Faculty Profiles - SONE, Hirohito

Papers - SONE, Hirohito

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Hepatic CREB3L3 Controls Whole-Body Energy Homeostasis and Improves Obesity and Diabetes Reviewed

Yoshimi Nakagawa, Aoi Satoh, Sachiko Yabe, Mika Furusawa, Naoko Tokushige, Hitomi Tezuka, Motoki Mikami, Wakiko Iwata, Akiko Shingyouchi, Takashi Matsuzaka, Shiori Kiwata, Yuri Fujimoto, Hidehisa Shimizu, Hirosuke Danno, Takashi Yamamoto, Kiyoaki Ishii, Tadayoshi Karasawa, Yoshinori Takeuchi, Hitoshi Iwasaki, Masako Shimada, Yasushi Kawakami, Osamu Urayama, Hirohito Sone, Kazuhiro Takekoshi, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Naoya Yahagi, Hiroaki Suzuki, Nobuhiro Yamada, Hitoshi Shimano

ENDOCRINOLOGY 155 ( 12 ) 4706 - 4719 2014.12

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

Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism. Here, we show that CREB3L3 confers a wide spectrum of metabolic responses to starvation in vivo. Adenoviral and transgenic overexpression of nuclear CREB3L3 induced systemic lipolysis, hepatic ketogenesis, and insulin sensitivity with increased energy expenditure, leading to marked reduction in body weight, plasma lipid levels, and glucose levels. CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor(PPAR) alpha promoter in an autoloop fashion and is crucial for the ligand transactivation of PPAR alpha by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1 alpha. CREB3L3 directly and indirectly controls fibroblast growth factor 21 expression and its plasma level, which contributes at least partially to the catabolic effects of CREB3L3 on systemic energy homeostasis in the entire body. Therefore, CREB3L3 is a therapeutic target for obesity and diabetes.

DOI： 10.1210/en.2014-1113

Log Reduction Levels of WT1 mRNA Expression in BM after Chemotherapies Are Predictive Markers of Good Prognosis in AML Patients Achieved CR after Induction Therapy Reviewed

Yasuhiko Shibasaki, Yoshinobu Seki, Tomoyuki Tanaka, Syukuko Miyakoshi, Kyoko Fuse, Takashi Kozakai, Hironori Kobayashi, Takashi Ushiki, Takashi Abe, Toshio Yano, Masato Moriyama, Takashi Kuroha, Noriatsu Isahai, Jun Takizawa, Miwako Narita, Satoru Koyama, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

BLOOD 124 ( 21 ) 2014.12

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

Authorship：Corresponding author 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

The circulating level of leptin and blood pressure in patients with multiple system atrophy Reviewed

Tetsutaro Ozawa, Jun Tokunaga, Musashi Arakawa, Atsushi Ishikawa, Ryoko Takeuchi, Akio Yokoseki, Hirohito Sone, Masatoyo Nishizawa

JOURNAL OF THE NEUROLOGICAL SCIENCES 347 ( 1-2 ) 349 - 351 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Patients with multiple system atrophy (MSA) frequently exhibit orthostatic hypotension (OH). Leptin, an adipose-derived hormone, contributes to the sympathetic control of blood pressure (BP), and loss of leptin may cause OH. We aimed to clarify the relationship between leptin and OH in MSA. Serum leptin levels were measured in 36 patients with MSA, 25 patients with other atypical parkinsonian disorders (APDs), including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome, and 26 control subjects. Blood samples were obtained after fasting for 12 h. In MSA patients, baseline BP was measured in the recumbent position after a 3-min rest, and orthostatic changes in BP were evaluated after 0-3 min of standing. Serum leptin levels did not differ significantly between MSA patients (5.9 +/- 0.8 ng/ml), other APD patients (5.2 +/- 0.8 ng/ml), and controls (6.1 +/- 1.3 ng/ml; P = 0.8). In MSA patients, serum leptin levels correlated significantly with body mass index ( P = 0.01), but not baseline BPs (systolic BP, P = 0.20; diastolic BP, P = 0.44) or orthostatic drop in BP (systolic BP, P = 0.13; diastolic BP, P = 0.58). Our observations indicated that the circulating level of leptin was preserved, and OH occurred independent of the leptin level in MSA patients. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2014.09.045

Stability and Changes in Metabolically Healthy Overweight or Obesity and Risk of Future Diabetes: Niigata Wellness Study Reviewed

