Associations of plasma sphingolipids with measures of insulin sensitivity, ß-cell function, and incident diabetes in Japanese Americans.

BACKGROUND AND AIMS: To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, ß-cell function, and incident diabetes in the Japanese American Community Diabetes Study. METHODS AND RESULTS: Baseline plasma samples from adults without diabetes (n = 349; mean age 56.7 years, 51 % men) were assayed for circulating ceramide and sphingomyelin species. Adjusted regression models examined cross-sectional and longitudinal associations with insulin sensitivity (HOMA2-%S), ß-cell function (oral disposition index: DIo) and with incident diabetes over 5 years follow-up. Concentrations of four species (Ceramide C16:0, C18:0, C20:0, and C22:0) were inversely associated with HOMA2-%S at baseline (all P values < 0.05, Q values < 0.05) and change in HOMA2-%S over 5 years (all P values < 0.05, Q values < 0.05). No sphingolipids were associated with baseline or change in DIo. Of the four species associated with HOMA2-%S, only Ceramide C18:0 was significantly and positively associated with incident diabetes (RR/1SD 1.44, 95 % CI 1.10-1.80, P = 0.006, Q = 0.024). The association of plasma Ceramide C18:0 with the risk of diabetes was partially mediated by change in HOMA2-%S between baseline and 5 years (mediation proportion: 61.5 %, 95 % CI 21.1%-212.5 %). CONCLUSION: Plasma Ceramide C18:0 was associated with higher risk of incident diabetes which was partially mediated through a decrease in insulin sensitivity between baseline and five years. Circulating Ceramide C18:0 could be a potential biomarker for identifying those at risk of developing diabetes.

Longitudinal changes in plasma sex hormone concentrations correlate with changes in CT-measured regional adiposity among Japanese American men over 10 years.

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 < .001) and testosterone decreased (P < .001). Median IAF and SCF increased from 0 to 10 years (both P < .001). In multivariate analyses, change in oestrone positively correlated (P = .019) while change in testosterone (P = .003) and dihydrotestosterone (P = .014) negatively correlated with change in IAF. Plasma oestradiol and oestrone positively correlated with change in SCF (P = .041 and P = .030, respectively) while testosterone (P = .031) negatively correlated in multivariate analysis. CONCLUSION: Among 190 community-dwelling, Japanese American men, increases in IAF were associated with decreases in plasma androgens and increases in plasma oestrone, but not oestradiol, at 10 years. Further research is necessary to understand whether changing hormone concentrations are causally related to changes in regional adiposity or whether the reverse is true.

Prevalence of Diabetes by Race and Ethnicity in the United States, 2011-2016.

Importance: The prevalence of diabetes among Hispanic and Asian American subpopulations in the United States is unknown. Objective: To estimate racial/ethnic differences in the prevalence of diabetes among US adults 20 years or older by major race/ethnicity groups and selected Hispanic and non-Hispanic Asian subpopulations. Design, Setting, and Participants: National Health and Nutrition Examination Surveys, 2011-2016, cross-sectional samples representing the noninstitutionalized, civilian, US population. The sample included adults 20 years or older who had self-reported diagnosed diabetes during the interview or measurements of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2-hour plasma glucose (2hPG). Exposures: Race/ethnicity groups: non-Hispanic white, non-Hispanic black, Hispanic and Hispanic subgroups (Mexican, Puerto Rican, Cuban/Dominican, Central American, and South American), non-Hispanic Asian and non-Hispanic Asian subgroups (East, South, and Southeast Asian), and non-Hispanic other. Main Outcomes and Measures: Diagnosed diabetes was based on self-reported prior diagnosis. Undiagnosed diabetes was defined as HbA1c 6.5% or greater, FPG 126 mg/dL or greater, or 2hPG 200 mg/dL or greater in participants without diagnosed diabetes. Total diabetes was defined as diagnosed or undiagnosed diabetes. Results: The study sample included 7575 US adults (mean age, 47.5 years; 52% women; 2866 [65%] non-Hispanic white, 1636 [11%] non-Hispanic black, 1952 [15%] Hispanic, 909 [6%] non-Hispanic Asian, and 212 [3%] non-Hispanic other). A total of 2266 individuals had diagnosed diabetes; 377 had undiagnosed diabetes. Weighted age- and sex-adjusted prevalence of total diabetes was 12.1% (95% CI, 11.0%-13.4%) for non-Hispanic white, 20.4% (95% CI, 18.8%-22.1%) for non-Hispanic black, 22.1% (95% CI, 19.6%-24.7%) for Hispanic, and 19.1% (95% CI, 16.0%-22.1%) for non-Hispanic Asian adults (overall P < .001). Among Hispanic adults, the prevalence of total diabetes was 24.6% (95% CI, 21.6%-27.6%) for Mexican, 21.7% (95% CI, 14.6%-28.8%) for Puerto Rican, 20.5% (95% CI, 13.7%-27.3%) for Cuban/Dominican, 19.3% (95% CI, 12.4%-26.1%) for Central American, and 12.3% (95% CI, 8.5%-16.2%) for South American subgroups (overall P < .001). Among non-Hispanic Asian adults, the prevalence of total diabetes was 14.0% (95% CI, 9.5%-18.4%) for East Asian, 23.3% (95% CI, 15.6%-30.9%) for South Asian, and 22.4% (95% CI, 15.9%-28.9%) for Southeast Asian subgroups (overall P = .02). The prevalence of undiagnosed diabetes was 3.9% (95% CI, 3.0%-4.8%) for non-Hispanic white, 5.2% (95% CI, 3.9%-6.4%) for non-Hispanic black, 7.5% (95% CI, 5.9%-9.1%) for Hispanic, and 7.5% (95% CI, 4.9%-10.0%) for non-Hispanic Asian adults (overall P < .001). Conclusions and Relevance: In this nationally representative survey of US adults from 2011 to 2016, the prevalence of diabetes and undiagnosed diabetes varied by race/ethnicity and among subgroups identified within the Hispanic and non-Hispanic Asian populations.

