Faculty Profiles - SONE, Hirohito

Papers - SONE, Hirohito

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Efficacy and safety in sitagliptin therapy for diabetes complicated by non-alcoholic fatty liver disease Reviewed

Yasuji Arase, Yusuke Kawamura, Yuya Seko, Mariko Kobayashi, Fumitaka Suzuki, Yoshiyuki Suzuki, Norio Akuta, Masahiro Kobayashi, Hitomi Sezaki, Satoshi Saito, Tetsuya Hosaka, Kenji Ikeda, Hiromitsu Kumada, Yuki Ohmoto-Sekine, Shiun Dong Hsieh, Kazuhisa Amakawa, Kyoko Ogawa, Naoki Matsumoto, Akiko Iwao, Hiroshi Tsuji, Shigeko Hara, Yasumichi Mori, Minoru Okubo, Hirohito Sone, Tetsuro Kobayashi

HEPATOLOGY RESEARCH 43 ( 11 ) 1163 - 1168 2013.11

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

AimThe aim of this case-control study was to assess the efficacy and safety of dipeptidyl peptidase-4 inhibitor (sitagliptin) for type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD).
MethodsTwenty NAFLD patients with T2DM treated by sitagliptin were retrospectively enrolled as the sitagliptin group. These patients were given sitagliptin between January 2010 and July 2011. Another 20 NAFLD patients with T2DM treated only with diet and exercise for 48weeks were selected as the control group. Serum levels of fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before and 12, 24, 36 and 48weeks after the initiation of treatment.
ResultsIn the sitagliptin group, average HbA1c levels decreased approximately 0.7% at 48weeks after the initiation of sitagliptin. Next, average FPG levels decreased approximately 15mg/dL at 48weeks after the initiation of sitagliptin. The serum levels of HbA1c and FPG in the sitagliptin group decreased with statistical significance compared to those in the control group (P<0.05). All the patients could take sitagliptin of 50mg/day without reduction necessitated by sitagliptin-related side-effects. There were no significant changes of average AST and ALT levels during follow up of 48weeks in both sitagliptin and control groups.
ConclusionOur results indicate sitagliptin is effective and safe for the treatment of T2DM complicated with NAFLD.

DOI： 10.1111/hepr.12077

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

Authorship：Corresponding author 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

Diabetic Cardiomyopathy and Oxidative Stress Reviewed

Somasundaram Arumugam, Vengadeshprabhu Karuppagounder, Rajarajan A. Thandavarayan, Vigneshwaran Pitchaimani, Hirohito Sone, Kenichi Watanabe

Diabetes: Oxidative Stress and Dietary Antioxidants 25 - 32 2013.11

Language：English Publishing type：Part of collection (book) Publisher：Elsevier Inc.

Diabetes mellitus (DM) is the most common metabolic disorder associated with high mortality, which is mostly due to its cardiovascular complications. Diabetic cardiomyopathy (CM) is characterized by abnormal ventricular function in the absence of DM-associated risk factors such as obesity, hypertension, hypercholesterolemia, or coronary artery disease. Oxidative stress plays a pivotal role in the development of diabetic CM, in which chronic hyperglycemia plays a major role. As this develops, the endogenous antioxidant system becomes suppressed and so cannot counter-balance the increased oxidative stress. The metabolic abnormalities of DM cause mitochondrial superoxide overproduction, which further enhances the production of other reactive species, including nitric oxide, hydroxyl radical, hydrogen peroxide and peroxy nitrite, causing aggravation of the myocardial damage. In addition, free-radical-mediated platelet activation in the narrowed arteries culminates in acute myocardial infarction and stroke, indirectly affecting cardiac function. This chapter focuses on various aspects of the oxidative stress induced by reactive species during the pathogenesis of diabetic CM. © 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/B978-0-12-405885-9.00003-6

Association of living alone with the presence of undiagnosed diabetes in Japanese men: The role of modifiable risk factors for diabetes: Toranomon hospital health management center study 13 (TOPICS 13) Reviewed

