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Aims: Visceral adiposity measured by computed tomography (CT) as intra-abdominal fat area (IAFA) predicts metabolic diseases. Existing adiposity surrogates have not been systematically compared to a regression-based model derived in individuals of Japanese ancestry. We developed and validated a method to estimate IAFA in individuals of Japanese ancestry and compared it to existing adiposity surrogates.Methods: We assessed age, BMI, waist circumference (WC), fasting lipids, glucose, smoking status, grip strength, mid-thigh circumference (MTC), humeral length, leg length, and IAFA by single-slice CT at the umbilicus for 622 Japanese Americans. We used stepwise linear regression to predict IAFA and termed the predicted value the Estimate of Visceral Adipose Tissue Area (EVA). For men, the final model included age, BMI, WC, high-density lipoprotein cholesterol (HDLc), glucose, and MTC; for women, age, BMI, WC, HDLc, low-density lipoprotein cholesterol, glucose, and MTC. We compared goodness-of-fit (R2) from linear regression models and mean-squared errors (MSE) from k-fold cross-validation to compare the ability of EVA to estimate IAFA compared to an estimate by Després et al., waist-to-height ratio, WC, deep abdominal adipose tissue index, BMI, lipid accumulation product, and visceral adiposity index (VAI). We classified low/high IAFA using area under receiver-operating characteristic curves (AUROC) for IAFA dichotomized at the 75th percentile.Results: EVA gave the least MSE and greatest R2 (men: 1244, 0.61; women: 581, 0.72). VAI gave the greatest MSE and smallest R2 (mean 2888, 0.08; women 1734, 0.14).Conclusions: EVA better predicts IAFA in Japanese-American men and women compared to existing surrogates for adiposity. [ABSTRACT FROM AUTHOR]

Aims: To describe the roles of intra-abdominal fat and its change in the remission of impaired glucose tolerance (IGT) to normal glucose tolerance (NGT).Methods: We followed 157 Japanese Americans with IGT at baseline for 10-11 years without external intervention. We measured intra-abdominal and abdominal subcutaneous fat area (IAFA and ASFA) by computed tomography at baseline and at 5-6 years of follow-up. Change in IAFA and ASFA (ΔIAFA and ΔASFA) were calculated by subtracting baseline fat area from 5-6 year follow-up fat area. Glucose and insulin at fasting and during a 75-g oral glucose tolerance test, insulinogenic index (IGI [Δinsulin/Δglucose (30-0 min)]) and homeostasis model assessment for insulin resistance (HOMA-IR) were measured at baseline.Results: Fourty-four subjects remitted to NGT. Among those with lower IAFA (≤median 91.31 cm2) and the lowest tertile of ΔIAFA, 45% remitted, while with higher IAFA (>91.31 cm2) and the highest tertile of ΔIAFA, only 12.5% remitted. ΔIAFA was significantly associated with remission to NGT (multiple-adjusted odd ratio [1-SD decrease] 1.93, 95% CI 1.10-3.36) independent of IAFA, ASFA, ΔASFA, IGI, HOMA-IR, age, sex, and family history of diabetes.Conclusions: In the natural history of IGT, change in intra-abdominal fat was associated with remission to NGT. [ABSTRACT FROM AUTHOR]

Background Although short sleep duration has been reported to be associated with future cardiometabolic diseases, it is not fully understood whether sleep duration is prospectively associated with the risk of each lipid profile abnormality. Methods Subjects were nondiabetic Japanese, 40–55 years of age, who were not taking oral lipid-lowering medications: for the incidence of low high-density lipoprotein cholesterol (HDL-C), 7627 men with an HDL-C level ≥40 mg/dL; for high triglycerides, 6973 men with a triglyceride level <200 mg/dL; for high low-density lipoprotein cholesterol (LDL-C), 7273 men with an LDL-C level <160 mg/dL; for high non-HDL-C, 7415 men with a non-HDL-C level <190 mg/dL; and for high total cholesterol (TC), 7196 men with a TC level <240 mg/dL. Lipid profile abnormalities were defined according to the Adult Treatment Panel III guidelines of the National Cholesterol Education Program. Results During the 6-year observation period, there were 1022 cases of low HDL-C. Multiple-adjusted hazard ratios for low HDL-C were 0.79 (95% confidence interval, 0.64–0.97) for sleep durations of 5 to <7 h and 0.62 (0.46–0.83) for ≥7 h compared with <5 h. There were 1473 cases of high triglycerides. Multiple-adjusted hazard ratios for high triglycerides were 0.81 (0.68–0.98) for sleep durations of 5 to <7 h and 0.90 (0.72–1.13) for ≥7 h compared with <5 h. However, no association between sleep duration and the risk of future high LDL-C, non-HDL-C, or TC was observed. Conclusions Moderate and/or long sleep durations decreased the risk of future low HDL-C and high triglycerides. [ABSTRACT FROM AUTHOR]

