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

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

DOI： 10.1136/bmjdrc-2023-003482

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

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

<p></p> Disclosure

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

Funding

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

DOI： 10.2337/db23-329-or

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

DOI： 10.1111/dom.15100

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Language：English  

DOI： 10.1177/10815589221149188

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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

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

DOI： 10.52082/jssm.2023.98

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/hjh.0000000000003362

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

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

DOI： 10.1007/s13340-022-00603-z

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

DOI： 10.3389/fpubh.2023.1090146

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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

DOI： 10.1093/fampra/cmac087

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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

DOI： 10.1186/s12933-022-01518-4

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本疫学会  

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Language：Japanese   Publisher：(一社)日本疫学会  

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

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

DOI： 10.1111/jdi.13736

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

DOI： 10.1016/j.amjmed.2021.10.018

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

DOI： 10.3390/nu13103478

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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

DOI： 10.1038/s41440-021-00632-2

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DOI： 10.1038/s41440-021-00645-x

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

DOI： 10.2337/dc20-2252

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

DOI： 10.1186/s13047-021-00474-8

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

DOI： 10.1002/pds.5213

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pds.5213

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

DOI： 10.1136/jim-2020-001489

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Language：Japanese   Publisher：(一社)日本内科学会  

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

DOI： 10.2196/22458

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

DOI： 10.2196/22148

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

DOI： 10.1007/s10557-020-07097-4

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

DOI： 10.1002/ehf2.12782

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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

DOI： 10.1016/j.neuint.2020.104745

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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

DOI： 10.1016/j.pcd.2020.05.002

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

DOI： 10.1136/bmjdrc-2019-000901

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Publishing type：Research paper (scientific journal)   Publisher：Japan Epidemiological Association  

DOI： 10.2188/jea.je20200034

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DOI： 10.2337/DB20-841-P

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DOI： 10.2337/DB20-1903-P

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DOI： 10.2337/DB20-389-P

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DOI： 10.2337/DB20-518-P

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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

DOI： 10.1093/fampra/cmy112

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

DOI： 10.1167/iovs.19-26749

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

DOI： 10.1016/j.clnesp.2018.07.001

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DOI： 10.1111/obr.12751

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Language：Japanese   Publisher：日本糖尿病眼学会  

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Language：Japanese   Publisher：日本糖尿病眼学会  

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

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

DOI： 10.2188/jea.JE20170280

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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DOI： 10.1016/j.diabet.2017.12.003

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Language：English   Publisher：Japan Epidemiological Association  

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

DOI： 10.2188/jea.JE20160151

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DOI： 10.1016/j.diabet.2017.08.002

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

Mechanisms of hepatic fibrogenesis induced by hepatitis C virus (HCV), one of the leading causes of liver fibrosis, are not fully understood. We studied transcriptional up-regulation of transforming growth factor b (TGF-b), especially TGF-b2, which is mediated by activation of liver-enriched transcription factor cAMP-responsive element-binding protein, hepatocyte specific (CREBH) triggered by HCV infection and its functional significance for induction of profibrogenic phenotypes by interaction of HCV-infected cells with hepatic stellate cells (HSCs). Compared to TGF-b1, expression of TGF-b2 mRNA was induced faster and to a higher level upon HCV infection. Serum TGF-b2 levels in hepatitis C patients were higher compared to those in healthy individuals and were positively correlated with hepatic fibrosis stages F0-F2. TGF-b2 promoter activity was decreased and increased, respectively, by silencing and overexpression of CREBH. CREBH recognition sites were identified in the TGF-b2 promoter. CREBH binding to the promoter and its increase in cells expressing HCV Core-NS2 were shown by gel mobility shift and chromatin immunoprecipitation, respectively. The active form of CREBH was detectable in HCV-infected chimeric mice with human livers and cells expressing HCV proteins. Involvement of CREBH in HCV-induced fibrogenic response was further demonstrated in the CREBH null-mutant mouse model. Fibrogenic phenotypes were assessed using co-cultures of HCV-infected cells and HSCs. Expressions of fibrogenic factors and TGF-b1 increasing in the co-cultures was prevented by TGF-b2-or CREBH silencing. Conclusion: CREBH was identified as a key positive regulator of TGF-b2 transcription in HCV-infected cells. TGF-b2 released from infected cells potentially contributes to cross-induction of TGF-b in an autocrine manner through its own signaling pathway, leading to an increase in fibrogenic responses in adjacent HSCs.

DOI： 10.1002/hep.29319

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

DOI： 10.1002/dmrr.2898

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BackgroundIn East Asian countries, which have a high prevalence of underweight individuals, there is little information about the association between dietary factors and abnormal glucose tolerance during pregnancy. We examined the association between carbohydrate intake and moderately abnormal glucose tolerance in Japanese pregnant women.
MethodsWe conducted a prospective study on 325 Japanese pregnant women without a diagnosis of diabetes mellitus prior to pregnancy. Dietary carbohydrate intake (% of total energy intake) was assessed using a 3-day dietary record during weeks 8-15 of pregnancy. Glucose tolerance was assessed by the 50g glucose challenge test (GCT) during weeks 24-28 of pregnancy. A positive GCT result was defined by a 1-hour plasma concentration7.8mmol/L. Odds ratios of a positive GCT were calculated for the top and middle tertile categories of carbohydrate intake using the bottom category as reference.
ResultsMean (standard deviation) body mass index at the first prenatal visit was 19.7 (1.9) kg/m(2), and 95 women were underweight. Seventy-four women had positive GCT results. Carbohydrate intake was negatively associated with a positive GCT result after adjusting for age, parity, body mass index at first prenatal visit, family history of diabetes mellitus, rate of gestational weight gain, energy intake, and dietary fiber intake (odds ratio for top category: 0.46 [95% CI, 0.23-0.93]).
ConclusionsThese findings suggest that high carbohydrate intake was negatively associated with moderately abnormal glucose tolerance in a population with a high prevalence of underweight individuals.

DOI： 10.1002/dmrr.2898

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

DOI： 10.1111/jdi.12623

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

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

DOI： 10.1111/jdi.12623

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Language：English   Publisher：AMER DIABETES ASSOC  

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DOI： 10.1016/j.diabet.2017.08.002

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

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

DOI： 10.1016/j.diabet.2016.09.001

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DOI： 10.1016/j.annepidem.2016.09.004

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OBJECTIVE: Nonblood-based risk assessment for type 2 diabetes mellitus (T2DM) that depends on data based on a questionnaire and anthropometry is expected to avoid unnecessary diagnostic testing and overdiagnosis due to blood testing. This meta-analysis aims to assess the predictive ability of nonblood-based risk assessment for future incident T2DM. METHODS: Electronic literature search was conducted using EMBASE and MEDLINE (from January 1, 1997 to October 1, 2014). Included studies had to use at least 3 predictors for T2DM risk assessment and allow reproduction of 2×2 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.

DOI： 10.1016/j.ypmed.2016.07.026

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Although a family history (FH) of hypertension is a risk factor for the development of hypertension, only a few studies have investigated in detail the impact of individual components of an FH on incident hypertension. We investigated the impact of individual components and their combinations on the presence or development of hypertension considering obesity, smoking habits, physical activity, and other metabolic parameters.Studied were 12,222 Japanese individuals without hypertension (n = 9,766) and with hypertension (n = 2,456) at the baseline examination. The presence or incidence of hypertension during 5 years after a baseline examination was assessed by the presence of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or a self-reported history of clinician-diagnosed hypertension. In this prospective study, the odds ratio for incident hypertension was 1.39 (95% confidence interval [CI], 1.22, 1.59) for individuals with any FH of hypertension compared with those without such an FH. Individuals with an FH of hypertension in both parents and one or more grandparents had an odds ratio of 3.05 (95% CI 1.74, 5.36) for hypertension compared with those without an FH of hypertension. FH was associated with incident hypertension independently of other modifiable risk factors such as obesity, smoking, physical inactivity, hyperglycemia, hyperuricemia, and hypertriglyceridemia.A parental history of hypertension was an essential component within an FH for incident hypertension. FH of hypertension over two generations with both parents affected was the most important risk factor for incident hypertension. Although an FH is not a modifiable risk factor, modifying other risk factors could contribute to reducing the risk of hypertension even among individuals with a family history of hypertension.

DOI： 10.1097/MD.0000000000004564

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

DOI： 10.1016/j.diabres.2016.01.026

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BACKGROUND: Our aim is to examine the dose-response association between cumulative genetic risk and actual risk of type 2 diabetes mellitus (T2DM) and the influence of adjustment for covariates on T2DM risk through a comprehensive meta-analysis of observational studies. METHODS: Electronic literature search using EMBASE and MEDLINE (from 2003 to 2014) was conducted for cross-sectional or longitudinal studies that presented the odds ratio (OR) for T2DM in each group with categories based on the total number of risk alleles (RAs) carried (RAtotal ) using at least two single-nucleotide polymorphisms. Spline regression model was used to determine the shape of the relationship between the difference from the referent group of each study in RAtotal (ΔRAtotal ) and the natural logarithms of ORs (log OR) for T2DM. RESULTS: Sixty-five eligible studies that included 68 267 cases among 182 603 participants were analysed. In both crude and adjusted ORs, defined by adjusting the risk for at least two confounders among age, gender and body mass index, the slope of the log OR for T2DM became less steep as the ΔRAtotal increased. In the analysis limited to 14 cross-sectional and four longitudinal studies presenting both crude and adjusted ORs, regression curves of both ORs in relation to ΔRAtotal were almost identical. CONCLUSION: Using only single-nucleotide polymorphisms for T2DM screening was of limited value. However, when genotypic T2DM risk was considered independently from risk in relation to covariates, it was suggested that genetic profiles might have a supplementary role related to conventional T2DM risk factors in identifying individuals at high risk of T2DM. Copyright © 2015 John Wiley & Sons, Ltd.

