Faculty Profiles - SONE, Hirohito

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

Sakiko Yoshizawa, Satoru Kodama, Kazuya Fujihara, Hajime Ishiguro, Masahiro Ishizawa, Yasuhiro Matsubayashi, Satoshi Matsunaga, Takaho Yamada, Hitoshi Shimano, Kiminori Kato, Osamu Hanyu, Hirohito Sone

PREVENTIVE MEDICINE 91 180 - 187 2016.10

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

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

Yoko Ibe, Happei Miyakawa, Yasuko Fuse-Nagase, Ayumi Sugawara Hirose, Reiko Hirasawa, Yoko Yachi, Kazuya Fujihara, Kazuto Kobayashi, Hitoshi Shimano, Hirohito Sone

Physiology & behavior 163 81 - 87 2016.9

Authorship：Corresponding author 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±1.2 and 18.8±0.8years, respectively, who underwent health checkups at a university in Japan in 2001 as the baseline and subsequently in 2003. Weight and height were measured at baseline and 2years later. Whether an individual ate three meals regularly was determined by a self-report questionnaire in 2001. RESULTS: During the 2-year follow-up, the BMI gain was 0.347 for men and 0.067 for women. In the logistic regression analysis, for men, eating three meals irregularly was significantly associated with a 4% BMI gain (OR 1.60, CI 1.11-2.30), 6% BMI gain (OR 1.72, CI 1.12-2.63), 4kg weight gain (OR 2.01, CI 1.29-3.13), 6kg weight gain (OR 1.86, CI 1.02-3.37), and incidence of obesity (BMI ≧ 25)(OR 2.96, CI 1.22-7.17). For women, eating three meals irregularly was significantly associated with a 4% BMI loss (OR 1.99, CI 1.01-3.94), 6% BMI loss (OR 2.79, CI 1.29-6.03), 4kg weight loss (OR 3.85, CI 1.62-9.12), 6kg weight loss (OR 7.65, CI 2.06-28.46), and the incidence of underweight (OR 3.95, CI 1.32-11.89). CONCLUSIONS: The current results suggested that eating three meals irregularly was associated with subsequent BMI and weight gains for men and subsequent BMI and weight losses for women; both groups were around 20years of age. Self-reported eating behavior in this study might be used to screen and evaluate young Japanese men and women at high risk for changes in BMI and weight in a practical clinical setting.

DOI： 10.1016/j.physbeh.2016.04.045

Impact of individual components and their combinations within a family history of hypertension on the incidence of hypertension: Toranomon hospital health management center study 22. Reviewed International journal

Risa Igarashi, Kazuya Fujihara, Yoriko Heianza, Masahiro Ishizawa, Satoru Kodama, Kazumi Saito, Shigeko Hara, Osamu Hanyu, Ritsuko Honda, Hiroshi Tsuji, Yasuji Arase, Hirohito Sone

Medicine 95 ( 38 ) e4564 2016.9

Authorship：Corresponding author 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

輸血依存患者における肝臓内鉄含有量を評価するための二重エネルギーCTの重要性(Significance of dual-energy CT to evaluate liver iron content in transfusion-dependent patients)

Kobayashi Hironori, Yoshimura Norihiko, Suwabe Tatsuya, Katagiri Takayuki, Miyakoshi Shukuko, Ushiki Takashi, Fuse Kyoko, Shibasaki Yasuhiko, Moriyama Masato, Takizawa Jun, Narita Miwako, Sone Hirohito, Masuko Masayoshi

臨床血液 57 ( 9 ) 1524 - 1524 2016.9

Maximum BMI and microvascular complications in a cohort of Japanese patients with type 2 diabetes: the Japan Diabetes Complications Study Reviewed

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

JOURNAL OF DIABETES AND ITS COMPLICATIONS 30 ( 5 ) 790 - 797 2016.7

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Aims: The aim of this study was to examine the associations between possible indices of obesity based on information on weight history and the incidence of microvascular complications.
Methods: A cohort of individuals with type 2 diabetes from 59 institutes in Japan was followed for 8 years. Patients were classified into three categories according to weight at entrance and past maximum weight: normal (BMI at baseline <25 kg/m(2) and maximum BMI <25 kg/m(2)), past obesity (BMI at baseline <25 kg/m2 and maximum BMI >= 25 kg/m(2)), and current obesity (BMI at baseline 25 kg/m(2)) groups. The outcomes were diabetic retinopathy and overt nephropathy.
Results: BMI at maximum and baseline of the 1809 patients was 26.5 +/- 3.5 and 23.1 +/- 3.0 kg/m(2) (p < 0.01), respectively (23.0 +/- 1.6 and 20.6 +/- 1.9 kg/m(2) for normal, 27.4 +/- 2.0 and 22.8 +/- 1.4 kg/m(2) for past obesity, and 30.1 +/- 2.9 and 27.0 +/- 1.8 kg/m(2) for current obesity). The hazard ratios of past and current obesity compared to normal were 1.92 (95% CI, 1.08-3.41; p = 0.03) and 221 (1.16-4.22; p = 0.02), respectively, for overt nephropathy and 138 (1.05-1.83; p = 0.02) and 1.64 (1.18-2.28; p < 0.01), respectively, for diabetic retinopathy after adjustment for confounders.
Conclusions: Past obesity as well as current obesity were associated with increased risks of microvascular complications. Further identification of high-risk populations may be possible by classifying normal weight patients by past obesity. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jdiacomp.2016.02.020