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

Diabetic Medicine 30 ( 11 ) 1355 - 1359 2013.11

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

Aims: To investigate whether living alone was associated with the presence of undiagnosed diabetes and whether this association could be attenuated by modifiable lifestyle habits. Methods: This cross-sectional study included 6400 Japanese men without a history of diagnosed diabetes. Individuals with currently undiagnosed diabetes were identified through fasting glucose concentration ≥7.0 mmol/l or HbA1c concentration ≥ 48 mmol/mol (≥ 6.5%). Effect modification was examined using body mass index, hypertension, history of dyslipidaemia, drinking habits, smoking habits, physical activity, vegetable intake, emotional stress and depressed mood. Results: Men who lived alone (n = 1098) had a significantly elevated odds ratio for having undiagnosed diabetes in an age-adjusted model (odds ratio 1.45, 95% CI 1.07, 1.96
P = 0.018). After adjustment for lifestyle factors, the association was slightly attenuated (odds ratio 1.40, 95% CI 1.02, 1.91
P = 0.036). After further adjustment for all factors mentioned above, living alone was still marginally significantly associated with the presence of undiagnosed diabetes (odds ratio 1.38, 95% CI 1.003, 1.90
P = 0.048). A significant association of living alone with the presence of undetected diabetes was particularly observed among men who were overweight, currently smoked and were physically inactive, or had any one of those three factors. Conclusions: The association between undiagnosed diabetes and living alone can be partially influenced by modifiable lifestyle factors. Men who lived alone, especially those who did not engage in favourable lifestyle habits, were more likely to have undiagnosed diabetes. Such individuals have a higher probability of having undetected diabetic hyperglycaemia and would need to undergo glucose tests to identify the disease. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

DOI： 10.1111/dme.12255

[Cutting-edge of medicine; clinical epidemiology regarding clinical and pathophysiological features of Japanese patients with type 2 diabetes mellitus]. Reviewed

Sone H, Akanuma Y, Yamada N

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 102 ( 10 ) 2714 - 2722 2013.10

Association Between Remission of Macroalbuminuria and Preservation of Renal Function in Patients With Type 2 Diabetes With Overt Proteinuria Reviewed

Hiroki Yokoyama, Shin-ichi Araki, Jun Honjo, Shinichiro Okizaki, Daishiro Yamada, Ryushi Shudo, Hitoshi Shimizu, Hirohito Sone, Tatsumi Moriya, Masakazu Haneda

DIABETES CARE 36 ( 10 ) 3227 - 3233 2013.10

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

OBJECTIVEStudies on the rate of remission of macroalbuminuria in patients with type 2 diabetes mellitus (T2DM) and the effects of reduction in albuminuria on renal prognosis in a primary care setting are absolutely lacking.RESEARCH DESIGN AND METHODSA total of 211 T2DM patients with albuminuria 300 mg/g were enrolled in a prospective observational study (mean of 4.5 years). The incidence of patients with remission of macroalbuminuria at every 1-year study time point after starting intensified diabetes treatment and the factors associated with remission were evaluated. The association of reduction in albuminuria with renal events (doubling of serum creatinine and end-stage renal disease) was also investigated.RESULTSDuring the 5-year study period, remission to microalbuminuria occurred in 116 patients and the 5-year cumulative incidence was 58.3%. Notably, most cases (82.8%) obtained remission at the 1-year study time point. The remission rate increased with achieving therapeutic targets for blood pressure and blood glucose. Remission and reduction in albuminuria of 50% were associated with preservation of renal function. In particular, patients who obtained both remission and 50% reduction at the 1-year study time point exhibited a significantly reduced risk for renal events as compared with those with no remission and no reduction (adjusted hazard ratio 0.30 [95% CI 0.12-0.76]).CONCLUSIONSRemission of macroalbuminuria occurs frequently and is associated with the preservation of renal function in T2DM patients. The initial adequate diabetes treatment aimed at reducing albuminuria may lead to improved renal prognosis in the primary care setting.

DOI： 10.2337/dc13-0281

TFE3 Controls Lipid Metabolism in Adipose Tissue of Male Mice by Suppressing Lipolysis and Thermogenesis Reviewed

Yuri Fujimoto, Yoshimi Nakagawa, Aoi Satoh, Kanako Okuda, Akiko Shingyouchi, Ayano Naka, Takashi Matsuzaka, Hitoshi Iwasaki, Kazuto Kobayashi, Naoya Yahagi, Masako Shimada, Shigeru Yatoh, Hiroaki Suzuki, Satomi Yogosawa, Tetsuro Izumi, Hirohito Sone, Osamu Urayama, Nobuhiro Yamada, Hitoshi Shimano

