Prognostic factors for regression from impaired glucose tolerance to normal glucose regulation in Japanese patients with nonalcoholic fatty liver disease.

OBJECTIVE: The 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). METHODS: A 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. RESULTS: Out 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). CONCLUSION: Our 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.

Metabolically healthy obesity, presence or absence of fatty liver, and risk of type 2 diabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 20 (TOPICS 20).

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.

Role of body mass index history in predicting risk of the development of hypertension in Japanese individuals: Toranomon Hospital Health Management Center Study 18 (TOPICS 18).

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, 1.58­2.27) and those with an elevated body mass index both at baseline and in the early 20s had the highest odds ratio of 2.26 (1.76­2.89). Individuals with an elevated body mass index both at baseline and at the maximum had a 2.26-fold (1.87­2.72) 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.

Effect of postmenopausal status and age at menopause on type 2 diabetes and prediabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 17 (TOPICS 17).

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.

Giant coronary artery aneurysms associated with Kawasaki disease detected on whole-heart magnetic resonance coronary angiographic screening.

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.

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

AIM: The 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). METHODS: Twenty 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 48 weeks 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 48 weeks after the initiation of treatment. RESULTS: In the sitagliptin group, average HbA1c levels decreased approximately 0.7% at 48 weeks after the initiation of sitagliptin. Next, average FPG levels decreased approximately 15 mg/dL at 48 weeks 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 50 mg/day without reduction necessitated by sitagliptin-related side-effects. There were no significant changes of average AST and ALT levels during follow up of 48 weeks in both sitagliptin and control groups. CONCLUSION: Our results indicate sitagliptin is effective and safe for the treatment of T2DM complicated with NAFLD.

Development of a screening score for undiagnosed diabetes and its application in estimating absolute risk of future type 2 diabetes in Japan: Toranomon Hospital Health Management Center Study 10 (TOPICS 10).

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.

Role of alcohol drinking pattern in type 2 diabetes in Japanese men: the Toranomon Hospital Health Management Center Study 11 (TOPICS 11).

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.

Low lung function and risk of type 2 diabetes in Japanese men: the Toranomon Hospital Health Management Center Study 9 (TOPICS 9).

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 ≥126 mg/dL, HbA(1c) ≥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 (FEV(1)) than were FPG concentrations. During a 4.0-year follow-up, diabetes developed in 214 individuals. A 10-point decrease in percentage of FEV(1) 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 FEV(1) 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.

Longitudinal trajectories of HbA1c and fasting plasma glucose levels during the development of type 2 diabetes: the Toranomon Hospital Health Management Center Study 7 (TOPICS 7).

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 ≥ 7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) ≥ 6.5%). Mean HbA(1c) values were >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 prediagnosis, 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.

Difference in malignancies of chronic liver disease due to non-alcoholic fatty liver disease or hepatitis C in Japanese elderly patients.

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 ≥60 years were enrolled, and 1600 HCV patients with age of ≥60 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.

High serum uric acid level and low urine pH as predictors of metabolic syndrome: a retrospective cohort study in a Japanese urban population.

The objective of this study was to evaluate whether hyperuricemia, acidic urine, or their combination predicts metabolic syndrome (MetS). In study 1, 69,094 subjects who received a general health checkup between 1985 and 2005 were included in a cross-sectional study of serum uric acid (SUA) and urine pH in relation to MetS. In study 2, the association of SUA and urine pH with MetS development over a 5-year period was evaluated in 5617 subjects with body mass index less than 25 kg/m(2) at the first examination. In study 1, higher SUA and lower urine pH were both positively correlated to MetS status (P < .001). The combination of high SUA and low urine pH was significantly associated with higher MetS prevalence compared with the combination of low SUA and high urine pH (odds ratio, 3.383; 95% confidence interval [CI], 3.034-3.784 in men; odds ratio, 4.000; 95% CI, 2.992-5.452 in women). In study 2, the top quartile of SUA levels was associated with higher MetS development compared with the bottom quartile during the 5-year period in men (hazard ratio [HR], 1.793; 95% CI, 1.084-2.966; P = .023). In women, the HR was 3.732 (95% CI, 0.391-35.62; P = .252) for the upper vs the lower half of SUA levels. For urine pH, the HR was 1.955 (95% CI, 1.089-3.509; P = .025) for the bottom vs the top quartile in men. A likelihood ratio test confirmed that high SUA and low urine pH act synergistically in the development of MetS. High SUA, low urine pH, and their combination are predictive risk factors for MetS development.