Cluster-randomized trial to improve the quality of diabetes management: The study for the efficacy assessment of the standard diabetes manual (SEAS-DM). Reviewed

Hiroshi Noto, Yukio Tanizawa, Toru Aizawa, Hirohito Sone, Narihito Yoshioka, Yasuo Terauchi, Nobuya Inagaki, Mitsuhiko Noda

Journal of diabetes investigation 7 ( 4 ) 539 - 43 2016.7

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

AIMS/INTRODUCTION: 'The Standard Diabetes Manual' has been developed by clinical researchers from multiple major institutions in Japan, such as the National Center for Global Health and Medicine, as a comprehensive disease management program, including collaboration between primary care physicians (PCPs) and specialist services. The present study evaluated the efficacy of the manual as a quality improvement strategy in diabetes care by PCPs. MATERIALS AND METHODS: A total of 42 PCPs in eight domestic districts of the Japan Medical Association were allocated to either the intervention group or the control group in a cluster-randomized design. The PCPs in both groups were provided with a copy of the Diabetes Treatment Guide published by the Japan Diabetes Society, and the PCPs in the intervention group additionally received a copy of the manual and a 30-min relevant seminar at the inception of the intervention. The primary end-point was the adherence to the following performances as quality indicators: evaluation of retinopathy, and urinary albumin excretion measurements and serum creatinine measurements, as recommended by the Japan Medical Association. RESULTS: A total of 416 patients were enrolled by 36 PCPs. During the 1-year follow-up period, the proportion of PCPs who adhered to recommendation-concordant measurements of urinary albumin excretion was significantly higher in the intervention group than in the control group (adherence: 17.9% vs 5.3%, P = 0.016). The other parameters were not statistically different between the two groups. CONCLUSIONS: Implementation of 'The Standard Diabetes Manual' potentially leads to an improved quality of diabetes management by PCPs.

DOI： 10.1111/jdi.12455

Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system. Reviewed International journal

Yoshimi Nakagawa, Fusaka Oikawa, Seiya Mizuno, Hiroshi Ohno, Yuka Yagishita, Aoi Satoh, Yoshinori Osaki, Kenta Takei, Takuya Kikuchi, Song-Iee Han, Takashi Matsuzaka, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Naoya Yahagi, Masaaki Isaka, Hiroaki Suzuki, Hirohito Sone, Satoru Takahashi, Nobuhiro Yamada, Hitoshi Shimano

Scientific reports 6 27857 - 27857 2016.6

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

cAMP responsive element binding protein 3-like 3 (CREB3L3), a transcription factor expressed in the liver and small intestine, governs fasting-response energy homeostasis. Tissue-specific CREB3L3 knockout mice have not been generated till date. To our knowledge, this is the first study using the one-step CRISPR/Cas9 system to generate CREB3L3 floxed mice and subsequently obtain liver- and small intestine-specific Creb3l3 knockout (LKO and IKO, respectively) mice. While LKO mice as well as global KO mice developed hypertriglyceridemia, LKO mice exhibited hypercholesterolemia in contrast to hypocholesterolemia in global KO mice. LKO mice demonstrated up-regulation of hepatic Srebf2 and its corresponding target genes. No phenotypic differences were observed between IKO and floxed mice. Severe liver injury was observed in LKO mice fed a methionine-choline deficient diet, a model for non-alcoholic steatohepatitis. These results provide new evidence regarding the hepatic CREB3L3 role in plasma triglyceride metabolism and hepatic and intestinal CREB3L3 contributions to cholesterol metabolism.

