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Background: Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.Methods: All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.Results: A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm2 in men and 63.1±39.5 cm2 in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.Conclusion: These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

OBJECTIVE Ageing in male adults is typically accompanied by adiposity accumulation and changes in circulating sex hormone concentrations. We hypothesized that an ageing-associated increase in oestrogens and decrease in androgens would correlate with an increase in adiposity. DESIGN 10-year prospective, observational study. STUDY SUBJECTS A total of 190, community-dwelling men in the Japanese American Community Diabetes Study. MEASUREMENTS At 0 and 10 years, CT scanning quantified intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas while plasma concentrations of oestradiol, oestrone, testosterone and dihydrotestosterone were measured by liquid chromatography-tandem-mass spectrometry at each time point. Multivariate linear regression analyses assessed correlations between 10-year changes in hormone concentrations and IAF or SCF, adjusting for age and baseline fat depot area. RESULTS Participants were middle-aged [median 54.8 years, interquartile range (IQR) 39.9-62.8] men and mostly overweight by Asian criterion (median BMI 24.9, IQR 23.3-27.1) and with few exceptions had normal sex-steroid concentrations. Median oestradiol and dihydrotestosterone did not change significantly between 0 and 10 years (P = .084 and P = .596, respectively) while median oestrone increased (P

Background High plasma apolipoprotein B (apoB) levels have been shown to be associated with hypertension, central obesity, and insulin resistance in cross-sectional research. However, it is unclear whether apoB levels predict future hypertension independent of body composition and insulin sensitivity. Therefore, we prospectively investigated whether plasma apoB concentrations independently predicted the risk of hypertension in a cohort of Japanese Americans. Methods A total of 233 normotensive Japanese Americans (77 men, 156 women; mean age, 46.4±11.0 years) were followed over 10 years to monitor them for the development of hypertension. Fasting plasma concentrations of apoB, glucose, and insulin were measured at baseline. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). The abdominal visceral and subcutaneous fat areas were measured at baseline using computed tomography. Logistic regression analysis was used to estimate the association between apoB concentrations and the odds of incident hypertension. Results The 10-year cumulative incidence of hypertension was 21.5%. The baseline apoB level was found to be positively associated with the odds of incident hypertension over 10 years after adjustment for age, sex, body mass index, systolic blood pressure, abdominal visceral fat area, abdominal subcutaneous fat area, total plasma cholesterol concentration, diabetes status, and HOMA-IR at baseline (odds ratio and 95% confidence interval for a 1-standard deviation increase, 1.89 [1.06 to 3.37]; P=0.030). Conclusion Higher apoB concentrations predicted greater risks of future hypertension independent of abdominal visceral fat area and insulin sensitivity in Japanese Americans.

BACKGROUND: Greater visceral fat area (VFA) is associated with cardiometabolic outcomes. We sought to identify cross-sectional and longitudinal associations between amino acid (AA) levels and VFA in Japanese-Americans. METHODS: From the cohort of 342 Japanese-American participants (51% men) in a study of diabetes risk factors who were free from diabetes, we measured levels of 20 AA by mass spectrometry, height, weight, waist circumference (WC), VFA, subcutaneous fat area by single-slice CT at the umbilicus. Using AA significantly associated with VFA in univariate analyses, we created a VFA prediction index, termed the 4A index. We compared area under receiver-operating characteristic curve (AUROC) of the 4A index to WC and an existing AA index (Yamakado et al. Clin Obes 2012) in classifying VFA at different cutoff values. We fit age-adjusted linear regression models to evaluate associations between AA levels and change in VFA over 5 years. RESULTS: All 20 AA levels significantly detected VFA excess, but WC was better. The 4A index performed better than Yamakado index at classifying VFA ≥100 cm(2) (0.798, 0.807 vs. 0.677, 0.671 for men and women, p

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

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.

OBJECTIVE Whether leptin and adiponectin are independently associated with regional body fat distribution was investigated in a prospective study of Japanese Americans. METHODS Nondiabetic participants 39 to 79 years of age were followed for 5 years to assess change in body composition. Leptin and adiponectin concentrations were evaluated at baseline and by single-slice computed tomography measurements of intra-abdominal fat (IAF), abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas at baseline and at 5 years. RESULTS Ninety-six men and ninety-five women without diabetes had the following baseline mean (SD) values: age 45.7 (3.5) years and 46.4 (3.9) years, IAF 78.7 (38.6) cm2 and 62.1 (39.0) cm2 , leptin concentration 4.5 (2.3) μg/L and 10.2 (5.2) μg/L, and adiponectin concentration 7.4 (3.2) μg/mL and 10.8 (4.7) μg/mL, respectively. Baseline leptin (β = 1.7722, P = 0.014) and adiponectin concentrations (β = -0.4162, P

Epigenetic changes precede the development of diabetes by many years, providing clues to its pathogenesis. We explored whether the epigenetic markers, circulating microRNAs (miRNAs), were associated with incident diabetes in Japanese Americans. We conducted a pilot study (n = 10) using plasma from age- and sex-matched participants who did or did not develop diabetes in the Japanese American Community Diabetes Study, an observational study of diabetes risk factors. Extraction and high-throughput sequencing of miRNAs were performed using samples collected at baseline. Regression models were fit comparing circulating miRNAs (N = 1640) among individuals who did or did not develop incident diabetes at 10-year follow-up. Participants averaged 51.7 years of age at baseline; 60% were male. We identified 36 miRNAs present at different (10 higher and 26 lower) levels in individuals who developed diabetes compared to those who did not (log2fold change ≥1.25 and false discovery rate ≤5%). These included miRNAs with functions in skeletal muscle insulin metabolism (miR-106b and miR-20b-5p) and miRNAs with functions in both skeletal muscle insulin metabolism and cell cycle regulation in endocrine pancreas (miR-15a and miR-17). Circulating miRNAs were associated with subsequent development of diabetes among Japanese Americans over 10 years of follow-up. Results are preliminary. Large-scale miRNA sequencing studies could inform our understanding of diabetes pathogenesis and development of therapies, based on gene expression regulation, that target diabetes.