Objective Butyrylcholinesterase is synthesized in the liver. The serum butyrylcholinesterase level has been cross-sectionally reported to be higher in patients with diabetes, hyperlipidaemia, obesity and fatty liver than in those without them. It is not known whether serum butyrylcholinesterase is associated with the risk of future type 2 diabetes. Design A prospective cohort study. Participants A total of 8470 Japanese men aged 40-55 years without type 2 diabetes at baseline. Measurements Type 2 diabetes was diagnosed if a fasting plasma glucose ( FPG) level was ≥7·0 mmol/l, if a HbA1c level was ≥6·5% or if participants were taking oral hypoglycaemic medication or insulin. Results During the 42 227 person-years of follow-up, 868 cases had developed type 2 diabetes. Serum butyrylcholinesterase was significantly positively correlated with body mass index ( BMI), FPG, alanine aminotransferase ( ALT), γ-glutamyltransferase ( GGT) and triglycerides ( TG), whereas negatively with high-density lipoprotein ( HDL) cholesterol. In Cox proportional hazards models, after adjusting for age, BMI, FPG, alcohol consumption, smoking habit, walk to work, regular leisure-time physical activity and family history of diabetes, the highest quartile (398-806 IU/l) of serum butyrylcholinesterase increased the risk of type 2 diabetes compared with the lowest quartile (56-311 IU/l) [hazard ratio ( HR) 1·41 (95% confidence interval ( CI), 1·14-1·74)]. After further adjusting for ALT and GGT, this association remained [ HR 1·40 (95% CI, 1·13-1·73)]. Furthermore, this association was significant independent of TG and HDL cholesterol. Conclusions Elevated serum butyrylcholinesterase was independently associated with an increased risk of future type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine whether the patterns of insulin concentration during the oral glucose tolerance test (OGTT) predict type 2 diabetes. RESEARCH DESIGN AND METHODS--We followed 400 nondiabetic Japanese Americans for 10-11 years. Insulin concentrations at 30, 60, and 120 min during a 2-h 75-g OGTT at baseline were used to derive the following possible patterns of insulin: pattern 1 (30-min peak, higher insulin level at 60 than at 120 min), pattern 2 (30-min peak, lower or equal level at 60 vs. 120 min), pattern 3 (60-min peak); pattern 4 (120-min peak, lower level at 30 than at 60 min), and pattern 5 (120-min peak, equal or higher level at 30 vs. 60 min). Insulin sensitivity was estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Insulin secretion was estimated by the insulinogenic index (IGI) [Δinsulin/Δglucose (30- 0 min)] and disposition index (IGI/HOMA-IR). RESULTS--There were 86 incident cases of type 2 diabetes. The cumulative incidence was 3.2, 9.8, 15.4, 47.8, and 37.5% for patterns 1, 2, 3, 4, and 5, respectively. Compared with pattern 1, patterns 4 and 5, characterized by a lasting late insulin response, were associated with significantly less insulin sensitivity as measured by the Matsuda index and lower early insulin response by the disposition index. The multiple-adjusted odds ratios of type 2 diabetes were 12.55 (95% CI 4.79-32.89) for pattern 4 and 8.34 (2.38-29.27) for pattern 5 compared with patterns 1 and 2. This association was independent of insulin secretion and sensitivity. CONCLUSIONS--The patterns of insulin concentration during an OGTT strongly predict the development of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Tonsillectomy is being frequently used in Japan, while Western nephrologists are more reluctant to adopt tonsillectomy as a treatment for IgAN…(In this issue of NDT) Isseki et al. report the outcome of 200 Japanese patients with biopsy-proven IgAN followed in mean for up to 7 years after renal biopsy.Background Indication of tonsillectomy in IgA nephropathy is controversial. The purpose of this study was to examine the efficacy of tonsillectomy on remission and progression of IgA nephropathy. Methods We conducted a single-center 7-year historical cohort study in 200 patients with biopsy-proven IgA nephropathy. Study outcomes were clinical remission defined as disappearance of urine abnormalities at two consecutive visits, glomerular filtration rate (GFR) decline defined as 30% GFR decrease from baseline and GFR slope during the follow-up. Results Seventy of the 200 patients received tonsillectomy. Tonsillectomy was associated with increased incidence of clinical remission (P + 0.01, log-rank test) and decreased incidence of GFR decline (P = 0.01, log-rank test). After adjustment for age and gender, hazard ratios in tonsillectomy were 3.90 (95% confidence interval 2.46–6.18) for clinical remission and 0.14 (0.02–1.03) for GFR decline. After further adjustment for laboratory (baseline mean arterial pressure, GFR, 24-h proteinuria and hematuria score), histological (mesangial score, segmental sclerosis or adhesion, endocapillary proliferation and interstitial fibrosis) or treatment variables (steroid and renin–angiotensin system inhibitors), similar results were obtained in each model. Even after exclusion of 69 steroid-treated patients, results did not change. GFR slopes in tonsillectomy and non-tonsillectomy groups were 0.60 ± 3.65 and − 1.64 ± 2.59 mL/min/1.73 m2/year, respectively. In the multiple regression model, tonsillectomy prevented GFR decline during the follow-up period (regression coefficient 2.00, P = 0.01). Conclusion Tonsillectomy was associated with a favorable renal outcome of IgA nephropathy in terms of clinical remission and delayed renal deterioration even in non-steroid-treated patients. [ABSTRACT FROM PUBLISHER]

Background Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes. However, the relationship between drinking patterns, such as the weekly frequency of alcohol consumption and the quantity per drinking day, and the incidence of type 2 diabetes has not been sufficiently addressed. Methods Study participants included 10 631 Japanese men aged 40e55 years without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was $7.0 mmol/l or if participants were taking diabetes medications. Data on alcohol consumption were obtained from questionnaires. Results During the 37 172 person-years of follow-up, we confirmed 878 cases of type 2 diabetes. Frequent alcohol consumption was associated with a low risk of type 2 diabetes. Compared to non-drinkers, the multiple-adjusted HR for those who drank 4e7 days weekly was 0.76 (95% CI, 0.63 to 0.92). To assess the association between drinking pattern and type 2 diabetes, we examined the joint association of the weekly frequency and the quantity per drinking day with type 2 diabetes. Men who consumed 0.1e2.0 or 2.1e4.0 US standard drinks per drinking day on 4e7 days weekly had a lower risk of type 2 diabetes (HR 0.74, 95% CI 0.58 to 0.95; HR 0.74, 95% CI 0.60 to 0.91, respectively) compared to non-drinkers. Conclusions More frequent alcohol consumption lowered the risk of type 2 diabetes. Light to moderate alcohol consumption per drinking day on 4e7 days weekly lowered the risk of type 2 diabetes compared to non-drinkers. [ABSTRACT FROM AUTHOR]

OBJECTIVE--It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed. RESEARCH DESIGN AND METHODS--The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was ≥126 mg/dl or if participants were taking oral hypoglycemic medications or insulin. RESULTS--During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of γ-glutamyhransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (≥42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT. CONCLUSIONS--GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Visceral adiposity is generally considered to play a key role in the metabolic syndrome. We sought to determine whether greater visceral adiposity directly measured by computed tomography (CT) is associated with increased future insulin resistance independent of other adipose depots. RESEARCH DESIGN AND METHODS--We followed 306 nondiabetic Japanese Americans over 10-11 years. Baseline variables included BMI; waist circumference; and abdominal, thoracic, and thigh fat areas measured by CT. Total fat area was estimated by the sum of all of these fat areas. Visceral adiposity was measured as intra-abdominal fat area at the umbilicus level. Total subcutaneous fat area was defined as total fat area minus intra-abdominal fat area. Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR), fasting plasma insulin level, Matsuda index, and area under the oral glucose tolerance test curve (AUC) of insulin. RESULTS--Both baseline intra-abdominal fat area (P = 0.002) and HOMA-IR (P < 0.001) were independently associated with increased HOMA-IR at 10-11 years in a multiple linear regression model after adjustment for abdominal subcutaneous fat area, age, sex, 2-h plasma glucose level, and incremental insulin response. Intra-abdominal fat area remained a significant predictor of increased HOMA-IR at 10-11 years even after adjustment for total subcutaneous fat area, total fat area, BMI, or waist circumference, but no other measure of CT-measured regional or total adiposity was significantly related with HOMA-IR at 10-11 years in models that contained intra-abdominal fat area. Similar results were obtained for predicting future fasting plasma insulin level, Matsuda index, and AUC of insulin. CONCLUSIONS--Greater visceral adiposity is associated with an increase in future insulin resistance. [ABSTRACT FROM AUTHOR]