DOI： 10.1002/dmrr.2680

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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

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Language：English   Publishing type：Research paper (scientific journal)   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 HbA1c [≥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 HbA1c would enlarge the effect size by 0.036%, while each increment of 1 kg/m2 in the baseline BMI decreased it by 0.070% in the range between 22.3 and 38.8 kg/m2. 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

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Aims/IntroductionWe aimed to investigate the long-term trajectory of general adiposity assessed by the body mass index (BMI) before the onset of type2 diabetes in Japanese individuals.
Materials and MethodsWe retrospectively examined data on 1,553 Japanese men without diabetes. Mean BMI and incident cases of diabetes (diabetes indicated by fasting glucose concentrations 7.0mmol/L, a self-reported history of clinician-diagnosed diabetes, or glycated hemoglobin 6.5% (48mmol/mol) were assessed on an annual basis over a 10-year period after the baseline examination.
ResultsMean (standard deviation) BMI at the time of diagnosis was 24.4kg/m(2) (3.1kg/m(2)) among cases of diabetes (n=191). An increasingly high BMI was associated with the early stage of the disease development, such as an 8- to 10-year prediagnosis period; individuals who developed diabetes experienced a prolonged and stable elevated BMI of 24.4kg/m(2) over the 8years before the diagnosis of diabetes. The mean BMI among the non-cases of diabetes did not exceed 23.2kg/m(2) throughout the period.
ConclusionsThese results suggested that Japanese men who eventually developed diabetes during the 10-year observation period were not characterized as obese, but had stable high-normal BMIs before the onset of diabetes. Previous evidence showed that values for glycemic markers rapidly increased before the development of diabetes; however, the present study showed a slight gain in BMI in the earlier stage of the natural history of diabetes followed by a prolonged period of overweight.

DOI： 10.1111/jdi.12308

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

DOI： 10.1111/dme.12646

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

We investigated the effect of elevated concentrations of fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c) on the risk of development of hypertension among apparently healthy Japanese. Studied were 9584 individuals without known diabetes and hypertension. During a 5-year follow-up period, 1098 individuals developed hypertension. Elevated concentrations of FPG, rather than of HbA1c, were significantly predictive of future hypertension. Compared with the lowest quartile category of FPG (&lt
4.9 mmol l-1), the second (4.9-&lt
5.2 mmol l-1), third (5.2-&lt
5.6 mmol l-1) and highest (≥ 5.6 mmol l-1) quartile categories had age-, sex- and body mass index-adjusted odds ratios (95% confidence interval) of 1.35 (1.10, 1.66), 1.39 (1.13, 1.71) and 1.85 (1.51, 2.28) for hypertension, respectively. In the highest quartile of FPG, the multivariate-adjusted OR was 1.37 (1.10, 1.70) compared with the lowest quartile. Results of these adjusted models showed no significant association across quartile categories of HbA1c concentrations and an increased risk of developing hypertension. The joint effect of hyperglycemia and overweight, older age or prehypertension resulted in further elevated ORs for hypertension than the absence of such an association. Higher FPG levels rather than HbA1c were strongly predictive of future hypertension among Japanese. Hyperglycemia along with older age, overweight and prehypertension contributed to identifying individuals at increased risk of developing hypertension.

DOI： 10.1038/jhh.2014.77

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AimTo investigate the potential impact of joint association of alanine aminotransferase (ALT) and -glutamyltransferase (GGT) on insulin resistance and -cell dysfunction in healthy Japanese individuals with a normal range of liver enzymes.
MethodsThis study included 1010 individuals (545 men and 465 women) aged 20-89 years who underwent an oral glucose tolerance test for health screening. Participants were divided into four groups on the basis of median values for ALT and GGT: (i) both ALT and GGT low (both-low); (ii) ALT high and GGT low (ALT-high); (iii) ALT low and GGT high (GGT-high); and (iv) both ALT and GGT high (both-high). Logistic regression analysis was used to investigate the relationship between liver enzyme and insulin dynamics, such as Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) and insulinogenic index (IGI). The insulin resistance was defined when HOMA-IR was 2.5 or more. IGI of less than 0.4 was considered to be decreased early-phase insulin secretion.
ResultsMean values of HOMA-IR in men was 1.5 in the both-low group, 1.8 in ALT-high, 1.8 in GGT-high and 2.8 in both-high. The mean HOMA-IR in women was 1.3 in the both-low group, 1.3 in ALT-high, 1.6 in GGT-high and 2.0 in both-high. HOMA-IR in the both-high group was significantly higher than that in the both-low group regardless of the difference of sex. Multivariate analysis showed that insulin resistance occurred when the patient had high liver enzymes.
ConclusionCombining the two liver function markers would be effective for identifying individuals with insulin resistance.

DOI： 10.1111/hepr.12343

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Aims/IntroductionDepression, anger, sleep disorders and cognitive impairment are regarded as presenting a high risk for diabetes. We investigated whether responses to single statements on a self-report questionnaire on the presence of each of these four factors were associated with the development of type 2 diabetes.
Materials and MethodsWe investigated 3,211 Japanese individuals without diabetes. Cumulative incidence rate and hazard ratios (HRs) for future type 2 diabetes over 7-13years were evaluated according to the presence of lack of perseverance, anger, memory loss or sleep disorders.
ResultsResults of Cox regression analysis showed that lack of perseverance (age- and sex-adjusted HR 1.41, 95% confidence interval 1.07-1.84), anger, (HR 1.51, 95% confidence interval 1.07-2.12) or memory loss (HR 1.47, 95% confidence interval 1.14-1.90) was predictive of the development of diabetes. Even after adjustment for metabolic factors including glycemic measurements, anger was significantly associated with an increased risk of future diabetes. Individuals with both anger and memory loss had a 1.94-fold (95% confidence interval 1.19-3.15) increased risk of type2 diabetes than those without those two symptoms.
ConclusionsResponses to a simple self-report questionnaire as to whether individuals were aware of anger or memory loss were associated with the development of type2 diabetes independent of traditional risk factors for diabetes in this cohort of Japanese individuals.

DOI： 10.1111/jdi.12274

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

Aims. To elucidate the levels of malondialdehyde-modified LDL (MDA-LDL)-related variables for predicting coronary artery stenosis (CAS) by coronary CT angiography (CCTA) in asymptomatic patients with type 2 diabetes (T2DM). Methods. Enrolled were 36 Japanese patients with T2DM who underwent CCTA and in whom MDA-LDL levels were measured. Definition of CAS was luminal narrowing of &gt;= 50%. Trends through tertiles of each MDA-LDL-related variable were analyzed with a general linear model. The ability of each MDA-LDL-related variable to predict CAS was compared to areas under the curve (AUCs) in receiver operating characteristic curve (ROC) analysis. Results. Seventeen patients had CAS. Each MDA-IDL-related variable was an independent predictor of CAS (P = 0.039 for MDALDL, P = 0.013 for MDA-LDL/LDL-C, P = 0.047 for MDA-LDL/HDL-C, and P = 0.013 for (MDA-LDULDL-C)/HDL-C). AUCs of MDA-LDL, MDA-LDL/LDL-C, MDA-LDL/HDL-C, and (MDA-LDULDLC)/HDL-C were 0.675 (95% CI 0.496-0.854), 0.765 (0.602-0.927), 0.752 (0.592-0.913), and 0.799 (0.643-0.955), respectively, for predicting CAS. Trends throughout the tertiles showed significant associations between N4DA-LDL/LDL-C, N4DA-LDL/41DL-C, or (MDALDL/LDL-C)/41DL-C and CAS (P 0.003 for MDA-LDL/LDL-C, P=0.042 for MDA-LDULIDL-C, and P 0.001 for (MDA-LDULDL-C)/HDL-C). Conclusions. Data suggest that measurements of MDA-LDL/LDL-C, MDA-LDL/HDLC, and (MakLDULDL-C)/HDL-C are useful for predicting CAS.

DOI： 10.1155/2015/507245

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Language：English   Publisher：Hindawi Publishing Corporation  

DOI： 10.1155/2015/541026

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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.

DOI： 10.1016/j.clnu.2014.03.001

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

Background The impact of early initiation of diabetes care soon after the identification of hyperglycaemia rather than leaving diabetes untreated on changes in glycaemic control has not been fully clarified. We aimed to quantify the effect of initiating and continuing diabetes care compared with not starting management of diabetes on short-term changes in glycaemic control among the Japanese with newly screening-detected diabetes.
Methods We retrospectively reviewed data from a nationwide claims database to assess histories of physician-diagnosed diabetes or hyperglycaemia, as well as the use of antidiabetic agents, blood testing for hyperglycaemia or dietary advice among individuals without a history of diabetes care. Changes in glycated haemoglobin (HbA1c) concentrations were evaluated using baseline data and data from a health examination during the following year.
Results Among 1393 individuals with newly screening-detected diabetes, 62% (n=864) did not initiate diabetes management during the follow-up period; 49.2% (n=425) of the untreated group had poor glycaemic control (HbA1c =7%) at the baseline examination. Only 38% (n=529) began diabetes management in medical settings. Individuals who remained untreated had a 1.87 (95% CI 1.38 to 2.52) or 1.63 (1.10 to 2.41) times higher risk of absolute increases in HbA1c &gt;= 0.5% or &gt;= 1%, respectively, compared with the treated patients, a difference that was significant. Making more frequent clinic visits especially after the first visit was dose-dependently associated with improved HbA1c levels compared with no diabetes management.
Conclusions In comparison with a lack of management of diabetes, immediately initiating and continuing diabetes care after identification of hyperglycaemia in a screening setting would contribute to clinically meaningful, improved glycaemic control in the Japanese.

DOI： 10.1136/jech-2014-204054

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

DOI： 10.1002/oby.20855

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DOI： 10.1111/dme.12471

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

DOI： 10.1111/dme.12555

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Aims: Eradication of Helicobacter pylori (HP) is an effective approach to improve intestinal symptoms and prevent gastric cancer. However, there has been concern that the presence of diabetes reduces the effectiveness of antibiotics. We performed this meta-analysis to investigate the effect of diabetes on the risk of failing eradication in patients with diabetes. Methods: An electronic literature search was conducted using Biosis, MEDLINE, Embase, PASCAL, and SciSearch through November 30, 2012. Selected studies had to provide data on the number of individuals who received treatment for HP infection and on the failure of HP eradication in groups with and without diabetes. Two authors independently extracted relevant data. Results: Data were obtained from 8 eligible studies (693 total participants including 273 participants with diabetes). Overall, the pooled risk ratio (RR) of failing HP eradication for diabetic patients compared with non-diabetic participants was 2.19 [95%CI, 1.65-2.90] (. P<. 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.

