Dietary Fiber Intake and Obesity in Japanese Adults with Type 2 Diabetes: A Cross-Sectional Study (JDDM 78). International journal

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

Public health nutrition 1 - 20 2025.2

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

OBJECTIVE: To evaluate the association between dietary fiber intake and obesity in Japanese outpatients with type 2 diabetes, as well as the demographic and dietary factors influencing this association. DESIGN: Cross-sectional study with nationwide registry data on Japanese type 2 diabetes outpatients (2014-2019). Diet was self-reported via a Food Frequency Questionnaire. Obesity was defined as BMI ≥25 kg/m2. SETTING: Clinics throughout Japan. PARTICIPANTS: 1,565 Japanese outpatients with type 2 diabetes (63.1% men; age range 30-89 years). RESULTS: Multivariate analysis revealed that a higher dietary fiber intake was associated with a lower risk of obesity in all participants (95% CI = 0.439-0.795, p < 0.001). Stratified analysis showed a significant inverse association between fiber intake and obesity in men and the older age groups (59-89 years), but not in women or the younger age group (30-58 years). In men, higher fiber intake was associated with healthier lifestyle behaviors, including increased physical activity (p < 0.001) and non-smoking (p < 0.001), with stronger associations compared to women. Vegetables, fruits, and soybeans/soy products were strongly correlated with fiber, while grains had a weak correlation. Folate was the micronutrient most strongly correlated with fiber. CONCLUSION: Higher fiber intake was associated with lower obesity risk, particularly in men and older age groups. These findings emphasize the need for targeted public health initiatives promoting the intake of diverse fiber-rich foods to effectively manage obesity. Further research is needed to understand sex- and age-specific factors in the fiber-obesity relationship in diverse populations.

DOI： 10.1017/S136898002500014X

Positive association of large alcohol intake per occasion with vision-threatening severe diabetic retinopathy or diabetic macular edema in Japanese men with type 2 diabetes. International journal

Masahiko Yamamoto, Kazuya Fujihara, Hiruma Hasebe, Yuta Yaguchi, Takaho Yamada, Satoru Kodama, Shiro Tanaka, Hirohito Sone

Preventive medicine 191 108220 - 108220 2025.2

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

OBJECTIVE: Differing from the overall consumption of alcohol, whether consuming large quantities of alcohol per drinking occasion is associated with higher risk of developing severe diabetic retinopathy remains unknown. METHODS: We examined whether the quantity per drinking occasion (QPO), including a large QPO, and the combinations of the frequency of alcohol consumption (FAC) and QPO were associated with higher risk of developing severe diabetic retinopathy or diabetic macular edema (DME) using adjusted Cox models. Severe diabetic retinopathy or DME was designated as a vision-threatening treatment-required diabetic eye disease (TRDED). For each man with type 2 diabetes who participated in this longitudinal retrospective cohort study, the date of the earliest health check-up during the inclusion period (April 2008 to August 2016) was set as the start date of follow-up. RESULTS: A TRDED was observed in 425 of 21,392 Japanese men aged 22-74 years with type 2 diabetes during a mean follow-up of 4.3 years (4.6/1000 person-years). Multivariable Cox analysis showed that a large QPO, defined as drinking three drinks or more per occasion, in low- (hazard ratio [HR], 4.76; 95 % CI, 2.06-10.97), intermediate- (HR, 1.58; 95 %CI, 1.001-2.50), and high-frequency categories (HR, 2.01; 95 % CI, 1.20-3.36) was significantly associated with elevated risks of TRDED. CONCLUSIONS: In addition to the total amount of ethanol, these findings imply the necessity of avoiding the consumption of large amounts of alcohol on a single occasion to prevent severe diabetic retinopathy or DME.

DOI： 10.1016/j.ypmed.2025.108220

Association of bodyweight loss with changes in lipids, blood pressure, and fasting serum glucose following tirzepatide treatment in Japanese participants with type 2 diabetes: A post hoc analysis of the SURPASS J‐mono trial

Hanaka Mimura, Tomonori Oura, Rina Chin, Masakazu Takeuchi, Kazuya Fujihara, Hirohito Sone

Journal of Diabetes Investigation 2025.2

Cross-sectional and Longitudinal Associations Between Family History of Type 2 Diabetes Mellitus, Hypertension, and Dyslipidemia and Their Prevalence and Incidence: Toranomon Hospital Health Management Center Study (TOPICS24). International journal

Izumi Ikeda, Risa Igarashi, Kazuya Fujihara, Yasunaga Takeda, Efrem d'Ávila Ferreira, Khin Lay Mon, Satoru Kodama, Yasumichi Mori, Takashi Kadowaki, Ritsuko Honda, Yasuji Arase, Hirohito Sone

Mayo Clinic proceedings 2025.1

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

OBJECTIVE: To examine the association between a positive family history (parents, siblings, and grandparents) of type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia and their prevalence and incidence in the same population. PATIENTS AND METHODS: Data on 41,361 participants who underwent health examinations between January 1, 1997, and December 31, 2007, were analyzed, and the results of logistic and Cox regression analyses in the same cohort were examined. RESULTS: Cross-sectional analyses showed that the prevalence of all three diseases increased with a positive family history, especially T2DM, with an odds ratio (OR) of 12.00 (95% CI, 7.82 to 18.41) when the number of affected relatives was greater than or equal to 3 with an OR of 20.43 (95% CI, 11.0 to 37.8) for a positive family history across three generations compared with no family history. However, redefining family history from "parents, siblings, and grandparents" to "parents and siblings" or "parents only" did not significantly change ORs for each disease. Among those with a positive family history and body mass index greater than or equal to 30.0 kg/m2 hypertension was 19 times more prevalent compared with no family history and body mass index of 18.5 to 24.9 kg/m2. In the longitudinal study, family history strongly influenced incident T2DM (hazard ratio[HR], 2.40; 95% CI, 1.93 to 2.98), hypertension (HR, 1.43; 95% CI, 1.26 to 1.62), and dyslipidemia (HR, 1.41; 95% CI, 1.08 to 1.83), respectively. CONCLUSION: Obtaining a family history of these diseases was useful in identifying high-risk groups. Also, for T2DM, the influence of a positive family history was strongest with a marked increase in risk with overlap of affected family members, suggesting that a family history is useful for early detection and prevention.

DOI： 10.1016/j.mayocp.2024.10.020

Impact of diabetes remission or progression on the incidence of cardiovascular disease in Japan: historical cohort study using a nationwide claims database. International journal

Chihiro Shimayama, Kazuya Fujihara, Laymon Khin, Hiroki Takizawa, Chika Horikawa, Takaaki Sato, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Hirohito Sone

Cardiovascular diabetology 24 ( 1 ) 37 - 37 2025.1

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

BACKGROUND: Previous studies demonstrated that diabetes remission can occur during intensive intervention and in real-world settings. However, the impact of diabetes remission in real-world settings on the incidence of cardiovascular disease (CVD) remains unclear. METHODS: This retrospective cohort study included 299,967 individuals aged 20-72 years who underwent multiple checkups between 2008 and 2020 and completed ≥ 3 years of follow-up. Patients were divided into four groups according to changes in glycated hemoglobin levels and the use of diabetes medications during the 1-year baseline period: diabetes mellitus (DM)+/no remission, DM+/remission, DM-/no progression, and DM-/progression. The risk of CVD was evaluated using multivariable Cox regression analysis. RESULTS: The median follow-up period was 5.0 years. The rates of CVD in the DM+/no remission, DM+/remission, DM-/no progression, and DM-/progression groups were 7.96, 4.76, 1.99, and 5.47 per 1000 person-years, respectively. Compared with DM+/no remission, DM+/remission reduced the risk of CVD [hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.57-0.89]. Meanwhile, the HR for CVD in the DM+/remission group was 0.75 (95% CI = 0.56-0.99) for change in BMI ≤ 0%, versus 0.66 (95% CI = 0.45-0.96) for change in BMI > 0%. CONCLUSIONS: In a real-world setting without intensive intervention, diabetes remission decreased the risk of CVD by approximately 30% regardless of changes in BMI, suggesting that diabetes remission can prevent CVD without weight loss in routine care and emphasizing the importance of achieving remission.

DOI： 10.1186/s12933-025-02578-y

Association of changes in the type 2 diabetes and MASLD/related SLD status with risk of developing cardiovascular disease. International journal

Yasuhiro Matsubayashi, Kazuya Fujihara, Laymon Khin, Efrem d'Àvila Ferreira, Shizuka Takabayashi, Yuko Yamashita, Takaho Yamada, Satoru Kodama, Hirohito Sone

Diabetes, obesity & metabolism 2025.1

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

BACKGROUND & AIMS: This study assessed the association of remission of type 2 diabetes mellitus (DM) or metabolic dysfunction-associated steatotic liver disease (MASLD)/related SLD (r-SLD; MASLD with excessive alcohol intake) as defined by the fatty liver index with the risk of cardiovascular disease (CVD). METHODS: Health examination data at baseline and after 2 years (2-Years) were extracted from a nationwide claims database in Japan. Among participants aged 18-72 years with at least 3 years of follow-up, 9345 participants with DM-associated MASLD/r-SLD and 71 932 participants with non-DM MASLD/r-SLD at baseline were included in the study. The participants were stratified by the achievement of remission of MASLD/r-SLD or DM at 2-Years. In each group after stratification, the risk of new-onset CVD during the observation period was analysed using multivariate Cox proportional hazards models. RESULTS: During a median follow-up of 4.9 years (starting from 2-Years), 1368 cases of CVD were observed. The hazard ratio (95% confidence interval) for CVD was 0.50 (0.31-0.80) for participants with remission of DM, 0.65 (0.47-0.91) for participants with remission of MASLD/r-SLD, and 0.34 (0.15-0.77) for participants with remission of both DM and MASLD/r-SLD. Conversely, remission of MASLD/r-SLD was not linked to a reduced risk of CVD in participants with non-DM MASLD/r-SLD. CONCLUSION: The association of MASLD/r-SLD remission with CVD risk differs greatly in the presence and absence of DM. In patients with DM-MASLD/r-SLD, MASLD/r-SLD remission can significantly reduce CVD risk similarly as remission of DM.

DOI： 10.1111/dom.16196

Dietary potassium intake and its interaction with sodium intake on risk of developing cardiovascular disease in persons with type 2 diabetes: The Japan Diabetes Complication and its Prevention Prospective study (JDCP study 12). International journal

Chika Horikawa, Mitsuyoshi Takahara, Naoto Katakami, Yasunaga Takeda, Mizuki Takeuchi, Kazuya Fujihara, Hiroaki Suzuki, Narihito Yoshioka, Hitoshi Shimano, Jo Satoh, Yasuaki Hayashino, Naoko Tajima, Rimei Nishimura, Yoshimitsu Yamasaki, Hirohito Sone

Diabetes, obesity & metabolism 27 ( 1 ) 394 - 406 2025.1

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

AIMS: Many guidelines recommend increases in potassium intake. However, the relationship of dietary potassium intake with incident cardiovascular disease (CVD) has not been examined in those with type 2 diabetes (T2DM), including sodium acting antagonistically with potassium. We investigated these relationships in Japanese patients with T2DM. MATERIALS AND METHODS: The investigation was part of the JDCP study, a nationwide prospective study begun in 2007. Analysed were 1477 persons with T2DM, 40-75 years of age, who completed a brief-type, self-administered Diet History Questionnaire at baseline. Primary outcome was a CVD event during the follow-up median 7 years (3.9-8.1 years). Hazard ratios (HRs) for CVD were estimated by Cox regression adjusted for confounders of daily potassium intake categorized by tertiles. Tertiles of sodium intake were also analysed. RESULTS: Mean daily potassium intake in tertiles was 1877, 2627 and 3532 mg, respectively, and significant associations were not shown between potassium intake and incidence of CVD. When HRs for CVD were stratified for potassium intake in tertiles (reference group, bottom tertile) and sodium intake (reference group, bottom tertile), potassium intake in the bottom tertile and sodium intake in the second and top tertiles were associated with significantly elevated HR for CVD (2.79 [1.02-7.63] and 3.92 [1.30-11.79], respectively). CONCLUSIONS: Low potassium intake in conjunction with high sodium intake was significantly associated with increased incident CVD in persons with T2DM. However, CVD incidence was not related to high potassium intake, regardless of sodium intake.

DOI： 10.1111/dom.16035

Japan Diabetes Complications Study: Revisiting one of the first large-scale clinical studies in East Asians with diabetes.