Yoriko Heianza, Kiminori Kato, Satoru Kodama, Akiko Suzuki, Shiro Tanaka, Osamu Hanyu, Koji Sato, Hirohito Sone

OBESITY 22 ( 11 ) 2420 - 2425 2014.11

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

ObjectiveStability and changes in obesity and metabolic health status from a baseline period and longitudinally investigated their impact on predicting future diabetes were assessed.
MethodsStudied were 27,478 Japanese individuals without diabetes. Metabolically healthy (MH) was indicated by having 1 among impaired fasting glucose, hypertension, hypertriglyceridemia and low HDL cholesterol concentration. Metabolically abnormal (MA) was indicated by having 2 of those metabolic abnormalities. A cut-off value of BMI 25.0 defined overweight or obesity (O) or normal weight (NW). Hazard ratio (HR) for diabetes for a 6-year period was investigated after changes in phenotypes were assessed during the previous 2 years.
ResultsCompared with maintaining MH-NW, transitioning to MH-O from MH-NW resulted in a multivariate-adjusted HR of 1.96 (95% CI: 1.18, 3.25) for diabetes. With a stable MH-O the HR for diabetes was 2.59 (2.00, 3.34) while change from MH-O to MH-NW resulted in an HR of 1.30 (0.61, 2.76). Transitioning to MA-O from MH-O was associated with an HR of 7.09 (5.41, 9.30). With a stable MA-O the risk of diabetes was substantially elevated with an HR of 12.5 (10.5, 14.9).
ConclusionsExamining the transitory nature of apparently benign or unhealthy obese phenotypes was effective for differentiating high-risk individuals for future diabetes.

DOI： 10.1002/oby.20855

Role of sleep duration as a risk factor for Type 2 diabetes among adults of different ages in Japan: the Niigata Wellness Study Reviewed

Y. Heianza, K. Kato, K. Fujihara, S. Tanaka, S. Kodama, O. Hanyu, K. Sato, H. Sone

DIABETIC MEDICINE 31 ( 11 ) 1363 - 1367 2014.11

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

AimTo compare the role of short sleep duration as a risk factor for diabetes among adults of different ages.
MethodsThe study enrolled 38987 Japanese individuals without diabetes, and the 8-year risk of developing diabetes attributable to different sleep durations (<5.5h, 5.5 to <6.5h, 6.5 to <7.0h, 7.0-7.5h, >7.5-8.0h, or >8.0h) was assessed among individuals aged 45, 46-59 or 60years.
ResultsDuring the 8-year follow-up period, 2085 individuals developed diabetes. Overall, individuals with a short sleep duration of <5.5h or 5.5 to <6.5h had, respectively, a 1.53-fold (95% CI 1.19, 1.97) or 1.25-fold (95% CI 1.10, 1.42) increased risk of diabetes as compared with those who had 7.0-7.5h of sleep. A sleep duration of <5.5h or 5.5 to <6.5h was predictive of the development of diabetes among individuals aged 45years, but not among those aged 60years. With increasing age, the effect of short sleep duration on the risk of diabetes was attenuated.
ConclusionsShort sleep duration was predictive of diabetes among young or middle-aged Japanese adults but not among elderly individuals after age was considered. Managing habitual short sleep and the possible reasons for having such short sleep duration could be particularly important for young or middle-aged adults in the development of future diabetes.

DOI： 10.1111/dme.12555

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

Authorship：Corresponding author 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

Dietary Sodium Intake and Incidence of Diabetes Complications in Japanese Patients with Type 2 Diabetes: Analysis of the Japan Diabetes Complications Study (JDCS) Reviewed

Chika Horikawa, Yukio Yoshimura, Chiemi Kamada, Shiro Tanaka, Sachiko Tanaka, Osamu Hanyu, Atsushi Araki, Hideki Ito, Akira Tanaka, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 99 ( 10 ) 3635 - 3643 2014.10