OBJECTIVE. The aim was to determine whether inhaled nitric oxide therapy improves neurodevelopmental outcomes for infants with preterm persistent pulmonary hypertension of the newborn. METHODS. We conducted a historical cohort study to compare the 3-year incidence of cerebral palsy in preterm singleton infants (<34 gestational weeks) with hypoxemic respiratory failure caused by persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (16 patients) or 100% oxygen (15 patients) therapy. All neonates had clinical and echocardiographic evidence of pulmonary hypertension without structural heart disease. RESULTS. The incidence of cerebral palsy among patients treated with inhaled nitric oxide was 12.5%, whereas that among patients treated with 100% oxygen was 46.7%. After adjustment for maternal fever (≥38°C) during delivery, birth weight, Apgar score at 5 minutes, high-frequency oscillatory ventilation, and surfactant therapy, inhaled nitric oxide therapy, compared with 100% oxygen therapy, was associated with a decreased risk of cerebral palsy in preterm infants with persistent pulmonary hypertension of the newborn. CONCLUSION. Inhaled nitric oxide therapy decreases the risk of cerebral palsy in preterm infants with persistent pulmonary hypertension of the newborn. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Japanese American is an ethnic group with a high risk for type 2 diabetes, which is linked to the metabolic syndrome. Central adiposity is considered to play a key role in the metabolic syndrome. Not known are the optimal cut point values for central and visceral adiposity to identify Japanese Americans at risk for the metabolic syndrome. RESEARCH DESIGN AND METHODS -- Study subjects included 639 Japanese Americans. The nonadipose variables of the metabolic syndrome were defined using modified International Diabetes Federation criteria, and the accuracy of identifying at least two of these by intra-abdominal fat area (IAFA) as measured by computed tomography and waist circumference was cross-sectionally assessed using area under receiver operating characteristic (ROC) curves. The values for IAFA and waist circumference that resulted in maximizing the Youden index were defined as "optimal." RESULTS -- The area under the ROC curve for IAFA exceeded that for waist circumference (men 0.787 vs. 0.686; women 0.792 vs. 0.721). For women, the optimal cut points for IAFA and waist circumference were 51.5 cm² and 80.8 cm (age ≤56 years) and 86.3 cm² and 89.0 cm (age >56 years). For men, the optimal cut points for IAFA and waist circumference were 88.6 cm² and 90.0 cm (age ≤57 years) and 96.1 cm² and 87.1 cm (age >57 years). CONCLUSIONS -- These results argue that current Japanese waist circumference cut points for the metabolic syndrome need to be revised. Moreover, the waist circumference and IAFA cut points should be age specific, especially in women. Appropriate waist circumference cut points are from 80 to 90 cm in women and from 87 to 90 cm in men. [ABSTRACT FROM AUTHOR]

Abstract: Background: QT dispersion is increased in acute myocardial infarction (AMI), but the relation of QT dispersion to left ventricular (LV) function has not yet been fully elucidated. The purpose of this study was to evaluate the relationship between QT dispersion and LV function in patients with successful coronary stenting in AMI. Methods: Seventy five patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA) were enrolled in this study. Corrected QT dispersion was measured before, immediately after, 24 h after, 48 h after, and 6 months after PTCA. Left ventricular ejection fraction (LVEF) was evaluated by left ventriculography at 6 months after PTCA. Results: Corrected QT dispersion at 24 h after and 48 h after PTCA were significantly related to LVEF by univariate analysis (r =−0.282, p <0.05 and r =−0.326, p <0.01, respectively). In multiple regression model, corrected QT dispersion at 24 h after and 48 h after PTCA revealed significant associations with LVEF (R 2 =0.441, coefficient=−0.283, p =0.006 and R 2 =0.411, coefficient=−0.225, p =0.039, respectively), but corrected QT dispersion before, immediately after, and 6 months after PTCA were not associated with LVEF. Conclusions: Corrected QT dispersion at 24 h after and 48 h after PTCA in AMI correlate with LVEF at 6 months after PTCA. [Copyright &y& Elsevier]

Background: Visceral adiposity is generally considered to play a key role in the metabolic syndrome. Objective: To examine the relationship between directly measured visceral adiposity and the risk for incident hypertension, independent of other adipose depots and fasting plasma insulin levels. Design: Community-based prospective cohort study with 10- to 11-year follow-up. Setting: King County, Washington. Participants: 300 Japanese Americans with a systolic blood pressure less than 140 mm Hg and a diastolic blood pressure less than 90 mm Hg who were not taking antihypertensive medications, oral hypoglycemic medications, or insulin at study entry. Measurements: Abdominal, thoracic, and thigh fat areas were measured by using computed tomography. Total subcutaneous fat area was calculated as the sum of these fat areas excluding the intra-abdominal fat area. Hypertension during follow-up was defined as having a systolic blood pressure of 140 mm Hg or greater, having a diastolic blood pressure of 90 mm Hg or greater, or taking antihypertensive medications. Results: There were 92 incident cases of hypertension during the follow-up period. The intra-abdominal fat area was associated with an increased risk for hypertension. Multiple-adjusted odds ratios of hypertension for quartiles of intra-abdominal fat area (1 = lowest; 4 = highest) were 5.07 (95% Cl, 1.75 to 14.73) for quartile 3 and 3.48 (Cl, 1.01 to 11.99) for quartile 4 compared with quartile I after adjustment for age, sex, fasting plasma insulin level, 2-hour plasma glucose level, body mass index, systolic blood pressure, alcohol consumption, smoking status, and energy expenditure through exercise (P = 0.003 for quadratic trend). The intra-abdominal fat area remained a significant risk factor for hypertension, even after adjustment for total subcutaneous fat area, abdominal subcutaneous fat area, or waist circumference; however, no measure of these fat areas was associated with risk for hypertension in models that contained the intra-abdominal fat area. Limitations: It is not known whether these results pertain to other ethnic groups. Conclusions: Greater visceral adiposity increases the risk for hypertension in Japanese Americans. [ABSTRACT FROM AUTHOR]