Hirohito Sone, Chika Horikawa, Sachiko Tanaka-Mizuno, Ryo Kawasaki, Kazuya Fujihara, Tatsumi Moriya, Atsushi Araki, Shiro Tanaka, Yasuo Akanuma

Journal of diabetes investigation 2024.12

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

This review highlights the significance of the Japan Diabetes Complications Study (JDCS), one of the earliest large-scale studies of people with type 2 diabetes outside Europe and the United States, in understanding type 2 diabetes mellitus among East Asian populations, particularly in Japan. Historically, large-scale clinical studies on type 2 diabetes mellitus have predominantly focused on Western populations, despite East Asians comprising the largest proportion of diabetic patients globally. The JDCS, which was initiated in 1996, enrolled 2,033 Japanese type 2 diabetes mellitus patients. It aimed to evaluate the effects of intensive lifestyle interventions on diabetic complications. The study demonstrated that lifestyle-focused interventions significantly reduced the risk of stroke and other complications compared to conventional treatment. Key findings of its sub-analyses include the unique characteristics of Japanese patients with type 2 diabetes mellitus, such as their lower body mass index (BMI) compared to Western counterparts and a stronger association between even modest BMI increases and beta cell dysfunction. Additionally, the JDCS provided insights into the risk factors for nephropathy, retinopathy, and macrovascular complications, emphasizing the importance of controlling blood pressure, glycemia, and lifestyle factors. The study also explored the impact of diet, exercise, and mental health on diabetic outcomes, revealing the protective effects of physical activity and a balanced diet, while highlighting the risks associated with high salt intake and depression. A risk prediction model tailored to Japanese patients was also developed. Overall, this study made a significant contribution to the evidence-based management of type 2 diabetes mellitus in East Asia.

DOI： 10.1111/jdi.14394

バセドウ病とうつ病を治療中に、破壊性甲状腺炎と悪性カタトニア発症し集学的な治療を要した一例

磯貝真理恵, 高澤遥子, 村井幸四郎, 佐藤隆明, 山本正彦, 北澤勝, 鈴木浩史, 松林泰弘, 藤原和哉, 山田貴穂, 小柴みなみ, 吉永清宏, 江川純, 曽根博仁

日本内分泌学会雑誌 100 ( 4 ) 907 - 907 2024.12

Coronary artery disease risk prediction by combined stratification of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol levels across different glucose statuses. International journal

Junko Yachida, Kazuya Fujihara, Mayuko Harada Yamada, Ayako Kobayashi, Lay Mon Khin, Hiroki Takizawa, Masahiko Yamamoto, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Satoru Kodama, Hirohito Sone

Diabetes, obesity & metabolism 26 ( 12 ) 5845 - 5856 2024.12

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

AIM: To investigate the association between low-density lipoprotein-cholesterol (LDL-C) levels and coronary artery disease (CAD) incidence based on combining high-density lipoprotein-cholesterol (HDL-C) levels and glucose status. MATERIALS AND METHODS: In this retrospective cohort study, we used data from a nationwide claims database (1,524,289 individuals without a history of CAD or familial hypercholesterolaemia; 2008-2019). Cox proportional hazards modelling identified the risk of incident CAD by a novel combination of four HDL-C levels, seven LDL-C levels and glucose status. RESULTS: During the follow-up period (mean: 5.5 years), 8301 (0.99/1000 person-years) events occurred. The risk of CAD increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of the glucose status. Using the most favourable levels of HDL-C and LDL-C (i.e. 60-99 mg/dL and <80 mg/dL, respectively) as references, the hazard ratios (95% confidence interval) for the group with HDL-C levels <40 mg/dL and LDL-C levels <80 mg/dL were 2.74 (1.47-5.11), 2.52 (1.30-4.91) and 2.85 (1.68-4.84) for normoglycaemia, borderline glycaemia and diabetes, respectively. Comparison of the most favourable levels of HDL-C and LDL-C with their least favourable levels (i.e. <40 mg/dL and 180-199 mg/dL, respectively) revealed that the risk of new-onset CAD exhibited a 19-, nine- and seven-fold increase in individuals with normoglycaemia, borderline glycaemia and diabetes, respectively. CONCLUSIONS: To prevent CAD, LDL-C levels should be strictly controlled in patients with low HDL-C levels regardless of glucose tolerance. Individualized treatment, which involves setting target LDL-C levels based on glucose tolerance and HDL-C values, is required.

DOI： 10.1111/dom.15956

Achieving normoglycaemia with tirzepatide: Post hoc exploratory analysis of the SURPASS J-mono and J-combo studies. International journal

Kazuya Fujihara, Yasuhiro Matsubayashi, Masaru Kitazawa, Takaaki Sato, Masakazu Takeuchi, Tomonori Oura, Hirohito Sone

Diabetes, obesity & metabolism 26 ( 11 ) 5304 - 5311 2024.11

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

AIM: Normoglycaemia was achieved in a significant proportion of Japanese participants with type 2 diabetes in two phase 3 studies of tirzepatide. This post hoc exploratory analysis aimed to identify predictive factors associated with normoglycaemia achievement. MATERIALS AND METHODS: SURPASS J-mono and SURPASS J-combo study data were pooled for this analysis. Characteristics of participants in whom normoglycaemia [glycated haemoglobin (HbA1c) <5.7%] was achieved were summarized. Logistic regression analyses were performed with HbA1c <5.7% achievement as the target variable. RESULTS: Of 912 participants, normoglycaemia was achieved in 553 (60.6%) following 52 weeks of tirzepatide treatment. Overall, the mean (SD) age was 56.7 (10.6) years and mean diabetes duration was 7.7 (6.0) years, and 76% of participants were men. Mean (SD) change from baseline in HbA1c and bodyweight was -2.87% (0.95) versus -2.47% (1.1) and -10.30 (5.8) kg versus -3.75 (4.3) kg for participants in whom normoglycaemia was and was not reached, respectively. Multivariate regression analyses showed that lower baseline body mass index, shorter disease duration and lower baseline HbA1c were significantly associated with higher rates of normoglycaemia achievement (p = 0.009, p = 0.008, p < 0.001, respectively) as was a tirzepatide dose of 10 or 15 mg compared with 5 mg (p < 0.001). The highest percentage of participants in whom normoglycaemia (94%) was achieved were those with lower baseline HbA1c (<8%) and the greatest weight reduction (≥15%). CONCLUSIONS: Baseline HbA1c and body mass index, disease duration and the tirzepatide treatment group were shown to be predictive factors for achieving normoglycaemia. A lower baseline HbA1c was most strongly associated with normoglycaemia achievement.

DOI： 10.1111/dom.15887

ラブフィリン3A抗体にて診断を行ったリンパ球性汎下垂体炎の一例

丹野貴文, 佐藤隆明, 木村智佑, 滝澤大輝, 山本正彦, 石黒創, 北澤勝, 鈴木浩史, 松林泰弘, 山田貴穂, 藤原和哉, 藤沢治樹, 鈴木敦詞, 椙村益久, 曽根博仁

日本内分泌学会雑誌 100 ( 2 ) 634 - 634 2024.10

Risk stratification for cardiovascular disease based on prior coronary artery disease, cerebrovascular disease and type 2 diabetes mellitus.

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

Journal of diabetes investigation 15 ( 10 ) 1464 - 1471 2024.10

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

AIMS/INTRODUCTION: History of coronary artery disease (CAD), cerebrovascular disease (CeVD), type 2 diabetes and their combined effect on cardiovascular disease are essential for cardiovascular risk management. We investigated the association of prior CAD, prior CeVD, type 2 diabetes and their combination with the risk of cardiovascular disease. MATERIALS AND METHODS: This is a historical cohort study including 342,033 participants (aged 18-72 years) followed up for ≥5 years between 2008 and 2016. Participants were classified into eight groups (with or without prior CAD, prior CeVD and type 2 diabetes). Type 2 Diabetes was defined by fasting plasma glucose and glycated hemoglobin levels, and antidiabetic drug prescription. Prior and subsequent CAD and CeVD were identified according to claims using International Classification of Diseases 10th Revision codes, medical procedures and questionnaires. Cox regression models were used to evaluate the risk of cardiovascular events. RESULTS: The median follow-up period was 6.4 years. The incidence of composite cardiovascular events of CAD and CeVD in the CAD-/CeVD-, CAD+/CeVD-, CAD-/CeVD+ and CAD+/CeVD+ groups were 1.92 and 6.94, 25.14 and 31.98 per 1,000 person-years in non-diabetes participants, and 8.66, 18.04, 39.98 and 60.72 in type 2 diabetes patients, respectively. Hazard ratios of cardiovascular events compared with CAD-/CeVD-/non-diabetes were 1.66 (95% confidence interval 1.55-1.78) in CAD-/CeVD-/type 2 diabetes and 1.84 (1.56-2.18) in CAD+/CeVD-/non-diabetes. CeVD+ was linked to a 4-7-fold increase in the risk of cardiovascular events regardless of CAD+ or type 2 diabetes. CONCLUSIONS: Type 2 diabetes increased the risk of cardiovascular disease as high as a history of CAD, whereas prior CeVD alone increased the risk of future CeVD without additional effects by type 2 diabetes.

DOI： 10.1111/jdi.14277

Healthy lifestyle factors as predictors of the initiation of dialysis in people with and without diabetes.

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

Diabetology international 15 ( 4 ) 786 - 793 2024.10

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

AIMS: To clarify the impact of Breslow's scores consisting of only lifestyle habits or American Heart Association's (AHA) Life's Simple 7 scores consisting of lifestyle habits and control targets on starting dialysis in people with or without diabetes mellitus (DM). METHODS: To pursue the study aims, we examined a nationwide database on 294,647 individuals with and without DM aged 19-72 y in Japan to pursue the study aims. Using multivariate Cox modeling, we evaluated and compared 5 risk factors based on the unfavorable lifestyle factors in Breslow's scores and the unfavorable lifestyle factors and clinical values in AHA Life's Simple 7 scores. RESULTS: DM increased the risk of the initiation of dialysis 5- to sixfold but that risk did not increase with worsening of Breslow risk factors. Compared with no risk factor, 5 risk factors derived from AHA's Life's Simple 7 presented 9.8-fold and 4.2-fold risks for the initiation of dialysis in non-DM and DM, respectively. In comparison with non-DM and no risk factor, risk of the initiation of dialysis dramatically increased up to 32.3 times according to the number of AHA risk factors in those with DM. CONCLUSIONS: DM and risk factors derived from AHA's Life's Simple 7 synergistically increased the risk of the initiation of dialysis. Factors similar to those used to predict cardiovascular disease would also be useful to predict the initiation of dialysis. These approaches might be helpful in clinical practice and patient education. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-024-00739-0.

DOI： 10.1007/s13340-024-00739-0

心血管疾患 2型糖尿病およびMASLDの寛解による心血管疾患(CVD)発症率の変化

松林泰弘, 藤原和哉, 山田万祐子, 佐藤隆明, 山本正彦, 石黒創, 大澤妙子, 北澤勝, 山田貴穂, 曽根博仁

糖尿病合併症 38 ( Suppl.1 ) 143 - 143 2024.9

心血管疾患糖尿病の寛解が心血管疾患発症に及ぼす影響の検討

島山千弥, 藤原和哉, 大江桃子, 上神洋平, 滝澤大輝, 佐藤隆明, 鈴木浩史, 北澤勝, 松林泰弘, 山田貴穂, 児玉暁, 曽根博仁

糖尿病合併症 38 ( Suppl.1 ) 143 - 143 2024.9

網膜症・動脈硬化1 糖尿病・冠動脈疾患・脳血管疾患の既往及び組み合わせがその後の心血管疾患リスクへ及ぼす影響の検討

大江桃子, 藤原和哉, 山田万祐子, 山本正彦, 大澤妙子, 北澤勝, 松林泰弘, 佐藤隆明, 矢口雄大, 山田貴穂, 曽根博仁

糖尿病合併症 38 ( Suppl.1 ) 154 - 154 2024.9

網膜症・動脈硬化2 脳卒中の既往と尿蛋白陽性が重症糖尿病網膜症発症に与える影響についての検討

山本正彦, 藤原和哉, 矢口雄大, 山田万祐子, 佐藤隆明, 鈴木浩史, 松林泰弘, 長谷部日, 山田貴穂, 児玉暁, 田中司朗, 曽根博仁

糖尿病合併症 38 ( Suppl.1 ) 155 - 155 2024.9

Impact of health practice index and cardiovascular health metrics on incident cardiovascular disease according to glucose tolerance status.