BACKGROUND Recent studies have suggested that high density lipoprotein (HDL) cholesterol is inversely associated with the development of hypertension. We aimed to determine the association between different HDL cholesterol subclasses and risk of future hypertension. METHODS A total of 270 Japanese Americans (130 men, 140 women) without hypertension between the ages of 34 to 75 years were enrolled. Blood pressure was measured with a mercury sphygmomanometer, and average blood pressure was calculated. Incident hypertension was determined 5 to 6 and 10 to 11 years after enrollment. HDL2, HDL3, and total HDL cholesterol were measured at baseline. RESULTS During 10 years of follow-up, the cumulative incidence of hypertension was 28.1% (76/270). In univariate analysis, age, diabetes, waist circumference, systolic and diastolic blood pressure, fasting glucose, insulin resistance index, total and low density lipoprotein cholesterol, and visceral adipose tissue were significant predictors for incident hypertension. Among the HDL cholesterol subclass, HDL2 cholesterol was inversely associated with hypertension incidence, but both total and HDL3 cholesterol were not. In addition, HDL2/HDL cholesterol was inversely associated with future hypertension risk. In multivariate analysis, age (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26 to 2.31; P=0.001), systolic blood pressure (OR, 1.83; 95% CI, 1.31 to 2.56; P

Objectives Pulse pressure (PP), a marker of arterial stiffness, and body composition are both risk factors for cardiovascular disease. Little is known about whether changes in body composition may be linked to future PP. We sought to determine whether change in amount of abdominal and thigh fat over 5 years predicted PP at 10 years. Methods Visceral fat as well as abdominal and thigh subcutaneous fat areas were measured by computed tomography at baseline and 5 years later in 284 Japanese Americans (mean age 49.3 years; 50.4% men) without hypertension, heart disease, and glucose-lowering medication use at baseline. PP at 10 years was calculated as the difference between SBP and DBP measured with a mercury sphygmomanometer. The association between change in fat at 5 years and arterial PP at 10 years, adjusted for baseline PP, was examined using linear regression analysis. Main results Change in abdominal visceral fat area at 5 years was positively associated with 10-year PP independent of sex, 5-year change in BMI, and baseline age, BMI, PP, abdominal visceral fat, smoking status, alcohol consumption, physical activity, homeostasis model assessment insulin resistance, and fasting plasma glucose. There were no significant associations between baseline amounts or change in abdominal or thigh subcutaneous fat areas and future PP. Conclusion The accumulation of abdominal visceral fat over time independently predicted future PP in Japanese Americans.

Aim We investigated the association between combined changes of visceral fat and thigh muscle over 5 years and incident type 2 diabetes in a prospective study of Japanese Americans. Methods We followed 420 nondiabetic Japanese American subjects for 5 years and assessed visceral fat and thigh muscle by computed tomography (CT) at baseline and at 5 years. We categorized study subjects into 4 body composition change groups: visceral fat loss/thigh muscle gain (VF-loss/TM-gain), visceral fat loss/thigh muscle loss (VF-loss/TM-loss), visceral fat gain/thigh muscle gain (VF-gain/TM-gain), and visceral fat gain/thigh muscle loss (VF-gain/TM-loss) by combining changes from baseline in CT measured visceral fat and estimated thigh muscle areas. We fit a logistic regression model to examine the association between body composition categories and the development of incident type 2 diabetes at 5 years. Results Cumulative incidence of type 2 diabetes was 9.8% at 5 years. VF-gain/TM-gain and VF-loss/TM-loss groups had higher risk for incident type 2 diabetes in a model adjusted for age, sex, family history of diabetes, and body mass index compared to VF-loss/TM-gain group as the reference category (OR = 6.83 (1.85–25.17), 4.55 (1.06–19.48), respectively). However, the VF-gain/TM-loss group did not show a significant association with the odds of incident diabetes (3.24; 95% CI. 0.78–13.47). Conclusions Concordant gain or loss in visceral fat and thigh muscle was related to higher risk of incident type 2 diabetes compared to the reference combination of loss of visceral fat and gain of thigh muscle in Japanese Americans.

Context: Plasma adiponectin concentration has been shown to be inversely associated with body mass index (BMI) and insulin resistance in cross-sectional research. However, it is unclear whether adiponectin predicts future body composition and insulin resistance. Objective: We aimed to investigate the potential relationship between adiponectin concentration and future regional body fat distribution and insulin resistance. Design and Setting: This was a community-based prospective cohort study with 5 years of follow-up. Participants: A total of 218 Japanese Americans without diabetes (79 men, 139 women, mean age 51.7 ± 10.1 years) were assessed at baseline and after 5 years of follow-up. Main Outcome Measures: Abdominal visceral and subcutaneous fat area and thigh subcutaneous fat area were measured by computed tomography (CT). Insulin resistance was evaluated by homeostasis model assessment 2 of insulin resistance (HOMA2-IR). Plasma total adiponectin was measured by radioimmunoassay. Results: Baseline adiponectin was inversely associated with abdominal visceral fat area (P = 0.037) and HOMA2-IR (P = 0.002) at 5 years in a multiple linear regression model after adjustment for baseline traits (including age, sex, BMI, abdominal visceral fat area, abdominal subcutaneous fat area, thigh subcutaneous fat area, HOMA2-IR) and weight change. However, no association was seen between baseline adiponectin concentration and BMI or other CT-measured regional fat depots at 5 years. Conclusions: Low plasma adiponectin concentration independently predicted future abdominal visceral fat accumulation and increased insulin resistance in Japanese Americans., We studied the relationship between baseline adiponectin and future body composition and insulin resistance. Low plasma adiponectin predicted visceral fat accumulation and greater insulin resistance.

OBJECTIVE Prehypertension is associated with increased risk for incident hypertension. However, little is known about how frequently prehypertension converts to normotension, and which variables predict this conversion. METHODS We identified 186 Japanese Americans with prehypertension (110 men, 76 women) aged 34-75 years (mean age of 52.3 years) who were followed at 5 and 10 years after enrollment. Blood pressure was measured with a mercury sphygmomanometer and average blood pressure was calculated. Subcutaneous adipose tissue, visceral adipose tissue (VAT), and subcutaneous thigh adipose tissue area were measured by computed tomography. RESULTS Approximately one-third of those with prehypertension converted to normotension over 10 years of follow-up. Those who converted to normotension were younger, less obese, and had significantly lower baseline SBP, fasting glucose, cholesterol levels, and homeostasis model assessment insulin resistance compared with study participants who continued to have prehypertension or progressed to hypertension. With regard to body fat compartments, study participants with conversion to normotension showed a significantly smaller VAT area compared with the nonconversion group (P

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.