Objective: Greater visceral adiposity, higher insulin resistance, and impaired insulin secretion increase the risk of type 2 diabetes. Whether visceral adiposity increases risk of impaired glucose tolerance (IGT) independent of other adipose depots, insulin resistance, and insulin secretion is not known.Research Design and Methods: Study subjects included 128 Japanese Americans with normal glucose tolerance at entry. Baseline variables included plasma glucose and insulin measured after an overnight fast and during a 75-g oral glucose tolerance test, fat areas by computed tomography, insulin secretion (incremental insulin response [IIR] [30 min insulin - fasting insulin]/30 min glucose), and insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR]).Results: During the 10- to 11-year follow-up period, we confirmed 57 cases of IGT. Significant predictors of IGT included intra-abdominal fat area (IAFA) (odds ratio [OR] for a 1 SD increase 3.82, 95% CI 1.63-8.94 at a fasting plasma glucose [FPG] level of 4.5 mmol/l), HOMA-IR (2.41, 1.15-5.04), IIR (0.30, 0.13-0.69 at an FPG level of 4.5 mmol/l), the interactions of IAFA by FPG (P = 0.003), and IIR by FPG (P = 0.030) after adjusting for age, sex, FPG, and BMI. The multiple-adjusted OR of IAFA increased and that of IIR decreased as FPG level decreased because of these interactions. Even after adjustment for total fat area, total subcutaneous fat area, or abdominal subcutaneous fat area, all of these associations remained a significant predictor of IGT incidence.Conclusions: Greater visceral adiposity increases the risk of IGT independent of insulin resistance, insulin secretion, and other adipose depots in Japanese Americans. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the relationship between daily alcohol consumption and the risk of type 2 diabetes in a large Japanese cohort. Research design and methods; Results; Conclusions.

Presents information on a study regarding the effect of impaired fasting glucose (IFG) in increasing the risk of hypertension on Japanese cohorts during 1980 and 1990. Diagnosis of diabetes, IFG and hypertension; Biochemical measurements and clinical characteristics of the study; Result and discussion.

Investigates the association of the duration of the walk to work and leisure-time physical activity with the risk for hypertension. Decrease in risk for hypertension in Japanese men engaged in walking to work and other types of physical activity; Importance of regular exercise.

Aims: We compared 20 previously reported indices of insulin sensitivity derived from samples during an oral glucose tolerance test (OGTT) to determine which was best in predicting incident type 2 diabetes.Methods: We prospectively followed 418 Japanese Americans without diabetes for 10-11 years. We compared ability to predict incident diabetes of 20 insulin sensitivity indices-9 based on fasting samples, 7 based on 2-h and/or fasting samples, and 4 based on multiple samples (0, 30, 60, 120 min) during an OGTT-by integrated discrimination improvement, category free net reclassification improvement, and area under the receiver operator characteristic curve.Results: There were 95 incident cases of diabetes. The Cederholm and Gutt indices, requiring more than only fasting samples, were the best to predict incident diabetes as judged by integrated discrimination improvement (0.187, 0.184), category free net reclassification improvement (0.962, 1.030), and area under the receiver operator characteristic curve (0.864, 0.863, respectively). Fasting indices were clearly inferior to both the Cederholm and Gutt indices.Conclusions: Among the 20 indices, the Cederholm and Gutt indices predicted diabetes best but the Gutt index may be preferable because it requires fewer samples during an OGTT. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes. RESEARCH DESIGN AND METHODS-- Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG ≥126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves. RESULTS -- During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001). CONCLUSIONS -- The combined measurement of FPG and A1C was effective for predicting type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes. RESEARCH DESIGN AND METHODS-- The study participants were nondiabetic Japanese men (n = 8,570) aged 40-55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was ≥ 126 mg/dl or if participants were taking oral hypoglycemic medication or insulin. RESULTS-- During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44-2.54) compared with those who had levels between 0.71 and 0.80 mg/dl. CONCLUSIONS -- Lower serum creatinine increased the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article discusses a study on the relationship between walking to work and the development of type 2 diabetes in Japanese men. It mentions that studies revealed that physical activity is effective in preventing diabetes. Men were examined based on their leisure-time physical activity, smoking habits and alcohol intake. The result of the study provided evidence that duration of the walk going to work has an independent effect on the risk of type 2 diabetes.

β-cell dysfunction is major risk factor for type 2 diabetes. As HOMA-β reflects fasting β-cell function and insulinogenic index reflects early phase insulin response during an oral glucose tolerance test (OGTT), these two indices represent different aspects of insulin and glucose metabolism. It is not known whether HOMA-β and insulinogenic index are independently associated with type 2 diabetes risk. In a prospective cohort study, 415 nondiabetic Japanese-American men and women were followed for 10-11 years. Insulin sensitivity was assessed by HOMA-IR. β-cell activity was assessed by HOMA-β [fasting plasma insulin (μU/mL) × 360/(fasting plasma glucose (mg/dL) - 63)] and the insulinogenic index [Δinsulin (30-0 min) (μU/mL)/Δglucose (30-0 min) (mg/dL)] obtained during a 75-g OGTT. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, 2-hour glucose level ≥200 mg/dL, or taking glucose-lowering medications. Logistic regression analysis was used to estimate odds ratios (OR) of incident diabetes. A total of 95 participants developed type 2 diabetes over 10-11 years. Insulinogenic index and HOMA-β were independently associated with the risk of type 2 diabetes. In multiple-adjusted models that included insulinogenic index, HOMA-β, HOMA-IR, age, BMI, gender, and family history of diabetes, OR of future type 2 diabetes for tertile 2 and 3 of insulinogenic index were 0.43 (95% CI, 0.22-0.85) and 0.31 (0.14-0.67), respectively, compared to tertile 1, and those for tertile 2 and 3 of HOMA-β were 0.31 (0.14-0.69) and 0.25 (0.10-0.63), respectively, compared to tertile 1. HOMA-IR was also associated with the risk of type 2 diabetes independent of these two indices. OR of tertile 2 and 3 of HOMA-IR were 1.75 (0.82-3.74) and 9.17 (3.78-22.28), respectively, compared to tertile 1. In conclusion, both higher insulinogenic index and HOMA-β were independently associated with a lower risk of type 2 diabetes independent of insulin sensitivity. Disclosure: K.K. Sato: None. T. Hayashi: None. S. Uehara: None. Y. Onishi: None. D.L. Leonetti: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. W.Y. Fujimoto: None. E.J. Boyko: None. [ABSTRACT FROM AUTHOR]