Koshiro Murai, Kazuya Fujihara, Mayuko Harada Yamada, Yasuhiro Matsubayashi, Takaho Yamada, Midori Iwanaga, Masaru Kitazawa, Masahiko Yamamoto, Taeko Osawa, Yuta Yaguchi, Satoru Kodama, Hirohito Sone

Diabetology international 15 ( 3 ) 456 - 464 2024.7

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

AIMS: To evaluate and compare the association of incident cardiovascular disease (CVD) with the Health Practice Index (HPI) reflecting only lifestyle habits and Ideal Cardiovascular Health Metrics (ICVHMs) consisting of lifestyle habits and factors targeted for control in the same population according to glucose status. METHODS: This retrospective cohort study included 1,28,162 participants aged 18-72 years with no history of CVD followed for ≥ 3 years between 2008 and 2016. Participants were classified according to normal glucose tolerance (86,174), prediabetes (36,096), or diabetes (5892). HPI and ICVHMs scores were classified into three groups (high/medium/low). Multivariate Cox regression hazard analysis examined CVD risk. RESULTS: During a mean follow-up of 5.2 years, 1057 CVD events occurred. In prediabetes, CVD risk was significantly higher in groups with both medium and low HPI scores and ICVHMs scores compared to high scores for normal glucose tolerance (hazard ratios [HRs] for high/medium/low HPI scores were 0.95 [0.78-1.17], 1.56 [1.29-1.89], and 2.41 [1.74-3.34] and for ICVHMs scores were 0.74 [0.50-1.11], 1.58 [1.26-1.98], and 2.63 [2.10-3.31], respectively). Regarding diabetes, compared with high HPI/ICVHMs scores in the normal glucose tolerance group, a significantly increased CVD risk was observed in the high-score HPI group, but not in the high-score ICVHMs group (HPI high/medium/low HR, 1.63 [1.22-2.18], 2.19 [1.69-2.83], and 2.26 [1.34 -3.83]; ICVHMs high/medium/low HR, 1.14 [0.47-2.81], 2.38 [1.75-3.23], and 3.31 [2.50-4.38], respectively). CONCLUSIONS: In diabetes, ideal lifestyle practices alone were insufficient for primary prevention of CVD but had a greater impact on primary prevention of CVD in prediabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-024-00708-7.

DOI： 10.1007/s13340-024-00708-7

1666-P: Effect of Obesity in Family History (FH) on the Prevalence of Type 2 Diabetes Mellitus (T2DM), Hypertension (HT), and Dyslipidemia (DL)

IZUMI IKEDA, KAZUYA FUJIHARA, YASUNAGA TAKEDA, CHIKA HORIKAWA, SATORU KODAMA, EFREM D. FERREIRA, YASUMICHI MORI, TAKASHI KADOWAKI, RITSUKO YAMAMOTO-HONDA, YASUJI ARASE, HIROHITO SONE

Diabetes 73 ( Supplement_1 ) 2024.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

Heritability and obesity are strongly associated with the prevalence of T2DM, HT, and DL. We compared the effects of an FH of T2DM, HT, and DL combined with obesity on the prevalence of each in the same population. Of 41931 participants who underwent health checkups, the effects of an FH and BMI on the prevalence of those conditions were analyzed cross-sectionally. Prevalences of T2DM, HT, and DL were 5%, 20%, and 48%, respectively. Logistic regression analysis showed that ORs increased for all three as the number of FH positive cases increased and was most pronounced for T2DM. An FH of obesity and increased BMI were additively associated with the prevalence of the three diseases compared to BMI 20.0-21.9 and no positive FH (Fig. A). In addition, the combination of the number of family members with FH positivity (0,1, 2, ≥3) and obesity was additively associated with an increased FH of the three diseases compared to non-obesity and no FH of any of these diseases (Fig. B). For T2DM, the OR increased sharply in non-obese participants when the number of those with an FH of T2DM was ≥3 (14.4 [8.88-23.5]), but in obese participants the OR increased sharply when the number of those with an FH of T2DM was 2 (12.2 [8.85-16.9]) (Fig. B). Results suggest that, especially for T2DM, avoidance of obesity may be effective in reducing the prevalence of these disorders in those with many FH-positive family members.

<p></p> Disclosure

I. Ikeda: None. K. Fujihara: None. Y. Takeda: None. C. Horikawa: None. S. Kodama: None. E.D. Ferreira: None. Y. Mori: None. T. Kadowaki: None. R. Yamamoto-Honda: None. Y. Arase: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

DOI： 10.2337/db24-1666-p

1148-P: Trajectories of Abnormalities in Metabolic Parameters in Japanese Adolescents and Young Adults

IZUMI IKEDA, KAZUYA FUJIHARA, HARUKA SHIOZAKI, SAKIKO Y. MORIKAWA, CHIKA HORIKAWA, YASUNAGA TAKEDA, HAJIME ISHIGURO, TAKAHO YAMADA, SATORU KODAMA, YOHEI OGAWA, HIROHITO SONE

Diabetes 73 ( Supplement_1 ) 2024.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

Childhood obesity mostly transitions into adulthood and leads to non-communicable diseases such as type 2 diabetes and metabolic syndrome. We aimed to examine individual-level transitions in metabolic parameters during adolescence and young adulthood. We analyzed metabolic parameters in 523 participants (311 males) who underwent health examinations at the ages of 14 y (8th grade) and 20 y. Weight status was assessed by the International Obesity Task Force at 14 y and by BMI (thinness: &lt;18.5; normal: 18.5-24.9; obesity: ≥25.0) at 20 y. HbA1c ≥5.7% was defined as high. Clustered metabolic risk score (CMR) was calculated by summing the sex-age specific Z-scores of each metabolic factor (mean arterial pressure, non-HDLC, and HbA1c) with ≥1 SD defined as high. Among participants who were obese at 14 y, 56% of males and 29% of females remained obese at 20 y. In both sexes, 30-50% had high HbA1c and 30-50% had high CMR as tracked from adolescence to adulthood (table). Furthermore, the high CMR of obese females increased markedly from about 20% at 14 y to 50% at 20 y. In addition, 60% of females who were obese at both 14 y and 20 y had high HbA1c at 20 y. Results suggested the importance of lifestyle interventions from childhood, as about half of the high metabolic parameters observed in adolescents were tracked into adulthood, and obesity complications, which were rarely shown at 14 y, appeared in many at age 20 y.

<p></p> Disclosure

I. Ikeda: None. K. Fujihara: None. H. Shiozaki: None. S.Y. Morikawa: None. C. Horikawa: None. Y. Takeda: None. H. Ishiguro: None. T. Yamada: None. S. Kodama: None. Y. Ogawa: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

DOI： 10.2337/db24-1148-p

1264-P: Impacts of Diabetes (DM) on Severe Functional Disability (FD) and Care-Need Level Deterioration in Japanese

IZUMI IKEDA, KAZUYA FUJIHARA, HARUKA SHIOZAKI, SAKIKO Y. MORIKAWA, KAHORI TSURUOKA, YAMASHITA YUKO, LAY MON KHIN, SIJIA WU, NORIKO YAGYUDA, CHIKA HORIKAWA, HIROHITO SONE

Diabetes 73 ( Supplement_1 ) 2024.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

Avoidance of FD and the deterioration of care level needs leading to a decline in ADL and increased medical costs is urgent. We aimed to clarify the association between lifestyle habits, non-communicable diseases (i.e., DM, HT, and dyslipidemia) and their combinations and the incidence of severe FD and deterioration of the care-level. Followed for a median of 3.7 years were 9673 people who underwent health checkups. Care-level ≥2 (total assistance needed) indicates severe FD and worsening from the initial examination indicates deterioration. During the study period, 111 cases of severe FD occurred. Multivariate analysis showed that aging (per 5y) (OR 2.24 [1.95-2.56]), male (1.76 [1.16-2.66]), BMI&lt;18.5 (2.46 [1.40-4.35]), DM (1.81 [1.06-3.08]), HT (1.58 [1.05-2.38]), and lack of physical activity (PA) (2.17 [1.37-3.45]) were associated with severe FD. Prevalence of DM additively associated with severe FD. DM and ≥2 risk factors had a 10 times greater association than non-DM and no risk factor. Of 85 cases with worsening care needs, only DM was significantly associated with deterioration (2.88 [1.08-7.65]). DM is a significant risk factor for with double the increased risk of severe FD and triple care-need deterioration compared with those without DM. Also, in DM patients, low BMI, HT, and lack of PA greatly increased the risk of severe FD, suggesting the need for comprehensive treatment strategies.

<p></p> Disclosure

I. Ikeda: None. K. Fujihara: None. H. Shiozaki: None. S.Y. Morikawa: None. K. Tsuruoka: None. Y. Yuko: None. L. Khin: None. S. Wu: None. N. Yagyuda: None. C. Horikawa: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

DOI： 10.2337/db24-1264-p

1372-P: Association between Fat Intake as the Percent of Total Energy and Incidence of Cardiovascular Disease in Persons with Type 2 Diabetes—Japan Diabetes Complication and Its Prevention Prospective Study (JDCP Study)

CHIKA HORIKAWA, MITSUYOSHI TAKAHARA, NAOTO KATAKAMI, YASUNAGA TAKEDA, MIZUKI TAKEUCHI, KAZUYA FUJIHARA, HIROAKI SUZUKI, NARIHITO YOSHIOKA, HITOSHI SHIMANO, JO SATOH, YASUAKI HAYASHINO, NAOKO TAJIMA, RIMEI NISHIMURA, YOSHIMITSU YAMASAKI, HIROHITO SONE

Diabetes 73 ( Supplement_1 ) 2024.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

Previous systematic reviews showed benefits of low-carbohydrate eating plans compared with low-fat eating plans in the treatment of diabetes (T2D) on parameters of cardiovascular disease (CVD) risk. However, studies on the relationship between fat intake as the % of total energy (F%E) and incidence of CVD in persons with T2D are insufficient. Therefore, we investigated this relationship as part of the JDCP study, a nationwide study launched in 2007. A total of 1477 persons with T2D aged 40-75 years completed a brief self-administered Diet History Questionnaire at baseline, and we analyzed the resultant data. Primary outcome was the 7-year risk of a CVD event. Hazard ratios for CVD according to quartiles of F%E (Q1-4) were estimated by Cox regression adjusted for confounders including sex, age, various laboratory tests, medication use, smoking history, drinking habits, physical activity, energy intake, protein intake, dietary fiber intake, and sodium intake. Mean F%E in Q1 to Q4 were 16.6%E, 21.8%E, 25.4%E, and 30.9%E, respectively. HbA1c, body mass index, triglycerides, and blood pressure were well controlled. No significant associations between F%E and incidence of CVD were shown for Q2, Q3, and Q4 relative to Q1 (Q2: 1.03 [95% CI, 0.47-2.28], Q3: 1.27 [0.58-2.76], and Q4: 1.10 [0.44-2.73]). Stratified analysis by sex and age also showed no significant difference between F%E and incidence of CVD. When %E from saturated fatty acids (SFA%E) was analyzed according to quartiles 1 and 4 SFA%E values were 4.9%E and 7.1%E, respectively. There were no significant differences in incidence of CVD among quartiles (Q1: Reference, Q2: 1.31 [0.66-2.61], Q3: 0.47 [0.18-1.25], and Q4: 1.02 [0.44-2.39]). Findings suggested that most Japanese with T2D during the study period consumed &lt; 30% of F%E and &lt;10% of SFA%E. No significant differences in incident CVD were observed within these ranges.

Disclosure

C. Horikawa: None. M. Takahara: None. N. Katakami: Speaker's Bureau; Abbott Japan Co., Ltd., Kowa Company, Ltd., MSD, Mitsubishi Tanabe Pharma Corporation, Lilly Diabetes, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Kyowa Kirin Co., Ltd., Daiichi Sankyo, Boehringer-Ingelheim, Sanofi. Y. Takeda: None. M. Takeuchi: None. K. Fujihara: None. H. Suzuki: Speaker's Bureau; Abbott Japan Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Boehringer-Ingelheim, Terumo Corporation, AstraZeneca, Bayer Inc., Kyowa Kirin Co., Ltd. N. Yoshioka: None. H. Shimano: None. J. Satoh: Speaker's Bureau; Lilly Diabetes, Merck & Co., Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Boehringer-Ingelheim. Y. Hayashino: Speaker's Bureau; Eli Lilly and Company, Merck & Co., Inc., Boehringer-Ingelheim, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk A/S. N. Tajima: None. R. Nishimura: Speaker's Bureau; Abbott. Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Medtronic, Sanofi, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Eli Lilly and Company, Novo Nordisk A/S. Consultant; Terumo Corporation. Y. Yamasaki: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

Funding

The Japan Diabetes Society, the Japan Society for the Promotion of Science(23K10873).