ENDOCRINOLOGY 154 ( 10 ) 3577 - 3588 2013.10

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

Transcription factor E3 (TFE3) is a transcription factor that binds to E-box motifs and promotes energy metabolism-related genes. We previously reported that TFE3 directly binds to the insulin receptor substrate-2 promoter in the liver, resulting in increased insulin response. However, the role of TFE3 in other tissues remains unclear. In this study, we generated adipose-specific TFE3 transgenic (aP2-TFE3 Tg) mice. These mice had a higher weight of white adipose tissue (WAT) and brown adipose tissue than wild-type (WT) mice under fasting conditions. Lipase activity in the WAT in these mice was lower than that in the WT mice. Them RNA level of adipose triglyceride lipase (ATGL), the rate-limiting enzyme for adipocyte lipolysis, was significantly decreased in aP2-TFE3 Tg mice. The expression of Foxo1, which directly activates ATG Lexpression, was also suppressed in transgenic mice. Promoter analysis confirmed that TFE3 suppressed promoter activities of the ATGL gene. In contrast, G0S2 and Perilipin1, which attenuate ATGL activity, were higher in transgenic mice than in WT mice. These results indicated that the decrease in lipase activity in adipose tissues was due to a decrease in ATGL expression and suppression of ATGL activity. We also showed that thermogenesis was suppressed in aP2-TFE3 Tg mice. The decrease in lipolysis in WAT of aP2-TFE3 Tg mice inhibited the supply of fatty acids to brown adipose tissue, resulting in the inhibition of the expression of thermogenesis-related genes such as UCP1. Our data provide new evidence that TFE3 regulates lipid metabolism by controlling the gene expression related to lipolysis and thermogenesis in adipose tissue.

DOI： 10.1210/en.2013-1203

Diabetic Retinopathy and Microalbuminuria Can Predict Macroalbuminuria and Renal Function Decline in Japanese Type 2 Diabetic Patients: Japan Diabetes Complications Study Reviewed

Tatsumi Moriya, Shiro Tanaka, Ryo Kawasaki, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada, Hirohito Sone, Hidetoshi Yamashita, Shigehiro Katayama

DIABETES CARE 36 ( 9 ) 2803 - 2809 2013.9

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

OBJECTIVE To examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline.RESEARCH DESIGN AND METHODS We explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (<150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR-)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR-)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years.RESULTS Annual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94-6.50; P = 0.07), 10.40 (4.91-22.03; P < 0.01), and 11.55 (5.24-25.45; P < 0.01) in NA(DR+), MA(DR-), and MA(DR+), respectively, in comparison with NA(DR-). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (-1.92 mL/min/1.73 m(2)/year) than in the other groups.CONCLUSIONS In normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists.

DOI： 10.2337/dc12-2327

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

Direct effect of dasatinib on proliferation and cytotoxicity of natural killer cells in in vitro study Reviewed

Takayoshi Uchiyama, Naoya Sato, Miwako Narita, Akie Yamahira, Minami Iwabuchi, Tatsuo Furukawa, Hirohito Sone, Masuhiro Takahashi

HEMATOLOGICAL ONCOLOGY 31 ( 3 ) 156 - 163 2013.9

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

Lymphocytosis predominantly due to natural killer (NK) cells has been reported in nearly a half of chronic myelogenous leukemia (CML) patients who were being treated with dasatinib. Besides, dasatinib-treated patients with lymphocytosis have a better prognosis than patients without lymphocytosis. In order to elucidate the effects of dasatinib on the proliferation of lymphocyte subset, dasatinib was added to the culture of peripheral blood mononuclear cells with IL-2 (lymphokine-activated killer culture) or a low dose of IL-2 with zoledronate ( T-cell culture). In both culture conditions, NK cells were increased in both percentage and absolute number in the culture with dasatinib compared with control culture without dasatinib. The increase of NK cells was dose dependent of dasatinib in the range of 2-25nM. NK cell cytotoxicity of cultured cells with dasatinib was demonstrated to be superior to control cells without dasatinib in cytotoxicity assay using EGFP-transfected K562 cells as target cells. The present study suggested that lymphocytosis in dasatinib-treated CML patients is at least partly associated with a direct effect of dasatinib to stimulate the proliferation of NK cells. Favourable prognosis in patients with dasatinib-induced lymphocytosis might be associated with the effects of dasatinib to potentiate NK cytotoxicity in vivo. Copyright (c) 2012 John Wiley & Sons, Ltd.