Objectives: The adipokines leptin and adiponectin are associated with change in body composition and are highly correlated, raising questions about whether they exert independent effects. We investigated whether these two adipokines are independently associated with regional body fat accumulation in a prospective study of Japanese Americans. Methods: Nondiabetic participants between the ages of 34 to 74 years were followed for 5 years to assess change in body composition. Leptin and adiponectin concentrations and single slice CT-measurements of intra-abdominal fat (IAF), abdominal (SCF) and thigh (TF) subcutaneous fat cross-sectional areas were evaluated at baseline and 5 year follow-up study visits. Multiple linear regression analysis was used to estimate the association between leptin and adiponectin and future 5-year accumulation of IAF. Results: 96 men and 95 women without diabetes included in this analysis had the following baseline mean (SD) values: age 45.7 (3.5) years and 46.4 (3.9) years; BMI 25.5 (3.1) kg/m2 and 24.0 (3.9) kg/m2; IAF 78.7 (38.6) cm2 and 62.1 (39.0) cm2; leptin concentration 4.5 (2.3) μg/L and 10.2 (5.2) μg/L; and adiponectin concentration 7.4 (3.2) μg/mL and 10.8 (4.7) μg/mL, respectively. Baseline leptin (β = 1.7722, p=0.014) and adiponectin concentrations (β = -0.4162, p Conclusions: In nondiabetic Japanese Americans, baseline concentrations of leptin and adiponectin were independent predictors of IAF accumulation at 5 years. Higher levels of leptin and adiponectin were associated with greater and lesser accumulation of IAF, respectively. These relationships were independent of age, sex, insulin sensitivity, and body composition. Disclosure S. Song: 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. D.L. Leonetti: None. W.Y. Fujimoto: None. E.J. Boyko: None. Funding National Institutes of Health DK31170, HL49293); University of Washington (DK017047, DK035816, RR-000037); VA Puget Sound Health Care System (to E.J.B., S.E.K.)

Background: Both intra-abdominal fat (IAF) and HDL cholesterol (HDL-C) are known to be associated with cardiometabolic health problems, with an inverse correlation between them. However, there is little information about the association between HDL-C concentration with future accumulation of IAF. We conducted a prospective study to evaluate whether baseline HDL-C concentration was associated with the accumulation of CT-measured intra-abdominal fat (IAF) over 5 years. Methods: All participants were Japanese-American men and women between the ages of 34 to 74 years. HDL-C concentration and CT-measurements of IAF, abdominal (SCF) and thigh (TF) subcutaneous fat cross-sectional areas were evaluated at baseline and 5 year follow-up visits. Data were analyzed to determine the association between HDL-C and future 5-year accumulation of IAF. Results: A total of 545 subjects with and without diabetes (296 men, 249 women, and mean age 53.6±11.4 and 54.0±12.0 years, respectively) were included. The mean (SD) HDL-C concentration was 1.3 mmol/L (0.4) in men and 1.7 mmol/L (0.4) in women and mean (SD) IAF was 102 cm2 (53.8) in men and 74.5 cm2 (46.8) in women. Baseline HDL-C concentration was inversely associated with Δ IAF over 5 years using multivariable regression analysis adjusting for age, sex, diabetes family history, weight change over 5 years, and baseline measurements of BMI, IAF, abdominal SCF, abdominal circumference, TF, and HOMA-IR. Conclusions: These results demonstrate that HDL-C concentration predicts significantly future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in nondiabetic Japanese-American men and women. Disclosure S. Song: None. Y. Hwang: 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. D.L. Leonetti: None. W.Y. Fujimoto: None. E.J. Boyko: None. Funding National Institutes of Health DK31170, HL49293); University of Washington (DK017047, DK035816, RR-000037); VA Puget Sound Health Care System (to E.J.B., S.E.K.)

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 25.4kg/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.

Background: We describe the association between high density lipoprotein cholesterol (HDL-C) concentration and computed tomography (CT)-measured fat depots. Methods: We examined the cross-sectional associations between HDL-C concentration and intra-abdominal (IAF), abdominal subcutaneous (SCF), and thigh fat (TF) areas in 641 Japanese-American men and women. IAF, SCF, and TF were measured by CT at the level of the umbilicus and mid-thigh. The associations between fat area measurements and HDL-C were examined us ing multivariate linear regression analysis adjusting for age, sex, diabetes family history, homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Non-linearity was assessed using fractional polynomials. Results: Mean±standard deviation of HDL-C concentration and IAF in men and women were 1.30±0.34 mg/dL, 105±55.3 ㎠, and 1.67±0.43 mg/dL, 74.4±46.6 ㎠ and differed significantly by gender for both comparisons (P

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 Despres 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.

Both diet and visceral adiposity play key roles in cardiometabolic disease. However, the association between dietary fat and subsequent visceral fat accumulation is not known. Thus, we prospectively examined future visceral fat accumulation in relation to dietary intake of animal and plant fats, or saturated and polyunsaturated fats in 312 nondiabetic Japanese-American men and women. Visceral adiposity was measured as intra-abdominal fat (IAF) area at the umbilicus by computed tomography at baseline and 10-11 years. Detailed dietary information was assessed at baseline using a food frequency questionnaire and 24-hour recall. Insulin sensitivity was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR) and insulin response by the insulinogenic index (IGI) [Δinsulin/Δglucose (30-0 minutes)]. After adjustment for baseline IAF, age, sex, smoking habits (non-smokers, past-smokers, current smokers), physical activity, alcohol consumption, HOMA-IR, IGI, total protein intake, and total carbohydrate intake in multiple linear regression models, baseline log transformed animal fat intake [coefficient=15.319 (P=0.002)], but not plant fat intake [0.163 (P=0.270)], was associated with future IAF change. In the model that included saturated and polyunsaturated fat substituted for animal and plant fat intake, saturated fat was associated with future IAF change in both men [0.892 (P=0.030)] and women [1.121 (P=0.022)], but a statistically significant interaction was present between sex and polyunsaturated fat, such that polyunsaturated fat intake was inversely associated with future IAF change in men [-1.290 (P=0.003)], but not women [-0.058 (P=0.905)]. In conclusion, in both men and women, higher intake of animal fat and saturated fat, not plant fat, precede more visceral fat accumulation, while in men only, higher polyunsaturated fat intake precedes less visceral fat accumulation. Disclosure T. Hayashi: None. K. Sato: None. D.L. Leonetti: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim GmbH, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Research & Development, Merck & Co., Inc., Novo Nordisk A/S. S. Uehara: None. W.Y. Fujimoto: None. E.J. Boyko: None.