DOI： 10.2337/db24-1372-p

1474-P: Cross-Sectional and Longitudinal Relationships between Detailed Family History (FH) of Type 2 Diabetes Mellitus (T2DM), Hypertension (HT), and Dyslipidemia (DL) and Prevalence of Each Disorder

IZUMI IKEDA, KAZUYA FUJIHARA, YASUNAGA TAKEDA, MARIKO HATTA, SIJIA WU, SATORU KODAMA, YASUMICHI MORI, TAKASHI KADOWAKI, RITSUKO YAMAMOTO-HONDA, YASUJI ARASE, HIROHITO SONE

Diabetes 73 ( Supplement_1 ) 2024.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

A FH of T2DM, HT, and DL are known risk factors; however, few studies have compared the impact of a FH of the 3 diseases in the same population. We examined the impact of a detailed FH of these conditions (i.e., in fathers, mothers, siblings and grandparents) on their prevalence and incidence in the study population. Data on 41,931 participants who underwent health checkups were examined and the results of a logistic regression and (Cox regression model in the same cohort were examined. Results of the cross-sectional study showed that odds ratios increased with the degree of a positive FH for all three diseases. Furthermore, in T2DM, the group with a three-generation positive FH was approximately 20 times larger than the control group which had no FH (Figure). In the longitudinal study, FH had a strong influence on the incidence of T2DM, HT, and DL, in that order, with a hazard ratio of 2.40 (1.93-2.98) for T2DM. A detailed FH was extremely useful for both quantitative screening for each disease and predicting the incidence of the three diseases, especially T2DM, for which a high risk was indicated in multiple generations with overlapping of positivity for a particular disease.

<p></p> Disclosure

I. Ikeda: None. K. Fujihara: None. Y. Takeda: None. M. Hatta: None. S. Wu: None. S. Kodama: None. Y. Mori: None. T. Kadowaki: None. R. Yamamoto-Honda: None. Y. Arase: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

DOI： 10.2337/db24-1474-p

1259-P: Relationship between Number of Multiple Risk Factors and Functional Disability (FD) in Those With and Without Diabetes Mellitus (DM)

HARUKA SHIOZAKI, KAZUYA FUJIHARA, KAHORI TSURUOKA, IZUMI IKEDA, MASARU KITAZAWA, YASUHIRO MATSUBAYASHI, MASAHIKO YAMAMOTO, TAKAHO YAMADA, SATORU KODAMA, HIROHITO SONE

Diabetes 73 ( Supplement_1 ) 2024.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

Although control of multiple risk factors is essential to prevent FD with and without DM, longitudinal studies are scarce that directly and quantitatively compare effects of such control. Thus, we assessed whether reaching multifactorial targets for HbA1c, blood pressure, non-HDLC, and lifestyle risks such as smoking and no physical activity are associated with FD in those with and without DM.

Enrolled were 9652 Japanese aged 39-98 y. FD was defined based on the Japanese long-term care insurance system, and targets were based on ADA and Japanese guidelines.

Of 8,861 non-DM persons, 6.3, 25.2 and 49.1% were on target for 0-2, 3 and 4 factors, respectively. Of 791 persons with DM, 12.4, 68.0 and 19.3% were on target for 0-2, 3-4 and 5 factors, respectively.

Multivariate Cox analysis showed increased FD with decreased targets reached regardless of DM (Table, upper). Compared with people with non-DM who achieved 4 targets, non-DM persons who achieved 0 to 2 targets and DM persons who achieved 3 to 4 targets had nearly twice the incidence of FD (Table, lower). Moreover, people with DM who achieved only 0 to 2 targets had an approximately 4 times higher incidence of FD (Table, lower). Control of modifiable risk factors was effective regardless of DM. Achievement of all 5 targets among people with DM may reduce FD to the same level as in non-DM persons who achieved all 4 targets.

<p></p> Disclosure

H. Shiozaki: None. K. Fujihara: None. K. Tsuruoka: None. I. Ikeda: None. M. Kitazawa: None. Y. Matsubayashi: None. M. Yamamoto: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

Funding

the Japan Society for the Promotion of Science (21K11569); Daiwa Securities Health Foundation

DOI： 10.2337/db24-1259-p

Usefulness of New Criteria for Metabolic Syndrome Optimized for Prediction of Cardiovascular Diseases in Japanese.

Yurie Yamazaki, Kazuya Fujihara, Takaaki Sato, Mayuko Harada Yamada, Yuta Yaguchi, Yasuhiro Matsubayashi, Takaho Yamada, Satoru Kodama, Kiminori Kato, Hitoshi Shimano, Hirohito Sone

Journal of atherosclerosis and thrombosis 31 ( 4 ) 382 - 395 2024.4

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

AIMS: We attempted to clarify whether the multiple criteria for metabolic syndrome (MetS) can sufficiently predict cardiovascular disease, whether waist circumference (WC) should be required, and whether sex-specific thresholds for each component are necessary. Only a few large-scale studies among East Asians have addressed the ability of MetS to predict cardiovascular disease. METHODS: We analyzed the data of 330,051 men and 235,028 women aged 18-74 years with no history of coronary artery disease (CAD) or cerebrovascular disease (CVD) from a nationwide Japanese claims database accumulated during 2008-2016. The association of each MetS component with CAD or CVD (CAD/CVD), MetS associated with CAD/CVD according to various criteria, and utility of modified criteria with more specific optimal values for each component were examined using multivariate Cox regression and receiver operating characteristic (ROC) analysis. RESULTS: During the study, 3,934 men (1.19%) and 893 women (0.38%) developed CAD/CVD. For each current MetS criteria, there was a 1.3- to 2.9-fold increased risk of CAD/CVD. Optimal thresholds for predicting CAD/CVD were WCs of 83 and 77 cm, triglycerides levels of 130 and 90 mg/dl, high-density lipoprotein cholesterol levels of 50 and 65 mg/dl, blood pressures of 130/80 and 120/80 mmHg, and fasting plasma glucose levels of 100 and 90 mg/dl for men and women, respectively. The existing MetS criteria and modified criteria were not significantly different in predicting CAD/CVD, but using the modified criteria markedly increased the prevalence of MetS and percentage of people with MetS developing CAD/CVD. CONCLUSIONS: Although various criteria for MetS similarly predicted CAD/CVD, the new criteria greatly reduced the number of high-risk individuals, especially women, overlooked by the current criteria.

DOI： 10.5551/jat.64380

糖尿病(DM)の有無別にみた生活習慣関連因子(Cardiovascular Health Metrics)が腎透析導入(HD)に及ぼす影響の検討

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 67 ( Suppl.1 ) S - 168 2024.4

糖尿病患者における重症合併症の複合アウトカム(CSDC)の発症リスク因子の検討

田中菜々子, 矢口雄大, 佐藤隆明, 大澤妙子, 鈴木浩史, 山田貴穂, 藤原和哉, 曽根博仁

糖尿病 67 ( Suppl.1 ) S - 186 2024.4

代謝異常を伴う脂肪肝(MASLD)サブタイプのトランジションとCVD新規発症との関連について

松林泰弘, 藤原和哉, 山田万祐子, 佐藤隆明, 矢口雄大, 山本正彦, 石黒創, 大澤妙子, 北澤勝, 山田貴穂, 曽根博仁

糖尿病 67 ( Suppl.1 ) S - 215 2024.4

新規開発した総合体力指標フィジカルスコアによる各種代謝疾患の発症予測能の検討

佐藤隆明, 藤原和哉, 矢口雄大, 山本正彦, 北澤勝, 鈴木浩史, 松林泰弘, 石黒創, 大澤妙子, 山田貴穂, 加藤公則, 曽根博仁

糖尿病 67 ( Suppl.1 ) S - 216 2024.4

糖尿病予備群(preDM)におけるHbA1c,空腹時血糖(FPG)およびそれらの組み合わせによる脳心血管疾患(CVD)発症リスクの関連

村井幸四郎, 藤原和哉, 山田万祐子, 矢口雄大, 北澤勝, 山本正彦, 佐藤隆明, 松林泰弘, 山田貴穂, 曽根博仁

糖尿病 67 ( Suppl.1 ) S - 247 2024.4

メタボリックシンドローム(MetS)の経年的変化と心血管疾患発症の関連

滝澤大輝, 藤原和哉, 三ツ間友里恵, 山田万祐子, 村井幸四郎, 佐藤隆明, 矢口雄大, 山本正彦, 大澤妙子, 北澤勝, 松林泰弘, 岩永みどり, 山田貴穂, 曽根博仁

糖尿病 67 ( Suppl.1 ) S - 249 2024.4

日本人2型糖尿病患者における,飽和脂肪酸エネルギー比率と心血管疾患発症との関係 JDCP studyの解析から

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, 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

糖尿病 67 ( Suppl.1 ) S - 169 2024.4

PHRスマートフォンアプリとisCGMを連動させた2型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

糖尿病 67 ( Suppl.1 ) S - 216 2024.4

詳細な家族歴が2型糖尿病,高血圧,脂質異常症の有病と発症に与える影響の横断縦断的検討

池田和泉, 五十嵐理沙, 藤原和哉, 武田安永, 松林泰弘, 児玉暁, 山田貴穂, 森保道, 門脇孝, 本田律子, 荒瀬康司, 曽根博仁

糖尿病 67 ( Suppl.1 ) S - 194 2024.4

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 & Metabolism 200257 - 200257 2024.3

Cross-Sectional and Longitudinal Associations between Forearm Bone Mineral Density and Anthropometry in Adult Japanese Men and Women

Masahiro Ishizawa, Kazuya Fujihara, Junko Yachida, Izumi Ikeda, Takaaki Sato, Takaho Yamada, Ayako Kobayashi, Shiro Tanaka, Yoshimi Nakagawa, Takashi Matsuzaka, Hitoshi Shimano, Minoru Tashiro, Satoru Kodama, Kiminori Kato, Hirohito Sone

Journal of Bone Metabolism 31 ( 1 ) 21 - 30 2024.2

Publishing type：Research paper (scientific journal)

Background: No consensus exists regarding which anthropometric measurements are related to bone mineral density (BMD), and this relationship may vary according to sex and age. A large Japanese cohort was analyzed to provide an understanding of the relationship between BMD and anthropometry while adjusting for known confounding factors. Methods: Our cohort included 10,827 participants who underwent multiple medical checkups including distal forearm BMD scans. Participants were stratified into four groups according to age (≥50 years or <50 years) and sex. The BMD values were adjusted for confounding factors, after which single and partial correlation analyses were performed. The prevalence of osteopenia was plotted for each weight index (weight or body mass index [BMI]) class. Results: Cross-sectional studies revealed that weight was more favorably correlated than BMI in the older group (R=0.278 and 0.212 in men and R=0.304 and 0.220 in women, respectively), whereas weight and BMI were weakly correlated in the younger age groups. The prevalence of osteopenia exhibited a negative linear relationship with weight among older women ≥50 years of age, and an accelerated increase was observed with decreasing weight in older men weighing <50 kg and younger women weighing <60 kg. When weight was replaced with BMI, the prevalence was low in most subgroups classified by weight. Conclusions: Weight, rather than BMI, was the most important indicator of osteopenia but it might not be predictive of future bone loss.

DOI： 10.11005/jbm.2024.31.1.21

機能性甲状腺結節による甲状腺中毒症を誘因として糖尿病性ケトアシドーシスを来し甲状腺クリーゼを発症した一例

間島貴之, 鈴木浩史, 木村智佑, 佐藤隆明, 山本雅彦, 石黒創, 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 99 ( 4 ) 884 - 884 2024.1

機能性甲状腺結節による甲状腺中毒症を誘因として糖尿病性ケトアシドーシスを来し甲状腺クリーゼを発症した一例

間島貴之, 鈴木浩史, 木村智佑, 佐藤隆明, 山本雅彦, 石黒創, 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 99 ( 4 ) 884 - 884 2024.1

副交感神経障害を伴わず糖尿病性動眼神経麻痺との鑑別に難渋した下垂体卒中による動眼神経麻痺の一例

深井悠未, 村井幸四郎, 今西明, 矢口雄大, 北澤勝, 鈴木浩史, 松林泰弘, 藤原和哉, 岩永みどり, 山田貴穂, 曽根博仁, 岡田正康

日本内分泌学会雑誌 99 ( 4 ) 895 - 895 2024.1

2型糖尿病患者におけるカリウム摂取量およびナトリウム摂取量と心血管疾患発症リスクの関係 JDCP study

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, 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

Journal of Epidemiology 34 ( Suppl. ) 163 - 163 2024.1

副交感神経障害を伴わず糖尿病性動眼神経麻痺との鑑別に難渋した下垂体卒中による動眼神経麻痺の一例

深井悠未, 村井幸四郎, 今西明, 矢口雄大, 北澤勝, 鈴木浩史, 松林泰弘, 藤原和哉, 岩永みどり, 山田貴穂, 曽根博仁, 岡田正康

日本内分泌学会雑誌 99 ( 4 ) 895 - 895 2024.1

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

Machine learning algorithms mimicking specialists decision making on initial treatment for people with type 2 diabetes mellitus in Japan diabetes data management study (JDDM76). International journal

Jenny Elizabeth Price, Kazuya Fujihara, Satoru Kodama, Katsuya Yamazaki, Hiroshi Maegawa, Tatsuya Yamazaki, Hirohito Sone

Diabetes & metabolic syndrome 18 ( 11-12 ) 103168 - 103168 2024

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

OBJECTIVE: To evaluate whether typical machine learning models that mimic specialists' care can successfully reproduce information, not only on whether to prescribe medications but also which hypoglycemic agents to prescribe as initial treatment for type 2 diabetes. RESEARCH DESIGN AND METHODS: A medical records database containing prescriptions for medications for 16,005 patients who visited a diabetologist's office for the first time was utilized to train five typical machine learning models as well-as a model used for logistic analysis. Prescribed were no medications (diet and exercise therapy), insulin, biguanides (BG), sulfonylureas (SU), dipeptidyl peptidase-4 inhibitors (DPP-4I), alpha-glucosidase inhibitors (α-GI) or glinides. Models were compared based on the F1 score and ROC/AUC scores. RESULTS: XGBoost, which splits decision-making into three sections, was the top performing model (42 % accuracy) among five models and conventional logistic regression (35 % accuracy). The second highest scoring model was Support Vector Machines, which had an accuracy of 40 %. When using XGBoost to compare decisions on no medication needed vs. needing medication the AUC was 0.96. Insulin vs. oral medications had an AUC of 0.78. With all remaining oral medications removed, the AUC was 0.76. CONCLUSIONS: Among the five models investigated, XGBoost outperformed the other machine learning models examined as well as the traditional logistic model, suggesting that its accuracy had the potential to assist non-specialists in decision-making regarding treatment of patients with type 2 diabetes in the future.

