Glucose metabolism in obesity: influence of body fat distribution

The dose-response relationships between portal venous insulin concentrations and hepatic glucose production and between peripheral insulin concentrations and peripheral glucose utilization were determined in 8 nonobese and 17 obese premenopausal women with either upper or lower body fat localization. The glucose production dose-response curves for the two obese groups were shifted to the right at all levels of portal insulinemia. The upper body obese women had a greater rightward shift compared to the lower body obese women. The peripheral glucose utilization dose-response curve was shifted to the right in the lower body obese women, but maximal glucose utilization was normal. The upper body obese women had both a greater rightward shift and a marked reduction in maximal glucose utilization. The insulin concentrations that had half-maximal effects on glucose production and utilization were similar in each group. These results indicate that the liver is not inherently more sensitive to insulin than peripheral tissues. Obesity is associated with a moderate diminution of hepatic and peripheral insulin sensitivity. Upper body fat localization in obese women is characterized by a greater diminution in insulin sensitivity and decline in peripheral insulin responsivity than is lower body fat localization. The marked peripheral insulin resistance in the former group may account for the increased prevalence of glucose intolerance.     

Effect of obesity and body fat distribution on sex hormones and insulin in men

To investigate the relationship between body fat distribution, sex hormones, and hyperinsulinemia in male obesity, we examined 52 obese men (body mass index [BMI], 35.0 +/- 6.1, mean +/- SD) and 20 normal-weight controls. Their waist to hip circumference ratio (WHR), which was used as an index of fat distribution, was 0.985 +/- 0.052 and 0.913 +/- 0.061 (P less than .005), respectively. Compared with controls, obese men presented significantly lower levels of total (357 +/- 132 v 498 +/- 142 ng/dL; P less than .005) and free testosterone (14.2 +/- 2.9 v 17.1 +/- 2.6 pg/mL; P less than .05) and sex hormone-binding globulin (SHBG; 41.7 +/- 31.9 v 66.2 +/- 18.6 nmol/L; P less than .001) without any significant difference on the other sex steroid or on gonadotropin concentrations. Fasting and glucose-stimulated insulin and C-peptide levels were significantly higher in obese than in controls, and in obese with the WHR value greater than 0.97 (corresponding to the distribution median) than in those with WHR lower or equal to 0.97. BMI was negatively correlated with testosterone (P less than .005), free testosterone (P less than .01), and SHBG (P less than .001) and positively with fasting (P less than .001) and glucose-stimulated (P less than .005) C-peptide concentrations, whereas no relationship was found between these variables and WHR values. On the contrary, WHR was significantly correlated with fasting and post-glucose insulin levels (P less than .05), but not with those of sex steroids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies in the distribution of body fat: I. Effects of age, sex, and obesity

The pattern of body fat distribution has been shown to be related to a large number of variables of clinical importance. A variety of indices have been devised, many of them simple enough to be useful in large-scale clinical studies. Relationships among these several indices and systematic information on the effects of age, sex, and obesity have, however, not been systematically studied. Five anthropometric ratios that classify individuals into different body types have been computed for 1179 men and women aged 17-96 years. These are: waist hip ratio, arm thigh ratio, waist thigh ratio, waist arm ratio, and subscapular triceps skinfold ratio. In general, the age patterns show progressive trends toward increasing upper and central body fat deposition with age. In women there tends to be a postmenopausal acceleration of this trend. The ratios are distinctly higher in men than in women and are also independently influenced by the body mass index. Predictive equations that take age and BMI into account for each of the indices for men and women have been provided.     

The relationship between body fat distribution and renal damage in Chinese with obesity.

OBJECTIVE: It has been recognized that in addition to being overweight, abnormal fat distribution may be associated with the etiology of metabolic syndrome. Asian people are more prone to develop visceral obesity than people in western countries. The present study was initiated to evaluate the relationship between visceral obesity and renal damage in Chinese obese people. METHODS: As measured by computed tomography, the areas of visceral fat were compared between 30 patients with biopsy-proven obesity-related glomerulopathy (ORG) and 20 obese volunteer controls that were free of renal diseases. The two groups were matched for age and sex. RESULTS: It was found that the areas of visceral fat were markedly increased in patients with ORG, while body mass indexes were similar in the two groups. Patients with ORG also showed higher levels of total cholesterol and a higher degree of insulin resistance than the controls. Multiple logistic regression analysis revealed that visceral obesity was significantly associated with the prevalence of ORG (OR 1.136; 95%CI, 1.106-1.166; P=0.003). Interestingly, proteinuria level was related directly with waist circumference, visceral obesity and levels of total cholesterol, fasting glucose, insulin and HOMA-IR ( P<0.05). Moreover, only HOMA-IR was independently associated with proteinuria level in stepwise linear regression ( R=0.641; P=0.001). CONCLUSIONS: The present study illustrated the positive association between visceral obesity and ORG and between insulin resistance and proteinuria level in Chinese obese subjects.     