Aims: Leptin has been shown to predict risk of metabolic syndrome (MetS), but it is not known whether this association is independent of body composition. Thus, we examined whether plasma leptin concentration predicted risk of MetS after adjustment for body composition measured using imaging. Methods: We used the modified ATP III MetS criteria for an Asian population to classify participants in the longitudinal Japanese-American Community Diabetes Study as to presence of MetS. Participants without MetS at baseline (n=283) were followed for its development over 5 years. CT-measured adipose depots included baseline and 5-year intra-abdominal and abdominal subcutaneous fat areas at the level of the umbilicus, subcutaneous mid-thigh fat area, and subcutaneous thorax fat area at the nipple level. Other measurements included fasting plasma leptin and serum HDL-cholesterol and triglyceride concentrations, fasting and 2 hour glucose from a 75 g OGTT, systolic blood pressure (SBP), and medication use. Logistic regression analysis was used to estimate the odds of incident MetS by leptin concentration, body composition, and baseline MetS features. Results: 65 participants developed MetS at 5-year follow-up. Multivariable logistic regression models showed a lower odds of incident MetS with 1-SD greater leptin concentration (OR = 0.45; 95% CI = 0.25-0.79; p = 0.006) adjusting for age, sex, CT-fat areas at baseline, and 5-year change in CT-fat areas. Additional adjustment for other MetS features at baseline (fasting and 2 hour glucose, triglycerides, HDL-cholesterol, SBP) yielded similar results (OR = 0.38; 95% CI = 0.20-0.71; p = 0.002). Conclusions: Leptin concentration predicts MetS risk in Japanese Americans independent of body composition. Further research is needed to confirm this association in other populations and to understand potential underlying biologic mechanisms. Disclosure C. Liao: None. W.Y. Fujimoto: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim GmbH, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Research & Development, Merck & Co., Inc., Novo Nordisk A/S. D.L. Leonetti: None. E.J. Boyko: None.

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.

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.

Background A proportion of obese subjects appear metabolically healthy (MHO) but little is known about the natural history of MHO and factors predicting its future conversion to metabolically unhealthy obese (MUO). Objectives The aim was to determine prospectively the frequency of conversion of MHO to MUO and the clinical variables that independently predicted this conversion, with a particular focus on the role of body composition. Methods We identified 85 Japanese Americans with MHO (56 men, 29 women), aged 34–73 years (mean age 49.8 years) who were followed at 2.5, 5, and 10 years after enrollment with measurements of metabolic characteristics, lifestyle, and abdominal and thigh fat areas measured by computed tomography. Obesity was defined using the Asian body mass index criterion of ≥ 25 kg/m2. Metabolically healthy was defined as the presence of ≤ 2 of 5 metabolic syndrome components proposed by the National Cholesterol Education Program Adult Treatment Panel III, while metabolically unhealthy was defined as ≥ 3 components. Results Over 10 years of follow-up, 55 MHO individuals (64.7%) converted to MUO. Statistically significant univariate predictors of conversion included dyslipidemia, greater insulin resistance, and greater visceral abdominal (VAT) and subcutaneous abdominal fat area (SAT). In multivariate analysis, VAT (odds ratio per 1 SD increment (95% confidence interval) 2.04 (1.11 – 3.72), P=0.021), high density lipoprotein (HDL) cholesterol (0.24 (0.11 – 0.53), P

Background Little is known about the natural course of normal fasting glucose (NFG) in Asians and the risk factors for future diabetes. Methods A total of 370 Japanese Americans (163 men, 207 women) with NFG levels and no history of diabetes, aged 34 to 75 years, were enrolled. Oral glucose tolerance tests were performed at baseline, 2.5, 5, and 10 years after enrollment. Results During 10 years of follow-up, 16.1% of participants met criteria for diabetes diagnosis, and 39.6% of subjects still had NFG levels at the time of diabetes diagnosis. During 5 years of follow-up, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01 to 1.10; P=0.026) and family history of diabetes (OR, 3.24; 95% CI, 1.42 to 7.40; P=0.005) were independently associated with future diabetes diagnosis; however, fasting glucose level was not an independent predictor. During 10 years of follow-up, family history of diabetes (OR, 2.76; 95% CI, 1.37 to 5.54; P=0.004), fasting insulin level (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.037), and fasting glucose level (OR, 3.69; 95% CI, 1.13 to 12.01; P=0.030) were associated with diabetes diagnosis independent of conventional risk factors for diabetes. Conclusion A substantial number of subjects with NFG at baseline still remained in the NFG range at the time of diabetes diagnosis. A family history of diabetes and fasting insulin and glucose levels were associated with diabetes diagnosis during 10 years of follow-up; however, fasting glucose level was not associated with diabetes risk within the relatively short-term follow-up period of 5 years in subjects with NFG.

The relationships between smoking and glycaemic variables have not been well explored. We compared HbA1c, fasting plasma glucose (FPG) and 2 h plasma glucose (2H-PG) in current, ex- and never-smokers. This meta-analysis used individual data from 16,886 men and 18,539 women without known diabetes in 12 DETECT-2 consortium studies and in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) and Telecom studies. Means of three glycaemic variables in current, ex- and never-smokers were modelled by linear regression, with study as a random factor. The I 2 statistic was used to evaluate heterogeneity among studies. HbA1c was 0.10% (95% CI 0.08, 0.12) (1.1 mmol/mol [0.9, 1.3]) higher in current smokers and 0.03% (0.01, 0.05) (0.3 mmol/mol [0.1, 0.5]) higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current and never-smokers (−0.004 mmol/l [−0.03, 0.02]) but FPG was higher in ex-smokers (0.12 mmol/l [0.09, 0.14]). In comparison with never-smokers, 2H-PG was lower (−0.44 mmol/l [−0.52, −0.37]) in current smokers, with no difference for ex-smokers (0.02 mmol/l [−0.06, 0.09]). There was a large and unexplained heterogeneity among studies, with I 2 always above 50%; I 2 was little changed after stratification by sex and adjustment for age and BMI. In this study population, current smokers had a prevalence of diabetes that was 1.30% higher as screened by HbA1c and 0.52% lower as screened by 2H-PG, in comparison with never-smokers. Across this heterogeneous group of studies, current smokers had a higher HbA1c and lower 2H-PG than never-smokers. This will affect the chances of smokers being diagnosed with diabetes.

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.

OBJECTIVE —Visceral adiposity is an important risk factor for cardiovascular disease and type 2 diabetes. We sought to determine whether change in intraabdominal fat area (IAF) over time predicts subsequent development of diabetes. RESEARCH DESIGN AND METHODS —We followed up 436 nondiabetic Japanese-American subjects (mean age 51.9 years, mean BMI 24.2 kg/m2, 54% male) for development of diabetes. We fit a logistic regression model to examine the association over a 10-year follow-up between change in IAF at 5-year follow-up and other fat areas (measured by computed tomography) and development of incident diabetes, adjusted for age, sex, family history of diabetes in a first-degree relative, second-generation versus third-generation Japanese American (Nisei vs. Sansei), baseline IAF, BMI, weight change over time, smoking status, physical activity level, and subcutaneous fat (SCF) depot areas. RESULTS —Cumulative incidence of diabetes was 20.4% at 10 years. Mean change in IAF was 10.9 cm2. An increase of 1 SD in IAF was associated with a 1.65-fold increase in the odds of diabetes over 10 years (OR = 1.65, 95% CI 1.21–2.25) after adjusting for the above covariates. This association was also independent of changes in thoracic, thigh, and abdominal SCF, as well as change in weight. CONCLUSIONS —We conclude that baseline IAF and accumulation of fat in this area over time are independent predictors of the development of type 2 diabetes in Japanese Americans.