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

Context: Many guidelines recommend that patients with type 2 diabetes should reduce their dietary sodium intake. However, the relationship between dietary sodium intake and incidence of diabetic complications in patients with type 2 diabetes has not been explored.
Objective: Our objective was to investigate the relationship between dietary sodium intake and incidence of diabetes complications.
Participants: The study was of a nationwide cohort of patients with type 2 diabetes aged 40 to 70 years with hemoglobin A1c (HbA1c) >= 6.5%.
Main Outcome Measures: After excluding nonresponders to a dietary survey, 1588 patients were analyzed. Baseline dietary intake was assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to cardiovascular disease (CVD), overt nephropathy, diabetic retinopathy, and all-cause mortality.
Results: Mean daily dietary sodium intake in quartiles ranged from 2.8 to 5.9 g. After adjustment for confounders, hazard ratios for CVD in patients in the second, third, and fourth quartiles of sodium intake compared with the first quartile were 1.70 (95% confidence interval, 0.98-2.94), 1.47 (0.82-2.62), and 2.07 (1.21-3.90), respectively (trend P < .01). In addition, among patients who had HbA1c >= 9.0%, the hazard ratio for CVD in patients in the top vs bottom quartile of sodium in take was dramatically elevated compared with patients with HbA1c <9.0% (1.16 [0.56-2.39] and 9.91 [2.66-36.87], interaction P < .01). Overt nephropathy, diabetic retinopathy, and all-cause mortality were not significantly associated with sodium intake.
Conclusions: Findings suggested that high dietary sodium intake is associated with elevated incidence of CVD in patients with type 2 diabetes and that there is a synergistic effect between HbA1c values and dietary sodium intake for the development of CVD.

DOI： 10.1210/jc.2013-4315

Importance of high-density lipoprotein cholesterol levels in elderly diabetic individuals with type IIb dyslipidemia: A 2-year survey of cardiovascular events Reviewed

Koichiro Ina, Toshio Hayashi, Atsushi Araki, Seinosuke Kawashima, Hirohito Sone, Hiroshi Watanabe, Takashi Ohrui, Koutaro Yokote, Minoru Takemoto, Kiyoshi Kubota, Mitsuhiko Noda, Hiroshi Noto, Qun-Fang Ding, Jie Zhang, Ze-Yun Yu, Byung-Koo Yoon, Hideki Nomura, Masafumi Kuzuya

GERIATRICS & GERONTOLOGY INTERNATIONAL 14 ( 4 ) 806 - 810 2014.10

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

AimThe risk factors for ischemic heart disease (IHD) or cerebrovascular accident (CVA) in elderly diabetic individuals with type IIb dyslipidemia are not fully known. Therefore, we investigated the relationship between lipid levels and IHD and CVA in diabetic individuals with type IIb dyslipidemia.
MethodThe Japan Cholesterol and Diabetes Mellitus Study is a prospective cohort study of 4014 type 2 diabetic patients (1936 women; age 67.49.5 years). The primary end-points were the onset of IHD or CVA. Lipid and glucose levels, and other factors were investigated in relation to the occurrence of IHD or CVA. A total of 462 participants were included in the group of patients with type IIb dyslipidemia.
ResultsThe 462 diabetic participants with type IIb dyslipidemia were divided into those who were aged <65 years, 65-74 years and >75 years (n=168, 190 and 104, respectively). High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol/HDL-C were significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <65 years, and HDL-C and diastolic blood pressure was significantly associated with cardiovascular events in patients aged 65-74 years. Non-HDL-C was not significantly associated with the risk of cardiovascular events. Multiple regression analysis showed that lower HDL-C was significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <65 years and 65-74 years.
ConclusionsLower HDL-C was an important risk factor for cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <75 years. Geriatr Gerontol Int 2014; 14: 806-810.

DOI： 10.1111/ggi.12168

A possible link between BDNF and mTOR in control of food intake Reviewed

Nobuyuki Takei, Kazuo Furukawa, Osamu Hanyu, Hirohito Sone, Hiroyuki Nawa

FRONTIERS IN PSYCHOLOGY 5 1093 2014.9

Language：English Publisher：FRONTIERS RESEARCH FOUNDATION

Food intake is intricately regulated by glucose, amino acids, hormones, neuropeptides, and trophic factors through a neural circuit in the hypothalamus. Brain-derived neurotrophic factor (BDNF), the most prominent neurotrophic factor in the brain, regulates differentiation, maturation, and synaptic plasticity throughout life. Among its many roles, BDNF exerts an anorexigenic function in the brain. However, the intracellular signaling induced by BDNF to control food intake is not fully understood. One candidate for the molecule involved in transducing the anorexigenic activity of BDNF is the mammalian target of rapamycin (mTOR). mTOR senses extracellular amino acids, glucose, growth factors, and neurotransmitters, and regulates anabolic reactions response to these signals. Activated mTOR increases protein and lipid synthesis and inhibits protein degradation. In the hypothalamus, mTOR activation is thought to reduce food intake. Here we summarize recent findings regarding BDNF- and mTOR-mediated feeding control, and propose a link between these molecules in eating behavior.