Aims: We examined the longitudinal association between change in body composition directly measured by computed tomography (CT) and future insulin sensitivity.Methods: This was a prospective study with 10 years of follow-up with 297 Japanese-American without diabetes. Intra-abdominal fat area (IAFA) and abdominal subcutaneous fat area (SCFA), and thigh SCFA were measured by CT. Insulin sensitivity was calculated by HOMA-IR and the Matsuda index.Results: Baseline and change in IAFA were significantly and independently associated with change in HOMA-IR and Matsuda index during follow-up. In multivariate analysis, IAFA and 10-year change in IAFA (Δ IAFA) was significantly and positively associated with 10-year HOMA-IR (p < 0.001) and significantly and negatively associated with 10-year Matsuda index (p < 0.001). The association with Matsuda index though was non-linear and best modeled as a quadratic function (Δ IAFA + Δ IAFA2). No significant associations in multivariate analyses were seen between thigh SCFA and insulin sensitivity or abdominal SCFA and HOMA-IR but an increase in abdominal SCFA was associated with diminished insulin sensitivity measured by the Matsuda index.Conclusions: An increase in visceral adiposity predicts diminished insulin sensitivity over 10 years of follow-up independent of the size of this adipose depot at baseline. [ABSTRACT FROM AUTHOR]

Central adiposity is generally considered to play a key role in the metabolic syndrome. The purpose of this study is whether abdominal fat depots directly measured by computed tomography (CT) and their changes during a follow-up period are associated with future levels of HDL cholesterol, triglycerides, and non-HDL cholesterol. In addition, we investigated whether these associations differed between men and women. We followed 376 Japanese Americans over 10-11 years who were not taking oral hypoglycemic medication or insulin at entry and not taking lipid lowering medications both at entry and at 10-11 year follow-up. Intra-abdominal fat area (IAFA) and abdomen subcutaneous fat area (ASFA) were measured at the umbilicus by CT. In men greater baseline IAFA was significantly associated with decreased future HDL cholesterol (standardized regression coefficient =-0.260 (p=0.007)) and increased future triglycerides (0.293 (p=0.003), but was not related to non-HDL cholesterol (0.088 (p=0.392)) in a regression model that included both baseline and change in IAFA, ASFA and its change, age, fasting plasma glucose, fasting plasma insulin, daily alcohol consumption, weekly energy expenditure, and smoking habit. Change over time in IAFA was significantly and positively correlated with higher future triglycerides (0.239 (p=0.002)) but not related to either future HDL cholesterol (-0.091 (p=0.222)) or non-HDL cholesterol (0.155 (p=0.057)). Neither ASFA nor its change were correlated with any future lipid level. In women both baseline and change in IAFA were correlated with decreased future HDL cholesterol (-0.610 (p<0.001), -0.396 (p<0.001) respectively), increased future triglycerides (0.315 (p=0.009), 0.434 (p<0.001) respectively), and non-HDL cholesterol (0.258 (p=0.045), 0.244 (p=0.007)) in a regression model that included the same variables as above. Greater ASFA at baseline was significantly correlated with higher future HDL cholesterol (0.248 (p=0.005) but was unrelated to triglycerides (-0.086 (p=0.379) or non-HDL cholesterol (-0.007 (p=0.948). In conclusion, greater IAFA and its change are independently associated with unfavorable future lipids levels. In women only, greater ASFA is independently associated with higher future HDL cholesterol. [ABSTRACT FROM AUTHOR]

Cigarette smoking is a risk factor for type 2 diabetes and cardiovascular disease. Not known is whether smoking habit is associated with the risk of developing the metabolic syndrome among men. Study subjects consisted of 7355 Japanese men aged 40 to 55 years without the metabolic syndrome. The metabolic syndrome was defined using modified Adult Treatment Panel III criteria using body mass index in place of waist circumference. Data on smoking habit was obtained from questionnaires. During the 4-year follow-up period, we confirmed 806 cases of the metabolic syndrome. After adjustment for age, body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, HDL cholesterol, fasting plasma glucose, alcohol daily consumption, and physical activity, the odds ratio (OR) of the metabolic syndrome among current smokers was 1.30 (95% confidence interval (CI) 1.04-1.61) in comparison to never smokers. Men who smoked more than 30 cigarettes a day had a higher risk compared with never smokers (OR 1.61, 95% CI 1.16-2.24) (Table 1). To evaluate the chronic effect of cigarettes smoking for the risk of the incidence of the metabolic syndrome, we assessed the relationship between pack-years and the risk of the metabolic syndrome. The value of pack-years is also associated with the increased risk of the metabolic syndrome in a dose-dependent manner. The multiple-adjusted OR for those whose pack-years value is more than 40 is 1.49 (95% CI 1.12-1.98). Furthermore, we assessed the association between cigarettes smoking and the incidence of the components of the metabolic syndrome. Cigarette smoking was associated with the risk of the incidence of hyperglycemia, high triglycerides, and low HDL cholesterol but not high blood pressure or high body mass index. In conclusion, cigarette smoking habit is an independent risk factor for the development of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background Endocrine and metabolic abnormalities may affect the survival of hemodialysis patients. Serum dehydroepiandrosterone sulfate (DHEA-S), an adrenal androgen with anabolic properties, is known to be lowered in ill patients and predicts poor outcome in the general population and in those with cardiac disease. The aims of this study were to examine a possible change in the DHEA-S level in dialysis patients and its association with survival in this population. Methods This was an observational cohort study in 494 prevalent hemodialysis patients (313 men and 181 women) in urban area of Osaka, Japan. The main exposure was the baseline DHEA-S level in December 2004 and the key outcome was all-cause mortality during the subsequent 5 years. Also, DHEA-S levels were compared between the hemodialysis patients and 122 matched healthy controls. Results The median (inter-quartile range) DHEA-S levels were 771 (447–1351) and 414 (280–659) ng/mL for male and female dialysis patients, respectively, and these values were significantly lower by 40–53% than the healthy control levels. Among the hemodialysis patients, DHEA-S was lower in women, those with older age, pre-existing cardiovascular disease, lower serum albumin and higher C-reactive protein. During the follow-up, we recorded 101 deaths. A low DHEA-S level was a significant predictor of all-cause mortality independent of potential confounders in male, but not in female, hemodialysis patients. Conclusions The serum DHEA-S level is decreased in hemodialysis patients and associated with mortality in men. These results support the growing observational evidence that uremia-induced endocrine alterations including decreased sex hormones may be linked to adverse clinical outcomes. [ABSTRACT FROM PUBLISHER]