Migrant Japanese populations in both the United States and Brazil have for a long time shown a higher prevalence of type 2 diabetes than in 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 epidemiologic 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 demonstrated. 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. Wepropose 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 beta-cell reserve in susceptible individuals, resulting in glucose intolerance and eventually in many the development of diabetes. We have shown that it may 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 may in many ways be applicable to other populations of Asian origin.

Men's hunting has dominated the discourse on energy capture and flow in the past decade or so. We turn to women's roles as critical to household formation, pair-bonding, and intergenerational bonds. Their pivotal contributions in food processing and distribution likely promoted kinship, both genetic and affinal, and appear to be the foundation from which households evolved. With conscious recognition of household social units, variable cultural constructions of human kinship systems that were sensitive to environmental and technological conditions could emerge. Kinship dramatically altered the organization of resource access for our species, creating what we term "kinship ecologies." We present simple mathematical models to show how hunting leads to dependence on women's contributions, bonds men to women, and bonds generations together. Kinship, as it organized transfers of food and labor energy centered on women, also became integrated with the biological evolution of human reproduction and life history.

Much is known about body composition and type 2 diabetes risk but less about body function such as strength. We assessed whether hand-grip strength predicted incident diabetes.We followed 394 nondiabetic Japanese-American subjects (mean age 51.9) for the development of diabetes. We fit a logistic regression model to examine the association between hand-grip strength at baseline and type 2 diabetes risk over 10 years, adjusted for age, sex, and family history.A statistically significant (p = 0.008) and negative (coefficient -0.208) association was observed between hand-grip strength and diabetes risk that diminished at higher BMI levels. Adjusted ORs for a 10-pound hand-grip strength increase with BMI set at the 25th, 50th or 75th percentiles were 0.68, 0.79, and 0.98, respectively.Among leaner individuals, greater hand-grip strength was associated with lower risk of type 2 diabetes, suggesting it may be a useful marker of risk in this population.

This paper uses data from eight past and present societies practicing intensive agriculture to measure the transmission of wealth across generations in preindustrial agricultural societies. Focusing on embodied, material, and relational forms of wealth, we compare levels of wealth between parents and children to estimate how effectively wealth is transmitted from one generation to the next and how inequality in one generation impacts inequality in the next generation. We find that material wealth is by far the most important, unequally distributed, and highly transmitted form of wealth in these societies, while embodied and relational forms of wealth show much weaker importance and transmission. We conclude that the unique characteristics of material wealth, and especially wealth in land, are key to the high and persistent levels of inequality seen in societies practicing intensive agriculture. We explore the implications of our findings for the evolution of inequality in the course of human history and s...

Origins of EgalitarianismWealthy contemporary societies exhibit varying extents of economic inequality, with the Nordic countries being relatively egalitarian, whereas there is a much larger gap between top and bottom in the United States.Borgerhoff Mulderet al.(p.682; see the Perspective byAcemoglu and Robinson) build a bare-bones model describing the intergenerational transmission of three different types of wealth—based on social networks, land and livestock, and physical and cognitive capacity—in four types of small-scale societies in which livelihoods depended primarily on hunting, herding, farming, or horticulture. Parameter estimates from a large-scale analysis of historical and ethnographic data were added to the model to reveal that the four types of societies display distinctive patterns of wealth transmission and that these patterns are associated with different extents of inequality.

Context: Although obesity has been, in general, associated with glomerular hyperfiltration, visceral adiposity has been suggested to be associated with reduced glomerular filtration. Objective: The aim of the study was to evaluate the differential effects of obesity and body fat distribution on glomerular filtration. Design and Setting: We conducted a cross-sectional study of the Japanese-American community in Seattle, Washington. Participants: We studied a representative sample of second-generation Japanese-American men and women with normal glucose tolerance (n = 124) and impaired glucose metabolism (impaired fasting glucose and/or impaired glucose tolerance) (n = 144) residing in King County, Washington. Main Outcome Measures: Glomerular filtration rate was estimated by 24-h urinary creatinine clearance, body size by body mass index (BMI), and intra-abdominal fat (IAF), sc fat (SCF), and lean thigh areas by CT scan. Results: Creatinine clearance was positively correlated with BMI (r = 0.429; P < 0.001), fasting glucose (r = 0.198; P = 0.001), and insulin levels (r = 0.125; P = 0.042), as well as IAF (r = 0.239; P < 0.001), SCF (r = 0.281; P < 0.001), and lean thigh (r = 0.353; P < 0.001) areas. The association between creatinine clearance and BMI remained significant after adjustments for IAF, SCF areas, and fasting insulin levels (r = 0.337; P < 0.001); whereas IAF and SCF areas were not independently associated with creatinine clearance after adjusting for BMI. Creatinine clearance increased with increasing BMI after adjusting for fasting insulin, fasting glucose, IAF and SCF areas in subjects with normal glucose tolerance (r = 0.432; P < 0.001) and impaired glucose metabolism (r = 0.471; P < 0.001). Conclusions: BMI rather than body fat distribution is an independent determinant of creatinine clearance in nondiabetic subjects. Lean body mass, rather than adiposity, may explain this association.

OBJECTIVE—We sought to determine whether an oral disposition index (DIO) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DIO by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and β-cell function. RESEARCH DESIGN AND METHODS—A total of 613 Japanese-American subjects (322 men and 291 women) underwent a 75-g oral glucose tolerance test (OGTT) at baseline, 5 years, and 10 years. Insulin sensitivity was estimated as 1/fasting insulin or homeostasis model assessment of insulin sensitivity (HOMA-S). Insulin response was estimated as the change in insulin divided by change in glucose from 0 to 30 min (ΔI0–30/ΔG0–30). RESULTS—ΔI0–30/ΔG0–30 demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S with a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the loge-transformed estimates included −1 for ΔI0–30/ΔG0–30 versus 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin sensitivity measure, the confidence limits for the slope included −1 only for subjects with normal glucose tolerance (NGT) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of ΔI0–30/ΔG0–30 and 1/fasting insulin was calculated (DIO) and decreased from NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DIO predicted cumulative diabetes at 10 years (P < 0.001) independent of age, sex, BMI, family history of diabetes, and baseline fasting and 2-h glucose concentrations. CONCLUSIONS—The DIO provides a measure of β-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.