DOI： 10.3389/fpsyg.2014.01093

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

Authorship：Corresponding author 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

Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice Reviewed

Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Mayumi Nomoto, Hirohito Sone, Kenji Suzuki, Kenichi Watanabe

NEUROSCIENCE LETTERS 579 134 - 139 2014.9

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

BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2014.07.009

Activation of the Leukemia Plasmacytoid Dendritic Cell Line PMDC05 by Toho-1, a Novel IDO Inhibitor Reviewed

Akie Yamahira, Miwako Narita, Minami Iwabuchi, Takayoshi Uchiyama, Shunpei Iwaya, Rie Ohiwa, Yoshinori Nishizawa, Takafumi Suzuki, Yusaku Yokoyama, Shigeo Hashimoto, Jun Takizawa, Hirohito Sone, Masuhiro Takahashi

ANTICANCER RESEARCH 34 ( 8 ) 4021 - 4028 2014.8

Language：English Publishing type：Research paper (scientific journal) Publisher：INT INST ANTICANCER RESEARCH

Background/Aim: Indoleamine-2,3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan metabolism and plays an immunosuppressive role. Antigen-presenting cells, when activated, increase the expression of IDO, which results in the suppression of subsequent immune reaction. A novel IDO inhibitor, Toho-1, was explored for its applicability to immunotherapy. Materials and Methods: We investigated the effects of Toho-1 on antigen presentation and antigen-specific cytotoxic T-lymphocyte-inducing ability of leukemia plasmacytoid dendritic cell line PMDC05, which was established in our laboratory. Results: While antigen presentation-associated molecules in PMDC05 cells were increased by stimulation with lipopolysaccharide and interferon-gamma, IDO mRNA and protein expression were also enhanced. Such treatment of PMDC05 cells in combination with Toho-1 enhanced the antigen-presenting and CTL-inducing ability of PMDC05 cells. Conclusion: These findings suggest the ability of Toho-1 to potentiate antigen-presenting cells and its applicability in immunotherapy of cancer.

Role of Body Mass Index History in Predicting Risk of the Development of Hypertension in Japanese Individuals Toranomon Hospital Health Management Center Study 18 (TOPICS 18) Reviewed

Yoriko Heianza, Satoru Kodama, Yasuji Arase, Shiun Dong Hsieh, Sakiko Yoshizawa, Hiroshi Tsuji, Kazumi Saito, Shiro Tanaka, Shigeko Hara, Hirohito Sone

HYPERTENSION 64 ( 2 ) 247 - + 2014.8

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

It has not been clarified whether overall adiposity in early adulthood or at the lifetime maximum weight would confer a residual risk of hypertension after considering the risk associated with current adiposity. Studied were 6121 Japanese without hypertension. The risk of developing hypertension 4 years after a baseline examination was investigated using the body mass index in the early 20s, at the lifetime maximum, or at the baseline examination. An elevated body mass index at baseline or at the maximum rather than in the early 20s was strongly associated with future hypertension. Compared with individuals with low body mass index both at baseline and in the early 20s, those with an elevated body mass index at the baseline alone had an odds ratio of 1.89 (95% confidence interval, 1.58-2.27) and those with an elevated body mass index both at baseline and in the early 20s had the highest odds ratio of 2.26 (1.76-2.89). Individuals with an elevated body mass index both at baseline and at the maximum had a 2.26-fold (1.87-2.72) increased risk of hypertension compared with those without the 2 factors. An elevated body mass index at the baseline examination weakened the favorable influence of a low body mass index in early adulthood on developing hypertension. Adding information on body mass index in early adulthood or at the maximum in addition to that at the baseline examination contributed to differentiating the risk of hypertension among Japanese, particularly among those with an elevated overall adiposity at present.