DOI： 10.1002/hon.2034

Molecular understanding of curcumin in diabetic nephropathy Reviewed

Vivian Soetikno, Kenji Suzuki, Punniyakoti T. Veeraveedu, Somasundaram Arumugam, Arun P. Lakshmanan, Hirohito Sone, Kenichi Watanabe

Drug Discovery Today 18 ( 15-16 ) 756 - 763 2013.8

Language：English

Diabetic nephropathy is characterized by a plethora of signaling abnormalities. Recent trials have suggested that intensive glucose-lowering treatment leads to hypoglycemic events, which can be dangerous. Curcumin is the active ingredient of turmeric, which has been widely used in many countries for centuries to treat numerous diseases. The preventive and therapeutic properties of curcumin are associated with its antioxidant and anti-inflammatory properties. Here, we highlight the renoprotective role of curcumin in diabetes mellitus (DM) with an emphasis on the molecular basis of this effect. We also briefly discuss the numerous approaches that have been undertaken to improve the pharmacokinetics of curcumin. © 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.drudis.2013.04.009

Genetic Variants of the Fatty Acid Desaturase Gene Cluster Are Associated with Plasma LDL Cholesterol Levels in Japanese Males Reviewed

Yasuko Sone, Toshimi Kido, Tomomi Ainuki, Mariko Sonoda, Ikuyo Ichi, Satoru Kodama, Hirohito Sone, Kazuo Kondo, Yutaka Morita, Shigenobu Egawa, Kazuo Kawahara, Yuzuru Otsuka, Yoko Fujiwara

JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY 59 ( 4 ) 325 - 335 2013.8

Language：English Publishing type：Research paper (scientific journal) Publisher：CENTER ACADEMIC PUBL JAPAN

Fatty acid (FA) compositions in tissues are related to metabolic disorders, and consequently the appropriate management of underlying FA compositions in tissues is considered to be important. However, the relationship among the serum lipid profiles, the FA composition of the red blood cell (RBC) membranes and genetic variations in the fatty acid desaturase (FADS) genes in Japanese men is unclear. In this study, the subjects recruited were 137 Japanese men, 40 to 60 y old, who had a regular health checkup. Their serum lipid profile and the relative FA composition of the RBC membranes were measured. They were genotyped for the single nucleotide polymorphisms (SNPs) rs174553, rs174546, rs99780 and rs174583 in FADS gene. Multiple regression analysis was conducted to detect the relationship among hyperlipidemia, the FA composition of the RBC and the FADS genotypes. As a result, the homozygous genotype for the minor alleles in rs174553, rs174546, rs99780 were found to be associated with lower low-density lipoprotein cholesterol (LDL-C) levels and a lower LDL-C/total-cholesterol ratio. The homozygous genotype for the minor alleles reduced the risk of high LDL-C level (R-2=0.50, beta=-0.20, p=0.009), whereas, the arachidonic acid (AA) levels in the carriers of the homozygous genotype for the minor alleles tended to be lower compared with the carriers of the major alleles. However, no significant differences were observed in any FA level among the three genotypes for four SNPs. These results indicate that the appropriate management of serum LDL-C levels depending on genetic predisposition in FADS genotypes should be encouraged.

DOI： 10.3177/jnsv.59.325

Importance of high-density lipoprotein cholesterol control during pravastatin treatment in hypercholesterolemic Japanese with type 2 diabetes mellitus: A post hoc analysis of MEGA study Reviewed

Rimei Nishimura, Hirohito Sone, Tomoko Nakagami, Naoko Tajima

DIABETES RESEARCH AND CLINICAL PRACTICE 100 ( 2 ) E31 - E33 2013.5

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

To investigate the role of HDL-C in cardiovascular risk reduction, we evaluated using data from a diabetic population in a large clinical trial with pravastatin. A significant risk reduction in CVD was found only in diabetic patients who had both a reduction in LDL-C and an increase in HDL-C. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.diabres.2013.02.003