DOI： 10.1016/j.dsx.2024.103168

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

"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

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

握力、閉眼片足立ち、立位体前屈による総合体力指標は代謝性疾患のスクリーニングに有用である

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

日本臨床運動療法学会学術集会プログラム・抄録集 42回 61 - 61 2023.10

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

溶血性貧血によるヘモクロマトーシスと甲状腺機能低下症の合併例

村井幸四郎, 矢口雄大, 今西明, 深井悠未, 北澤勝, 鈴木浩史, 佐藤隆明, 石黒創, 山本正彦, 石澤正博, 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 99 ( 2 ) 599 - 599 2023.10

頭蓋咽頭腫術後の視床下部障害から低体温症を来した1例

赤壁尚太, 土田大介, 滝澤大輝, 北澤勝, 松林泰弘, 山田貴穂, 藤原和哉, 平石哲也, 大石誠, 曽根博仁

日本内分泌学会雑誌 99 ( 2 ) 591 - 591 2023.10

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

心血管疾患脂肪肝の表現型,及び2型糖尿病が心不全の新規発症に与えるインパクト

松林泰弘, 藤原和哉, 山田万祐子, 佐藤隆明, 矢口雄大, 山本正彦, 石黒創, 大澤妙子, 北澤勝, 岩永みどり, 山田貴穂, 曽根博仁

糖尿病合併症 37 ( Suppl.1 ) 164 - 164 2023.9

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

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

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.

DOI： 10.1080/02640414.2023.2268358

心血管疾患脂肪肝の表現型,及び2型糖尿病が心不全の新規発症に与えるインパクト

松林泰弘, 藤原和哉, 山田万祐子, 佐藤隆明, 矢口雄大, 山本正彦, 石黒創, 大澤妙子, 北澤勝, 岩永みどり, 山田貴穂, 曽根博仁

糖尿病合併症 37 ( Suppl.1 ) 164 - 164 2023.9

網膜症 2型糖尿病男性におけるアルコール摂取と重症糖尿病眼疾患発症の関連

山本正彦, 藤原和哉, 長谷部日, 山田万祐子, 矢口雄大, 大澤妙子, 岩永みどり, 児玉暁, 山田貴穂, 曽根博仁

糖尿病合併症 37 ( Suppl.1 ) 135 - 135 2023.9

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

Fujihara K, Khin L, Murai K, Yamazaki Y, Tsuruoka K, Yagyuda N, Yamazaki K, Maegawa H, Tanaka S, Kodama S, Sone, H, JDDM Study Group

Diabetes Obes Metab 2023.7

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

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.

DOI： 10.1111/dom.15206

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

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

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.

DOI： 10.1136/bmjdrc-2023-003482

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

劇症1型糖尿病発症時にST上昇を呈し偽性心筋梗塞と考えられた1例

佐藤駿匡, 北澤勝, 滝澤祥子, 今西明, 山田万祐子, 松林泰弘, 藤原和哉, 山田貴穂, 保屋野真, 曽根博仁

糖尿病 66 ( 7 ) 570 - 570 2023.7

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

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

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)

DOI： 10.2337/db23-329-or

1381-P: Effect of Dietary Potassium Intake and Its Interaction with Sodium Intake on Risk of Developing Cardiovascular Disease (CVD) in Persons with Type 2 Diabetes (T2D)—Japan Diabetes Complication and Its Prevention Prospective Study (JDCP Study)

CHIKA HORIKAWA, MITSUYOSHI TAKAHARA, NAOTO KATAKAMI, YASUNAGA TAKEDA, MIZUKI TAKEUCHI, KAZUYA FUJIHARA, HIROAKI SUZUKI, KINSUKE TSUDA, NARIHITO YOSHIOKA, HITOSHI SHIMANO, JO SATOH, YASUAKI HAYASHINO, NAOKO TAJIMA, RIMEI NISHIMURA, YOSHIMITSU YAMASAKI, HIROHITO SONE

Diabetes 72 ( Supplement_1 ) 2023.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

Many guidelines recommend increased potassium intake. However, the relationship between dietary potassium intake and incidence of CVD in persons with T2D has not been explored, nor is it known if this relationship varies with sodium intake in such persons. Therefore, we investigated these relationships as part of the JDCP study, a nationwide study launched in 2007. A total of 1477 persons with T2D aged 40-75 years completed a brief self-administered Diet History Questionnaire at baseline, and resultant data were analyzed. Primary outcome was the 7-year risk of a CVD event. Hazard ratios (HRs) for CVD according to tertiles of dietary potassium and sodium intake were estimated by Cox regression adjusted for confounders in addition to a stratified analysis of tertiles of sodium intake. Mean daily potassium and sodium intakes in tertiles 1 to 3 were 1.9, 2.6, and 3.5 g and 3.3, 4.2, and 5.3 g, respectively. HbA1c, BMI, triglycerides, and blood pressure were well controlled. No significant associations between potassium and sodium intakes and incidence of CVD were shown for the second and third tertiles relative to the first tertile (potassium: 0.64 [95% CI, 0.34-1.23] and 0.59 [0.28-1.25]; sodium: 1.02 [0.51-2.04] and 1.15 [0.58-2.30]). In the stratified analysis of tertiles of sodium intake, in the high sodium intake groups (T2 and T3) HRs for CVD in the high potassium intake group were significantly lower compared to the low potassium intake group (T2: 0.40 [0.12-1.35] and 0.06 [0.01-0.69]; T3: 0.23 [0.07-0.82] and 0.26 [0.07-0.88]). Associations of potassium intake with CVD in those with low sodium intake (T1) were not significant. Findings suggested that high potassium intake under high sodium intake is associated with a deceased incidence of CVD in persons with T2D although potassium intake under low sodium intake was not associated with incident CVD.

Disclosure

C.Horikawa: None. H.Shimano: None. J.Satoh: None. Y.Hayashino: Advisory Panel; Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Santen, Daiichi Sankyo, Kowa Company, Ltd. N.Tajima: None. R.Nishimura: Speaker's Bureau; Sanofi K.K., Medicure Inc., Boehringer Ingelheim Inc., Takeda Pharmaceutical Company Limited, Kissei Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Novo Nordisk, Merck & Co., Inc., Abbott Japan Co., Ltd., Astellas Pharma Inc., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca. Y.Yamasaki: 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. Jdcp study group: n/a. M.Takahara: None. N.Katakami: Speaker's Bureau; Abbott Japan Co., Ltd., Daiichi Sankyo, MSD, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Ono Pharmaceutical Co., Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Bayer Inc., Lilly, Teijin Pharma Limited, Kyowa Kirin Co., Ltd., Boehringer Ingelheim Japan, Inc., Sanofi. Y.Takeda: None. M.Takeuchi: None. K.Fujihara: None. H.Suzuki: None. K.Tsuda: None. N.Yoshioka: None.

DOI： 10.2337/db23-1381-p

1713-P: Dietary Manganese (Mn) Intake Is Independently Associated with a Lower BMI in Younger Japanese with Type 2 Diabetes Mellitus (T2DM)

LAY MON KHIN, KAZUYA FUJIHARA, MARIKO HATTA, YASUNAGA TAKEDA, SAKIKO Y. MORIKAWA, CHIKA HORIKAWA, NORIKO KATO, MITSUTOSHI KATO, HIROSHI MAEGAWA, HIROHITO SONE

Diabetes 72 ( Supplement_1 ) 2023.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

We analyzed the association between dietary Mn intake and obesity measured by BMI after adjustment for intake of nutrients and food groups in people with T2DM in Japan. Participants were 1567 people, 63% male, aged 30 to 89 y who were in the Japan Diabetes Clinical Data Management Study Group (JDDM), one of the largest cohorts of Japanese with diabetes. Intake of food groups was determined by a validated self-administered food frequency questionnaire based on food groups. Obesity was defined as BMI ≥25 kg/m2. Multivariate logistic regression analysis assessed the relationship between quartiles of dietary Mn intake and obesity stratified by age. Participants aged 30 to 89 y were grouped according to the following quartiles for age: 30-54 y, 55-63 y, 64-71 y, and 72-89 y. Compared to the lowest quartile (Q1) for Mn, a significant negative association between Mn and BMI was found in males for all quartiles of Mn (OR [95%CI] of Q2= 0.643 [0.424 - 0.973], Q3= 0.607 [0.374 - 0.986], Q4= 0.398 [0.218 - 0.728], p trend = 0.028) with adjustment for characteristics such as age, sex, current smoking, drinking, insulin, oral hypoglycemic agents treatment, activity, energy intake and macronutrients intake. However, statistical significance disappeared after adding total fiber as a covariate. Compared to the lowest quartile for Mn, the highest quartile of Mn was inversely associated with BMI in the younger age group (30-54 y [OR= 0.296 [0.088 - 0.996]]) even after total fiber adjustment. Multivariate analysis of food groups (rice, vegetables, soy products) that were highly correlated with Mn as covariates showed that the relationships between Mn intake and obesity were maintained (p trend for rice, vegetables, soy = &lt;0.001, 0.187, 0.010) in all participants. In summary, higher dietary Mn intake was independently associated with a lower BMI, especially in the younger group and males. Future prospective or intervention studies are expected to confirm this result.

Disclosure

L.Khin: 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. Jddm study group: n/a. K.Fujihara: None. M.Hatta: None. Y.Takeda: None. S.Y.Morikawa: None. C.Horikawa: None. N.Kato: None. M.Kato: None. H.Maegawa: None.

DOI： 10.2337/db23-1713-p

738-P: Lifestyle Intervention Program with Smartphone App Augmented by Intermittently Scanned Continuous Glucose Monitoring for People at High Risk of Diabetes—Randomized Controlled Trial

MASARU KITAZAWA, HIROSHI SUZUKI, CHIKA HORIKAWA, YASUNAGA TAKEDA, IZUMI IKEDA, MARIKO HATTA, MIDORI IWANAGA, TAKAHO YAMADA, KAZUYA FUJIHARA, HIROHITO SONE

Diabetes 72 ( Supplement_1 ) 2023.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

We examined the effects of a lifestyle intervention program with a smartphone app augmented by intermittently scanned continuous glucose monitoring (isCGM) of persons at high risk of developing diabetes in a 12-week randomized open-label trial (UMIN00004640). The program monitored blood glucose fluctuations and lifestyle habits and displayed them in an easy-to-understand interface as well as provided personalized lifestyle intervention messages. The primary endpoint was the change in time in range (TIR) of 70-140 mg/dL between intervention (App) and control (C) groups. 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 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 (&gt;140 mg/dL; -20.9 min/day vs. -22.6 min/day, p=0.86) did not differ, whereas time below range (&lt;70 mg/dL; +23.5 min/day vs. -8.9 min/day, p=0.02) improved in App compared to C. BMI (-0.26 vs. -0.59, p=0.017) and carbohydrate intake (-4.4 kcal/day vs. -22.7 kcal/day, p=0.049) also improved in App compared to C. Intervention with a smartphone app and isCGM increased glycemic control with a decrease in carbohydrate intake and weight loss.