Aim: The prevalence of underweight women, who have an increased risk for small-for-gestational-age (SGA) birth, is increasing in Japan. We examined the associations of pre-pregnancy body mass index and gestational weight gain (GWG) with SGA birth among Japanese women. Material and Methods: We conducted a prospective cohort study of 1391 women who delivered full-term singleton babies. SGA was defined as below the 10th percentile of birthweight at each gestational age, baby sex, and parity. We calculated the 5th percentile of birthweight in the same way for another threshold for SGA. According to pre-pregnancy body mass index, we divided the participants into three groups: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), and overweight and obese (≥25.0 kg/m2). Results: SGA birth was observed most frequently among the underweight group (13.8%). Underweight was associated with an increased risk of SGA birth. The multiple-adjusted odds ratio for underweight was 1.96 (95% confidence interval, 1.23-3.11) compared with normal weight. Sufficient GWG reduced the incidence and the multiple-adjusted odds ratio for 1-kg increase of GWG was 0.86 (0.81-0.92). The same tendency was observed for the delivery of infants below the 5th birthweight percentile. Women with underweight and normal weight who had 9.0 kg or less of GWG had a significantly higher risk of SGA birth than women with normal weight who had 9.1-11.0 kg of GWG. Conclusions: Underweight and poor GWG were associated with a higher incidence of SGA birth. However, the incidence of SGA birth among underweight women was not increased significantly if they had sufficient GWG. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Small-for-gestational-age (SGA) infants, who have growth restriction, have higher perinatal morbidity and mortality. Excessive inflammatory reaction such as neutrophil activation has been observed in pregnant women whose offspring had restricted fetal growth, but the association between white blood cell (WBC) counts and SGA birth has not yet been assessed. We therefore examined the association of WBC count and its change with the risk of SGA birth. Study design: We enrolled 2356 pregnant women who had full-term singleton delivery at a private maternity hospital in Hirakata, Japan. SGA was defined as under the 10th percentile of birthweight for gestational age, baby sex, and mother''s parity according to the Japanese neonatal anthropometric charts renewed in 2010. Blood samples were measured in the first and third trimesters. We performed multiple logistic regression analysis to assess associations between total and differential WBC counts and SGA birth. Results: Women with SGA birth tended to have higher total WBC count in the third trimester compared with women who did not have SGA birth. This tendency was not observed for total WBC count in the first trimester. After adjustment for age, height, body mass index at entry, smoking habit, weekly gestational weight gain, and pregnancy-induced hypertension, higher total WBC count in the third trimester was associated with an increased risk of SGA birth. Total WBC count in the first trimester did not show any significant association with SGA birth. The ratio of total WBC count in the third trimester to that in the first trimester was associated with SGA birth; the odds ratio for 1 unit increase was 3.02 (95% CI: 1.54–5.92). Regarding differential WBC counts in the third trimester, neutrophil count but not lymphocyte count was associated positively with SGA birth. Conclusions: Higher total WBC and absolute neutrophil counts in the third trimester were associated with SGA birth. In addition, greater ratio of increase in total WBC counts during pregnancy showed a positive association with the incidence of SGA birth. These associations may reflect a vicious cycle of inflammation and placental dysfunction as a cause of fetal growth restriction. [Copyright &y& Elsevier]

Migrant Japanese populations in both the USA and Brazil have for a long time shown a higher prevalence of type 2 diabetes than native Japanese, suggesting an interaction of lifestyle and genetic predisposition in the etiology of type 2 diabetes. The overall objective of the Seattle Japanese American Community Diabetes Study was to learn more about the etiology and pathogenesis of type 2 diabetes in Japanese Americans. This metabolically based epidemiological study included extensive assessments of insulin sensitivity, insulin response, and adiposity with the latter including measurements of body fat distribution by both anthropometry and computed tomography. Because of this, the importance of visceral adiposity as a risk factor for abnormal glucose tolerance, hypertension, coronary heart disease and the metabolic syndrome was shown. In conjunction with an examination of diet and physical activity patterns, the result was a clearer understanding of the etiology and pathogenesis of type 2 diabetes in Japanese Americans. We propose that a lifestyle that fosters increased weight gain, especially in the visceral adipose depot, promotes the development of insulin resistance, which in turn exposes an underlying reduced β-cell reserve in susceptible individuals, resulting in glucose intolerance and, eventually in many, the development of diabetes. We have shown that it might be possible to delay or prevent the development of diabetes through dietary and exercise interventions in individuals identified as having impaired glucose tolerance. The lessons learned from studying migrant Japanese in Seattle might in many ways be applicable to other populations of Asian origin. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00195.x, 2012) [ABSTRACT FROM AUTHOR]

Objective: Recent studies have suggested that HDL cholesterol is inversely associated with the development of type 2 diabetes. However, little is known about the association between different HDL subclasses and the risk for future type 2 diabetes.Research Design and Methods: The study enrolled 406 Japanese Americans (51% male) without diabetes, aged 34-75 years. Oral glucose tolerance tests were performed to determine type 2 diabetes status at baseline, 2.5 years, 5 years, and 10 years after enrollment. HDL2, HDL3, total HDL cholesterol, and visceral adipose tissue (VAT) area by computed tomography were measured at baseline.Results: In univariate analysis, total HDL and HDL2 cholesterol were inversely associated with the incidence of type 2 diabetes, but HDL3 cholesterol was not. In multivariate analysis, total HDL cholesterol (odds ratio per 1-SD increment, 0.72 [95% CI 0.52-0.995], P = 0.047) and HDL2 cholesterol (odds ratio per 1-SD increment, 0.64 [95% CI 0.44-0.93], P = 0.018) were inversely associated with the risk for type 2 diabetes independent of age, sex, BMI, waist circumference, family history of diabetes, lifestyle factors, systolic blood pressure, lipid-lowering medication use, triglyceride level, HOMA-insulin resistance, and 2-h glucose; however, HDL3 cholesterol was not associated with diabetes risk. The association between diabetes risk and total HDL and HDL2 cholesterol became insignificant after adjustment for VAT area.Conclusions: Subjects with higher HDL2 cholesterol were at lower risk for incident type 2 diabetes, but this association was confounded by and not independent of VAT. Higher HDL3 cholesterol was not associated with diabetes risk. [ABSTRACT FROM AUTHOR]

