OBJECTIVE:The aim of this study was to clarify the indications for oral glucose tolerance tests (OGTT) in non-alcoholic fatty liver disease (NAFLD) subjects with a HbA1c level of ≤6.4%, fasting plasma glucose (FPG) level of <126 mg/dL and no history of diabetes.PATIENTS:A total of 569 NAFLD subjects underwent 75-g OGTT. The plasma glucose and insulin levels were analyzed periodically for three hours during the OGTT examinations. Impaired fasting glucose (IFG) was defined as a plasma glucose level of ≥100 mg/dL to <126 mg/dL. Diabetes was defined as a two-hour post-load plasma glucose level of ≥200 mg/dL. Elevated insulin resistance was defined as a homeostasis model assessment-insulin resistance (HOMA-IR) of ≥2.5. Insulin secretory insufficiency was defined as an insulinogenic index of <0.4.RESULTS:The prevalence of diabetes on the OGTT was 7.7% (44/569) among the NAFLD patients with an HbA1c level of ≤6.4%, FPG level of <126 mg/dL and no history of diabetes. A multivariate analysis showed that diabetes occurred more frequently when the subjects had IFG [odds ratio (OR) 5.13; 95% confidential interval (CI) 3.01-8.76; p<0.001] and an HbA1c level of 5.7-6.4% (OR 5.45; 95% CI 3.33-8.93; p<0.001). Of the NAFLD subjects with both IFG and an HbA1c level of 5.7-6.4%, 22.8% (28/123) exhibited a pattern of diabetes on OGTT. Regarding insulin dynamics, among the NAFLD subjects with both IFG and an HbA1c level of 5.7-6.4%, 25.2% (31/123) had elevated IR alone, 25.2% (31/123) had insulin secretory deficiency alone and 27.6% (34/123) had both elevated insulin resistance and insulin secretory deficiency.CONCLUSION:NAFLD subjects with IFG and an HbA1c level of 5.7-6.4% should undergo OGTT in order to determine whether they have diabetes and/or abnormal insulin dynamics.

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 abnormal NW individuals, 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.

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.

OBJECTIVEThe aim of this retrospective cohort study was to assess the predictive factors for the regression from impaired glucose tolerance (IGT) to normal glucose regulation (NGR) in patients with nonalcoholic fatty liver disease (NAFLD).METHODSA total of 164 NAFLD patients who had IGT in the first 75-g oral glucose tolerance test (OGTT) and underwent a repeated OGTT five years later were enrolled. A multivariate logistic regression analysis was carried out to identify factors predicting the regression from IGT to NGR.RESULTSOut of the 164 patients, 29 regressed from IGT to NGR within five years after the first OGTT. The multivariate analysis by logistic regression showed that regression from IGT to NGR occurred when the patient was young (risk ratio for ten years: 0.38; 95% confidence interval [CI] 0.20-0.72; p=0.003), had a fasting plasma glucose (FPG) level of <100 mg/dL (risk ratio: 6.53; 95%CI 1.88-21.73; p=0.003), had a 2-hr post-load plasma glucose (PG) level of <160 mg/dL (risk ratio: 4.86; 95%CI 1.08-22.72; p=0.040), a body mass index (BMI) decrease of ≥1.5 (risk ratio: 5.20; 95% CI 1.41-19.24; p=0.014), physical activity of ≥2 Metabolic Equivalent of Task (MET) h/day (risk ratio: 5.57; 95%CI 1.68-18.44; p=0.005), and showed disappearance of the fatty liver by ultrasonography at five years (risk ratio: 9.92; 95%CI 2.87-34.34; p<0.001).CONCLUSIONOur results suggest that six factors: young age, FPG <100 mg/dL, 2-hr post-load PG of <160 mg/dL, BMI decrease of ≥1.5, physical activity of ≥2 MET h/day, and the disappearance of fatty liver predict the regression from IGT to NGR in NAFLD patients.

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

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 premenopausal women, 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 <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.

Kawasaki disease (KD) is one of the most important causes of coronary artery aneurysms in children and young adults. However, the natural course of the disease and the patient prognosis remain obscure. A 72-year-old asymptomatic man with undiagnosed KD underwent whole-heart magnetic resonance coronary angiography during a health checkup. The imaging disclosed giant aneurysms in the proximal portion of the right coronary artery and the left anterior descending artery. The patient was successfully treated with coronary artery bypass grafting. The present case suggests that there may be a substantial number of patients who have attained middle to old age with undiagnosed KD.

OBJECTIVE The objective of the study was to develop a screening score for undiagnosed diabetes by eliciting information on noninvasive clinical markers and to assess its effectiveness for identifying the presence of diabetes and predicting future diabetes. DESIGN, SETTING, AND PARTICIPANTS A screening score was cross-sectionally developed for 33 335 Japanese individuals aged 18-88 years without known diabetes who underwent a health examination. We validated its utility and compared it with existing screening tools in an independent population (n = 7477). After initial assessment of the instrument, 7332 nondiabetic individuals were followed up for a mean 4.0 years. RESULTS Prevalence of undiagnosed diabetes (fasting plasma glucose ≥ 7.0 mmol/L or glycated hemoglobin ≥ 6.5%) was 2.9% (n = 965). Diabetes score included age, sex, family history of diabetes, current smoking habit, body mass index, and hypertension with an area under the receiver-operating characteristics curve of 0.771. Screening with 8 or more points yielded a sensitivity of 72.7% and a specificity of 68.1%. In the validation cohort, the area under the receiver-operating characteristics curve was 0.806. The developed score with 8 or more points had better positive predictive value (9.6%) and positive likelihood ratio (2.52) compared with existing tools (positive predictive value, from 6.9% to 9.4%; positive likelihood ratio, from 1.77 to 2.46) in which each tool's highest combination of sensitivity and specificity was observed. The 4-year cumulative risk of developing diabetes gradually escalated in association with higher screening scores at the initial examination. CONCLUSIONS Our algorithm 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.