DOI： 10.1038/srep27857

MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B-cell lymphoma Reviewed

Keisuke Kawamoto, Hiroaki Miyoshi, Noriaki Yoshida, Naoya Nakamura, Koichi Ohshima, Hirohito Sone, Jun Takizawa

CANCER SCIENCE 107 ( 6 ) 853 - 861 2016.6

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

Genomic alterations and protein expression levels have been established as prognostic factors for survival in patients with diffuse large B-cell lymphoma (DLBCL). In particular, double-hit DLBCL (DHL), which exhibits translocations in MYC and BCL2 and/or BCL6, is known to be associated with a poor prognosis. However, the clinical significance of gene alterations and protein expression levels for MYC, B-cell lymphoma (BCL)2, and BCL6 are unclear. In this study, we analyzed 61 adult patients diagnosed with DLBCL without DHL, who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, or similar regimens. There were no differences in the distribution of MYC expression rates among the different MYC gene statuses. In log-rank tests, MYC translocation was a prognostic factor for overall survival (OS; P = 0.011), whereas BCL2 and BCL6 translocation were not prognostic indicators (P = 0.999 and P = 0.925, respectively). Although the expression levels of MYC and BCL6 were not significantly associated with OS, the expression of BCL2 was a prognostic factor for OS (P = 0.027). Furthermore, copy number gains in the MYC, BCL2, and BCL6 genes did not affect OS. MYC translocation (hazard ratio, 4.769; range, 1.518-14.98; P = 0.007) and BCL2 protein expression (hazard ratio, 3.072; range, 1.002-9.413; P = 0.049) were independent prognostic factors for survival in multivariate analyses. In conclusion, MYC translocation and BCL2 expression may need to be investigated at the initial diagnosis to predict prognosis in patients with DLBCL.

DOI： 10.1111/cas.12942

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

The Dinakara equation for adjusting DLCO for hemoglobin in the HCT-CI is superior to the Cotes equation for predicting high-risk patients in allogeneic hematopoietic stem cell transplantation Reviewed

Yasuhiko Shibasaki, Takayuki Katagiri, Hironori Kobayashi, Takashi Ushiki, Miwako Narita, Hirohito Sone, Tatsuo Furukawa, Masayoshi Masuko

AMERICAN JOURNAL OF HEMATOLOGY 91 ( 5 ) E296 - E297 2016.5

[Features of Japanese diabetic macroangiopathy]. Reviewed

Masanori Kaneko, Kazuo Furukawa, Hirohito Sone

Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 2 22 - 6 2016.4

[The 43rd Scientific Meeting: Perspectives of Internal Medicine; Genetic predisposition and related life-style underlying metabolic disorders; 2. Genetic and Environmental Susceptibility; 3) Epidemiology and large-scale clinical data analysis in metabolic diseases]. Reviewed

Hirohito Sone

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 105 ( 3 ) 383 - 90 2016.3

Comparison of clinical characteristics in patients with type 2 diabetes among whom different antihyperglycemic agents were prescribed as monotherapy or combination therapy by diabetes specialists. Reviewed

Kazuya Fujihara, Osamu Hanyu, Yoriko Heianza, Akiko Suzuki, Takaho Yamada, Hiroki Yokoyama, Shiro Tanaka, Hiroaki Yagyu, Hitoshi Shimano, Atsunori Kashiwagi, Katuya Yamazaki, Koichi Kawai, Hirohito Sone

Journal of diabetes investigation 7 ( 2 ) 260 - 9 2016.3

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

AIMS/INTRODUCTION: We compared clinical characteristics in patients with type 2 diabetes for whom different antihyperglycemic agents were prescribed as monotherapy or combination therapy by diabetes specialists in Japan. MATERIALS AND METHODS: Prescription data for 2005, 2008 and 2011 from diabetes specialists' patient registries identified variables related to prescription of different antihyperglycemic agents. RESULTS: A total of 33,251 prescriptions in 2005, 25,119 in 2008 and 20,631 in 2011 were analyzed. Prescribing insulin was related to younger age, long duration of diabetes and glycated hemoglobin (HbA1c) ≥8.0%, but was negatively associated with obesity. Prescribing sulfonylureas was related to older age and long duration of diabetes, but not to obesity. Use of biguanides was related to younger age, short duration of diabetes and obesity, but was negatively associated with HbA1c ≥8.0%. A short duration of diabetes and HbA1c ≥8.0% were associated with use of a DPP-4 inhibitor, but not with obesity. Prescribing GLP-1 receptor agonists was related to younger age, obesity and HbA1c ≥8.0%. Odds ratios for each antihyperglycemic combination therapy were determined based on the characteristics of each included antihyperglycemic agent. CONCLUSIONS: These results could be expected to reflect in part the consensus of diabetes specialists, and might provide guidance regarding pharmacotherapy in the clinical setting.