<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. H.Suzuki: None. C.Horikawa: None. Y.Takeda: None. I.Ikeda: None. M.Hatta: None. M.Iwanaga: None. T.Yamada: None. K.Fujihara: None.

DOI： 10.2337/db23-738-p

1357-P: Conflicting Significance of High BMI as a Predictor of Individual Diabetic Complications

YUTA YAGUCHI, KAZUYA FUJIHARA, LAY MON KHIN, SIJIA WU, EFREM D. FERREIRA, TAKAAKI SATO, CHIKA HORIKAWA, YASUHIRO MATSUBAYASHI, KIMINORI KATO, HIROHITO SONE

Diabetes 72 ( Supplement_1 ) 2023.6

Publishing type：Research paper (scientific journal) Publisher：American Diabetes Association

Although weight management plays a central role in diabetes treatment, the association between body weight and diabetic complications is not fully elucidated. Therefore, we investigated the relationship between BMI and risk of diabetic complications in patients with diabetes mellius (DM) using nationwide claims data. Analyzed were 91097 patients with DM without prior treatment-requiring diabetic eye disease (TRDED), initiation of dialysis (dialysis), coronary artery disease (CAD), cerebrovascular disease (CVD), heart failure (HF) or amputation (mean age 52 y, HbA1c 7.2%, median follow-up 4.5 y). Participants were divided into 6 groups according to BMI (BMI&lt;20.0, 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.0, ≥30.0). Risk of diabetic complications was examined by Cox regression analysis. There was an inverse correlation between the risk of dialysis and BMI; hazard ratio (HR) for dialysis in patients with BMI ≥30.0 was 0.46 (0.29-0.74). There was a U-shaped relationship between the risk of HF and BMI; HRs for HF in patients with BMI &lt;20.0 and ≥30.0 were 1.97 (1.15-3.37) and 1.76 (1.27-2.45), respectively (Figure). High BMI was significantly associated with a higher risk of HF, but lower risks of TRDED and dialysis. The relationship between BMI and diabetic complications was inconsistent among complications, suggesting that the target weight should be individualized according to diabetic complications.

<p></p> Disclosure

Y.Yaguchi: 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. K.Fujihara: None. L.Khin: None. S.Wu: None. E.D.Ferreira: None. T.Sato: None. C.Horikawa: None. Y.Matsubayashi: None. K.Kato: None.

DOI： 10.2337/db23-1357-p

Incidence and predictors of remission and relapse of type 2 diabetes mellitus in Japan: Analysis of a nationwide patient registry (JDDM73). Reviewed International journal

Fujihara K, Khin L, Murai K, Yamazaki Y, Tsuruoka K, Yagyuda N, Yamazaki K, Maegawa H, Tanaka S, Kodama S, Sone H, JDDM Study Group

Diabetes Obes Metab 25 ( 8 ) 2227 - 2235 2023.5

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

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.

DOI： 10.1111/dom.15100

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

日本人ビッグデータにより血糖を含む全構成項目閾値を心血管疾患予測に最適化した新メタボリックシンドローム基準の有用性評価

三ツ間友里恵, 藤原和哉, 山田万祐子, 村井幸四郎, 佐藤隆明, 矢口雄大, 山本正彦, 大澤妙子, 北澤勝, 松林泰弘, 岩永みどり, 山田貴穂, 曽根博仁

糖尿病 66 ( Suppl.1 ) S - 172 2023.4

糖尿病/高血圧/肥満と脂肪肝との関連が心不全発症に与える影響についての検討

松林泰弘, 藤原和哉, 山田万祐子, 佐藤隆明, 矢口雄大, 山本正彦, 石黒創, 大澤妙子, 北澤勝, 岩永みどり, 山田貴穂, 曽根博仁

糖尿病 66 ( Suppl.1 ) S - 174 2023.4

JDDM登録患者4万8千人の2型糖尿病患者における新たに定義された世界共通定義による寛解(remission)の発生頻度と関連因子

藤原和哉, 松林泰弘, 佐藤隆明, 山田万祐子, 矢口雄大, 大澤妙子, 岩永みどり, 山崎勝也, 前川聡, 山田貴穂, 曽根博仁

糖尿病 66 ( Suppl.1 ) S - 194 2023.4

糖尿病(DM)に5つの生活習慣関連因子(Cardiovascular Health Metrics)不良を伴うと腎透析導入(HD)リスクは著明に上昇する

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 66 ( Suppl.1 ) S - 197 2023.4

新規に開発された体力指標フィジカルスコアによるメタボリックシンドローム発症予測能の検討

佐藤隆明, 藤原和哉, 山田万由子, 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 66 ( Suppl.1 ) S - 309 2023.4

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

Kodama S, Fujihara K, Ishiguro H, Matsubayashi Y, Kitazawa M, Iwanaga M, Yamada T, Kato K, Nakagawa Y, Tanaka S, Shimano H, Sone H

J Investig Med 2023.4

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

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

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

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

Takaaki Sato, Kazuya Fujihara, Mayuko Harada Yamada, Kaori Chou, Yuta Yaguchi, Masaru Kitazawa, Hajime Ishiguro, Taeko Osawa, Takaho Yamada, Satoru Kodama, Kiminori Kato, Hirohito Sone

Journal of sports science & medicine 22 ( 1 ) 98 - 110 2023.3

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

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.

DOI： 10.52082/jssm.2023.98

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

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

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

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

Ayako Kobayashi, Kazuya Fujihara, Mayuko Harada Yamada, Takaaki Sato, Yuta Yaguchi, Masaru Kitazawa, Yasuhiro Matsubayashi, Midori Iwanaga, Takaho Yamada, Satoru Kodama, Hirohito Sone

Journal of Hypertension Publish Ahead of Print 2023.1

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.

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

Diabetology international 14 ( 1 ) 86 - 93 2023.1

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

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.

DOI： 10.1007/s13340-022-00603-z

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

Kazuya Fujihara, Mayuko Yamada Harada, Chika Horikawa, Midori Iwanaga, Hirofumi Tanaka, Hitoshi Nomura, Yasuharu Sui, Kyouhei Tanabe, Takaho Yamada, Satoru Kodama, Kiminori Kato, Hirohito Sone

Frontiers in public health 11 1090146 - 1090146 2023

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

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.

DOI： 10.3389/fpubh.2023.1090146

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

握力、閉眼片足立ち、立位体前屈による総合体力指標はメタボリックシンドロームの発症予測に有用である

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

日本臨床運動療法学会学術集会プログラム・抄録集 41回 57 - 57 2022.9

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

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

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

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

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

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

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

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

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.

DOI： 10.1093/fampra/cmac087

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

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

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.

DOI： 10.1016/j.heliyon.2022.e10284

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

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

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.

DOI： 10.3390/nu14153034

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

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

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

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.

DOI： 10.1186/s12933-022-01518-4

【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

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

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

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

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

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

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

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

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

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

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

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

アレルギーの食餌制限によりヨード欠乏症を来した成人男性の一例

滝澤大輝, 日向裕大, 橋本浩平, 松林泰弘, 岩永みどり, 山田貴穂, 藤原和哉, 長崎啓祐, 曽根博仁

日本内分泌学会雑誌 98 ( 1 ) 349 - 349 2022.4

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

Language：Japanese Publisher：(公社)日本栄養士会

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)

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

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

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.

DOI： 10.1111/sms.14089

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

Efrem d'Ávila Ferreira, 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

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

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.

DOI： 10.3390/nu14010211

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

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

XGBoost: Interpretable Machine Learning Approach in Medicine

Jenny Price, Tatsuya Yamazaki, Kazuya Fujihara, Hirohito Sone

WSCE 2022 - 2022 5th World Symposium on Communication Engineering 109 - 113 2022

Publishing type：Research paper (international conference proceedings)

This research tries to establish a communication bridge between the decision making of a practicing physician and a machine learning model. Machine learning has long been used to assist in diagnosing patients through deep learning and medical image analysis. However, in medical science, it is possible to have multiple right answers when treating patients. This leaves the practitioners room to exercise their judgement on what would be best for the patient. The machine learning model can be a communication tool to assist the practitioners in reach the final decision. In this paper, the machine learning model used for this experiment is XGBoost, a gradient boosted decision tree. Through the experiment with the real patient data, we show how decision tree constructions are easily readable for medical determination.

DOI： 10.1109/WSCE56210.2022.9916029

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

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

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.

DOI： 10.1111/jdi.13736

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

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 ) 2021.12

Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

<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>

DOI： 10.1186/s12933-021-01367-7

Other Link： https://link.springer.com/article/10.1186/s12933-021-01367-7/fulltext.html

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

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

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.

DOI： 10.1016/j.amjmed.2021.10.018

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

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

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

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.

DOI： 10.3390/nu13103478

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 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

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

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.

DOI： 10.3390/nu13103428

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

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

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.

DOI： 10.3390/nu13093167

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

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

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

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

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

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.

DOI： 10.1136/bmjdrc-2021-002177

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

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

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

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 dc202252 - dc202252 2021.5

Accuracy of Japanese claims data in identifying diabetes-related complications. 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

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

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.

DOI： 10.1002/pds.5213

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

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

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

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

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

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

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

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

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

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

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

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

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%.

DOI： 10.1186/s13047-021-00474-8

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

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

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

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

Association of estimated plasma volume and weight loss after long-term administration and subsequent discontinuation 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 23 ( 7 ) 1660 - 1665 2021.3

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

Sodium/glucose-cotransporter 2 inhibitors (SGLT2is) are drugs that have been reported to have several effects through the regulation of plasma volume such as antihypertensive effects, etc. This study aimed to clarify the impact of long-term administration and subsequent discontinuation of the SGLT2i 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 analyzed. Changes in variables or correlations among them during a 52-week administration and 2-week post-treatment period were investigated. Percent change in ePV was calculated by 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. This article is protected by copyright. All rights reserved.

DOI： 10.1111/dom.14387

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 2021.3

The DPP-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

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

AIMS/INTRODUCTION: This study investigated the impact of the DPP-4 inhibitor, anagliptin, on hepatic insulin clearance (HIC) in Japanese type 2 diabetes patients and explored its relation 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 placebo. HIC was calculated as the ratio, c-peptide area under the curve (AUC)0-120min to insulin AUC0-120min, 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. Further, multivariate analysis investigated the association between baseline HIC levels and glycemic status. RESULTS: Anagliptin significantly reduced HbA1c levels (p<0.001 vs. placebo) and HIC levels (p<0.01). Longer duration of diabetes, lower BMI, higher HbA1c and lower insulin secretion capacity were observed with increases in baseline HIC levels. Improvements in HbA1c, 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 may result in improved hyperglycemia through reduced HIC.

DOI： 10.1111/jdi.13543

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 ) 885 - 887 2021.3

Body flexibility and incident hypertension: The Niigata wellness study. 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

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

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.

DOI： 10.1111/sms.13867

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

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

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.

DOI： 10.1136/jim-2020-001489

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

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

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

Language：Japanese Publisher：(公社)日本人間ドック学会

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)

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

Language：Japanese Publisher：(公社)日本人間ドック学会

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)

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). 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

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

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.

DOI： 10.3390/nu13020689

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

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

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

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

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

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

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.

DOI： 10.2196/22458

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

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

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

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

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

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.

DOI： 10.1016/j.pcd.2020.05.002

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

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

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

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

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

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

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.

DOI： 10.1007/s10557-020-07097-4

A Prospective Cohort Study of Muscular and Performance Fitness and Incident Glaucoma: The Niigata Wellness Study. 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 ) 1 - 8 2020.10

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

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.

DOI： 10.1123/jpah.2019-0660

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

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

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.

DOI： 10.1002/ehf2.12782

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

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

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.

DOI： 10.3390/nu12092649

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 37 ( 8 ) 1316 - 1325 2020.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Blackwell Publishing Ltd

Aims: To examine the effects of a sodium–glucose co-transporter 2 (SGLT2) inhibitor, tofogliflozin, on resting heart rate by exploring baseline factors that independently influenced changes in the resting heart rate. Methods: Data on 419 participants in tofogliflozin phase 2/3 trials were analysed. Changes in resting heart rate from baseline to week 24 were analysed using an analysis of covariance (ANCOVA) model with groups (tofogliflozin/placebo) as a fixed effect and baseline values as covariates. The antilipolytic effect was evaluated as adipose tissue insulin resistance (Adipo-IR) and was calculated as the product of fasting insulin and free fatty acid. Multivariate analysis evaluated independent factors for changes in resting heart rate from baseline to week 24. Results: Of the participants, 58% were men, and mean age, HbA1c, BMI and resting heart rate were 57.6 years, 65 mmol/mol (8.1%), 25.5 kg/m2 and 66 bpm, respectively. At week 24, adjusted mean difference vs. placebo in the change from baseline was −2.3 bpm [95% confidence interval (CI) −4.6, −0.1] with tofogliflozin. Changes in resting heart rate were positively correlated with changes in Adipo-IR, whereas reductions in HbA1c, body weight and blood pressure were similar independent of changes in resting heart among quartiles of resting heart rate change. On multivariate analysis, higher baseline resting heart rates and Adipo-IR values were significantly associated with greater reductions in resting heart rate. Conclusions: Tofogliflozin corrected resting heart rate levels in accordance with baseline levels. Correction of high resting heart rates may be attributed to improved adipose tissue insulin resistance, leading to correction of hyperinsulinaemia.