Human behavioral ecologists have shown that the reproductive lives of women are affected by both their husbands and the grandmothers of their children. Study of the combined effect of the roles of the husbands and mothers of 650 Khasi women aged 16–50 years supports the ideas that the reproductive agendas of husbands may require more than women want to invest and that mothers provide support and protective services to their daughters and grandchildren. In the absence of the woman’s mother, the husband’s agenda appears to have more influence on her reproductive career. In a cooperative vein, women's mothers may contribute to good marital choices. A view of reproductive pursuits that incorporates in‐laws enhances behavioral ecology approaches to the evolutionary comprehension of human reproductive behavior. This view also more readily interfaces with the cultural systems that set up the ecologies of reproductive life.

Background Epidemiologic evidence suggests that dietary changes associated with acculturation to a Western diet may increase the risk of type 2 diabetes in Japanese Americans. Objective We hypothesized that dietary acculturation patterns could be measured by confirmatory factor analysis (CFA) by using a culturally sensitive food-frequency questionnaire (FFQ). We examined the utility of the estimated factor scores by testing for associations with diabetes and 2 risk factors for diabetes-body mass index (BMI; in kg/m(2)) and C-reactive protein (CRP). Design By using cross-sectional data from a sample of 219 Nisei (second-generation Japanese American; mean age 70 y) and 277 Sansei (third-generation Japanese American; mean age 42 y) participants in the Japanese American Family Study, we conducted CFA on 5 items characteristic of a Japanese diet and 4 items characteristic of a Western diet. The resulting factor scores were examined for associations with diabetes by using logistic regression and for associations with BMI and CRP by using linear regression. Results CFA confirmed the presence of Japanese and Western food factors. The Nisei had a significantly higher average factor score for the Japanese food factor and significantly lower average factor score for the Western food factor than did the Sansei. In Sansei persons, but not in Nisei persons, the Western food factor score was significantly associated with plasma CRP concentration (P = 0.02), BMI (P = 0.02), and diabetes (P = 0.001). Conclusions In this Japanese American sample, dietary acculturation can be estimated by using CFA on FFQ data. Future studies should investigate the effects of dietary acculturation on disease risk independent of other lifestyle factors.

Family planning is the usual modern route to producing a small family. Can human behavioral ecology provide a framework for understanding family planning behavior? Hillard S. Kaplan (Yearb. Phys. Anthropol. 39:91-135) has proposed a general theory of human parental investment based on the importance of skills development in children. As modern, skills-based, competitive market economies are established, parental investment strategies would be predicted to become oriented toward producing increasingly competitive offspring in a pattern of coordinated investment in their embodied capital-in other words, skills training along with good health to ensure their long-term productivity. Parental embodied capital and resources are also expected to be associated with motivation to produce competitive offspring. The basic parental investment trade-off between quality and quantity should predict greater investment in fewer children and the adoption of family planning behavior. Data on family planning in two ethnic groups in Northeast India (Khasi and Bengali) currently experiencing early-phase transition into modern market economies from very different social and ecological baselines are examined within this analytical framework. The results show a mixture of strategies in conjunction with family planning that involve decreased as well as increased investment in the embodied capital of children among Bengali and a divergence of investments in education and health among Khasi. These mixtures of strategies provide some insight into the motivations to use family planning in the face of economic transition, given differing local cultural and ecological conditions and the opportunity structures they provide.

Atherogenic dyslipidemia is frequently observed in persons with a greater amount of visceral adipose tissue (VAT). However, it is still uncertain whether VAT is independently associated with the future development of atherogenic dyslipidemia.The aim of this study was to determine whether baseline and changes in VAT and subcutaneous adipose tissue (SAT) are associated with future development of atherogenic dyslipidemia independent of baseline lipid levels and standard anthropometric indices.Community-based prospective cohort study with 5 years of follow-up.A total of 452 Japanese Americans (240 men, 212 women), aged 34-75 years were assessed at baseline and after 5 years of follow-up.Abdominal fat areas were measured by computed tomography. Atherogenic dyslipidemia was defined as one or more abnormalities in high-density lipoprotein (HDL) cholesterol, triglycerides, or non-HDL cholesterol levels.Baseline VAT and change in VAT over 5 years were independently associated with log-transformed HDL cholesterol, log-transformed triglyceride, and non-HDL cholesterol after 5 years (standardized β = -0.126, 0.277, and 0.066 for baseline VAT, respectively, and -0.095, 0.223, and 0.090 for change in VAT, respectively). However, baseline and change in SAT were not associated with any future atherogenic lipid level. In multivariate logistic regression analysis, incremental change in VAT (odds ratio [95% confidence interval], 1.73 [1.20-2.48]; P = .003), triglycerides (4.01 [1.72-9.33]; P = .001), HDL cholesterol (0.32 [0.18-0.58]; P.001), and non-HDL cholesterol (7.58 [4.43-12.95]; P.001) were significantly associated with the future development of atherogenic dyslipidemia independent of age, sex, diastolic blood pressure, homeostasis model assessment insulin resistance, body mass index (BMI), change in BMI, SAT, and baseline atherogenic lipid levels.Baseline and change in VAT were independent predictors for future development of atherogenic dyslipidemia. However, BMI, waist circumference, and SAT were not associated with future development of atherogenic dyslipidemia.

Human kinship and family systems are likely to be anciently rooted in the behavioral ecology of sharing food, and further interdependencies evolved to include cooperative breeding, pair bonds, and other sociopolitical alliances. The balancing of investment with respect to the advantages/disadvantages that come from such alliances (such as mating privileges, resource access, and defense versus exploitation and competition), which can affect inclusive fitness, may have been one of the most challenging aspects of early human experience and requires more exploration. Multigenerational and collateral investment and dependency, as well as the evolving cognitive capability for tracking and evaluating these relationships, create the basis for the generation of cultural constructs of kinship (e.g., marriage, families, lineages, in-laws) and the norms regarding them. Furthermore, the association of investment with long-term dependencies creates reinforcing attachment responses to others involved in these ties—attachments that involve expectations of and identification with others that became coded in kinship ideologies. We ask how investment is connected to cultural notions of kinship that create kinship ecologies through various manipulations of resources and currencies. Then, how these notions set up a framework for kin investment that may be a less-thanperfect reflection of biology but nonetheless have adaptive efficiencies (such as resource access) for members of kinship groups—for example, by adding the effects of reciprocity to those of kin selection (Alvard 2003). Moreover, in the presence of cultural constructions of kinship we can ask if and how kin selection operates. One payoff to the study of kin investment is a growing, ecologically founded comprehension of cultural kinship. Harrell (1997) focuses on families as organized and mobilized around the activities they must accomplish. Family organization Hum Nat (2008) 19:227–230 DOI 10.1007/s12110-008-9040-6