BACKGROUND Findings of past studies on the effect of drinking patterns on diabetes risk have been inconsistent. OBJECTIVE We aimed to investigate the role of drinking frequency and usual quantity consumed in the development of type 2 diabetes. DESIGN Enrolled were 1650 Japanese men without diabetes (diabetes: fasting plasma glucose ≥7.0 mmol/L, glycated hemoglobin ≥6.5%, or self-reported clinician-diagnosed diabetes). Average alcohol consumption and 12 combinations of frequency and usual quantity per drinking occasion were assessed at the baseline examination. The absolute risk and HR for the development of diabetes were calculated. RESULTS During a mean follow-up period of 10.2 y, 216 individuals developed diabetes. Lifetime abstainers (n = 153) had a relatively low incidence of diabetes (9.1/1000 person-years), similar to moderate consumers (99-160 g ethanol/wk; 9.0/1000 person-years). Increasingly higher quantities of alcohol usually consumed per occasion increased the risk of diabetes regardless of drinking frequency. The lowest incidence rate of diabetes (8.5/1000 person-years) was associated with the consumption of <1 drink (<23 g ethanol) per occasion over ≥6 times/wk. Binge drinking (≥3 drinks per occasion) significantly increased the risk of future diabetes regardless of frequency (HR: 1.79; 95% CI: 1.17, 2.74) compared with <1 drink per occasion. CONCLUSIONS Among current drinkers, a drinking pattern of <1 drink per occasion regularly over 6 times within a week was associated with the lowest risk of developing diabetes. Usual quantity per drinking occasion was a more important determinant than was weekly drinking frequency in the association between alcohol consumption and risk of diabetes in Japanese men.

Aim: Malignancies that include hepatocellular carcinoma often occurred in patients with chronic liver disease. The aim of this retrospective match control study was to assess the cumulative development incidence and predictive factors for total malignancies in elderly Japanese patients with non-alcoholic hepatic diseases (NAFLD) or hepatitis C virus (HCV).Methods: A total of 1600 NAFLD patients with age of 360 years were enrolled, and 1600 HCV patients with age of 360 years were selected as control by matching 1: 1 with NAFLD group for age, sex, and follow-up period. The primary goal is the first development of malignancies. Evaluation was performed by the use of the Wilcoxon rank sum test, the Kaplan-Meier method, and Cox proportional hazard model. The mean observation period is 8.2 years in both NAFLD and HCV group, respectively.Results: The number of patients with the development of malignancies was 167 in the NAFLD group and 395 in the HCV group. The 10th development rate of malignancies was 13.9% in the NAFLD group and 28.2% in the HCV group (risk ratio 2.27; P < 0.001). The incident rates of hepatocellular carcinoma in all the malignancies were 6.0% (10/ 167) in the NAFLD group and 67.6% (267/ 395) in the HCV group (P < 0.001). The malignancies in the NAFLD group were observed in the following order: gastric cancer 34 cases (20.4%) > colon cancer 31 cases (18.6%) > prostate cancer 21 cases (12.6%).Conclusions: The incident rates of hepatocellular carcinoma in all the malignancies were approximately 6% in the NAFLD group and two-thirds in the HCV group.

Background: Both eating till feeling full and eating rapidly may increase metabolic risk factors including obesity. The associations of such habits with psychosomatic problems and preference for strong tastes require further exploration.Methods: The associations between various eating behaviors and 12 psychosomatic problems (mental burden, sleep disorder, tendency to palpitation, diarrhea, pessimism, amnesia, anger, poor personal relationship, fatigue, epigastric distress, shoulder stiffness, and lumbago), and preference for strong tastes were compared in 8240 men and 2955 women who underwent routine health examinations. The subjects were divided into four groups defined by subjective reporting - G1: not eating till feeling full and not eating rapidly; G2: eating till feeling full only; G3: eating rapidly only; G4: eating both rapidly and till feeling full.Results: Compared to G1, the age-adjusted odds ratios were significantly higher in G2-G4 for mental burden [1.17 (1.01-1.35), 1.26 (1.14-1.41), 1.50 (1.31-1.73) in men; and 1.28 (1.003-1.62), 1.50 (1.21-1.85), 1.94 (1.50-2.51) in women], and for 8, 8, 11 items in men and 9, 6, 11 items in women among 11 psychosomatic problems other than mental burden, and for preference for strong tastes [2.25 (1.91-2.64), 1.89 (1.67-2.14), 3.36 (2.89-3.91) in men; and 3.26 (2.34-4.51), 2.88 (2.10-3.93), 5.59 (4.02-7.78) in women].Conclusions: Both eating till feeling full and eating rapidly are associated with mental burden, clustering of psychosomatic problems and a preference for strong tastes. Mental consultation and attention to choosing mild tasting foods may alleviate such eating behaviors and improve health. (C) 2011 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

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 >= 7.0 mmol/L and/or HbA1c >= 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 >= 7.0 mmol/L alone were characterized as having poorly controlled hypertension while those with HbA1c >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.

Objective To evaluate the effect of elevated fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) 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 ≥126 mg/dL, HbA1c ≥6.5%, or self-reported clinician-diagnosed diabetes) were estimated for spirometry indices as continuous and categorical variables. Results Elevated HbA1c 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 HbA1c concentrations but was attenuated substantially after adjustment for baseline HbA1c 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 HbA1c (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.