HbA1c, fasting and 2 h plasma glucose in current, ex- and never-smokers: a meta-analysis.

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSION/INTERPRETATION: 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.

Plasma amino acid profile, a biomarker for visceral adipose tissue that can substitute for waist circumference 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 cm2 (0.798, 0.807 vs. 0.677, 0.671 for men and women, p < 0.0033) and VFA ≥ sex-specific median values (0.797, 0.786 vs. 0.676, 0.629 for men and women, p < 0.0017). AA significantly associated with change in VFA over 5 years were asparagine, glutamate, glutamine, glycine, methionine, proline, threonine in men; and histidine, isoleucine, tyrosine in women (p < 0.05). CONCLUSIONS: The 4A index can serve as a biomarker for VFA in Japanese-Americans and be considered for this purpose when WC is not available.

Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat.

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.

Leptin and Adiponectin Concentrations Independently Predict Future Accumulation of Visceral Fat in Nondiabetic Japanese Americans.

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 (ß = 1.7722, P = 0.014) and adiponectin concentrations (ß = -0.4162, P < 0.001) were significantly associated with IAF change over 5 years in multivariable models adjusting for age, sex, diabetes family history, weight change over 5 years, and baseline measurements of BMI, IAF, abdominal SCF, waist circumference, thigh fat, and homeostatic model assessment of insulin resistance. CONCLUSIONS: In nondiabetic Japanese Americans, a higher concentration of leptin was associated with greater accumulation of IAF and a higher concentration of adiponectin with lesser accumulation of IAF over 5 years.

Comparison of twenty indices of insulin sensitivity in predicting type 2 diabetes in Japanese Americans: The Japanese American Community Diabetes Study.

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.

Adrenal crisis precipitated by influenza A led to the diagnosis of Sheehan's syndrome 18 years after postpartum hemorrhage.

Physicians must recognize and treat adrenal crisis that may occur with acute viral illnesses such as influenza in women with Sheehan's syndrome that has been undiagnosed and hence untreated, sometimes for many years, after postpartum hemorrhage.

Intra-Abdominal Fat and High Density Lipoprotein Cholesterol Are Associated in a Non-Linear Pattern in Japanese-Americans.

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 using 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 cm², and 1.67±0.43 mg/dL, 74.4±46.6 cm² and differed significantly by gender for both comparisons (P<0.001). In univariate analysis, HDL-C concentration was significantly associated with CT-measured fat depots. In multivariate analysis, IAF was significantly and non-linearly associated with HDL-C concentration adjusted for age, sex, BMI, HOMA-IR, SCF, and TF (IAF: ß=-0.1012, P<0.001; IAF²: ß=0.0008, P<0.001). SCF was also negatively and linearly associated with HDL-C (ß=-0.4919, P=0.001). CONCLUSION: HDL-C does not linearly decline with increasing IAF in Japanese-Americans. A more complex pattern better fits this association.

Apolipoprotein B Levels Predict Future Development of Hypertension Independent of Visceral Adiposity and Insulin Sensitivity.

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.

Short Report: Circulating microRNAs are associated with incident diabetes over 10 years in Japanese Americans.

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.

Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension.

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<0.001), and HDL2/HDL cholesterol (OR, 0.71; 95% CI, 0.52 to 0.98; P=0.035), were associated with future development of hypertension. CONCLUSION: A higher proportion of HDL2 cholesterol among total HDL cholesterol predicted a lower risk for incident hypertension. However, concentrations of total HDL, HDL2, and HDL3 cholesterol were not independent predictors of incident hypertension.

Change in CT-measured abdominal subcutaneous and visceral but not thigh fat areas predict future insulin sensitivity.

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

Prevalence and determinants of elevated apolipoprotein B and dense low-density lipoprotein in youths with type 1 and type 2 diabetes.