Inheritance of the amount and distribution of human body fat

Despite recent advances, controversy continues about the inheritance of the amount and distribution of body fat. We have studied the genetic and 'cultural' (nongenetic) transmission between generations of the body mass index, sum of six skinfold measurements, percentage of body fat, fat mass, fat-free mass, and two indicators of fat distribution. These data were obtained in 1698 members of 409 families, which included the following pairs of family members: spouses, (maximum number of pairs = 348), foster parent-adopted child (322), siblings by adoption (120), first-degree cousins (95), uncle/aunt-nephew/niece (88), parent-natural child (1239), full sibs (370), dizygotic twins (69), and monozygotic twins (87). The total transmissible variance ranged from about 40 percent for the amount of subcutaneous fat to 60 percent for the pattern of subcutaneous fat distribution. Biological inheritance accounted for only 5 percent of the variance for subcutaneous fat and the body mass index, but 20 to 30 percent for the percentage of body fat, fat mass, fat-free mass, and fat distribution. These data suggest that the amount of internal fat is influenced by heredity more than the amount of subcutaneous fat. Furthermore, we consistently found that nongenetic influences are quite important in determining the amount and distribution of body fat in the population. These estimates may differ in the subpopulation of obese individuals.     

Psychosocial and socio-economic factors in women and their relationship to obesity and regional body fat distribution

BACKGROUND: Abdominal obesity, as well as psychosocial and socio-economic handicaps are risk factors for serious, prevalent diseases. Connections between these variables have been found in men. OBJECTIVE: The principal aim of the present study was to analyse the associations between psychosocial and socioeconomic factors with body mass index (BMI) and the waist-to-hip circumference ratio (WHR) in women. DESIGN: A cohort study of data derived from questionnaires. SUBJECTS: 1137 women from a population sample of 1464 women born in 1956. MEASUREMENTS: Occupational, social and leisure time conditions, smoking and alcohol habits, as well as height, weight and waist and hip circumferences. RESULTS: BMI was associated with teetotalism and negatively to wine drinking. WHR correlated directly with cigarette smoking and negatively with consumption of wine and beer. Both BMI and WHR, adjusted for each other and for smoking and alcohol, showed independent associations with low education, unemployment and problems at work when employed, as well as with little physical activity and much TV-watching. In addition, the WHR showed a negative, independent relationship to housing conditions. CONCLUSION: These observations suggest psychosocial and socio-economic handicaps as well as a low physical activity in abdominally obese women. Similar observations have been made previously in men, but only with the WHR, suggesting an influence of obesity in these relationships in women only. Another interesting gender difference is the positive relationship between being married with BMI in men, as well as being divorced and living alone with the WHR in men only.     

Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity

BACKGROUND: Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease. The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown. OBJECTIVE: The objective of this study was to determine the effects of testosterone therapy on intraabdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity. METHODS: IN this multicenter, randomized, placebo-controlled, double-blind trial, 88 HIV-positive men with abdominal obesity (waist-to-hip ratio > 0.95 or mid-waist circumference > 100 cm) and total testosterone 125-400 ng/dl, or bioavailable testosterone less than 115 ng/dl, or free testosterone less than 50 pg/ml on stable antiretroviral regimen, and HIV RNA less than 10,000 copies per milliliter were randomized to receive 10 g testosterone gel or placebo daily for 24 wk. Fat mass and distribution were determined by abdominal computerized tomography and dual energy x-ray absorptiometry during wk 0, 12, and 24. We used an intention-to-treat approach and nonparametric statistical methods. RESULTS: Baseline characteristics were balanced between groups. In 75 subjects evaluated, median percent change from baseline to wk 24 in visceral fat did not differ significantly between groups (testosterone 0.3%, placebo 3.1%, P = 0.75). Total (testosterone -1.5%, placebo 4.3%, P = 0.04) and sc (testosterone-7.2%, placebo 8.1%, P < 0.001) abdominal fat mass decreased in testosterone-treated men, but increased in placebo group. Testosterone therapy was associated with significant decrease in whole body, trunk, and appendicular fat mass by dual energy x-ray absorptiometry (all P < 0.001), whereas whole body and trunk fat increased significantly in the placebo group. The percent of individuals reporting a decrease in abdomen (P = 0.01), neck (P = 0.08), and breast size (P = 0.01) at wk 24 was significantly greater in testosterone-treated than placebo-treated men. Testosterone-treated men had greater increase in lean body mass than placebo (testosterone 1.3%, placebo -0.3, P = 0.02). Plasma insulin, fasting glucose, and total high-density lipoprotein and low-density lipoprotein cholesterol levels did not change significantly. Testosterone therapy was well tolerated. CONCLUSIONS: Testosterone therapy in HIV-positive men with abdominal obesity and low testosterone was associated with greater decrease in whole body, total, and sc abdominal fat mass and a greater increase in lean mass compared to placebo. However, changes in visceral fat mass were not significantly different between groups. Further studies are needed to determine testosterone effects on insulin sensitivity and cardiovascular risk.     