Both eating till feeling full and rapid eating are associated with clustering of psychosomatic problems and preference for strong tastes.

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.

Impact of introducing HbA1c into the diagnostic criteria on prevalence and cardiovascular risk profiles of individuals with newly diagnosed diabetes in Japan: the Toranomon Hospital Health Management Center Study 2 (TOPICS 2).

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 γ-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.

Association of short sleep duration with obesity, diabetes, fatty liver and behavioral factors in Japanese men.

OBJECTIVE: Sleep is one of the major means to maintain health. The association of short sleep duration with obesity, diabetes, fatty liver and behavioral factors requires further exploration. METHODS: A total of 8157 Japanese men who underwent health evaluations were divided into 3 groups by sleep duration <5 hours, 5~<7 hours and ≥7 hours. Poor sleep was self-reported, being defined as difficulty of getting to sleep or awakening easily. The age-adjusted and age and poor sleep-adjusted odds ratios of the 3 groups for obesity, diabetes, fatty liver, mental stress, poor sleep, regular exercise and late dinner time were investigated. RESULTS: Compared to the sleep duration 5~<7 hours group, the age-adjusted odds ratios of the <5 hours group were significantly higher for obesity (1.42), diabetes (1.63), mental stress (1.75), poor sleep (1.85), late dinner time (1.47), and significantly lower for regular exercise (0.61); while those of the ≥7 hours group were significantly lower for obesity (0.73), fatty liver (0.82), mental stress (0.73), poor sleep (0.69), late dinner time (0.45), and significantly higher for regular exercise (1.27). Above significances still existed after adjustment for age and poor sleep. CONCLUSION: Short sleep duration is associated with obesity, diabetes, fatty liver and multiple behavioral factors. The optimal sleep duration for health promotion and effective actions for obtaining optimal sleep, including modifications of behavioral and environmental factors, should be one of the major concerns of public health.

HbA1c 5·7-6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study.

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 ≥7·0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) ≥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. FUNDING: Japan Society for the Promotion of Science; Ministry of Health Labor and Welfare, Japan.

The development of chronic kidney disease in Japanese patients with non-alcoholic fatty liver disease.

Objective Chronic kidney disease (CKD) is present in patients with nonalcoholic fatty liver disease (NAFLD). The aim of this retrospective study was to assess the cumulative development incidence and predictive factors for new onset of CKD in Japanese patients with NAFLD. Methods A total of 5,561 NAFLD patients without CKD were enrolled. CKD was defined as either an estimated glomerular filtration rate of <60 mL/min/1.73 m(2) or dipstick proteinuria (≥+1). A blood sample and a urine sample were taken for routine analyses during follow-up. The mean observation period was 5.5 years. The primary goal is the new development of CKD. Independent factors associated with new development of CKD were analyzed by using the Kaplan-Meyer method and the Cox proportional hazards model. Results Of 5.561 NAFLD patients, 263 patients developed CKD. The cumulative development rate of CKD was 3.1% at the 5th year and 12.2% at the 10th year. Multivariate Cox proportional hazards analysis showed that CKD development in patients with NAFLD occurred when patient had low level of GFR of 60-75 mL/min/1.73 m(2) [hazard ratio:2.75; 95% confidence interval (CI)=1.93-3.94; p<0.001], age of ≥50 years (hazard ratio: 2.67; 95% CI=2.06-3.46; p<0.001), diabetes (hazard ratio: 1.92; 95% CI=1.45-2.54; p<0.001), hypertension (hazard ratio: 1.69; 95% CI=1.25-2.29; p<0.001), and elevated serum gamma-glutamyltransferase of ≥109 IU/L (hazard ratio: 1.35; 95% CI=1.02-1.78; p=0.038). Conclusion Our retrospective study indicates that the annual incidence of CKD in Japanese patients with NAFLD is about 1.2%. Five factors of low eGFR level, aging, type 2 diabetes, hypertension, and elevated gamma-glutamyltransferase, increases the risk of the development of CKD.

Eating until feeling full and rapid eating both increase metabolic risk factors in Japanese men and women.