DOI： 10.1016/j.diabres.2014.07.009

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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

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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

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

Conclusion: Nasal resistance and the OSA-18 score were useful for evaluating surgical treatments. The sleep disturbance score may also be useful for predicting the severity of obstructive sleep apnea (OSA) in children. Objective: We evaluated the effect of surgery on children with OSA using polysomnography (PSG) parameters, nasal resistance, and the OSA-18 questionnaire, and also investigated the cut-off OSA-18 score to screen for pediatric OSA. Methods: This was a retrospective study in which PSG parameters and nasal resistance were measured using a rhinomanometer and the OSA-18 score was obtained from the OSA-18 questionnaire before and after surgery in 45 children with OSA. Results: The mean age of the 45 patients was 5.7 +/- 2.0 years. The mean value of the obstructive apnea hypopnea index (O-AHI) improved from 16.2 +/- 14.3/h before surgery to 1.1 +/- 1.7/h after surgery, the mean nasal resistance improved from 0.44 +/- 0.19 to 0.32 +/- 0.10 Pa/cm(3)/s, and the mean OSA-18 score improved from 61.1 + 13.7 to 30.4 + 5.8, and all these improvements were significant. The O-AHI value was lower than 1/h after surgery in 64.4% of patients (29/45). The O-AHI value was significantly correlated with the sleep disturbance score (r = 0.352, p = 0.018). When the cut-off OSA-18 score for screening was set at 40, sensitivity was 100%.

DOI： 10.3109/00016489.2014.905703

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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

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

Results of epidemiologic studies that investigated the significance of pulse pressure (PP) and mean arterial pressure (MAP) in terms of risk of cardiovascular disease (CVD) in patients with diabetes mellitus are inconsistent. We performed a quantitative meta-analysis to estimate CVD risk in relation to PP or MAP. Electronic literature search was conducted for prospective studies providing data on CVD risk for an increment in baseline MAP or PP in patients with diabetes mellitus. The pooled CVD risk for a 10-mm Hg increase in each blood pressure (BP) index was estimated with a random-effects model. There were 17 eligible studies consisting of 52,647 patients and 5,112 CVD cases. The pooled relative risk (95% confidence interval) of CVD for an increment of 10 mm Hg was 1.10 (1.04 to 1.16) for PP and 1.09 (0.98 to 1.21) for MAP. Significant between-study heterogeneity was observed (I(2) [p value]; 76.5% [p <0.001] for PP, 67.8% [p = 0.005] for MAP). In studies concurrently investigating CVD risk for the 4 indexes (i.e., PP, MAP, systolic BP, and diastolic BP), the pooled relative risk (95% confidence interval) was 1.17 (1.09 to 1.26) for PP, 1.11 (1.06 to 1.15) for MAP, 1.14 (1.06 to 1.22) for systolic BP, and 1.06 (0.94 to 1.19) for diastolic BP. In conclusion, the current meta-analysis suggested that PP was the strongest indicator among the 4 commonly used BP indexes. However, the large heterogeneity urged cautious interpretation of the study results.

DOI： 10.1016/j.amjcard.2013.12.005

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This meta-analysis quantified the risk of type 2 diabetes mellitus (T2DM) preceded by body weight (BW) gain in the general population. Systematic literature searches retrieved 15 eligible studies. The BW gain was divided into early weight-gain, which was defined as BW gain from early adulthood (18-24 years of age) to cohort entry (≥25 years of age), and late weight-gain, which was defined as BW gain from cohort entry. The pooled relative risk (RR; 95% confidence interval [CI]) of T2DM for an increment of BW gain standardized into a 5-kg m(-2) increment in the body mass index (BMI) was 3.07 (2.49-2.79) for early weight-gain and 2.12 (1.74-2.58) for late weight-gain. When limiting analysis to studies that concurrently examined T2DM risk for current BMI (defined in both groups as BMI at cohort entry), a larger magnitude of T2DM risk was revealed for early weight-gain compared with current BMI (RR [95% CI], 3.38 [2.20-5.18] vs. 2.39 [1.58-3.62]), while there was little difference between late weight-gain (RR [95% CI], 2.21 [1.91-2.56]) and current BMI (RR [95% CI], 2.47 [1.97-3.30]). The meta-analysis suggested that BW gain was a quantifiable predictor of T2DM, as well as current obesity in adults. Particularly, BW gain in early rather than middle-to-late adulthood played an important role in developing T2DM.

DOI： 10.1111/obr.12129

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

Peroxisome proliferator-activated receptor gamma (PPAR gamma) responds to thiazolidinedione derivatives, which are ligands of PPAR gamma, and affects insulin resistance. Recently, a PPAR gamma study reported that in high-fat-diet-induced obesity, the phosphorylation of PPAR gamma prevented the transcription of specific PPAR gamma targets that have anti-obesity effects. We previously reported that genetic variants of the fatty acid desaturase were associated with plasma lipid profiles and could contribute to dyslipidemia in Japanese males. The aim of this study was to investigate the anti-obesity effects of PPAR gamma variants on lipid profiles. One hundred and thirty-eight (138) Japanese males participated in the study. Their serum lipid markers and the fatty acid composition of their red blood cell (RBC) membranes were determined. The stearoyl-CoA desaturase 1 (SCD1) indices were represented as the fatty acid product : precursor ratios. The participants were genotyped for the single-nucleotide polymorphism rs2938392 in the PPAR gamma gene. The participants' fitness habits were also surveyed by questionnaire. The effects of habitual exercise on the measured lipid parameters were compared in each genotype group. No association between the genotypes in the PPAR gamma gene and the biochemical data was found. However, the serum triglyceride levels and the SCD1 indices in RBC membranes were significantly higher in the participants who carried the major rs2938392 allele (A/A) and did not habitually exercise than in those who did exercise. These findings indicate that the risk for detrimental lipid profiles in the absence of habitual exercise depends on the PPAR gamma genotype in Japanese males.

DOI： 10.3177/jnsv.60.66

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

Aims: To compare the efficacy of Framingham Risk Score (FRS), UK Prospective Diabetes Study (UKPDS) risk engine, a risk score based on the Japanese Atherosclerosis Longitudinal Study-Existing Cohorts Combine (JALS-ECC), the maximum intima-media thickness (max-IMT) determined on coronary computed tomography angiography (CCTA) and their combination in asymptomatic patients with type 2 diabetes.
Methods: A total of 116 Japanese patients with type 2 diabetes underwent CCTA. The risk of coronary heart disease was calculated according to the FRS, UKPDS and JALS-ECC. We evaluated the reclassification of coronary artery stenosis (CAS) based on the risk score categories after adding each IMT related variable.
Results: Sixty-eight patients had CAS. The areas under the curves (AUCs) in the receiver operating characteristic curve analyses of FRS, UKPDS and JALS-ECC were 0.763 (95% confidence interval [CI]: 0.674-0.853), 0.785 (95% CI: 0.703-0.868) and 0.767 (95% CI: 0.681-0.853), respectively. The AUCs for FRS, UKPDS and JALS-ECC combined with the max-IMT were 0.788 (95% CI: 0.705-0.872), 0.800 (95% CI: 0.720-0.879) and 0.786 (95% CI: 0.703-0.869), respectively. Combining the max-IMT with the risk scores improved the identification of subjects with stenotic lesions, in particular, those in the first, second and third tertiles of the FRS, first and second tertiles of the UKPDS and first and second tertiles of the JALS-ECC (P=0.054, P=0.056, P=0.015, P=0.082, P=0.060, P=0.007, and P=0.080, respectively). The net reclassification improvement increased following the addition of a max-IMT of &gt;= 1.9 mm (32.4% in FRS, 19.9% in UKPDS and 51.7% in JALS-ECC).
Conclusions: These data suggest that combining a risk score with the max-IMT improves the prediction of CAS in comparison with the risk score alone.

DOI： 10.5551/jat.20487

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

OBJECTIVE. To assess the association between Helicobacter pylori (HP) infection and glycemic control in patients with diabetes through a meta-analytic approach. RESEARCH DESIGN AND METHODS. Electronic literature searches were conducted for cross-sectional studies that examined the hemoglobin A1c (A1C) level by whether patients with diabetes were or were not carriers of HP. Mean differences in A1C between groups with and without HP infection were pooled with a random-effects model. RESULTS. Thirteen eligible studies were included in this meta-analysis. Overall, the HP carriers did not have significantly higher A1C levels compared with HP noncarriers (mean difference (95% CI), 0.19% (-0.18 to 0.46), P = 0.16). When the analysis was limited to studies targeting patients with type 1 diabetes, there was also no significant difference in A1C (0.69% (-0.31 to 1.68), P = 0.18). CONCLUSIONS. There was insufficient evidence that HP infection worsened glycemic control in patients with diabetes.

DOI： 10.1155/2014/250620

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DOI： 10.11402/cookeryscience.47.165

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Objective-Findings on the effect of menopause or age at menopause on the presence of hyperglycemia are controversial, and why women after menopause have a higher probability of having hyperglycemia than men in the same age range remains unknown. Research design and methods-We reviewed data on 29,189 men, 6,308 premenopausalwomen, and 4,570 postmenopausal women in Japan. Odds ratios (ORs) for diabetes or prediabetes indicated by American Diabetes Association criteria were calculated for men and for pre- and postmenopausal women. Results-Compared with premenopausal women, women after natural menopause had an age-adjusted OR of 1.40 (95% CI 1.03-1.89) for diabetes, and women after menopause by surgical or other causes had an age-adjusted OR of 1.59 (1.07-2.37). The age-adjusted OR in men was 4.02 (3.15-5.14). Compared with premenopausal nondiabetic women, postmenopausal nondiabetic women had a significantly elevated OR of 1.33 (1.20-1.48) for prediabetes
nondiabetic men had an OR of 1.93 (1.77-2.10) independently of age and demographic and metabolic factors. Even among women aged &lt
50 years, postmenopausal status was significantly associated with an elevated OR (1.50 [1.18-1.91]) for dysglycemia (either diabetes or prediabetes). Postmenopausal women aged ≥50 years had a particularly elevated OR for dysglycemia, regardless of age at menopause. Conclusions-The postmenopausal state was significantly associated with the presence of dysglycemia independently of normal aging, although the increased probability in postmenopausal women did not equal that in men. Among women, menopause and older age might additively influence the elevated probability of dysglycemia. © 2013 by the American Diabetes Association.