DOI： 10.1161/HYPERTENSIONAHA.113.02918

Cohort Profile: The Japan Diabetes Complications Study: a long-term follow-up of a randomised lifestyle intervention study of type 2 diabetes Reviewed

Shiro Tanaka, Sachiko Tanaka, Satoshi Iimuro, Hidetoshi Yamashita, Shigehiro Katayama, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 43 ( 4 ) 1054 - 1062 2014.8

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

The Japan Diabetes Complications Study, a randomised lifestyle intervention study of type 2 diabetes conducted at 59 institutes throughout Japan that enrolled 2033 eligible patients from January 1995 to March 1996, was directed at: (i) determining the incidence and progression rates of complications of diabetes; (ii) exploring clinical risk factors for complications of diabetes; and (iii) determining the association between lifestyle factors, including diet and physical activity, and complications of diabetes, in addition to comparing, in a randomised manner, the effects on type 2 diabetes of an extensive lifestyle intervention and conventional treatment. The protocol for the study originally specified four study populations according to primary outcomes, consisting of: (1) a macroangiopathy group (N = 1771); (ii) a nephropathy group (N = 1607); (iii) a retinopathy-incident group (N = 1221); and (iv) a retinopathy-progression group (N = 410). The primary outcomes were: (i) development of retinopathy; (ii) progression of retinopathy; (iii) development of overt nephropathy; and (iv) occurrence of macroangiopathic events including proven coronary heart disease and stroke. The study was originally planned to follow patients for 8 years, and an extended follow-up is ongoing. Information about primary outcomes, laboratory tests, and other clinical variables for each patient was collected at a central data centre through an annual report from each investigator. Additionally, extensive lifestyle surveys were conducted at baseline and 5 years after the beginning of the study intervention in both the intervention and conventional treatment groups. A description of the occurrence of complications of diabetes and of all-cause mortality, provided in this paper, demonstrated a clear gender-based difference in cardiovascular disease and all-cause mortality. The data set of the study is not freely available, but collaborative ideas are welcome. Potential collaborators should discuss ideas informally with the principal investigator by e-mail.

DOI： 10.1093/ije/dyt057

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

Authorship：Corresponding author 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

[Successful treatment with bortezomib in a patient with systemic primary AL amyloidosis manifesting severe gastrointestinal bleeding]. Reviewed

Ida T, Hayashi K, Ida T, Hirano S, Nakamura F, Sone H, Fujiwara M

[Rinsho ketsueki] The Japanese journal of clinical hematology 55 ( 7 ) 808 - 814 2014.7

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

We present a systemic primary AL amyloidosis patient with severe gastrointestinal bleeding for whom treatment with bortezomib and dexamethasone was very effective. An 83-year-old woman was admitted to our hospital suffering from multiple gastric ulcers with bleeding. She had monoclonal protein (IgG, λ) in her serum. Systemic primary AL amyloidosis was diagnosed. She was also suspected of having amyloid deposition in cardiac muscle, as well as her bladder and intestinal mucosa. However, we were unable to carry out other invasive examinations due to her bleeding tendency. She was treated with bortezomib and dexamethasone. Her bleeding tendency gradually diminished. After one year, the bleeding tendency had completely resolved. However, she still had amyloid deposition in her gastric mucosa and skin.

DOI： 10.11406/rinketsu.55.808

Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion Reviewed

Nie Tang, Takashi Matsuzaka, Marii Suzuki, Yuta Nakano, Hui Zao, Tomotaka Yokoo, Noriko Suzuki-Kemuriyama, Motoko Kuba, Yuka Okajima, Yoshinori Takeuchi, Kazuto Kobayashi, Hitoshi Iwasaki, Shigeru Yatoh, Akimitsu Takahashi, Hiroaki Suzuki, Hirohito Sone, Masako Shimada, Yoshimi Nakagawa, Naoya Yahagi, Nobuhiro Yamada, Hitoshi Shimano

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 450 ( 1 ) 318 - 323 2014.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids and is related to the development of obesity-induced insulin resistance via the modification of the fatty acid composition. In this study, we investigated the role of systemic Elovl6 in the pancreatic islet and beta-cell function. Elovl6 is expressed in both islets and beta-cell lines. In mice fed with chow, islets of the Elovl6(-/-) mice displayed normal architecture and beta-cell mass compared with those of the wild-type mice. However, when fed a high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin resistance observed in normal mice was attenuated and glucose-stimulated insulin secretion (GSIS) increased in the islets of Elovl6(-/-) mice compared with those of the wild-type mice. Enhanced GSIS in the HFHS Elovl6-/- islets was associated with an increased ATP/ADP ratio and the suppression of ATF-3 expression. Our findings suggest that Elovl6 could be involved in insulin secretory capacity per beta-cell and diabetes. (C) 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2014.05.113

Food groups and weight gain in Japanese men.

Ibe Y, Takahashi Y, Sone H

2014.6

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