OBJECTIVE: To investigate the association between eating behaviour and metabolic risk in the broader population. DESIGN: The association between metabolic risk factors (overweight, hypertension, hyperglycaemia, hypertriacylglycerolaemia, low HDL cholesterol, hyperuricaemia and fatty liver) and various eating behaviours were compared for four groups defined by subjective reporting: not eating until feeling full and not eating rapidly (G1); eating until feeling full only (G2); eating rapidly only (G3); and eating both rapidly and until feeling full (G4). SETTING: A medical centre for health examinations in Tokyo, Japan. SUBJECTS: Men (n 8240) and women (n 2955) who underwent health examinations. RESULTS: The distribution of participants in G1 to G4 was 49·8 %, 11·5 %, 26·3 % and 12·4 % among men and 55·3 %, 15·0 %, 19·0 % and 10·7 % among women, respectively. Compared with G1, the age-adjusted OR (95 % CI) for overweight were significantly higher in G2 to G4, being respectively 1·85 (1·58, 2·17), 1·98 (1·76, 2·23) and 3·46 (2·99, 4·01) for men and 2·20 (1·62, 2·97), 2·59 (1·97, 3·39) and 3·12 (2·27, 4·26) for women. The age-adjusted OR were also significantly higher for hypertriacylglycerolaemia, hyperuricaemia and fatty liver in G2 and for all risks in G3 and G4 among men; and for hyperuricaemia in G2, for hyperglycaemia, hypertriacylglycerolaemia and fatty liver in G3 and for hypertriacylglycerolaemia and fatty liver in G4 among women. CONCLUSIONS: Both eating until feeling full and eating rapidly increase metabolic risk factors. Although the mechanism between rapid eating and metabolic risk requires further exploration, eating slowly and ending meals shortly before feeling full are important public health messages for reducing metabolic risk factors.

A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0·5 could be a suitable global boundary value.

This systematic review collated seventy-eight studies exploring waist-to-height ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and CVD, published in English between 1950 and 2008. Twenty-two prospective analyses showed that WHtR and WC were significant predictors of these cardiometabolic outcomes more often than BMI, with similar OR, sometimes being significant predictors after adjustment for BMI. Observations from cross-sectional analyses, forty-four in adults, thirteen in children, supported these predictions. Receiver operator characteristic (ROC) analysis revealed mean area under ROC (AUROC) values of 0·704, 0·693 and 0·671 for WHtR, WC and BMI, respectively. Mean boundary values for WHtR, covering all cardiometabolic outcomes, from studies in fourteen different countries and including Caucasian, Asian and Central American subjects, were 0·50 for men and 0·50 for women. WHtR and WC are therefore similar predictors of diabetes and CVD, both being stronger than, and independent of, BMI. To make firmer statistical comparison, a meta-analysis is required. The AUROC analyses indicate that WHtR may be a more useful global clinical screening tool than WC, with a weighted mean boundary value of 0·5, supporting the simple public health message 'keep your waist circumference to less than half your height'.

Virus clearance reduces bone fracture in postmenopausal women with osteoporosis and chronic liver disease caused by hepatitis C virus.

Osteoporosis is often present in postmenopausal women. The aim of this retrospective cohort study was to assess the cumulative incidence and predictive factors for bone fracture after cessation of interferon (IFN) in postmenopausal women with osteoporosis and chronic liver disease caused by hepatitis C virus (HCV). A total of 420 postmenopausal women treated with IFN monotherapy were enrolled. The mean observation period was 7.2 years. The primary goal was the development of bone fracture. Evaluation was carried out by using the Kaplan-Meier method and the Cox proportional hazards analysis. Thirty-one out of 420 patients sustained bone fracture. The cumulative development rate of bone fracture was 3.6% at 5th year, 9.2% at 10th year, and 17.4% at 15th year. Multivariate Cox proportional hazards analysis showed that bone fracture after cessation of IFN therapy occurred when histological staging of the liver was advanced (hazard ratio (HR): 2.54; 95% confidence interval (CI) = 1.21-5.31; P = 0.013), serum albumin level was < 3.5g/dl (HR: 2.25; 95% CI = 1.10-4.59; P = 0.026), and virus clearance was not achieved (HR: 3.65; 95% CI = 1.11-12.05; P = 0.033). The results indicate that virus clearance causes a reduction of two-thirds in the risk of bone fracture after cessation of IFN therapy in postmenopausal women with osteoporosis and chronic liver disease caused by HCV. J. Med. Virol. 82:390-395, 2010. (c) 2010 Wiley-Liss, Inc.