OBJECTIVE Asian Americans manifest type 2 diabetes at low BMI levels but may not undergo diagnostic testing for diabetes if the currently recommended BMI screening cut point of ≥25 kg/m2 is followed. We aimed to ascertain an appropriate lower BMI cut point among Asian-American adults without a prior diabetes diagnosis. RESEARCH DESIGN AND METHODS We consolidated data from 1,663 participants, ages ≥45 years, without a prior diabetes diagnosis, from population- and community-based studies, including the Mediators of Atherosclerosis in South Asians Living in America study, the North Kohala Study, the Seattle Japanese American Community Diabetes Study, and the University of California San Diego Filipino Health Study. Clinical measures included a 2-h 75-g oral glucose tolerance test, BMI, and glycosylated hemoglobin (HbA1c). RESULTS Mean age was 59.7 years, mean BMI was 25.4 kg/m2, 58% were women, and type 2 diabetes prevalence (American Diabetes Association 2010 criteria) was 16.9%. At BMI ≥25 kg/m2, sensitivity (63.7%), specificity (52.8%), and Youden index (0.16) values were low; limiting screening to BMI ≥25 kg/m2 would miss 36% of Asian Americans with type 2 diabetes. For screening purposes, higher sensitivity is desirable to minimize missing cases, especially if the diagnostic test is relatively simple and inexpensive. At BMI ≥23 kg/m2, sensitivity (84.7%) was high in the total sample and by sex and Asian-American subgroup and would miss only ∼15% of Asian Americans with diabetes. CONCLUSIONS The BMI cut point for identifying Asian Americans who should be screened for undiagnosed type 2 diabetes should be

We prospectively examined the relationship between leptin and markers of insulin resistance and secretion and future visceral adipose tissue accumulation. In this study, 518 nondiabetic Japanese-American men and women underwent the following measurements at baseline and at 5- and 10-year follow-ups: plasma glucose and insulin measured after an overnight fast and during a 75-g oral glucose tolerance test, insulin secretion ratio (ISR) [(30-min insulin − fasting insulin)/30-min glucose], fasting C-peptide levels, plasma leptin (baseline only), and fat areas (intra-abdominal and subcutaneous) measured by computed tomography. Predictors of future intra-abdominal fat (IAF) were determined using multiple linear regression. Fasting insulin and C-peptide levels at baseline were significantly associated with IAF area at 5 years (coefficient = 0.041, P = 0.001 and coefficient = 1.283, P < 0.001, respectively) and 10 years (coefficient = 0.031, P = 0.020 and coefficient = 0.221, P = 0.035, respectively). ISR was not significantly associated with IAF at 5 or 10 years. Leptin level at baseline was positively associated with IAF at 5 years (coefficient = 0.055, P = 0.002) and 10 years (coefficient = 0.059, P = 0.003). In conclusion, higher levels of fasting insulin, C-peptide, and circulating leptin level predicted visceral fat accumulation independent from subcutaneous fat accumulation in nondiabetic Japanese-American men and women in both short-term (5 years) and long-term (10 years) follow-up.

Numerous studies have demonstrated that increased C-reactive protein (CRP) levels predict coronary heart disease, stroke, peripheral vascular disease, and diabetes, and are associated with features of the metabolic syndrome. Only three previous studies have investigated the heritability of CRP levels, primarily in samples of Caucasian families. The purpose of the present study was to estimate the magnitude of genetic influences on CRP levels, and to examine potential associations between variation in the APOE gene and CRP levels, using a sample of 562 individual Japanese Americans from 68 extended kindreds. In general, correlation coefficients between first-degree relatives for CRP were approximately 0.2, and spouse correlations did not differ from zero, consistent with genetic influences. Heritability estimates were approximately 0.3 (p < 0.01), even with adjustment for factors known to influence CRP levels. A significant relationship was seen between unadjusted CRP levels and APOE genotypes (p = 0.02), with the highest mean CRP level among epsilon2 carriers (1.20 mg/L), and nearly the same mean levels among epsilon3/epsilon3 subjects and epsilon4 carriers (0.72 and 0.74 mg/L, respectively). However, this relationship was diminished with adjustment for covariates (p = 0.07). These results demonstrate the presence of both genetic and environmental effects on CRP levels among Asian Americans, and additional studies are needed to determine if the APOE gene contributes to these genetic influences.

A rapidly growing body of evidence demonstrates important associations between the metabolic syndrome, characterized by a cluster of risk factors or phenotypes that include dyslipidemia, central obesity, hypertension, and hyperinsulinemia, and both cardiovascular disease and type 2 diabetes. The purpose of the present study was to characterize the metabolic syndrome in a sample of 432 individuals from 68 Japanese-American families, using factor analysis of quantitative phenotypes, and to estimate the heritability of these independent factors. Using nine characteristic phenotypes that included LDL particle size and C-reactive protein (CRP), factor analysis identified three multivariate factors interpreted as lipids, body fat/insulin/glucose/CRP, and blood pressure, explaining 65% of the variance. Heritability analysis revealed significant genetic effects on all of the factors: lipids (h2 = 0.52, P < 0.001), body fat/insulin/glucose/CRP (h2 = 0.27, P = 0.016), and blood pressure (h2 = 0.25, P = 0.026). This analysis shows that independent, multivariate factors of the metabolic syndrome are heritable, demonstrating genetic influences on the underlying pathophysiological mechanisms of the syndrome.

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.

OBJECTIVE The study objective was to examine the associations among visceral fat (VF), all-cause mortality, and obesity-related mortality. RESEARCH DESIGN AND METHODS A total of 733 Japanese Americans were followed for 16.9 years. Hazard ratios (HRs) per interquartile range increase in VF were calculated using time-dependent Cox proportional hazard models censored at age 82 years, with age as the time axis adjusted for sex and smoking. RESULTS Higher VF was associated with all-cause mortality (HR 1.39 [95% CI 1.11–1.75] 107 deaths) and obesity-related mortality (1.39 [1.04–1.85], 68 deaths from cardiovascular disease, diabetes, or obesity-related cancer). After further adjustment for waist circumference, VF remained significantly associated with all-cause mortality (1.41 [1.04–1.92]) but not with obesity-related mortality. The associations between mortality and VF were not independent of BMI. CONCLUSIONS VF was associated with all-cause mortality and obesity-related mortality in Japanese Americans. VF did not significantly improve mortality risk assessment beyond that of BMI.