OBJECTIVE: The objective of the study was to assess the prevalence and determinants of elevated apolipoprotein B (apoB) and dense low-density lipoprotein (LDL) in United States youth with type 1 or type 2 diabetes. METHODS: We conducted cross-sectional analyses of apoB concentrations, LDL density, and prevalence of elevated apoB levels and dense LDL from the SEARCH for Diabetes in Youth study, a six-center U.S.-based study of youth with diabetes onset younger than 20 years of age (2657 with type 1 and 345 with type 2). RESULTS: Among youth with type 1 diabetes, 11% had elevated apoB (>or=100 mg/dl, 1.95 mm/liter), 8% had dense LDL (relative flotation rateor=130 mg/dl, 3.36 mm/liter). In contrast, among youth with type 2 diabetes, 36% had elevated apoB, 36% had dense LDL, but only 23% had elevated LDL-cholesterol. Dense LDL and apoB each increased with hemoglobin A1c in both types. Among type 1 diabetics in poor glycemic control (hemoglobin A1c>or=9.5%), 28% had elevated apoB, and 18% had dense LDL, whereas 72% of poorly controlled type 2 diabetics had elevated apoB and 62% had dense LDL. CONCLUSIONS: In youth with type 1 diabetes, elevated apoB and dense LDL were not highly prevalent, whereas elevated apoB and dense LDL were common lipoprotein abnormalities in youth with type 2 diabetes. The prevalence of these risk factors substantially increased with poor glycemic control in both groups, stressing the importance of achieving and maintaining an optimal glucose control.

Linkage and association analyses of type 2 diabetes/impaired glucose metabolism and adiponectin serum levels in Japanese Americans from Hawaii.

Type 2 diabetes is a common disorder associated with obesity. Lower plasma levels of adiponectin were associated with type 2 diabetes. Candidate regions on chromosomes 1 ( approximately 70 cM) and 14 ( approximately 30 cM) were evaluated for replication of suggestive linkage results for type 2 diabetes/impaired glucose homeostasis in an independent sample of Japanese Americans. Replication of independent linkage evidence for serum levels of adiponectin on chromosome 14 was also evaluated. We investigated 529 subjects from 175 sibships who were originally part of the Honolulu Heart Program. Analyses included nonparametric linkage and association using SAGE (Statistical Analysis for Genetic Epidemiology) and FBAT (family-based test of association) programs and Monte Carlo simulation of Fisher's exact test in SAS. For type 2 diabetes/impaired glucose metabolism, nominal linkage evidence (P < 0.02) followed-up by genotypic association (P = 0.016) was found with marker D14S297 at 31.8 cM; linkage analyses using only diabetes phenotype were also nominally significant at this marker (P < 0.02). Nominal evidence for genotypic association to adiponectin serum level phenotype (P = 0.04) was found with the marker D14S1032 at 23.2 cM. The present study was limited by relatively small sample size. Nevertheless, these results corroborate earlier studies, suggesting that further research is warranted in the candidate region approximately 30 cM on chromosome 14.

Minimum waist and visceral fat values for identifying Japanese Americans at risk for the metabolic syndrome.

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 cm(2) and 80.8 cm (age < or = 56 years) and 86.3 cm(2) and 89.0 cm (age > 56 years). For men, the optimal cut points for IAFA and waist circumference were 88.6 cm(2) and 90.0 cm (age < or = 57 years) and 96.1 cm(2) 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.

Change in visceral adiposity is an independent predictor of future arterial pulse pressure.

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.

Association of Thigh Muscle Mass with Insulin Resistance and Incident Type 2 Diabetes Mellitus in Japanese Americans.

BACKGROUND: Skeletal muscle plays a major role in glucose metabolism. We investigated the association between thigh muscle mass, insulin resistance, and incident type 2 diabetes mellitus (T2DM) risk. In addition, we examined the role of body mass index (BMI) as a potential effect modifier in this association. METHODS: This prospective study included 399 Japanese Americans without diabetes (mean age 51.6 years) who at baseline had an estimation of thigh muscle mass by computed tomography and at baseline and after 10 years of follow-up a 75-g oral glucose tolerance test and determination of homeostasis model assessment of insulin resistance (HOMA-IR). We fit regression models to examine the association between thigh muscle area and incidence of T2DM and change in HOMA-IR, both measured over 10 years. RESULTS: Thigh muscle area was inversely associated with future HOMA-IR after adjustment for age, sex, BMI, HOMA-IR, fasting plasma glucose, total abdominal fat area, and thigh subcutaneous fat area at baseline (P=0.033). The 10-year cumulative incidence of T2DM was 22.1%. A statistically significant interaction between thigh muscle area and BMI was observed, i.e., greater thigh muscle area was associated with lower risk of incident T2DM for subjects at lower levels of BMI, but this association diminished at higher BMI levels. CONCLUSION: Thigh muscle mass area was inversely associated with future insulin resistance. Greater thigh muscle area predicts a lower risk of incident T2DM for leaner Japanese Americans.

Predictors of Incident Type 2 Diabetes Mellitus in Japanese Americans with Normal Fasting Glucose Level.

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.