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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]

Summary Problem The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. Methods This is a longitudinal observational study in community-dwelling Japanese-American men ( n = 215, mean age 52 years, BMI 25.4 kg/m 2 ). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Results Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area ( r = −0.05 for both time points, p = 0.45 and p = 0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change ( p = 0.52 and p = 0.55, respectively). Conclusions Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. [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]

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]

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--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 -- 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]

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]

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]