DOI： 10.1111/jdi.12387

Assessment of kidney dysfunction with cystatin C- and creatinine-based estimated glomerular filtration rate and predicting type 2 diabetes: Toranomon Hospital Health Management Center Study 21 Reviewed

Yoriko Heianza, Shigeko Hara, Kazumi Saito, Hiroshi Tsuji, Shiro Tanaka, Satoru Kodama, Tetsuro Kobayashi, Yasuji Arase, Hirohito Sone

DIABETES RESEARCH AND CLINICAL PRACTICE 113 60 - 68 2016.3

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

Objective: Whether early stages of kidney dysfunction assessed by the estimated glomerular filtration rate from cystatin C measurements (eGFRCysC) rather than from creatinine measurements (eGFRCr) would more precisely reflect the risk of developing type 2 diabetes (T2D) has not been clarified. We compared the risk of developing T2D associated with renal dysfunction indicated by eGFRCysC or eGFRCr measurements.
Methods: Studied were 2131 Japanese individuals without diabetes. Hazard ratios (HRs) for the development of T2D over 3-5 y were calculated across categories of eGFRCysC and eGFRCr, respectively.
Results: Reduced levels of eGFRCysC were associated with a step-wise increase in the cumulative incidence rate of T2D (p = 0.007). In comparison with the eGFRCysC >85th percentile group (>= 117.4 ml/min/1.73 m(2)), the lowest group, which was the eGFRCysC <15th percentile group (<86.2 ml/min/1.73 m(2)), had an adjusted HR of 2.30 (95% CI 1.13, 4.68) for T2D. Compared with the eGFRCr >85th percentile group, the lowest eGFRCr group (<15th percentile) had an HR of 1.19 (0.63, 2.24) for T2D. However, individuals with eGFRCr <60 ml/min/1.73 m(2) had a significantly increased risk of T2D. Clustering of both low eGFRCysC and low eGFRCr further elevated the HR for T2D compared with the presence of either.
Conclusions: Although eGFRCr in ranges indicating chronic kidney disease reflected an elevated risk of developing diabetes, earlier stages of kidney dysfunction indicated by reduced eGFRCysC, which could not be captured by reduced eGFRCr, would be a marker for an elevated risk of developing T2D. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.diabres.2016.01.026

Comparison of lipid parameters to predict cardiovascular events in Japanese mild-to-moderate hypercholesterolemic patients with and without type 2 diabetes: Subanalysis of the MEGA study Reviewed

Hirohito Sone, Tomoko Nakagami, Rimei Nishimura, Naoko Tajima

DIABETES RESEARCH AND CLINICAL PRACTICE 113 14 - 22 2016.3

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

Aims: To determine whether specific lipid parameters are better predictors of cardiovascular disease (CVD) in Japanese mild-to-moderate hypercholesterolemic patients with and without diabetes.
Methods: Mildly or moderately hypercholesterolemic patients with no history of CVD received diet therapy or diet therapy plus pravastatin. In this post-hoc subanalysis, 5-year data from 3170 patients (668 diabetes, 2502 non-diabetes) on diet therapy alone were used to compare lipid parameters as predictors of CVD. We examined the data by tertiles, using hazard ratio (HR) per one-standard deviation (SD) increment (decrease for high-density lipoprotein cholesterol, HDL-C), chi(2) value, receiver operating characteristic curve analysis, and spline analysis.
Results: In mild-to-moderate hypercholesterolemic patients with diabetes, increased total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C and decreased HDL-C were strongly associated with increased incidence of CVD (tertile analysis). In non-diabetes, increased non-HDL-C, and LDL-C/HDL-C were significantly associated with increased incidence of CVD. A one-SD decrease in HDL-C and a one-SD increment in non-HDL-C, TC/HDL-C, and LDL-C/HDL-C were significantly associated with increased HRs for CVD in both diabetes and non-diabetes. Linear CVD risk increases were found for non-HDL-C in diabetes and for non-HDL-C and HDL-C in non-diabetes (spline analysis).
Conclusions: In mild-to-moderate hypercholesterolemia, CVD risk prediction by stratifications of single or combination of traditional lipid parameter values illustrates various patterns. Parameters including HDL-C are better predictors of cardiovascular risk than only using TC or LDL-C alone. Non-HDL-C could be the most useful lipid parameter to assess CVD risk, considering it is easy to calculate and less affected by food intake. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.diabres.2015.12.002

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

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

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

Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

Mari Katsura, Hiromasa Cyou-Nakamine, Qin Zen, Yang Zen, Hiroko Nansai, Shota Amagasa, Yasuharu Kanki, Tsuyoshi Inoue, Kiyomi Kaneki, Akashi Taguchi, Mika Kobayashi, Toshiyuki Kaji, Tatsuhiko Kodama, Kiyoshi Miyagawa, Youichiro Wada, Nobuyoshi Akimitsu, Hideko Sone

Scientific Reports 6 2016.1

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

The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

DOI： 10.1038/srep20027

Scopus

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

Authorship：Corresponding author 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