OBJECTIVE—To determine whether diet and endurance exercise improved adiposity-related measurements in Japanese Americans with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS—This study compared the effects of an American Heart Association (AHA) step 2 diet ( RESULTS—At 6 months, the treatment group showed significantly greater reduction in percent, body fat (−1.4 ± 0.4 vs. −0.3 ± 0.3%); BMI (−1.1 ± 0.2 vs. −0.4 ± 0.1 kg/m2); subcutaneous fat by computed tomography at the abdomen (−29.3 ± 4.2 vs. −5.7 ± 5.9 cm2), thigh (−13.2 ± 3.6 vs. −3.6 ± 3.0 cm2), and thorax (−19.6 ± 3.6 vs. −8.9 ± 2.6 cm2); and skinfold thickness at the bicep (−2.0 ± 0.6 vs. 1.1 ± 0.6 mm) and tricep (−3.7 ± 0.8 vs. −0.9 ± 0.6 mm), which continued despite moving to home-based exercise for the last 18 months. CONCLUSIONS—Diet and endurance exercise improved BMI, body composition, and body fat distribution and, thus, may delay or prevent type 2 diabetes in Japanese Americans with IGT.

In Japanese Americans, intra-abdominal fat area measured by computed tomography is positively associated with the prevalence and incidence of hypertension. Evidence in other populations suggests that other fat areas may be protective. We sought to determine whether a change in specific fat depots predicts the development of hypertension. We prospectively followed up 286 subjects (mean age, 49.5 years; 50.4% men) from the Japanese American Community Diabetes Study for 10 years. At baseline, subjects did not have hypertension (defined as blood pressure ≥140/90 mm Hg) and were not taking blood pressure or glucose-lowering medications. Mid-thigh subcutaneous fat area, abdominal subcutaneous fat area, and intra-abdominal fat area were directly measured by computed tomography at baseline and 5 years. Logistic regression was used to estimate odds of incident hypertension over 10 years in relation to a 5-year change in fat area. The relative odds of developing hypertension for a 5-year increase in intra-abdominal fat was 1.74 (95% confidence interval, 1.28–2.37), after adjusting for age, sex, body mass index, baseline intra-abdominal fat, alcohol use, smoking status, and weekly exercise energy expenditure. This relationship remained significant when adjusted for baseline fasting insulin and 2-hour glucose levels or for diabetes mellitus and pre–diabetes mellitus classification. There were no significant associations between baseline and change in thigh or abdominal subcutaneous fat areas and incident hypertension. In conclusion, in this cohort of Japanese Americans, the risk of developing hypertension is related to the accumulation of intra-abdominal fat rather than the accrual of subcutaneous fat in either the thigh or the abdominal areas.

OBJECTIVE: We conducted a prospective study among Japanese Americans of diabetes incidence in relation to visceral and regional adiposity, fasting insulin and C-peptide, and a measure of insulin secretion, because little prospective data exist on these associations. RESEARCH DESIGN AND METHODS: Baseline variables included plasma glucose, C-peptide, and insulin measured after an overnight fast and 30 and 120 min after a 75-g oral glucose tolerance test; abdominal, thoracic, and thigh fat areas by computed tomography (CT); BMI (kg/m2); and insulin secretion (incremental insulin response [IIR]). RESULTS: Study subjects included 290 second-generation (nisei) and 230 third-generation (sansei) Japanese Americans without diabetes, of whom 65 and 13, respectively, developed diabetes. Among nisei, significant predictors of diabetes risk for a 1 SD increase in continuous variables included intra-abdominal fat area (IAFA) (odds ratio, 95% CI) (1.6, 1.1-2.3), fasting plasma C-peptide (1.4, 1.1-1.8), and the IIR (0.5, 0.3-0.9) after adjusting for age, sex, impaired glucose tolerance, family diabetes history, and CT-measured fat areas other than intra-abdominal. Intra-abdominal fat area remained a significant predictor of diabetes incidence even after adjustment for BMI, total body fat area, and subcutaneous fat area, although no measure of regional or total adiposity was related to development of diabetes. Among sansei, all adiposity measures were related to diabetes incidence, but, in adjusted models, only IAFA remained significantly associated with higher risk (2.7, 1.4-5.4, BMI-adjusted). CONCLUSIONS: Greater visceral adiposity precedes the development of type 2 diabetes in Japanese Americans and demonstrates an effect independent of fasting insulin, insulin secretion, glycemia, total and regional adiposity, and family history of diabetes.

Islet amyloid is a characteristic feature of type 2 diabetes. Its major component is the normal beta-cell secretory product amylin, or islet amyloid polypeptide (IAPP). To determine whether increased or disproportionate release of amylin may explain the propensity for amyloid deposition in type 2 diabetes, we measured plasma amylin-like immunoreactivity (ALI) and immunoreactive insulin (IRI) release in response to an oral glucose load in 94 Japanese-American subjects with normal glucose tolerance (NGT; n=56), impaired glucose tolerance (IGT; n=10), and type 2 diabetes (n=28) as defined by World Health Organization criteria. The incremental increase in ALI, IRI, and glucose (G) at 30 min after oral glucose ingestion was used to calculate deltaALI/deltaG and deltaIRI/deltaG as measures of beta-cell function. Overall glucose metabolism was assessed as the incremental glucose area (glucose AUC) during the 2 h of the oral glucose tolerance test. As expected, plasma glucose concentrations at both fasting (NGT, 5.0+/-0.4; IGT, 5.5+/-0.1; type 2 diabetes, 6.2+/-0.3 mmol/l; P < 0.0001) and 2 h (NGT, 6.7+/-0.1; IGT, 9.4+/-0.3; type 2 diabetes, 13.2 +/-0.5 mmol/l; P < 0.0001) were elevated in individuals with IGT and type 2 diabetes. In response to glucose ingestion, plasma IRI and ALI increased in all subjects, but these increments were lower in individuals with reduced glucose tolerance, as reflected in the deltaIRI/deltaG (NGT, 119+/-10.3; IGT, 60.7+/-7.1; type 2 diabetes, 49.7 +/-5.4 pmol/l; P < 0.0001) and deltaALI/deltaG (NGT, 2.6+/-0.2; IGT, 1.8+/-0.3; type 2 diabetes, 1.2+/-0.1 pmol/l; P < 0.0001). Moreover, these reductions in the 30-min incremental ALI and IRI responses were proportionate such that the molar ratio of ALI to IRI was not different among the three groups (NGT, 2.6+/-0.2; IGT, 2.9 +/-0.3; type 2 diabetes, 2.9+/-0.3%; NS). Further, the relationship between beta-cell function, measured as either deltaIRI/deltaG or deltaALI/deltaG, and glucose metabolism, assessed as glucose AUC, was nonlinear and inverse in nature, with r2 values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), respectively. We conclude that the reduced beta-cell function of IGT and type 2 diabetes includes proportionate reductions in both IRI and ALI release. Thus, it is unlikely that the development of islet amyloid in type 2 diabetes is the result of increased release of ALI.