DOI： 10.1111/dme.14279

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

DOI： 10.1016/j.neuint.2020.104745

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

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

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

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.

DOI： 10.3390/nu12061629

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

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

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.

DOI： 10.1007/s00394-019-02014-4

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

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

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 2020.1

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

AIMS: Obesity and hepatic fat accumulation diminish hepatic insulin clearance, which can cause hyperinsulinaemia. Sodium/glucose-cotransporter 2 inhibitors (SGLTis) 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 SGLT2is on hepatic insulin clearance. We examined the impact of an SGLT2i on hepatic insulin clearance and explored the clinical influence associated with changes in hepatic insulin clearance via an SGLT2i and the mechanism of the effects of SGLT2i. MATERIALS AND METHODS: Data were analysed from 419 patients with type 2 diabetes controlled by diet and exercise. Patients received a placebo or the SGLT2i 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 SGLT2i 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.

DOI： 10.1111/dom.13980

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

Language：English

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.

DOI： 10.1136/bmjdrc-2019-000901

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 Reviewed

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

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

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

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.

DOI： 10.6133/apjcn.202012_29(4).0022

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

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 2020

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

Ikeda, Izumi, Fujihara, Kazuya, Nedachi, Rina, Morikawa, Sakiko Y., Ishiguro, Hajime, Yamada, Mayuko H., Matsubayashi, Yasuhiro, Yamada, Takaho, Sone, Hirohito

Diabetes 2020

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

Komatsu, Takeshi, Fujihara, Kazuya, Yamada, Mayuko H., Sato, Takaaki, Kitazawa, Masaru, Yamamoto, Masahiko, Seida, Hiroyasu, Yamanaka, Nauta, Matsubayashi, Yasuhiro, Yamada, Takaho, Sone, Hirohito

Diabetes 2020

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

Yaguchi, Yuta, Fujihara, Kazuya, Yamada, Mayuko H., Sato, Takaaki, Kitazawa, Masaru, Yamamoto, Masahiko, Seida, Hiroyasu, Yamanaka, Nauta, Matsubayashi, Yasuhiro, Sone, Hirohito

Diabetes 2020

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

Kodama, Satoru, Sato, Takaaki, Yamamoto, Masahiko, Ishiguro, Hajime, Iwanaga, Midori, Fujihara, Kazuya, Yamada, Takaho, Kato, Kiminori, Sone, Hirohito

Diabetes 2020

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

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

Diabetes 2020

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

Morikawa, Sakiko Y., Fujihara, Kazuya, Nedachi, Rina, Ikeda, Izumi, Takeda, Yasunaga, Takeuchi, Mizuki, Hatta, Mariko, Ishiguro, Hajime, Yamada, Takaho, Sone, Hirohito

Diabetes 2020

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

Ikeda, Izumi, Fujihara, Kazuya, Risa, Igarashi, Yamada, Mayuko H., Nedachi, Rina, Hatta, Mariko, Kodama, Satoru, Mori, Yasumichi, Matsubayashi, Yasuhiro, Arase, Yasuji, Sone, Hirohito, Yamamoto-Honda, Ritsuko

Diabetes 2020

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

Sato, Takaaki, Fujihara, Kazuya, Yamada, Mayuko H., Yaguchi, Yuta, Kitazawa, Masaru, Matsubayashi, Yasuhiro, Iwanaga, Midori, Yamada, Takaho, Kato, Kiminori, Sone, Hirohito

Diabetes 2020

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

Yamada, Mayuko H., Fujihara, Kazuya, Yaguchi, Yuta, Osawa, Taeko, Kitazawa, Masaru, Matsubayashi, Yasuhiro, Iwanaga, Midori, Yamada, Takaho, Yamanaka, Nauta, Seida, Hiroyasu, Ogawa, Wataru, Sone, Hirohito

Diabetes 2020

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

Kodama, Satoru, Yamada, Mayuko H., Yaguchi, Yuta, Kitazawa, Masaru, Kaneko, Masanori, Matsubayashi, Yasuhiro, Fujihara, Kazuya, Iwanaga, Midori, Kato, Kiminori, Sone, Hirohito

Diabetes 2020

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

Yamamoto, Masahiko, Harada, Sei, Okamura, Tomonori, Fujihara, Kazuya, Yaguchi, Yuta, Komatsu, Takeshi, Sato, Takaaki, Kitazawa, Masaru, Yamada, Mayuko H., Kaneko, Masanori, Osawa, Taeko, Matsubayashi, Yasuhiro, Yamada, Takaho, Kodama, Satoru, Sone, Hirohito, Takebayashi, Toru

Diabetes 2020

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

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

Diabetes 2020

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

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

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+.

DOI： 10.1016/j.metabol.2019.153991

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

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

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.

DOI： 10.1210/jc.2019-00168

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

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

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

The Journal of clinical endocrinology and metabolism 104 ( 9 ) 3647 - 3660 2019.9

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

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/m2; estimated glomerular filtration rate, 83.9 mL/min/1.73m2; 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.

DOI： 10.1210/jc.2018-02254

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

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

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

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

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

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

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.

DOI： 10.1093/fampra/cmy112

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

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

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

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.

DOI： 10.1167/iovs.19-26749

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

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

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.

DOI： 10.1007/s13300-019-0610-x

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

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

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.

DOI： 10.1161/JAHA.118.010627

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

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

Journal of epidemiology 29 ( 4 ) 139 - 146 2019.4

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

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.

DOI： 10.2188/jea.JE20170280

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

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

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

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

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

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

(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

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

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

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

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.

DOI： 10.1002/dmrr.3120

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

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

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.

DOI： 10.1007/s00394-017-1592-y

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

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

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

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

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.

DOI： 10.1016/j.clnesp.2018.07.001

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

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

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

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

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

Malondialdehyde-modified LDL-related variables are associated with diabetic kidney disease in type 2 diabetes Reviewed

Shoko Furukawa, Hiroaki Suzuki, Kazuya Fujihara, Kazuto Kobayashi, Hitoshi Iwasaki, Yoko Sugano, Shigeru Yatoh, Motohiro Sekiya, Naoya Yahagi, Hitoshi Shimano

Diabetes Research and Clinical Practice 141 237 - 243 2018.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Ireland Ltd

Background and aims: Oxidized low-density lipoprotein (oxLDL) causes the development of atherosclerosis and kidney injury. Although circulating oxLDL levels were reportedly increased in type 2 diabetic patients with macroalbuminuria, it remains unclear whether albuminuria or the reduced glomerular filtration rate (GFR) is independently associated with the circulating oxLDL level. This study aimed to elucidate the association between the stage of diabetic nephropathy and serum malondialdehyde-modified LDL (MDA-LDL) and the ratio of MDA-LDL to LDL-cholesterol (MDA-LDL/LDL). Methods and results: This retroactive cross-sectional study used data from 402 patients with type 2 diabetes. Patients undergoing hemodialysis were excluded. Serum MDA-LDL levels were significantly increased with increases in severity of albuminuria (103 ± 44 U/L, 109 ± 54 U/L, and 135 ± 72 U/L for normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively
P for trend = 0.020) but not according to the estimated GFR (eGFR). An increased MDA-LDL/LDL ratio was significantly associated with both increased albuminuria (35 ± 13, 37 ± 14, and 40 ± 15 for normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively
P for trend = 0.003) and reduced eGFR (34 ± 13, 36 ± 13, 38 ± 12, and 51 ± 28 for grade 1, 2, 3 and 4, respectively
P for trend = 0.002). Multiple linear regression analysis showed that neither the albumin excretion rate nor eGFR but ln-transformed triglycerides and LDL-C levels were independent determinants of both serum MDA-LDL levels and MDA-LDL/LDL ratios. Conclusion: Serum MDA-LDL levels and MDA-LDL/LDL ratios were increased in those with dyslipidemia associated with diabetic kidney disease.

DOI： 10.1016/j.diabres.2018.05.019

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

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

Pediatric diabetes 2018.6

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

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

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.

DOI： 10.1111/pedi.12623

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Fujihara K, Sone H

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

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

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.

DOI： 10.3400/avd.ra.17-00109

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

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

Diabetes Metab 44 ( 2 ) 135 - 142 2018.3

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

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

Diabetes Metab 44 ( 2 ) 172 - 174 2018.3

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

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

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.

DOI： 10.2188/jea.JE20160151

Two-year assessment of the therapeutic efficacy of dipeptidyl peptidase-4 inhibitors or sulfonylureas in Japanese drug-naive patients with type 2 diabetes (JDDM 44)

Koichi Kawai, Shinobu Motohashi, Kazuya Fujihara, Katsuya Yamazaki, Yoshio Kurihara, Koichi Hirao, Hidekatsu Sugimoto, Hiroshi Takamura, Azuma Kanatsuka, Hiroshi Maegawa

Journal of the Japan Diabetes Society 61 ( 4 ) 161 - 170 2018

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Diabetes Society

We retrospectively analyzed the CoDiC data from 33 institutes in the Japan Diabetes Clinical Data Management Study Group in order to clarify the therapeutic efficacy of DPP-4 inhibitors (DPP-4is) and sulfonylureas (SUs) in Japanese patients with type 2 diabetes who have not previously received pharmacologic treatment. At the end of July in 2015, 498 and 349 patients were treated for more than two years with DPP-4is and SUs, respectively. In comparison to SUs, the DPP-4is group showed a more prominent HbA1c reduction (even in patients with a higher initial HbA1c [＜9.0 %]), a higher proportion of patients who continued monotherapy with the initial agent, and a higher proportion of patients with an HbA1c value of ＜7.0 %. Additional hypoglycemic therapy was administered to 42 % of the patients treated with DPP-4is and 54 % of the patients treated with SUs
this mainly involved biguanide treatment (DPP-4i vs SU
53 % vs 56 %). Among the DPP-4itreated patients, weight gain was only observed in the patients with an initial HbA1c value of ＞10 %, whereas it was observed irrespective of the initial HbA1c value in the SU-treated patients. These results were confirmed by a propensity score matching analysis. In conclusion, these results suggest that DPP-4is show superior therapeutic efficacy to SUs as an insulin secretion promoting agent in the treatment of drug-naive type 2 diabetes patients.

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

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

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.

DOI： 10.1016/j.diabet.2017.08.002

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

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 3 years 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.

DOI： 10.1016/j.jpsychores.2017.05.020

Unstable bodyweight and incident type 2 diabetes mellitus: A 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 diabetes investigation 8 ( 4 ) 501 - 509 2017.7

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

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.

DOI： 10.1111/jdi.12623

Unstable bodyweight and incident type 2 diabetes mellitus: A 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 DIABETES INVESTIGATION 8 ( 4 ) 501 - 509 2017.7

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

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.

DOI： 10.1111/jdi.12623

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

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

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

DIABETES & METABOLISM 43 ( 3 ) 261 - 264 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：MASSON EDITEUR

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.

DOI： 10.1016/j.diabet.2016.09.001

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

Reversible splenial lesion syndrome with a hyperosmolar hyperglycemic state and neuroleptic malignant syndrome caused by olanzapine Reviewed

Kenta Kaino, Ryo Kumagai, Shoko Furukawa, Momoko Isono, Aiko Muramatsu, Masanao Fujii, Yumiko Muta, Tomoyuki Asada, Kazuya Fujihara, Hiroaki Yagyu

Journal of Diabetes Investigation 8 ( 3 ) 392 - 394 2017.5

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

A 27-year-old woman with panic disorder taking 20 mg olanzapine daily for 4 months was admitted to Mito Kyodo General Hospital, Mito, Ibaraki, Japan, because of disturbed consciousness with fever, hyperglycemia, hyperosmolarity and elevated creatine phosphokinase. She was diagnosed with a hyperosmolar hyperglycemic state and neuroleptic malignant syndrome. Brain magnetic resonance imaging showed transiently restricted diffusion in the splenium of the corpus callosum, with a high signal intensity on diffusion-weighted imaging. The neurological abnormalities disappeared along with improvement of metabolic derangements, and the follow-up magnetic resonance imaging carried out on the 26th day of admission showed complete resolution of the lesions in the splenium of the corpus callosum. These clinical and radiological features are highly suggestive of clinically mild encephalitis/encephalopathy with a reversible splenial lesion. The first case of mild encephalitis/encephalopathy with a reversible splenial lesion caused by olanzapine-induced hyperosmolar hyperglycemic state and neuroleptic malignant syndrome is reported.