Impact of body composition, fat distribution and sustained weight loss on cardiac function in obesity

Background

Older age is an independent predictor of all-cause mortality in patients with mild to moderate heart failure (HF). Whether older age is also an independent predictor of mortality in patients with more advanced HF is unknown.

Methods

Of the 2707 Beta-Blocker Evaluation of Survival Trial (BEST) participants with ambulatory chronic HF (New York Heart Association class III/IV and left ventricular ejection fraction < 35%), 1091 were elderly (≥ 65 years). Propensity scores for older age, estimated for each of the 2707 patients, were used to assemble a cohort of 603 pairs of younger and older patients, balanced on 66 baseline characteristics.

Results

All-cause mortality occurred in 33% and 36% of younger and older matched patients respectively during 4 years of follow-up (hazard ratio {HR} associated with age ≥65 years, 1.05; 95% confidence interval {CI}, 0.87-1.27; P = 0.614). HF hospitalization occurred in 38% and 40% of younger and older matched patients respectively (HR, 1.01; 95% CI, 0.84-1.21; P = 0.951). Among 603 pairs of unmatched and unbalanced patients, all-cause mortality occurred in 28% and 36% of younger and older patients respectively (HR, 1.34; 95% CI, 1.10-1.64; P = 0.004) and HF hospitalization occurred in 34% and 40% of younger and older unmatched patients respectively (HR, 1.24; 95% CI, 1.03-1.50; P = 0.024).

Conclusion

Significant bivariate associations suggest that older age is a useful marker of poor outcomes in patients with advanced chronic systolic HF. However, lack of significant independent associations suggests that older age per se has no intrinsic effect on outcomes in these patients.     

Evidence for a role of developmental genes in the origin of obesity and body fat distribution

Obesity, especially central obesity, is a hereditable trait associated with a high risk for development of diabetes and metabolic disorders. Combined gene expression analysis of adipocyte- and preadipocyte-containing fractions from intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depot-specific differences in expression of multiple genes involved in embryonic development and pattern specification. These differences were intrinsic and persisted during in vitro culture and differentiation. Similar depot-specific differences in expression of developmental genes were observed in human subcutaneous versus visceral adipose tissue. Furthermore, in humans, several genes exhibited changes in expression that correlated closely with body mass index and/or waist/hip ratio. Together, these data suggest that genetically programmed developmental differences in adipocytes and their precursors in different regions of the body play an important role in obesity, body fat distribution, and potential functional differences between internal and subcutaneous adipose tissue.     

Effects of long-term physical training on body fat, metabolism, and blood pressure in obesity.

Twenty-seven women with varying degrees of obesity were physically trained for 6 mo on an ad lib. diet. Body fat changes were positively correlated with the number of fat cells in adipose tissue. Obese women with fewer fat cells decreased in weight during training whereas women with severe obesity and an increased number of fat cells even gained weight. Blood pressure decreased consistently after training. Blood pressure elevation was not associated with body fat mass, nor was a decrease in blood pressure associated with a decrease in body fat or with pretraining blood pressure level. There were, instead, correlations between decreases in blood pressure on the one hand and initial concentrations and decreases in plasma insulin and triglycerides and blood glucose on the other. These results suggest an association between elevated blood pressure and metabolic variables. The possibility of treating and preventing early essential hypertension with methods that also correct the metabolic derangement, such as diet and exercise, should be given high priority in further research.     

Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: a dose-response study.