Predicting Macro- and Microvascular Complications in Type 2 Diabetes Reviewed

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

DIABETES CARE 36 ( 5 ) 1193 - 1199 2013.5

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

OBJECTIVE-To develop and validate a risk engine that calculates the risks of macro- and microvascular complications in type 2 diabetes.
RESEARCH DESIGN AND METHODS-We analyzed pooled data from two clinical trials on 1,748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7.2 years. End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy. We fit a multistate Cox regression model to derive an algorithm for prediction. The predictive accuracy of the calculated 5-year risks was cross-validated.
RESULTS-Sex, age, HbA(1c), years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro- and microvascular complications and were incorporated into the risk engine. The observed-to-predicted (O/P) ratios for each event were between 0.93 and 1.08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events. In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0.30 for CHD and 0.72 for stroke). C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0.725, 0.696, and 0.767) but moderate for stroke and progression of retinopathy (0.636 and 0.614). By combining macro- and microvascular risks, the classification of low- and high-risk patients was improved by a net reclassification improvement of 5.7% (P = 0.02).
CONCLUSIONS-The risk engine accurately predicts macro- and microvascular complications and would provide helpful information in risk classification and health economic simulations.

DOI： 10.2337/dc12-0958

Leisure-time physical activity is a significant predictor of stroke and total mortality in Japanese patients with type 2 diabetes: Analysis from the Japan Diabetes Complications Study (JDCS) Reviewed

H. Sone, S. Tanaka, S. Tanaka, S. Suzuki, H. Seino, O. Hanyu, A. Sato, T. Toyonaga, K. Okita, S. Ishibashi, S. Kodama, Y. Akanuma, N. Yamada

Diabetologia 56 ( 5 ) 1021 - 1030 2013.5

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

Aims/hypothesis: Our aim was to clarify the association between leisure-time physical activity (LTPA) and cardiovascular events and total mortality in a nationwide cohort of Japanese diabetic patients. Methods: Eligible patients (1,702) with type 2 diabetes (mean age, 58.5 years
47% women) from 59 institutes were followed for a median of 8.05 years. A comprehensive lifestyle survey including LTPA and occupation was performed using standardised questionnaires. Outcome was occurrence of coronary heart disease (CHD), stroke and total mortality. The adjusted HR and 95% CI were calculated by Cox regression analysis. Results: A significant reduction in HR in patients in the top (≥15.4 metabolic equivalents [MET] h/week) vs the bottom tertile (≤3.7 MET h/week) of LTPA, adjusted by age, sex and diabetes duration, was observed in stroke (HR 0.55, 95% CI 0.32, 0.94) and total mortality (HR 0.49, 95% CI 0.26, 0.91) but not in CHD (HR 0.77, 95% CI 0.48, 1.25). The HR for stroke became borderline significant or nonsignificant after adjustment for lifestyle or clinical variables including diet or serum lipids. The significantly reduced total mortality by LTPA was independent of these variables and seemed not to be, at least mainly, attributed to reduced cardiovascular disease. Conclusions/interpretation: In Japanese persons with type 2 diabetes, LTPA of 15.4 MET h/week or more was associated with a significantly lower risk of stroke partly through ameliorating combinations of cardiovascular risk factors. It was also associated with significantly reduced total mortality but independently of cardiovascular risk factors or events. These findings, implying differences from Western diabetic populations, should be considered in the clinical management of East Asians with diabetes. © 2013 Springer-Verlag Berlin Heidelberg.

DOI： 10.1007/s00125-012-2810-z

Two authors reply Reviewed

Satoru Kodama, Hirohito Sone

American Journal of Epidemiology 177 ( 8 ) 863 2013.4

[Effect of smoking on diabetes mellitus and dyslipidemia (effect of smoking on glucose and lipid metabolism)]. Reviewed

Saito K, Sone H

Nihon rinsho. Japanese journal of clinical medicine 71 ( 3 ) 443 - 448 2013.3

Development of a Screening Score for Undiagnosed Diabetes and Its Application in Estimating Absolute Risk of Future Type 2 Diabetes in Japan: Toranomon Hospital Health Management Center Study 10 (TOPICS 10) Reviewed

Yoriko Heianza, Yasuji Arase, Kazumi Saito, Shiun Dong Hsieh, Hiroshi Tsuji, Satoru Kodama, Shiro Tanaka, Yasuo Ohashi, Hitoshi Shimano, Nobuhiro Yamada, Shigeko Hara, Hirohito Sone