DOI： 10.2337/dc13-1048

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

The Internet is used by many consumers interested in healthy living. The aim of the present study was to explore the variations among Internet information concerning a healthy diet and to evaluate the potential for misleading information. To conduct a descriptive analysis, the search term "healthy diet'' was entered into three search engines and the first 100 results were examined. Of the evaluated 48 websites, 5, 26 and 11, respectively, gave references, date when information was updated and cautioned users. For assessment of accuracy, six dietary guidelines were used as references and the website was scored according to the number of recommended dietary features that matched the guidelines. Websites that specified their objectives scored significantly higher when matched with each guideline than the websites that did not state four guidelines (p&lt;0.05). Internet information on a "healthy diet'' was likely to only partially follow recommendations of the guidelines.

DOI： 10.3109/09637486.2013.812620

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BACKGROUND: Using high-normal levels of haemoglobin A1C (Abnormal-A1C ) or fasting plasma glucose (FPG) (Abnormal-FPG) for diabetes screening are expected to improve the ability to detect persons with or at high risk of diabetes. We assessed the diagnostic and predictive capacity for diabetes of Abnormal-A1C and Abnormal-FPG. We compared these to the combined use of the two measures to the single use of either measurement. METHODS: We analysed 31 eligible cross-sectional or cohort studies that assessed diagnostic or predictive ability, respectively, by using lower A1C and FPG cutoff values than recommended by current diabetes criteria. Positive and negative likelihood ratios (LR+ and LR-) were calculated to assess the ability to confirm or exclude diabetes, respectively, on the basis of a bivariate random-effects model. RESULTS: With both Abnormal-A1C and Abnormal-FPG, the pooled LR+ was above 4 for diagnosing diabetes and above 3 for predicting diabetes. However, the pooled LR- for predicting diabetes was higher with Abnormal-A1C (0.48) and Abnormal-FPG (0.49) in comparison with that for diagnosing diabetes (0.27, Abnormal-A1C ; 0.28, Abnormal-FPG). In eight studies that assessed the predictive ability of the combination of A1C and FPG, using either Abnormal-A1C or Abnormal-FPG could lower LR- to 0.17 from 0.43 for only Abnormal-A1C and from 0.38 for only Abnormal-FPG. Accordingly, LR+ was also lowered to 2.37 from 3.36 for only Abnormal-A1C and from 3.84 for only-Abnormal-FPG. CONCLUSION: The use of the two blood glucose tests had insufficient capacity to identify subjects at high risk for diabetes but had considerable capacity to identify undiagnosed diabetes.

DOI： 10.1002/dmrr.2445

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DOI： 10.1007/s00125-013-3042-6

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

DOI： 10.1111/dme.12255

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/EDE.0b013e31829f6c31

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

DOI： 10.3177/jnsv.59.325

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DOI： 10.1007/s00125-012-2810-z

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DOI： 10.1093/aje/kwt036

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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 &gt;= 7.0 mmol/L, glycated hemoglobin &gt;= 6.5%, or self-reported clinician-diagnosed diabetes). Average alcohol consumption and 12 combinations of frequency and usual quantity per drinking occasion were assessed at the baseline examination. The absolute risk and HR for the development of diabetes were calculated.
Results: During a mean follow-up period of 10.2 y, 216 individuals developed diabetes. Lifetime abstainers (n = 153) had a relatively low incidence of diabetes (9.1/1000 person-years), similar to moderate consumers (99-160 g ethanol/wk; 9.0/1000 person-years). Increasingly higher quantities of alcohol usually consumed per occasion increased the risk of diabetes regardless of drinking frequency. The lowest incidence rate of diabetes (8.5/1000 person-years) was associated with the consumption of &lt;1 drink (&lt;23 g ethanol) per occasion over &gt;= 6 times/wk. Binge drinking (&gt;= 3 drinks per occasion) significantly increased the risk of future diabetes regardless of frequency (HR: 1.79; 95% CI: 1.17, 2.74) compared with &lt;1 drink per occasion.
Conclusions: Among current drinkers, a drinking pattern of &lt;1 drink per occasion regularly over 6 times within a week was associated with the lowest risk of developing diabetes. Usual quantity per drinking occasion was a more important determinant than was weekly drinking frequency in the association between alcohol consumption and risk of diabetes in Japanese men. Am J Clin Nutr 2013;97:561-8.

DOI： 10.3945/ajcn.112.043364

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DOI： 10.1016/j.ultrasmedbio.2012.10.003

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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 &gt;= 7.0 mmol/L or glycated hemoglobin &gt;= 6.5%) was 2.9% (n = 965). Diabetes score included age, sex, family history of diabetes, current smoking habit, body mass index, and hypertension with an area under the receiver-operating characteristics curve of 0.771. Screening with 8 or more points yielded a sensitivity of 72.7% and a specificity of 68.1%. In the validation cohort, the area under the receiver-operating characteristics curve was 0.806. The developed score with 8 or more points had better positive predictive value (9.6%) and positive likelihood ratio (2.52) compared with existing tools (positive predictive value, from 6.9% to 9.4%; positive likelihood ratio, from 1.77 to 2.46) in which each tool's highest combination of sensitivity and specificity was observed. The 4-year cumulative risk of developing diabetes gradually escalated in association with higher screening scores at the initial examination.
Conclusions: Our algorism could serve as a self-assessment tool for undiagnosed diabetic patients needing timely medical care and as a prognostic tool for individuals without present diabetes who must be closely followed up to prevent future diabetes. (J Clin Endocrinol Metab 98: 1051-1060, 2013)

DOI： 10.1210/jc.2012-3092

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

OBJECTIVE: The association between habitual physical activity (PA) and lowered risk of all-cause mortality (ACM) and cardiovascular disease (CVD) has been suggested in patients with diabetes. This meta-analysis summarizes the risk reduction in relation to PA, focusing on clarifying dose-response associations. RESEARCH DESIGN AND METHODS: Electronic literature searches were conducted for cohort studies that examined relative risk (RR) of ACM or CVD in relation to PA in patients with diabetes. For the qualitative assessment, RR for the highest versus the lowest PA category in each study was pooled with a random-effects model. We added linear and spline regression analyses to assess the quantitative relationship between increases in PA and ACM and CVD risk. RESULTS: There were 17 eligible studies. Qualitatively, the highest PA category had a lower RR [95% CI] for ACM (0.61 [0.52-0.70]) and CVD (0.71 [0.60-0.84]) than the lowest PA category. The linear regression model indicated a high goodness of fit for the risk of ACM (adjusted R(2) = 0.44, P = 0.001) and CVD (adjusted R(2) = 0.51, P = 0.001), with the result that a 1 MET-h/day incrementally higher PA was associated with 9.5% (5.0-13.8%) and 7.9% (4.3-11.4%) reductions in ACM and CVD risk, respectively. The spline regression model was not significantly different from the linear model in goodness of fit (P = 0.14 for ACM risk; P = 0.60 for CVD risk). CONCLUSIONS: More PA was associated with a larger reduction in future ACM and CVD risk in patients with diabetes. Nevertheless, any amount of habitual PA was better than inactivity.

DOI： 10.2337/dc12-0783

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CONTEXT: Recently, several studies have investigated the relationship between diabetes and hearing impairment, but results were inconsistent. OBJECTIVE: Our objective was to compare the prevalence of hearing impairment between diabetic and nondiabetic adults. DATA SOURCES: We performed a systematic literature search using MEDLINE (1950 to May 30, 2011) and EMBASE (1974 to May 30, 2011). STUDY SELECTION: Cross-sectional studies were included if data on numbers of hearing-impaired and non-hearing-impaired cases with diabetes were presented. Hearing impairment was limited to that assessed by pure-tone audiometry that included at least 2 kHz of frequency range and was defined as progressive, chronic, sensorineural, or without specified cause. DATA EXTRACTION: Two authors independently extracted relevant data. Odd ratios (ORs) of hearing impairment related to diabetes calculated in each study were pooled with the random-effects model. DATA SYNTHESIS: Data were obtained from 13 eligible studies (20,194 participants and 7,377 cases). Overall pooled OR (95% confidence interval) of hearing impairment for diabetic participants compared with nondiabetic participants was 2.15 (1.72-2.68). OR was higher in younger participants (mean age, ≤60 yr) than in those over 60 yr among which the OR remained significant (2.61 and 1.58, P = 0.008). The strength of the association between diabetes and prevalence of hearing impairment was not significantly influenced by whether participants were matched for age and gender (P = 0.68) or whether participants chronically exposed to noisy environments were excluded (P = 0.19). CONCLUSIONS: Current meta-analysis suggests that the higher prevalence of hearing impairment in diabetic patients compared with nondiabetic patients was consistent regardless of age.

DOI： 10.1210/jc.2012-2119

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AIMS: Maternal obesity and weight gain since early adulthood are known predictors of gestational diabetes in Western countries. However, their impact has not been evaluated well in Asia, where mean BMI levels are generally lower than in Western countries. We therefore examined the associations of BMI at age 20 years and BMI change since age 20 years with the risk of gestational diabetes in Japanese pregnant women. METHODS: Six hundred and twenty-four consecutive pregnant women without recognized diabetes before pregnancy, whose initial obstetric clinic visit was before 13 weeks' gestation, were prospectively observed. Weight at age 20 years was self-reported. Baseline height and weight measurements were obtained at the initial obstetric visit. Multivariate logistic regression analysis estimated the risk of incident gestational diabetes for BMI change since 20 years and BMI at age 20 years. RESULTS: Twenty-eight women developed incident gestational diabetes. By multivariate logistic regression analysis that adjusted for maternal age, parity and baseline BMI, we observed a statistically significant inverse association between BMI at age 20 years and incidence of gestational diabetes (odds ratio 0.68, 95% CI 0.51-0.92). Similarly, when we assessed the association of BMI change since age 20 years, adjusted for maternal age and parity, BMI change was associated with an increased risk of gestational diabetes (odds ratio 1.26, 95% CI 1.03-1.53). When we focused on the threshold of risk of gestational diabetes, women with BMI at 20 years of less than 18 kg/m(2) had a 6.30-fold (2.26-17.59) greater risk than women with both BMI at age 20 years of 18 kg/m(2) or more and BMI change since age 20 years of less than 1.85. CONCLUSIONS: Both low BMI at age 20 years and BMI change since age 20 years were significantly associated with increased risk of incident gestational diabetes.

