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.

Design and validation of a novel estimator of visceral adipose tissue area and comparison to existing adiposity surrogates.

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

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.

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years.

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/m2). 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.

Change in Intra-Abdominal Fat Predicts the Risk of Hypertension in Japanese Americans.

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.

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.

Impact of differences in glucose tolerance on the prevalence of a negative insulinogenic index.

OBJECTIVE: To determine the prevalence of a negative insulinogenic index (change in plasma insulin/change in plasma glucose from 0 to 30 min) from an oral glucose tolerance test according to glucose tolerance category. MATERIALS AND METHODS: Data from the San Antonio Heart Study (n=2494), Japanese American Community Diabetes Study (JACDS; n=594) and Genetics of NIDDM Study (n=1519) were examined. Glucose tolerance was defined by ADA criteria. RESULTS: In the combined cohort, the prevalence of a negative insulinogenic index was significantly higher in diabetes 20/616 (3.2%) compared to normal glucose tolerance 43/2667 (1.6%) (p<0.05). Longitudinally, in the JACDS cohort, the prevalence did not change from baseline (3/594; 0.5%) to 5 (4/505; 0.7%) and 10 years (8/426; 1.9%) (p=0.9) and no subject had a repeat negative insulinogenic index. CONCLUSIONS: A negative insulinogenic index occurs at a low prevalence across glucose tolerance categories although more often in diabetes, but without recurrence over time.

Change in visceral adiposity independently predicts a greater risk of developing type 2 diabetes over 10 years in Japanese Americans.

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/m(2), 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 cm(2). 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.

Associations among visceral fat, all-cause mortality, and obesity-related mortality 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.

Intra-abdominal fat accumulation is greatest at younger ages in Japanese-American adults.

AIMS: We evaluated whether changes over 10-11 years in weight, subcutaneous abdominal fat (SQAF), and intra-abdominal fat (IAF) differ by age and contrasted age-related adiposity changes by gender. METHODS: This is a prospective cohort study of non-diabetic, Japanese-American men and women aged 34-74 years. IAF and SQAF were measured by CT scan at baseline and 10-11-year follow-up visits. RESULTS: The youngest participants gained the most weight, SQAF and IAF over 10-11 years. Older age at baseline was associated with significantly less change in weight (beta-coefficient: -0.19, 95% CI -0.22, -0.15), SQAF (beta-coefficient: -0.07, 95% CI -0.11, -0.02) and IAF (beta-coefficient: -0.74, 95% CI -1.03, -0.45) that persisted even after adjustments for sex, smoking, caloric intake, adiposity at baseline, and change in physical activity. Age was positively correlated with change in SQAF (beta-coefficient: 0.14, 95% CI 0.10, 0.18) and IAF (beta-coefficient: 0.51, 95% CI 0.21, 0.81) in separate models after further adjustment for weight change. Gender did not alter the associations between adiposity change and age. CONCLUSIONS: Men and women gained the greatest absolute amount of weight, SQAF, and IAF at younger ages; however, older adults with comparable weight changes had relatively greater fat accumulation within IAF and SQAF depots.

Measuring dietary acculturation in Japanese Americans with the use of confirmatory factor analysis of food-frequency data.

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.

The association between birth weight and visceral fat in middle-age adults.

OBJECTIVE: Low birth weight, a proxy for fetal underdevelopment, is associated with increased risk of developing type 2 diabetes during adulthood. Low birth weight is also associated with central obesity, but little is known about the association between birth weight and visceral adiposity. The purpose of this study is to test the hypothesis that lower birth weight is associated with increased amounts of visceral fat in middle-age adults. RESEARCH METHODS AND PROCEDURES: This is an observational study of 91 adults (58 men and 33 women) 40+/-6 years of age (mean+/-standard deviation). Ethnicity was either Japanese American (79%) or non-Hispanic white (21%). Birth weight was obtained from State Departments of Health. Measurements included smoking status, BMI, and visceral (intra-abdominal) fat measured by computed tomography. RESULTS: Visceral fat was not associated with birth weight after adjustment for age, sex, ethnicity, BMI, or smoking status (p=0.76). There was no evidence that the association between birth weight and visceral fat varied by age, sex, or ethnicity. DISCUSSION: We found no evidence that low birth weight is associated with increased visceral fat in middle-age adults.

Association of endothelial lipase gene (LIPG) haplotypes with high-density lipoprotein cholesterol subfractions and apolipoprotein AI plasma levels in Japanese Americans.

The LIPG gene on chromosome 18 encodes for endothelial lipase, a member of the triglyceride lipase family. Mouse models suggest that variation in LIPG influences high-density lipoprotein (HDL) metabolism, but only limited data are available in humans. This study examined associations of LIPG haplotypes, comprising a single nucleotide polymorphism (SNP) in the promoter region (-384A>C), and a nonsynonymous SNP in exon 3 (Thr111Ile or 584C>T), with lipoprotein risk factors in 541 adult Japanese Americans. A marginal association was found between LIPG diplotypes and HDL cholesterol (p=0.045). Stronger associations were seen for HDL3 cholesterol (p=0.005) and Apolipoprotein AI plasma levels (p=0.002). After adjustment for age, gender, smoking and medications, individuals homozygous for the minor allele at both SNPs (*4 haplotype) had a more favorable risk factor profile, compared to other haplotype combinations. No relationship was seen for plasma triglyceride levels or low-density lipoprotein (LDL) size, but the homozygous *4 diplotype was also associated with lower Apolipoprotein B and LDL cholesterol levels (p=0.001 and 0.015, respectively). In conclusion, this community-based family study of Japanese Americans demonstrates that LIPG variants are associated with HDL related risk factors, and may play a role in susceptibility to cardiovascular disease in this population.

Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans.

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