Background: Visceral adiposity is generally considered to play a key role in the metabolic syndrome.Objective: To examine the relationship between directly measured visceral adiposity and the risk for incident hypertension, independent of other adipose depots and fasting plasma insulin levels.Design: Community-based prospective cohort study with 10- to 11-year follow-up.Setting: King County, Washington.Participants: 300 Japanese Americans with a systolic blood pressure less than 140 mm Hg and a diastolic blood pressure less than 90 mm Hg who were not taking antihypertensive medications, oral hypoglycemic medications, or insulin at study entry.Measurements: Abdominal, thoracic, and thigh fat areas were measured by using computed tomography. Total subcutaneous fat area was calculated as the sum of these fat areas excluding the intra-abdominal fat area. Hypertension during follow-up was defined as having a systolic blood pressure of 140 mm Hg or greater, having a diastolic blood pressure of 90 mm Hg or greater, or taking antihypertensive medications.Results: There were 92 incident cases of hypertension during the follow-up period. The intra-abdominal fat area was associated with an increased risk for hypertension. Multiple-adjusted odds ratios of hypertension for quartiles of intra-abdominal fat area (1 = lowest; 4 = highest) were 5.07 (95% CI, 1.75 to 14.73) for quartile 3 and 3.48 (CI, 1.01 to 11.99) for quartile 4 compared with quartile 1 after adjustment for age, sex, fasting plasma insulin level, 2-hour plasma glucose level, body mass index, systolic blood pressure, alcohol consumption, smoking status, and energy expenditure through exercise (P = 0.003 for quadratic trend). The intra-abdominal fat area remained a significant risk factor for hypertension, even after adjustment for total subcutaneous fat area, abdominal subcutaneous fat area, or waist circumference; however, no measure of these fat areas was associated with risk for hypertension in models that contained the intra-abdominal fat area.Limitations: It is not known whether these results pertain to other ethnic groups.Conclusions: Greater visceral adiposity increases the risk for hypertension in Japanese Americans. [ABSTRACT FROM AUTHOR]

Leptin and adiponectin are two major adipocytokines reported to be associated with type 2 diabetes. However, it is unknown whether their associations with the risk of incident type 2 diabetes are independent of visceral adiposity and liver fat in a prospective cohort study. We included 787 Japanese men aged 28 to 77 years without type 2 diabetes at baseline. The subjects were classified into four groups based on leptin-adiponectin profile at baseline, with the median concentration value as the cut-off point (median levels of leptin and adiponectin were 4.8 ng/dL and 5.7 µg/mL, respectively): low-high, low-low, high-high, and high-low group. Visceral fat was measured by computed tomography (CT) as intra-abdominal fat area at the umbilicus level. Liver fat was assessed by liver-to-spleen attenuation ratio measured by CT. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, HbA1c ≥6.5%, or taking oral hypoglycemic medications or insulin. Cox proportional hazard models were used to estimate hazard ratios (HR) for developing type 2 diabetes. During 5215 person-years of follow-up, 72 subjects developed type 2 diabetes. Incidence rates of type 2 diabetes per 1000 person-years were 3.2, 9.2, 18.6, and 26.1 for the low-high, low-low, high-high, and high-low group, respectively. After adjustment for age, smoking status, alcohol consumption, regular physical activity, family history of diabetes, visceral fat, and liver fat, multiple-adjusted HRs (95% CI) of incident type 2 diabetes were 1.87 (0.63-5.50), 2.90 (1.02-8.21), and 3.41 (1.23-9.47) for the low-low, high-high, and high-low group compared with the low-high group. In conclusion, leptin and adiponectin were associated with incident type 2 diabetes independent of both visceral fat and liver fat. Disclosure: I. Shibata: None. W. Y. Fujimoto: None. E. J. Boyko: None. T. Hayashi: None. M. Shibata: None. K. K. Sato: None. S. Uehara: None. N. Nishida: None. K. Okamura: None. Y. Yuyama: None. H. Koh: None. Y. Hikita: None. [ABSTRACT FROM AUTHOR]

Although glomerular hyperfiltration (GHF) is a major risk of diabetic nephropathy and it is important to prevent GHF in subjects with prediabetes, it is not known which factors are associated with the risk of GHF. We prospectively examined the relationship of alcohol consumption and smoking habits to the risk of GHF in subjects with impaired fasting glucose (IFG). Study population was 2811 middle-aged Japanese men who had IFG, no proteinuria, no GHF, and no low estimated glomerular filtration rate (eGFR) at baseline, and who did not have low eGFR before the onset of GHF during the follow-up period. GHF was defined as eGFR ≥117 mL/min/1.73 m2, which was the upper 2.5th percentile value of eGFR in the all study population of our cohort. Low eGFR was defined as eGFR <60 mL/min/1.73 m2. Based on daily alcohol consumption, subjects were classified as follows: non-drinkers, 0.1-23.0, 23.1-46.0, and ≥46.1 g ethanol/day. As for smoking habits, subjects were divided into non-smokers, past smokers, and current smokers. During the 6-year follow-up period, 103 men developed GHF. After adjusted for BMI, fasting plasma glucose, systolic blood pressure, use of anti-hypertensive medications, and regular physical exercise, both daily alcohol consumption and smoking habits were independently associated with the risk of the incident GHF. Multiple-adjusted HRs of incident GHF for those who drank 0.1-23.0, 23.1-46.0, and ≥46.1 g ethanol/day were 0.94 (95% CI, 0.46-1.95), 1.34 (0.66-2.70), and 2.48 (1.19-5.15), respectively, compared with non-drinkers. Multiple-adjusted HRs of those for past smokers and current smokers were 0.86 (0.42-1.75), and 1.77 (1.00-3.14), respectively, compared with non-smokers. In conclusion, high daily alcohol consumption and current smoking increased the risk of GHF in subjects with IFG. Disclosure: M. Shibata: None. T. Hayashi: None. K. K. Sato: None. S. Uehara: None. N. Nishida: None. K. Okamura: None. I. Shibata: None. H. Koh: None. K. Oue: None. M. Morimoto: None. [ABSTRACT FROM AUTHOR]