DOI： 10.1111/j.1464-5491.2012.03712.x

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Aims. High prevalence of sleep apnea syndrome (SAS) has been reported in patients with diabetes. However, whether diabetic neuropathy (DN) contributes to this high prevalence is controversial. Our aim of this study is to compare the prevalence of SAS between patients with and without DN. Methods. Systematic literature searches were conducted for cross-sectional studies that reported the number of patients with DN and SAS using MEDLINE (from 1966 to Nov 5, 2012) and EMBASE (from 1974 to Nov 5, 2012). Odds ratios (ORs) of SAS related to DN were pooled with the Mantel-Haenszel method. Results. Data were obtained from 5 eligible studies (including 6 data sets, 880 participants, and 429 cases). Overall, the pooled OR of SAS in patients with DN compared with that in non-DN patients was significant (OR (95% CI), -1.95 (1.03-3.70)). The pooled OR of SAS was 1.90 (0.97-3.71) in patients with type 2 diabetes. Excluding data on patients with type 1 diabetes, a higher OR was observed in younger patients (mean age <60 years) than in those ≥60 years among whom the OR remained significant (3.82; 95% CI, 2.24-6.51 and 1.17; 95% CI, 0.81-1.68). Conclusions. Current meta-analysis suggested the association of some elements of neuropathy with SAS in type 2 diabetes. Further investigations are needed to clarify whether the association is also true for patients with type 1 diabetes.

DOI： 10.1155/2013/150371

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Aims: To investigate the clinical predictors of coronary atherosclerosis and to assess the utility of maximum-IMT for predicting coronary atherosclerosis in asymptomatic type 2 diabetic patients. Methods: One hundred one Japanese patients with type 2 diabetes underwent computed tomography coronary angiography. Definitions of coronary artery stenosis and vulnerable coronary plaque were luminal narrowing of ≥50% and any coronary plaque with positive vessel remodeling and low attenuation, respectively. Carotid intima-media thickness (IMT) was assessed using B-mode ultrasound. Results: Of the 101 patients, 40 had coronary artery stenosis without vulnerable coronary plaque, 7 had vulnerable coronary plaque without coronary artery stenosis, and 23 had coronary artery stenosis with vulnerable coronary plaque. Male sex (p= 0.031), duration of diabetes (p= 0.024), systolic blood pressure (SBP) (p=0.039), and the LDL/HDL ratio (LDL/HDL) (p=0.013) were independent predictors of coronary artery stenosis and the LDL/HDL (p=0.042) independently predicted vulnerable coronary plaque by logistic regression analyses. Areas under the curves in receiver operating characteristic curve analysis of the maximum-IMT, LDL/HDL, and these two parameters combined were 0.711 (95% CI 0.601-0.820), 0.618 (0.508-0.728), and 0.732 (0.632-0.831), respectively, for predicting coronary artery stenosis and 0.655 (0.537-0.773), 0.629 (0.504-0.754), and 0.710 (0.601- 0.818), respectively, for predicting vulnerable coronary plaque. Conclusions: Male sex, duration of diabetes, elevated SBP, and LDL/HDL were independent predictors of coronary artery stenosis. LDL/HDL was an independent predictor of vulnerable coronary plaque. Maximum-IMT predicted both coronary stenosis and vulnerable coronary plaque. Adding LDL/HDL improved the prediction of coronary artery stenosis and vulnerable coronary plaque.

DOI： 10.5551/jat.14977

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

The aim of this meta-analysis was to compare the association of waist-to-height ratio (WHtR) with risk of incident diabetes with the associations of 3 other conventional obesity indicators (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) with risk of incident diabetes. Literature searches in MEDLINE (January 1950 to April 27, 2011) and EMBASE (January 1974 to April 27, 2011) were conducted for prospective studies that made it possible to estimate the relative risk of diabetes per 1-standard deviation increase in WHtR, in addition to the RR of BMI, WC, or WHR. Strength of the estimated pooled relative risk for a 1-standard deviation increase of each indicator (expressed as RR(WHtR), RR(BMI), RR(WC), and RR(WHR)) was compared with a bivariate random-effects model. Pooled relative risks of the 15 eligible studies with 6,472 diabetes cases were 1.62 (95% CI: 1.48, 1.78) for RR(WHtR), 1.55 (95% CI: 1.43, 1.69) for RR(BMI), 1.63 (95% CI: 1.49, 1.79) for RR(WC), and 1.52 (95% CI: 1.40, 1.66) for RR(WHR). WHtR had an association stronger than that of BMI (P<0.001) or WHR (P<0.001). The present meta-analysis showed that WHtR has a modestly but statistically greater importance than BMI and WHR in prediction of diabetes. Nevertheless, measuring height in addition to WC appeared to have no additional benefit.

DOI： 10.1093/aje/kws172

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DOI： 10.1007/s00125-012-2712-0

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Language：English   Publisher：Japan Society of Ningen Dock  

<b>Objective: </b>Metabolic syndrome enhances coronary heart disease and cerebral stroke. However, few longitudinal studies have been conducted on the incidence of coronary heart disease and cerebral stroke in Japanese patients with non-alcoholic fatty liver disease (NAFLD) and the risk factors for its development. <br><b>Methods: </b>A total of 1,798 NAFLD patients with an age of ≥60 years were enrolled. The primary event was the first onset of coronary heart disease or cerebral stroke. Independent factors associated with the incidence rate of such events were analyzed by the Kaplan-Meyer method and the Cox proportional hazard model. The mean observation period was 7.5 years.<br><b>Results: </b>The number of cases of coronary heart disease or cerebral stroke that developed was 137. The 10th year cumulative development rate was 11.7% in the NAFLD patients. Cox proportional hazards analysis revealed the following: 1) Coronary heart disease occurred with statistical significance when patients had poor control of blood pressure, smoking, low high density lipoprotein level, and high glucose level. 2) Ischemic stroke occurred with statistical significance when patients had poor control of blood pressure, an age of ≥70 years, and high glucose level. 3) Hemorrhagic stroke occurred with statistical significance when patients had poor control of blood pressure, age ≥70 years, low albumin level of <3.9 g/dL and high aspartate aminotransferase to platelet ratio index. <br><b>Conclusion: </b>Our study indicates that the risk factors for the development of vascular disease are different for coronary heart disease, ischemic stroke and hemorrhagic stroke in Japanese elderly patients with NAFLD.

DOI： 10.11320/ningendock.27.561

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

Objective: To evaluate the effect of elevated fasting plasma glucose (FPG) and hemoglobin A(1c) (HbA(1c)) concentrations on lung dysfunction and to prospectively investigate whether reduced lung function would be independently predictive of diabetes.
Participants and Methods: From January 6, 1997, through December 22, 2008, we observed 5346 men with no history of diabetes or lung dysfunction. Hazard ratios (HRs) for incident diabetes (FPG &gt;= 126 mg/dL, HbA(1c)&gt;= 6.5%, or self-reported clinician-diagnosed diabetes) were estimated for spirometry indices as continuous and categorical variables.
Results: Elevated HbA(1c) concentrations within the normal range were significantly and more strongly associated with reduced forced vital capacity and forced expiratory volume in the first second after expiration (FEV1) than were FPG concentrations. During a 4.0-year follow-up, diabetes developed in 214 individuals. A 10-point decrease in percentage of FEV1 predicted value was associated with an increased HR of 1.21 (95% confidence interval [CI], 1.09-1.34; P=.001) for diabetes after adjustment for demographic factors and body mass index. This association remained significant even after adjustment for metabolic factors, smoking status, and FPG or HbA(1c) concentrations but was attenuated substantially after adjustment for baseline HbA(1c) values (HR, 1.13; 95% CI, 1.01-1.26; P=.03). Lower quartile (Q) categories of percentage of FEV1 predicted value were associated with increased risk of diabetes independently of known predictors including HbA(1c) (HR, 1.73; 95% CI, 1.14-2.62 for Q1; and HR, 1.76; 95% CI, 1.15-2.69 for Q2).
Conclusion: Reduced lung function was significantly related to chronic glycemic exposure within a normal range. Relatively low pulmonary function was an independent risk factor for diabetes in apparently healthy Japanese men. (C) 2012 Mayo Foundation for Medical Education and Research square Mayo Clin Proc. 2012:87(9);853-861

DOI： 10.1016/j.mayocp.2012.04.016

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

DOI： 10.1111/j.1464-5491.2012.03686.x

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

The aim of this study was to examine the association between HbA(1c) variability and the development of microalbuminuria as defined by an albumin/creatinine ratio a parts per thousand yen3.4 mg/mmol (a parts per thousand yen30 mg/g) in at least two of three consecutive urine samples in Japanese patients with type 2 diabetes.
HbA(1c) level was measured in 812 serially registered normoalbuminuric adults aged 21-79 years with type 2 diabetes. After registration, a 1-year period to establish baseline values for mean HbA(1c) and HbA(1c) variability (measured as the intrapersonal SD of serially collected HbA(1c)) was decided upon. The association between HbA(1c) variability and the development of microalbuminuria was determined by Cox regression analysis after adjustment for other risk factors for microalbuminuria.
Microalbuminuria occurred in 193 patients during the observation period of (mean +/- SD) 4.3 +/- 2.7 years. Even after adjustment for mean HbA(1c), HbA(1c) variability was a significant predictor of microalbuminuria independently of the mean HbA(1c); the HR for every 1% (95% CI) increase in mean HbA(1c) was 1.22 (1.06, 1.40) (p = 0.005), and that for HbA(1c) variability was 1.35 (1.05, 1.72) (p = 0.019). The effects of these two variables were quite similar when 1 SD was used; the HR for every 1 SD increase (95% CI) in HbA(1c) was 1.23 (1.07, 1.43) (p = 0.005), and that for HbA(1c) variability was 1.20 (1.03, 1.39) (p = 0.019).
HbA(1c) variability affects the development of microalbuminuria independently of mean HbA(1c) in type 2 diabetes. Further studies should be performed to evaluate the influence of HbA(1c) variability on other complications and in individuals of other ethnicities with type 2 diabetes.