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 98 ( 3 ) 1051 - 1060 2013.3

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

Objective: The objective of the study was to develop a screening score for undiagnosed diabetes by eliciting information on noninvasive clinical markers and to assess its effectiveness for identifying the presence of diabetes and predicting future diabetes.
Design, Setting, and Participants: A screening score was cross-sectionally developed for 33 335 Japanese individuals aged 18-88 years without known diabetes who underwent a health examination. We validated its utility and compared it with existing screening tools in an independent population (n = 7477). After initial assessment of the instrument, 7332 nondiabetic individuals were followed up for a mean 4.0 years.
Results: Prevalence of undiagnosed diabetes (fasting plasma glucose >= 7.0 mmol/L or glycated hemoglobin >= 6.5%) was 2.9% (n = 965). Diabetes score included age, sex, family history of diabetes, current smoking habit, body mass index, and hypertension with an area under the receiver-operating characteristics curve of 0.771. Screening with 8 or more points yielded a sensitivity of 72.7% and a specificity of 68.1%. In the validation cohort, the area under the receiver-operating characteristics curve was 0.806. The developed score with 8 or more points had better positive predictive value (9.6%) and positive likelihood ratio (2.52) compared with existing tools (positive predictive value, from 6.9% to 9.4%; positive likelihood ratio, from 1.77 to 2.46) in which each tool's highest combination of sensitivity and specificity was observed. The 4-year cumulative risk of developing diabetes gradually escalated in association with higher screening scores at the initial examination.
Conclusions: Our algorism could serve as a self-assessment tool for undiagnosed diabetic patients needing timely medical care and as a prognostic tool for individuals without present diabetes who must be closely followed up to prevent future diabetes. (J Clin Endocrinol Metab 98: 1051-1060, 2013)

DOI： 10.1210/jc.2012-3092

Fruit Intake and Incident Diabetic Retinopathy with Type 2 Diabetes Reviewed

Shiro Tanaka, Yukio Yoshimura, Ryo Kawasaki, Chiemi Kamada, Sachiko Tanaka, Chika Horikawa, Yasuo Ohashi, Atsushi Araki, Hideki Ito, Yasuo Akanuma, Nobuhiro Yamada, Hidetoshi Yamashita, Hirohito Sone

EPIDEMIOLOGY 24 ( 2 ) 204 - 211 2013.3

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

Background: Antioxidants and dietary fiber are postulated to have preventive effects on diabetic retinopathy, but evidence is lacking. We investigated this association in a cohort with type 2 diabetes 40-70 years of age with hemoglobin (Hb)A(1C) 6.5%, originally part of the Japan Diabetes Complications Study.
Methods: After excluding people who did not respond to a dietary survey and patients with diabetic retinopathy or a major ocular disease at baseline, we analyzed 978 patients. Baseline dietary intake was assessed by a food frequency questionnaire based on food groups and 24-hour dietary records. Primary outcome was incident diabetic retinopathy determined using international severity scales.
Results: Mean fruit intake in quartiles ranged from 23 to 253 g/day, with increasing trends across quartiles of fruit intake for vitamin C, vitamin E, carotene, retinol equivalent, dietary fiber, potassium, and sodium. Mean energy intake ranged from 1644 to 1863 kcal/day, and fat intake was approximately 25%. HbA(1C), body mass index, triglycerides, and systolic blood pressure were well controlled. During the 8-year follow-up, the numbers of incident cases of diabetic retinopathy from the first through the fourth quartiles of fruit intake were 83, 74, 69, and 59. Multivariate-adjusted hazard ratios for the second, third, and fourth quartiles of fruit intake compared with the first quartile were 0.66 (95% confidence interval = 0.46-0.92), 0.59 (0.41-0.85), and 0.48 (0.32-0.71) (test for trend, P < 0.01). There was no substantial effect modification by age, sex, HbA(1C), diabetes duration, overweight, smoking, and hypertension. Risk for diabetic retinopathy declined with increased intake of fruits and vegetables, vitamin C, and carotene.
Conclusion: Increased fruit intake in ranges commonly consumed was associated with reduced incident diabetic retinopathy among patients adhering to a low-fat energy-restricted diet. (Epidemiology 2013;24: 204-211)

DOI： 10.1097/EDE.0b013e318281725e

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

Authorship：Corresponding author 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

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