There is increasing evidence that the abdominal obesity phenotype may be associated with multiple alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis activity in both sexes. Our hypothesis is that the lack of adequate cortisol suppression after the dexamethasone test may constitute an indirect marker of HPA axis hyperactivity in the presence of the abdominal obesity phenotype. A total of 34 normal-weight (13 men and 21 women) and 87 obese (36 men and 51 women), healthy, nondepressed subjects therefore underwent four different dexamethasone suppression tests randomly performed at varying intervals of at least 1 wk between each test. After a standard overnight 1-mg dexamethasone test, which served as a reference, three other tests were randomly performed at 1-wk intervals by administering 0.0035, 0.0070, and 0.015 mg oral dexamethasone per kilogram of body weight overnight. Blood samples were obtained for cortisol, ACTH, and dexamethasone. Results were analyzed separately in men and women as well as in normal-weight [body mass index (BMI) < or = 25 kg/m(2)] and overweight or obese (BMI > 25 kg/m(2)) subjects. The waist circumference and the waist to hip ratio (WHR) were used as markers of body fat distribution. After the standard 1-mg test, cortisol suppression was greater than 90% in all subjects. However, after each test, obese women had significantly higher values of percent cortisol and percent ACTH suppression than normal-weight women without any difference between obese and normal-weight men. Considering the response to the three variable-dose tests, a clear dose- response pattern (P < 0.001 for trend analysis) in percent cortisol and percent ACTH suppression was found in all subjects. After each test men had significantly higher dexamethasone levels than women, regardless of BMI. However, obese women, but not men, had significantly higher dexamethasone levels after each test than their normal-weight counterpart. Plasma dexamethasone concentrations were dose related (P < 0.001 for trend analysis) in all subjects, but the dose-related increase was significantly higher in normal-weight men than normal-weight women, whereas it was similar in obese subjects of both sexes. Stepwise multiple regression analysis revealed that both percent cortisol and percent ACTH variations were significantly and negatively influenced by dexamethasone levels, as well as by waist circumference values in men, and independently by BMI and waist circumference in women. However, in contrast to what has been found in men, a divergent contribution of BMI and waist circumference was found in women indicating that, with increasing waist values, a smaller suppression of the HPA axis was found with respect to that expected on the basis of BMI values. In conclusion, this study provides data of both physiological and physiopathological relevance. Overall, our data indicated that adjustment of the dexamethasone dose to body weight does not seem to substantially improve the sensitivity of the test, even in obese individuals, particularly when near-maximal doses are administered. However, this study demonstrated a highly significant effect of dexamethasone blood level concentrations on cortisol and ACTH suppression to low-dose dexamethasone tests. In addition, a significant effect of gender on postdexamethasone cortisol concentrations, suppression of the HPA axis, and dexamethasone levels were found, which may be dependent on related differences in both cortisol and dexamethasone metabolism. We showed that pituitary sensitivity to feedback inhibition by dexamethasone is preserved in obesity in both sexes even at low dosages. On the other hand, our data suggest that, at least in women, abdominal fat distribution may partially counteract the progressively greater suppressibility of the HPA axis that would be expected according to increasing BMI.     

Weight loss and sex steroid metabolism in massively obese man

To evaluate the effect of weight loss and diet therapy on plasma sex hormone behavior in male obesity, 9 men with a BMI of 43.4 +/- 6.3 participated in an 8-week semistarvation program [whose energy content ranged from 320 to 500 k calorie/day (proteins 44 to 60 g and carbohydrates 54 to 81 g per day)] followed by a two-week hypocaloric (1000 k calorie/day) refeeding. In basal conditions, obese patients presented higher estrogen and lower dehydroepiandrosterone sulphate, testosterone (total and free) and sex-hormone binding globulin concentrations with respect to a group of control normal-weight subjects. Cumulative weight loss was 23.9 +/- 3.6 kg after semistarvation and 24.4 +/- 4.8 kg after refeeding (p = NS). A significant increase in testosterone, free testosterone and dehydroepiandrosterone sulfate was observed throughout the study, irrespective of dietary intake. A transient increase occurred in estrone levels while 17B-estradiol did not change. Gonadotropins and sex-hormone binding globulin values remained unaltered. No relationship was found between sex hormones and dietary energy content or composition. Daily urine free cortisol, which was used as a parameter of adrenal function, fell approximately 50% during semistarvation but returned to baseline values after refeeding. These results show that in massively obese patients weight loss per se may partially reverse sex hormone abnormalities but not sex-hormone binding globulin concentrations. It remains to be determined whether the return to "normal weight" can normalize steroid metabolic derangements in the obese man.     