DOI： 10.1007/s00125-012-2572-7

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OBJECTIVE: Web-based treatment programs are attractive in primary care because of their ability to reach numerous individuals at low cost. Our aim of this meta-analysis is to systematically review the weight loss or maintenance effect of the Internet component in obesity treatment programs. METHODS: MEDLINE and EMBASE literature searches were conducted to identify studies investigating the effect of Web-based individualized advice on lifestyle modification on weight loss. Randomized controlled trials that consisted of a Web-user experimental and non-Web user control group were included. Weight changes in the experimental group in comparison with the control group were pooled with a random-effects model. RESULTS: A total of 23 studies comprising 8697 participants were included. Overall, using the Internet had a modest but significant additional weight-loss effect compared with non-Web user control groups (-0.68 kg, P=0.03). In comparison with the control group, stratified analysis indicated that using the Internet as an adjunct to obesity care was effective (-1.00 kg, P<0.001), but that using it as a substitute for face-to-face support was unfavorable (+1.27 kg, P=0.01). An additional effect on weight control was observed when the aim of using the Internet was initial weight loss (-1.01 kg; P=0.03), but was not observed when the aim was weight maintenance (+0.68 kg; P=0.26). The relative effect was diminished with longer educational periods (P-trend=0.04) and was insignificant (-0.20 kg; P=0.75) in studies with educational periods of 12 months or more. CONCLUSION: The current meta-analysis indicates that the Internet component in obesity treatment programs has a modest effect on weight control. However, the effect was inconsistent, largely depending on the type of usage of the Internet or the period of its use.

DOI： 10.1038/ijo.2011.121

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CAMBRIDGE UNIV PRESS  

Objective: The present study aimed to evaluate the quality of Internet information on the Mediterranean diet and to determine the relationship between the quality of information and the website source.
Design: Website sources were categorized as institutional, pharmaceutical, non-pharmaceutical commercial, charitable, support and alternative medicine. Content quality was evaluated using the DISCERN rating instrument, the Health On the Net Foundation's (HON) code principles, and Journal of the American Medical Association (JAMA) benchmarks. Readability was graded by the Flesch Reading Ease score and Flesch-Kincaid Grade Level score.
Setting: The phrase 'Mediterranean diet' was entered as a search term into the six most commonly used English-language search engines.
Subjects: The first thirty websites forthcoming by each engine were examined.
Results: Of the 180 websites identified, thirty-two met our inclusion criteria. Distribution of the website sources was: institutional, n 8 (25 %); non-pharmaceutical commercial, n 12 (38 %); and support, n 12 (38 %). As evaluated by the DISCERN, thirty-one of the thirty-two websites were rated as fair to very poor. Non-pharmaceutical commercial sites scored significantly lower than institutional and support sites (P=0.002). The mean Flesch Reading Ease score and mean Flesch-Kincaid Grade Level were 55.9 (fairly difficult) and 7.2, respectively. The Flesch-Kincaid Grade Level score determines the difficulty of material by measuring the length of words and sentences and converting the results into a grade level ranging from 0 to 12 (US grade level).
Conclusions: Due to the poor quality of website information on the Mediterranean diet, patients or consumers who are interested in the Mediterranean diet should get advice from physicians or dietitians.

DOI： 10.1017/S1368980011002345

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OBJECTIVE-To describe the trajectory of HbA(1c), and glucose concentrations before the diagnosis of diabetes.
RESEARCH DESIGN AND METHODS-The study comprised 1,722 nondiabetic Japanese individuals aged 26-80 years. Fasting plasma glucose (FPG) and HbA(1c) were measured annually for a mean of 9.5 (SD 1.8) years.
RESULTS-Diabetes occurred in 193 individuals (FPG &gt;= 7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) &gt;= 6.5%). Mean HbA(1c) values were &gt;5.6% each year before diagnosis in diabetes cases. Mean HbA(1c) (5.69% [95% CI 5.50-5.88]) was higher in the 21 individuals who developed diabetes 10 years after the baseline examination than in nondiabetic individuals after 10 years (5.27% [5.25-5.28]). From 3 years to 1 year prediagriosis, HbA(1c) increased 0.09% (SE 0.01)/year, reaching 5.90% (5.84-5.96) 1 year prediagnosis. In the entire group, marked increases in HbA(1c) of 0.3% (SE 0.05%)/year and FPG of 0.63 (0.07) mmol/L/year predicted diabetes.
CONCLUSIONS HbA(1c) trajectory increased sharply after gradual long-term increases in diabetic individuals.

DOI： 10.2337/dc11-1793

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

Objective: To evaluate the impact of HbA1c for diagnosis of diabetes and investigate whether cardiovascular risks profiles differ among individuals with diabetes diagnosed by HbA1c or fasting plasma glucose (FPG).
Methods: This cross-sectional study involved 26,884 participants (30.6% women; aged 20-91 years) without known diabetes. Subjects were categorized into 4 groups according to the presence or absence of FPG &gt;= 7.0 mmol/L and/or HbA1c &gt;= 6.5%, which were American Diabetes Association criteria. Oral glucose tolerance test data were not available.
Results: Prevalence of undiagnosed diabetes was 3.6%. Of those individuals, 47.5% fulfilled both two criteria and 26.0% fulfilled only HbA1c criterion. Individuals with diabetes according to FPG &gt;= 7.0 mmol/L alone were characterized as having poorly controlled hypertension while those with HbA1c &gt;6.5% alone were characterized as older, female, and having lower blood pressure and gamma-glutamyltransferase values. Persons with newly diagnosed diabetes by HbA1c had low HDL cholesterol and high LDL or non-HDL cholesterol levels.
Conclusions: Introducing HbA1c into the diagnosis allowed detection of many previously undiagnosed cases of diabetes in Japanese individuals. Those diagnosed by FPG were characterized by hypertension and those diagnosed by HbA1c had unfavorable lipid profiles, reflecting an atherosclerotic trait. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.diabres.2011.10.024

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Language：English   Publisher：Japan Atherosclerosis Society  

Aim: The post-challenge glucose (PCG) level has been suggested to be superior to the fasting blood glucose (FG) level for predicting the risk of future cardiovascular disease (CVD); however, the extent of its superiority has not been consistently shown among previous cohort studies. Therefore, we conducted a meta-analysis to summarize the quantitative association of FG and PCG with CVD risk and compared the strengths of the two associations.<BR>Method: Electronic literature searches using MEDLINE and EMBASE with an additional manual search were conducted for prospective observational studies of the association of FG and PCG with CVD risk. Studies were included if they were prospective studies in which the relative risk (RR) of CVD per 1 standard deviation increase in both FG and PCG could be estimated. Pooled relative risks for the incremental increase were calculated as RR_FG and RR_PCG using a bivariate random-effects model.<BR>Result: Data were obtained from 14 eligible studies that included 70,889 participants and 2,927 cases. The pooled RR_FG and RR_PCG (95% confidence interval) were, respectively, 1.15 (1.06 to 1.26) and 1.24 (1.12 to 1.36); the difference was significant (<i>P</i> =0.001). The association of PCG with CVD risk was stronger in studies that targeted participants with a baseline mean FG < 100 mg/dl (<i>P</i> < 0.001) or mean age &ge; 55 years (<i>P</i> =0.004).<BR>Conclusions: Overall, the association of PCG with CVD risk was stronger than that of FG by approximately 50% on a log scale. Measuring PCG is especially important in populations with relatively low FG levels or in the elderly, although it is often burdensome in routine clinical practice.

DOI： 10.5551/jat.10975

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We examined the relationship between psychological stress and the worsening of glycemic control in diabetic patients at the time of the Great East Japan Earthquake. HbA1c levels in diabetic patients before and after the disaster were evaluated with the General Health Questionnaire (GHQ) and other questions including those on changes in diet, exercise, psychological stress and drug intake in 320 consecutive diabetic patients who had been followed in a diabetes clinic. Logistic regression analysis revealed that the total GHQ scores (odds ratio [OR] 1.03 [95% confidence interval 1.01-1.06]
p&lt
0.01) and interruption of drug intake (OR 4.48 [1.57-12.7]
p=0.01) were independently associated with worsening of glycemic control defined as an increase in the HbA1c level equal to or greater than 0.5%. Among the scores on the GHQ, those for somatic symptoms (OR 1.18 [1.01-1.38]
p=0.03) and sleep disturbances or anxiety (OR 1.26 [1.08-1.46]
p&lt
0.01) were independently associated with glycemic control. These results suggest that psychological stress during a disaster has independent effects on worsening of glycemic control. © Georg Thieme Verlag KG Stuttgart · New York.

DOI： 10.1055/s-0032-1314873

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We recorded self-reported eating patterns in 172 Japanese men and women who were subsequently followed for 3 years for the occurrence of impaired glucose tolerance (IGT).
Incidence of IGT was significantly higher in those who reported eating fast. Self-reported eating fast is a potent risk factor for development of IGT. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.diabres.2011.08.015

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

We investigated the effects of vitamin C administration on vitamin C-specific transporters in ODS/ShiJcl-od/od rat livers. The vitamin C-specific transporter levels increased in the livers of the rats not administered vitamin C and decreased in the livers of those administered vitamin C at 100 mg/d, indicating that these transporter levels can be influenced by the amount of vitamin C administered.

DOI： 10.1271/bbb.110312

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

OBJECTIVE: In Western countries, skipping breakfast is associated with a high prevalence of overweight and obesity. This meta-analysis aimed to determine if the same relationship exists in Asian and Pacific regions. METHODS: A systematic literature search was performed for observational studies using a cross-sectional design that examined the relationship between frequency of eating breakfast and overweight or obesity. Odds ratios (ORs) for overweight or obesity were pooled with a variance-based method. RESULTS: Nineteen studies (93,108 total participants and 19,270 overweight or obese cases) were included. The pooled OR [95% confidence intervals (CI)] of overweight or obesity for the lowest vs. highest category of breakfast frequency was 1.75 [1.57 to 1.95] (P<0.001). Between-study heterogeneity in the association's strength was highly significant (I-squared=36.4%, P<0.001), although a positive OR was shown in all but one included study. However, no study characteristics could be identified to explain the heterogeneity. CONCLUSION: This meta-analysis suggests that a positive association between skipping breakfast and overweight and obesity is globally observed regardless of cultural diversity among countries. Promoting the eating of breakfast in all populations may be beneficial.