Objective: We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes.Research Design and Methods: Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG >or=126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves.Results: During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001).Conclusions: The combined measurement of FPG and A1C was effective for predicting type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes.Research Design and Methods: The study participants were nondiabetic Japanese men (n = 8,570) aged 40-55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was >or=126 mg/dl or if participants were taking oral hypoglycemic medication or insulin.Results: During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44-2.54) compared with those who had levels between 0.71 and 0.80 mg/dl.Conclusions: Lower serum creatinine increased the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Prediabetes is a key risk for type 2 diabetes and its remission to normal glucose regulation has been shown to prevent or delay the onset of diabetes. However, which factors play roles in remission is not fully understood. We prospectively examined the relationships between liver enzymes at baseline and future remission from impaired fasting glucose (IFG) to normal fasting glucose (NFG). We included 3334 middle-aged Japanese men with IFG and not taking diabetic medications at baseline. They were followed for up to 11 years. IFG was defined as fasting plasma glucose level 100-125 mg/dL and HbA1c <6.5%. Remission to NFG was defined as fasting plasma glucose level <100 mg/dL detected two times consecutively at the annual checkup. Those who had developed diabetes before they achieved remission to NFG were not counted as remission. Cox proportional hazard models were used to estimate hazard ratios (HRs) for achieving remission to NFG. Alanine transaminase (ALT) and aspartate transaminase (AST) were divided into the following quartiles: 5-19, 20-26, 27-37, and ≥38 IU/L for ALT; 11-19, 20-23, 24-29, and ≥30 IU/L for AST. A total of 1224 subjects remitted to NFG during 19780 person-years. Incidence rates per 1000 person-years for quartiles 1, 2, 3, and 4 of ALT/AST were 81/65, 62/67, 56/60, and 49/56, respectively. In a multiple-adjusted model that included age, fasting plasma glucose, body mass index, smoking status, regular physical exercise, alcohol consumption, and family history of diabetes, HRs of future remission to NFG for quartiles 2, 3, and 4 of ALT were 0.84 (95% CI, 0.72-0.99), 0.84 (0.72-0.99), and 0.82 (0.69-0.97), respectively, compared to quartile 1. In the same model except AST was substituted for ALT, HRs of those for quartiles 2, 3, and 4 of AST were 1.04 (0.89-1.22), 1.02 (0.87-1.20), and 1.02 (0.87-1.21), respectively, compared to quartile 1. In conclusion, elevated ALT was inversely associated with future remission from IFG to NFG, but AST was not. Disclosure: I. Shibata: None. K.K. Sato: None. M. Shibata: None. H. Koh: None. S. Uehara: None. K. Oue: None. H. Kambe: None. M. Morimoto: None. T. Hayashi: None. [ABSTRACT FROM AUTHOR]

Decline in kidney function is a major concern for patients with type 2 diabetes. The importance of serum uric acid level as the risk factor for chronic kidney disease (CKD) remains unconfirmed. We therefore evaluated the relationship between baseline serum uric acid level and the risk of incident CKD among men with untreated type 2 diabetes at baseline examination in a 10-11 years prospective cohort study. We included 717 middle-aged Japanese subjects with fasting plasma glucose level ≥126 mg/dL or HbA1c ≥6.5% at baseline who were not taking hypoglycemic medications nor insulin, who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, who did not have proteinuria nor malignant tumors, and who were not taking anti-hypertensive medications nor urate-lowering medications at baseline. CKD was defined as eGFR <60 ml/min/1.73 m2. Cox proportional hazards models were used in the multivariate analysis. During the 5961 person-years follow-up period, 87 subjects developed CKD. Higher serum uric acid level was associated with an increased risk of CKD after adjustment for age, body mass index, systolic blood pressure, diastolic blood pressure, HbA1c, smoking habits (nonsmokers, past smokers, and current smokers), regular leisure-time physical activity (yes/no), daily alcohol consumption (g ethanol/day), and eGFR at baseline. Multiple-adjusted hazard ratios of CKD for quintile 4 (6.2-6.9 mg/dL) and quintile 5 (≥7.0 mg/dL) of serum uric acid levels were 1.30 (95% CI, 0.73-2.30) and 1.80 (95% CI, 1.04-3.11), respectively, compared with quintile 1 to 3 (0.7-6.1 mg/dL). Moreover, when we modeled serum uric acid level as a continuous variable, serum uric acid level per 1.0 mg/dL increase was significantly associated with a 25% increased risk of incident CKD. In conclusion, higher serum uric acid level is independently and significantly associated with an increased risk of CKD in patients with untreated type 2 diabetes. Disclosure: Y. Okada: None. K.K. Sato: None. M. Shibata: None. S. Uehara: None. H. Koh: None. K. Oue: None. H. Kambe: None. M. Morimoto: None. T. Hayashi: None. [ABSTRACT FROM AUTHOR]

The β-cell plays a major role in type 2 diabetes (T2DM). HOMA-β reflects fasting β-cell activity. Insulin responses during an OGTT reflect β-cell activity during glucose loading, which has two phases, early and late. HOMA-β, early, and late β-cell activity have different pathophysiologies. However, no research has examined whether HOMA-β and early and late phase β-cell activity during an OGTT are independently associated with the risk of T2DM. In a prospective cohort study, 415 nondiabetic Japanese-American men and women were followed for 10-11 years. β-cell activity was assessed by HOMA-β [fasting insulin × 360/(fasting glucose − 63)] as fasting activity, the insulinogenic index (IGI) [?insulin (30-0 min)/?glucose (30-0 min)] during an OGTT as early phase activity, and (area under the curve (AUC) of insulin 60-120 min)/(AUC glucose 60-120 min) as late phase activity. Insulin sensitivity was estimated by Matsuda index [10000/square root of ((fasting glucose) × (fasting insulin) × (AUC glucose 0-120 min/120) × (AUC insulin 0-120 min/120))]. T2DM was diagnosed as fasting plasma glucose level ≥126 mg/dL, 2-hour glucose level ≥200 mg/dL, or taking glucose-lowering medications. During the 10-11 year follow-up, 95 cases of T2DM occurred. HOMA-β, IGI, and late phase β-cell activity were all independently associated with the risk of T2DM. Multiple-adjusted odds ratios of T2DM for tertile 1, 2, and 3 of HOMA-β were 1.00 (reference), 0.25 (95% CI, 0.11-0.57), and 0.14 (0.05-0.37), respectively; those of IGI were 1.00, 0.35 (0.17-0.75), and 0.19 (0.07-0.47), respectively; and those of late phase β-cell activity were 1.00, 0.34 (0.14-0.82), and 0.16 (0.05-0.53), respectively, in the model that included HOMA-β, IGI, late phase β-cell activity, Matsuda index, age, BMI, sex, and family history of T2DM. In conclusion, higher β-cell activity while fasting and in both the early and late phase during an OGTT were all independently associated with a lower risk of T2DM. Disclosure: T. Shimojo: None. C. Izumi: None. K.K. Sato: None. D.L. Leonetti: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. W.Y. Fujimoto: None. E.J. Boyko: None. T. Hayashi: None. [ABSTRACT FROM AUTHOR]

No useful predictor of risk of acute heart failure in peripheral-blood stem-cell transplantation (PBSCT) regimens, including high-dose cyclophosphamide, has previously been available. Corrected QT dispersion can predict acute heart failure after high-dose cyclophosphamide chemotherapy used in PBSCT. [ABSTRACT FROM AUTHOR]