DOI： 10.1111/jdi.12597

Reversible splenial lesion syndrome with a hyperosmolar hyperglycemic state and neuroleptic malignant syndrome caused by olanzapine Reviewed

Kenta Kaino, Ryo Kumagai, Shoko Furukawa, Momoko Isono, Aiko Muramatsu, Masanao Fujii, Yumiko Muta, Tomoyuki Asada, Kazuya Fujihara, Hiroaki Yagyu

JOURNAL OF DIABETES INVESTIGATION 8 ( 3 ) 392 - 394 2017.5

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

A 27-year-old woman with panic disorder taking 20 mg olanzapine daily for 4 months was admitted to Mito Kyodo General Hospital, Mito, Ibaraki, Japan, because of disturbed consciousness with fever, hyperglycemia, hyperosmolarity and elevated creatine phosphokinase. She was diagnosed with a hyperosmolar hyperglycemic state and neuroleptic malignant syndrome. Brain magnetic resonance imaging showed transiently restricted diffusion in the splenium of the corpus callosum, with a high signal intensity on diffusion-weighted imaging. The neurological abnormalities disappeared along with improvement of metabolic derangements, and the follow-up magnetic resonance imaging carried out on the 26th day of admission showed complete resolution of the lesions in the splenium of the corpus callosum. These clinical and radiological features are highly suggestive of clinically mild encephalitis/encephalopathy with a reversible splenial lesion. The first case of mild encephalitis/encephalopathy with a reversible splenial lesion caused by olanzap-ine- induced hyperosmolar hyperglycemic state and neuroleptic malignant syndrome is reported.

DOI： 10.1111/jdi.12597

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

Kazuya Fujihara, Risa Igarashi, Satoshi Matsunaga, Yasuhiro Matsubayashi, Takaho Yamada, Hiroki Yokoyama, Shiro Tanaka, Hitoshi Shimano, Hiroshi Maegawa, Katsuya Yamazaki, Koichi Kawai, Hirohito Sone

MEDICINE 96 ( 7 ) e6122 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

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.

DOI： 10.1097/MD.0000000000006122

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

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

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

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.

DOI： 10.1007/s13340-016-0260-4

Quantitative assessment of genetic testing for type 2 diabetes mellitus based on findings of genome-wide association studies Reviewed

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

Utility of nonblood-based risk assessment for predicting type 2 diabetes mellitus: A meta-analysis Reviewed

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

Language：English Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

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.

DOI： 10.1016/j.ypmed.2016.07.026

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

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.

DOI： 10.1097/MD.0000000000004564

Association of eating three meals irregularly with changes in BMI and weight among young Japanese men and women: A 2-year follow-up Reviewed

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

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

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 +/- 12 and 18.8 +/- 0.8 years, 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 2 years 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 1.11-230), 6% BMI gain (OR 1.72, CI 1.12-2.63), 4 kg weight gain (OR 2.01, CI 1.29-3.13), 6 kg weight gain (OR 1.86, CI 1.02-337), and incidence of obesity (BMI >= 25)(OR 2.96, CI 122-7.17). 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 129-6.03), 4 kg weight loss (OR 3.85, CI 1.62-9.12), 6 kg weight loss (OR 7.65, CI 2.06-28.46), and the incidence of underweight (OR 3.95, CI 132-11.89).
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 20 years 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. (C) 2016 Elsevier Inc All rights reserved.

DOI： 10.1016/j.physbeh.2016.04.045

Serum malondialdehyde-modified LDL levels are increased in type 2 diabetic patients with nephropathy

Suzuki, H, Furukawa, S, Fujihara, K, Kobayashi, K, Iwasaki, H, Yatoh, S, Sugano, Y, Sekiya, M, Yahagi, N, Yagyu, H, Shimano, H

DIABETOLOGIA 59 ( 1 ) S538 - S538 2016.8

血糖治療自己中断後に、中耳炎からBezold膿瘍に至った2型糖尿病の1例

北原多佳子, 古川祥子, 熊谷亮, 五十野桃子, 城川泰司郎, 小林裕幸, 青柳安典, 秋月浩光, 矢野晴美, 藤原和哉, 野牛宏晃

糖尿病 59 ( 8 ) 600 - 600 2016.8

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

Comparison of clinical characteristics in patients with type2 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 - 269 2016.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Aims/IntroductionWe compared clinical characteristics in patients with type2 diabetes for whom different antihyperglycemic agents were prescribed as monotherapy or combination therapy by diabetes specialists in Japan.
Materials and MethodsPrescription data for 2005, 2008 and 2011 from diabetes specialists' patient registries identified variables related to prescription of different antihyperglycemic agents.
ResultsA 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.
ConclusionsThese results could be expected to reflect in part the consensus of diabetes specialists, and might provide guidance regarding pharmacotherapy in the clinical setting.

DOI： 10.1111/jdi.12387

Meta-analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus Reviewed

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 - 186 2016.2

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

BackgroundOur 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.
MethodsElectronic 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 (RA(total)) 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 RA(total) (RA(total)) and the natural logarithms of ORs (log OR) for T2DM.
ResultsSixty-five eligible studies that included 68267 cases among 182603 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 RA(total) 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 RA(total) were almost identical.
ConclusionUsing 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 (c) 2015 John Wiley & Sons, Ltd.

DOI： 10.1002/dmrr.2680

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

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

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.

DOI： 10.1002/dmrr.2680

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

Language：English Publisher：ADIS INT LTD

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 (>= 21 vs. <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 (<6 vs. >= 6 years; P = 0.04) or a high baseline HbA(1c) [>= 7.5 % (58 mmol/mol) vs. <7.5 %; P = 0.01] while a smaller effect size was observed in studies with a particularly high mean baseline BMI value (>= 32 vs. <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.

DOI： 10.1007/s40279-015-0379-7

Pioglitazone-induced Pulmonary Injury in a Very Elderly Patient Reviewed

Kohta Katayama, Ryo Kumagai, Momoko Isono, Kazuya Fujihara, Hiroaki Yagyu, Gen Ohara, Katsunori Kagohashi, Hiroaki Satoh

INTERNAL MEDICINE 55 ( 13 ) 1779 - 1782 2016

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

An 85-year-old woman with diabetes mellitus was admitted to our hospital due to progressive dyspnea. Two months previously, pioglitazone had been newly prescribed for diabetes management. Bilateral ground-glass opacities and progressive respiratory deterioration suggested respiratory failure due to a drug-induced lung injury. With discontinuation of pioglitazone and the administration of a corticosteroid, an improvement in her respiratory condition was achieved, although sequelae remained in some areas of the lungs. Results of drug-induced lymphocyte stimulation tests were positive for pioglitazone. Resumption of other drugs did not reinduce the lung injury. Therefore, a diagnosis of pioglitazone-induced lung injury was made. Although pioglitazone-induced lung injury is very rare, clinicians should keep it in mind when pioglitazone is used.

DOI： 10.2169/internalmedicine.55.6330

Fulminant Type 1 Diabetes Mellitus Presenting 11 Days after Delivery in a Patient of Mixed Genetic Background Reviewed

Shoko Furukawa, Kazuya Fujihara, Ryo Kumagai, Momoko Isono, Hiroaki Yagyu

INTERNAL MEDICINE 55 ( 14 ) 1881 - 1885 2016

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

The patient was a 25-year-old woman whose paternal family was Japanese, maternal grandfather was Filipino, and maternal grandmother was Chinese. Eleven days after delivery, she presented with excessive thirst and disturbed consciousness due to diabetic ketoacidosis. She was diagnosed as having fulminant type 1 diabetes associated with pregnancy (PF). The antibody concentration against glutamic acid decarboxylase was 1.2 (<1.5) U/mL, and human leukocyte antigen (HLA) class II haplotypes were DRB1*04:10-DQB1*03: 02 and DRB1*15: 02-DQB1*05:01. The present case had unique HLA class II haplotypes that have not been previously reported in association with PF.

DOI： 10.2169/internalmedicine.55.6052

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

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

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.

DOI： 10.1111/jdi.12274

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

Language：English Publishing type：Research paper (scientific journal) Publisher：HINDAWI PUBLISHING CORPORATION

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 >= 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.

DOI： 10.1155/2015/507245

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

Language：English Publishing type：Research paper (scientific journal) Publisher：BMJ PUBLISHING GROUP

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 >= 0.5% or >= 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.

DOI： 10.1136/jech-2014-204054

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

Language：English Publishing type：Research paper (scientific journal) Publisher：CHURCHILL LIVINGSTONE

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.

DOI： 10.1016/j.clnu.2014.03.001

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

Diabet Med 31 ( 11 ) 1363 - 1367 2014.11

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

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 < 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.

DOI： 10.1016/j.diabres.2014.07.009

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

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.

DOI： 10.1016/j.diabres.2014.02.006

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ENDOCRINE SOC

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.

DOI： 10.1210/jc.2013-4427

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

Language：English Publishing type：Research paper (scientific journal) Publisher：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC

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 < 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.

DOI： 10.1016/j.amjcard.2013.12.005

Quantitative relationship between body weight gain in adulthood and incident type 2 diabetes: a meta-analysis. Reviewed International journal

Kodama S, Horikawa C, Fujihara K, Yoshizawa S, Yachi Y, Tanaka S, Ohara N, Matsunaga S, Yamada T, Hanyu O, Sone H

Obesity review 15 ( 3 ) 202 - 214 2014.3

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

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 (≥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.

DOI： 10.1111/obr.12129

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

Language：English Publishing type：Research paper (scientific journal) Publisher：HINDAWI PUBLISHING CORPORATION

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.

DOI： 10.1155/2014/250620

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

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN ATHEROSCLEROSIS SOC

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.

DOI： 10.5551/jat.22913

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

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN ATHEROSCLEROSIS SOC

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 >= 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.

DOI： 10.5551/jat.20487

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

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

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.

DOI： 10.1002/dmrr.2445

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC NUTRITION-ASN

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 >= 7.0 mmol/L, glycated hemoglobin >= 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 <1 drink (<23 g ethanol) per occasion over >= 6 times/wk. Binge drinking (>= 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 <1 drink per occasion.
Conclusions: Among current drinkers, a drinking pattern of <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.

DOI： 10.3945/ajcn.112.043364

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

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER DIABETES ASSOC

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

DOI： 10.2337/dc12-0783

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ENDOCRINE SOC

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, <= 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)

DOI： 10.1210/jc.2012-2119

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

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

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.

DOI： 10.5551/jat.14977

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

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

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.

DOI： 10.1155/2013/150371

Comparisons of the Strength of Associations With Future Type 2 Diabetes Risk Among Anthropometric Obesity Indicators, Including Waist-to-Height Ratio: A Meta-Analysis Reviewed

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

Language：English Publisher：OXFORD UNIV PRESS INC

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

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) Reviewed

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

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

Aims We aimed to characterize the association of insulin resistance, impaired insulin secretion and β-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 36mmol/mol (5.4%). A HbA1c concentration of 36-37mmol/mol (5.4-5.5%) (Q3) was significantly associated with a 15% lower homeostasis model assessment of β-cell function value and 31% lower insulinogenic index value compared with HbA1c≤32mmol/mol (≤5.1%) (Q1) (P&lt
0.01). Further, a HbA1c concentration of 38-40mmol/mol (5.6-5.8%) (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 41mmol/mol (5.9%). Individuals with HbA1c≥41mmol/mol (≥5.9%) (Q5) had a 69% lower disposition index than those with a HbA1c concentration of ≤32mmol/mol (≤5.1%) (Q1). Conclusions Elevated HbA1c levels ≥41mmol/mol (≥5.9%) were associated with substantial reductions in insulin secretion, insulin sensitivity and β-cell dysfunction in Japanese individuals not treated for diabetes. High normal HbA1c levels of 36-40mmol/mol (5.4-5.8%) were also associated with impaired insulin secretion without marked insulin resistance in Japanese individuals. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

DOI： 10.1111/j.1464-5491.2012.03667.x

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)

Heianza, Y, Arase, Y, Fujihara, K, Tsuji, H, Saito, K, Hsieh, S. D, Kodama, S, Shimano, H, Yamada, N, Hara, S, Sone, H

DIABETIC MEDICINE 29 ( 9 ) E279 - E285 2012.9

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) Reviewed

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

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER DIABETES ASSOC

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 >= 7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) >= 6.5%). Mean HbA(1c) values were >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.

DOI： 10.2337/dc11-1793

[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

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

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

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]
p&lt
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.

DOI： 10.1055/s-0032-1314873

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

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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