DOI： 10.1016/j.ypmed.2011.08.030

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Publisher：The Oto-Rhino-Laryngological Society of Japan, Inc.  

Dacryocystorhinostomy (DCR) is done commonly in subjects with chronic dacryocystitis and nasolacrimal duct stenosis, and endoscopic DCR is now an established alternative to external approaches. Mucosal preservation is important in preventing granulation tissue and synechia from forming around the ostium. Our modified endoscopic DCR using a mucosal flap involves creating a large bony opening to form an anastomosis for the lacrimal sac and nasal mucosa. Instead of silicon tubing, we use a silicon sheet to avoid manipulating the canaliculi. Our modifications enable an easy, safe, effective form of DCR easily implemented by otolaryngologists familiar with endoscopic sinus surgery.

DOI： 10.3950/jibiinkoka.114.820

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DOI： 10.1007/bf03325127

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Other Link： http://link.springer.com/article/10.1007/BF03325127/fulltext.html

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

Background The clinical relevance of the diagnostic criteria for prediabetes to prediction of progression to diabetes has been little studied. We aimed to compare the prevalence of prediabetes when assessed by the new glycated haemoglobin A(1c) (HbA(1c)) 5.7-6.4% criterion or by impaired fasting glucose, and assessed differences in progression rate to diabetes between these two criteria for prediabetes in a Japanese population.
Methods Our longitudinal cohort study included 4670 men and 1571 women aged 24-82 years without diabetes at baseline (diabetes was defined as fasting plasma glucose &gt;= 7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) &gt;= 6.5%) who attended Toranomon Hospital (Tokyo, Japan) for a routine health check between 1997 and 2003. Participants with a baseline diagnosis of prediabetes according to impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/L) or HbA(1c) 5.7-6.4%, or both, were divided into four groups on the basis of baseline diagnosis of prediabetes. Rate of progression to diabetes was assessed annually.
Findings Mean follow-up was 4.7 (SD 0.7) years. 412 (7%) of 6241 participants were diagnosed with prediabetes on the basis of the HbA(1c) 5.7-6.4% criterion. Screening by HbA(1c) alone missed 1270 (61%) of the 2092 prediabetic individuals diagnosed by a combination of impaired fasting glucose and HbA(1c) 5.7-6.4%. Overall cumulative probability of progression to diabetes did not differ significantly between participants with prediabetes discordantly diagnosed by either HbA(1c) or impaired fasting glucose alone (incidence was 7% for HbA(1c) alone [n=412 individuals and 30 incident cases] and 9% for impaired fasting glucose alone [n=1270,108 cases]; log-rank test, p=0.3317). Multivariate-adjusted hazard ratios for incident diabetes were 6.16 (95% CI 4.33-8.77) for those diagnosed with prediabetes by impaired fasting glucose alone and 6.00 (3.76-9.56) for diagnosis by HbA(1c) alone, and were substantially increased to 31.9 (22.6-45.0) for diagnosis by both impaired fasting glucose and HbA(1c) compared with normoglycaemic individuals.
Interpretation Diagnosis of prediabetes by both the new HbA(1c) criterion and impaired fasting glucose identified individuals with an increased risk of progression to diabetes. Although the new HbA(1c) criterion identified fewer individuals at high risk than did impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA(1c) 5.7-6.4% was similar to that assessed by impaired fasting glucose alone. The two tests used together could efficiently target people who are most likely to develop diabetes and allow for early intervention.

DOI： 10.1016/S0140-6736(11)60472-8

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Language：Japanese   Publisher：THE JAPAN DIABETES SOCIETY  

DOI： 10.11213/tonyobyo.54.2

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OBJECTIVES: The purpose of this meta-analysis is to summarize the estimated risk of atrial fibrillation (AF) related to alcohol consumption. BACKGROUND: Results from observational studies examining the relationship between alcohol consumption and AF are inconsistent. METHODS: A systematic electronic search of Medline (January 1966 to December 2009) and Embase (January 1974 to December 2009) databases was conducted for studies using key words related to alcohol and AF. Studies were included if data on effect measures for AF associated with habitual alcohol intake were reported or could be calculated. The effect measures for AF for the highest versus lowest alcohol intake in individual studies were pooled with a variance-based method. Linear and spline regression analyses were conducted to quantify the relationship between alcohol intake and AF risk. RESULTS: Fourteen eligible studies were included in this meta-analysis. The pooled estimate of AF for the highest versus the lowest alcohol intake was 1.51 (95% confidence interval: 1.31 to 1.74). A linear regression model showed that the pooled estimate for an increment of 10 g per day alcohol intake was 1.08 (95% confidence interval: 1.05 to 1.10; R(2) = 0.43, p < 0.001). A spline regression model also indicated that the AF risk increased with increasing levels of alcohol consumption. CONCLUSIONS: Results of this meta-analysis suggest that not consuming alcohol is most favorable in terms of AF risk reduction.

DOI： 10.1016/j.jacc.2010.08.641

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Objective: High levels of serum cholesterol are associated with the risk of stroke. However, the association of serum cholesterol with silent brain infarcts (SBIs) is unclear. We investigated the association between SBI and various clinical factors.
Methods: We conducted a cross-sectional study that included 324 apparently healthy Japanese men(mean age 53.8 +/- 9.2 years). Combinations of three types of scan (T1-weighted, T2-weighted and FLAIR images) were used to detect and discriminate SBI.
Results: Serum cholesterol was significantly associated with SBI [total cholesterol, odds ratio (OR) 3.75 (95% confidence interval (CI) 1.45-9.68); LDL-cholesterol, OR 2.54 (95% CI 1.03-6.27), and non-HDL-cholesterol, OR 2.54 (95% CI 1.03-6.27)] after adjustment for age, smoking status, serum triglycerides, maximal-intima-media thickness, obesity, hypertension, diabetes mellitus, hyperuricemia, coronary heart disease and lipid-lowering agent use.
Conclusion: Our cross-sectional data suggest that serum cholesterol levels are associated with SBI independently of known confounders. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2010.01.008

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OBJECTIVE: To systematically evaluate the association between serum uric acid (SUA) level and subsequent development of type 2 diabetes. RESEARCH DESIGN AND METHODS: We searched Medline (31 March from 1966 to 2009) and Embase (31 March from 1980 to 2009) for observational cohort studies examining the association between SUA and the risk of type 2 diabetes by manual literature search. Relative risks (RRs) for each 1 mg/dl increase in SUA were pooled by using a random-effects model. The studies included were stratified into subgroups representing different study characteristics, and meta-regression analyses were performed to investigate the effect of these characteristics on the association between SUA level and type 2 diabetes risk. RESULTS: The search yielded 11 cohort studies (42,834 participants) that reported 3,305 incident cases of type 2 diabetes during follow-up periods ranging from 2.0 to 13.5 years. The pooled RR of a 1 mg/dl increase in SUA was 1.17 (95% CI 1.09-1.25). Study results were consistently significant (i.e., >1) across characteristics of participants and study design. Publication bias was both visually and statistically suggested (P = 0.03 for Egger's test, 0.06). Adjustment for publication bias attenuated the pooled RR per mg/dl increase in SUA (RR 1.11 [95% CI 1.03-1.20]), but the association remained statistically significant (P = 0.009). CONCLUSIONS: The current meta-analysis suggests that SUA level is positively associated with the development of type 2 diabetes regardless of various study characteristics. Further research should attempt to determine whether it is effective to utilize SUA level as a predictor of type 2 diabetes for its primary prevention.

DOI： 10.2337/dc09-0288

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DOI： 10.1016/j.annepidem.2009.03.020

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CONTEXT: Epidemiological studies have indicated an inverse association between cardiorespiratory fitness (CRF) and coronary heart disease (CHD) or all-cause mortality in healthy participants. OBJECTIVE: To define quantitative relationships between CRF and CHD events, cardiovascular disease (CVD) events, or all-cause mortality in healthy men and women. DATA SOURCES AND STUDY SELECTION: A systematic literature search was conducted for observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008). The Medical Subject Headings search terms used included exercise tolerance, exercise test, exercise/physiology, physical fitness, oxygen consumption, cardiovascular diseases, myocardial ischemia, mortality, mortalities, death, fatality, fatal, incidence, or morbidity. Studies reporting associations of baseline CRF with CHD events, CVD events, or all-cause mortality in healthy participants were included. DATA EXTRACTION: Two authors independently extracted relevant data. CRF was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units. Participants were categorized as low CRF (< 7.9 METs), intermediate CRF (7.9-10.8 METs), or high CRF (> or = 10.9 METs). CHD and CVD were combined into 1 outcome (CHD/CVD). Risk ratios (RRs) for a 1-MET higher level of MAC and for participants with lower vs higher CRF were calculated with a random-effects model. DATA SYNTHESIS: Data were obtained from 33 eligible studies (all-cause mortality, 102 980 participants and 6910 cases; CHD/CVD, 84 323 participants and 4485 cases). Pooled RRs of all-cause mortality and CHD/CVD events per 1-MET higher level of MAC (corresponding to 1-km/h higher running/jogging speed) were 0.87 (95% confidence interval [CI], 0.84-0.90) and 0.85 (95% CI, 0.82-0.88), respectively. Compared with participants with high CRF, those with low CRF had an RR for all-cause mortality of 1.70 (95% CI, 1.51-1.92; P < .001) and for CHD/CVD events of 1.56 (95% CI, 1.39-1.75; P < .001), adjusting for heterogeneity of study design. Compared with participants with intermediate CRF, those with low CRF had an RR for all-cause mortality of 1.40 (95% CI, 1.32-1.48; P < .001) and for CHD/CVD events of 1.47 (95% CI, 1.35-1.61; P < .001), adjusting for heterogeneity of study design. CONCLUSIONS: Better CRF was associated with lower risk of all-cause mortality and CHD/CVD. Participants with a MAC of 7.9 METs or more had substantially lower rates of all-cause mortality and CHD/CVD events compared with those with a MAC of less 7.9 METs.

DOI： 10.1001/jama.2009.681

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/EDE.0b013e31819ed09f

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/EDE.0b013e31819ed4ed

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OBJECTIVE: The effects of dietary macronutrient composition on metabolic profiles in patients with type 2 diabetes have been inconsistent. This meta-analysis aimed to elucidate the effect of replacing dietary fat with carbohydrate on glucose and lipid parameters in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We searched for randomized trials that investigated the effects of two kinds of prescribed diets (a low-fat, high-carbohydrate [LFHC] diet and a high-fat, low-carbohydrate [HFLC] diet); in these studies, energy and protein intake did not differ significantly between the two dietary groups. Nineteen studies that included 306 patients met our inclusion criteria. Median diet composition of carbohydrate/fat in the LFHC and HFLC diets was 58%/24% and 40%/40%, respectively. RESULTS: Changes in values for A1C, fasting plasma glucose (FPG), and total and LDL cholesterol did not differ significantly between the LFHC and HFLC groups. However, the LFHC diet significantly increased fasting insulin and triglycerides by 8% (P = 0.02) and 13% (P < 0.001), respectively, and lowered HDL cholesterol by 6% (P < 0.001) compared with the HFLC diet. There were positive associations among the magnitude of changes in FPG, fasting insulin, and triglycerides for the diets analyzed. However, stratified analysis indicated that the increase in triglycerides was insignificant when accompanied by energy intake restriction. CONCLUSIONS: Our findings suggested that replacing fat with carbohydrate could deteriorate insulin resistance while the adverse effect on triglycerides from the LFHC diet could be avoided by restricting energy intake to a degree sufficient for the attainment of weight reduction.

DOI： 10.2337/dc08-1716

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Language：English   Publisher：HUMAN KINETICS PUBL INC  

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BACKGROUND: Aerobic exercise is believed to reduce the risk of cardiovascular disease partially through increasing serum levels of high-density lipoprotein cholesterol (HDL-C). However, this effect varies considerably among exercise intervention studies. METHODS: Electronic database searches of MEDLINE (1966-2005) for randomized controlled trials that examined the effect of exercise training on HDL-C level. RESULTS: Twenty-five articles were included. Mean net change in HDL-C level was statistically significant but modest (2.53 mg/dL [0.065 mmol/L]; P<.001). Minimal weekly exercise volume for increasing HDL-C level was estimated to be 900 kcal of energy expenditure per week or 120 minutes of exercise per week. Univariate regression analysis indicated that every 10-minute prolongation of exercise per session was associated with an approximately 1.4-mg/dL (0.036-mmol/L) increase in HDL-C level. In contrast, there was no significant association between exercise frequency or intensity. Multiple meta-regression analyses demonstrated that subjects with a body mass index (calculated as weight in kilograms divided by height in meters squared) less than 28 and total cholesterol level of 220 mg/dL [5.7 mmol/L] or more experienced an approximately 2.1-mg/dL (0.054-mmol/L) larger increase in HDL-C level than those with a body mass index of 28 or more and total cholesterol level less than 220 mg/dL (5.7 mmol/L). CONCLUSIONS: Regular aerobic exercise modestly increases HDL-C level. There appears to exist a minimum exercise volume for a significant increase in HDL-C level. Exercise duration per session was the most important element of an exercise prescription. Exercise was more effective in subjects with initially high total cholesterol levels or low body mass index.

DOI： 10.1001/archinte.167.10.999

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DOI： 10.2337/dc06-2149

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

Objective Moderate to high intensity exercise training is known to ameliorate the coronary risk factors in relation to an improvement in body composition. However, the benefit of low-intensity and low-volume training for these risk factors remains unclear in elderly people. Therefore, we investigated the effects of low-intensity and low-volume exercise training on blood lipid values and insulin resistance in the elderly.
Methods A total of 56 healthy elderly individuals (42 females and 14 males) aged 64 +/- 6 years participated in a 12-week exercise program, comprising aerobic training and resistance training.
Results After the program, there were no significant changes in high-density lipoprotein cholesterol, triglyceride serum levels, or in peak oxygen uptake on average. However, the homeostasis of minimal assessment of insulin resistance (HOMA-IR) value was significantly reduced by 21%. The participants were categorized into tertiles based on initial Body Mass Index (BMI). The Middle-BMI group (non-obese subjects) showed reduced HOMA-IR (2.0 -&gt; 1.3, P&lt;0.01), but this reduction was not associated with the reduction in BMI (r=0.08, P=0.74), whereas the two reductions were significantly associated in the High-BMI group (r=0.61, P=0.01).
Conclusion Even low-intensity and low-volume exercise training, which would ordinarily be insufficient for improving mean lipid values or aerobic fitness, was found to be effective in improving insulin resistance in the elderly. The improvement in insulin resistance was independent of the improvement in obesity.

DOI： 10.2169/internalmedicine.46.0096

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DOI： 10.1016/j.cbpa.2006.06.043

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Language：English   Publisher：Japan Society of Physical Education, Health and Sport Sciences  

Exercise training suppresses cardiovascular risk factors by improving lipid/glucose metabolism, insulin resistance and hypertension. There is an optimum amount and intensity of exercise that will suppress each risk factor, although limited information is currently available on this area. For instance, the level of high-density lipoprotein cholesterol seems to be dependent more on the amount than on the intensity of exercise training; the situation with exercise-induced suppression of triglyceride levels is less clear. It is notable that the ability of mild intensity or a low amount of exercise to suppress or prevent cardiovascular risk factors is largely unknown. This knowledge is essential for prescribing safe and effective exercise training to elderly people. At the same time, very few studies on the associations between cardiovascular risk factors in response to exercise can be found. For example, improvement in lipid metabolism or insulin resistance seems to be related to the weight loss seen during exercise training but weight-independent effects could also be observed. The optimal intensity and amount of exercise training for each cardiovascular risk factor and the relationships between the effects of exercise training on each risk factor need to be clarified in the near future in order to establish guidelines that can be applied to the majority of elderly people at risk of cardiovascular diseases.

DOI： 10.5432/ijshs.4.325

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Other Link： http://search.jamas.or.jp/link/ui/2007328852

Language：Japanese   Publisher：THE JAPAN DIABETES SOCIETY  

DOI： 10.11213/tonyobyo1958.46.903

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Other Link： https://jlc.jst.go.jp/DN/JALC/00234747009?from=CiNii

Language：Japanese   Publisher：THE JAPAN DIABETES SOCIETY  

DOI： 10.11213/tonyobyo1958.38.238

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DOI： 10.2337/db18-442-P

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DOI： 10.2337/db18-444-P

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DOI： 10.2337/db18-823-P

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情報化社会の普及に伴い、医療情報が氾濫し信頼性の低い情報の増加に繋がっている。現在では臨床医が最新の診療を実践するためには、治療手技などの医療情報は、system(教科書型の情報源)ではなく、個別の医学研究であるstudyから入手しなければならない場合が多い。信頼できる研究の着眼点を以下の項目に分けて概説した。1)医学研究の分類、2)観察研究の分類、3)医学研究の信頼性、4)介入研究の簡便評価法、5)観察研究の簡便評価法、6)診断研究の簡便評価法、について述べた。

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第3回日本DOHaD研究会学術集会 抄録集 【ポスター発表】

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

DOI： 10.1093/aje/kwt036

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

大学生の栄養教育プログラム作成の検討に資することを目的に、本学(大学)農学部1年生80名(男子35名、女子45名)へ食物摂取状況および食物摂取の知識・態度・行動などについてアンケート調査を行った。その結果、国民健康栄養調査(18〜29歳)との比較では、男女とも食物繊維・鉄分・カルシウムが不足傾向、野菜、魚介類の摂取が不足傾向であった。また、食物摂取に対する知識・態度・行動レベルでは、男子学生より女子学生の方が高値を示す項目が多かった。

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Language：English   Publisher：WILEY-BLACKWELL  

Diabet. Med. 29, 12851290 (2012) Abstract Aims We aimed to characterize the association of insulin resistance, impaired insulin secretion and beta-cell dysfunction in relation to HbA1c levels in a non-diabetic range in Japanese individuals without clinically diagnosed diabetes. Methods This cross-sectional study included 1444 individuals without a history of outpatient treatment of diabetes or use of insulin or oral hypoglycaemic agents. The homeostasis model assessment of insulin resistance and beta-cell function, insulinogenic index, Matsuda index and disposition index were calculated using data from 75-g oral glucose tolerance tests and compared across quintile (Q) categories of HbA1c levels. Results Fasting plasma glucose and 30-min and 60-min plasma glucose (PG) levels were significantly higher when HbA1c exceeded 36 mmol/mol (5.4%). A HbA1c concentration of 3637 mmol/mol (5.45.5%) (Q3) was significantly associated with a 15% lower homeostasis model assessment of beta-cell function value and 31% lower insulinogenic index value compared with HbA1c = 32 mmol/mol (= 5.1%) (Q1) (P &lt;0.01). Further, a HbA1c concentration of 3840 mmol/mol (5.65.8%) (Q4) was associated with 17% (P &lt;0.01) and 24% (P &lt;0.05) reductions in those indexes, respectively. However, the homeostasis model assessment of insulin resistance was not significantly elevated and the Matsuda index was not significantly lower unless HbA1c exceeded 41 mmol/mol (5.9%). Individuals with HbA1c = 41 mmol/mol (= 5.9%) (Q5) had a 69% lower disposition index than those with a HbA1c concentration of = 32 mmol/mol (= 5.1%) (Q1). Conclusions Elevated HbA1c levels = 41 mmol/mol (= 5.9%) were associated with substantial reductions in insulin secretion, insulin sensitivity and beta-cell dysfunction in Japanese individuals not treated for diabetes. High normal HbA1c levels of 3640 mmol/mol (5.45.8%) were also associated with impaired insulin secretion without marked insulin resistance in Japanese individuals.

DOI： 10.1111/j.1464-5491.2012.03667.x

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