Perturbed sex steroid status in men with idiopathic osteoporosis and their sons

We reported previously that a gender-specific defect of acquisition of lumbar bone mass plays an important role in the pathogenesis of male idiopathic osteoporosis (IO) and that there is a strong heritability of this maturational defect, which is particularly manifest in sons of men with IO. A hypothetical role of an altered sex steroid status and/or of a (TTTA)(n)- repeat polymorphism of the aromatase (CYP19) gene in male IO remains to be established. We evaluated bone mineral density (BMD) at the lumbar spine and femoral neck in 64 male IO probands (selected on the basis of a z-score of -2 or less), 21 of their sons, 41 of their brothers, and 126 healthy, age-matched controls. Serum testosterone (T), estradiol (E(2)), and SHBG levels were measured by immunoassays. Free T (FT) and free E(2) (FE(2)) levels were calculated from total T, E(2), SHBG, and albumin concentrations using a previously validated equation. Probands, sons, and brothers had lower body weight than age-matched controls, with mean differences of 5.0, 4.6, and 4.0 kg, respectively. In probands, sons, and brothers, SHBG levels were higher compared with controls. Significantly lower FE(2) levels were observed in probands and sons compared with their respective controls (P < 0.05 and P < 0.01, respectively). The brothers had nonsignificantly lower FE(2) levels compared with their controls. In the total group of sons with significantly lower FE(2) levels, tertile analysis according to lumbar spine BMD showed that only in the subgroup of sons belonging to the lowest tertile both FE(2) and FT were decreased compared with their controls. The differences in FE(2) levels in IO probands and their sons remained significant after adjustment for body mass index (BMI), even though in multivariate analyses BMI was a major determinant of BMD. The frequency distribution of the CYP19 gene (TTTA)(n)- repeat length (determined by fragment analysis, GeneScan) was not different between men with IO and their controls. In conclusion, the finding of a relative FE(2) deficit in both men with IO as well as their affected sons, even after adjustment for BMI, suggests that estrogen-related perturbances may be involved in the pathogenesis of the deficient acquisition of peak bone mass in male IO.     

老年男性体脂分布类型与代谢相关性疾病的关系研究

目的：探讨老年男性体脂分布类型与代谢相关疾病的关系。方法：群体随机抽查上海地区海军离退休干部356人，根据体重指数(BMI)和腰围(WC)进行体脂分型分组，统计各组TC、LDL—C、HDL-C、TG、FBG值和糖尿病、高血压病、高脂血症、冠心病与高尿酸血症患病率，及其并存病种效。结果：老年男性各项检测值异常率、代谢相关性疾病患病率以及共存二种疾病以上的百分比，以中心型超重组为最高，非中心型非超重组(正常组)最低，中心型非超重组、非中心型超重组居中；无代谢相关性疾病百分比以非中心型非超重组(正常组)最高，中心型超重组最低。结论：体脂分布是影响与代谢有关疾病发病率的重要因素。     

Interrelationships between weight loss, body fat distribution and sex hormones in pre- and postmenopausal obese women

Objectives. Relationships between regional body fat distribution and sex hormones as well as changes in sex hormones after weight loss were evaluated. Setting. All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona. Subjects. Twenty-six premenopausal (age 33.7± 10.2 years) and 15 postmenopausal (age 57.9±5.9 years) obese women. Interventions. Body weight, body-mass index, waist and hip circumferences, visceral fat by computed tomography and sex hormones were evaluated before and after 4 weeks on a very low energy diet. Results. Body-mass index was higher in pre- than in postmenopausal women, although the difference was not significant. Total and free testosterone were significantly higher in the pre- than in the postmenopausal group (P<0.001). Significant negative correlations were found between age and total testosterone (r=?0.65; P<0.001), free testosterone (r=?0.54; P<0.001), androstenedione (r=?0.46; P<0.01) and urinary cortisol excretion (r=?0.50; P<0.01). A negative correlation was found between visceral fat and total testosterone (r=?0.41; P<0.01). After adjusting for age, the negative correlation between total testosterone and visceral fat encountered both in the subject group as a whole and in premenopausal women was no longer significant, whilst a significant negative association between visceral fat and sex hormone binding globulin (SHBG) (r=?0.56; P<0.001) was always found. When step-down regression analysis was used to evaluate the joint effect of age, menopausal status, and anthropometric and metabolic variables on sex hormones, age was the most powerful independent variable for predicting total testosterone, free testosterone and androstenedione levels, whilst menopausal status was the most powerful predictor of FSH and LH levels. Changes in hormones after VLED were analysed separately in pre- and postmenopausal women. None of the hormones changed significantly after VLED in the postmenopausal group, except for FSH values. LH, free testosterone and urinary cortisol excretion values decreased significantly after VLED in the premenopausal group. Conclusions. Our data show that age, to a greater extent than visceral fat, seems to be negatively associated with steroid sex hormones. Weight loss seems to be associated with changes in sex hormones only in premenopausal women.     

HLA system, body fat and fat distribution in children and adults

The association between the genotypes and the alleles at the A, B or C locus of the HLA system and body fat was studied in a total of 1578 individuals subdivided in four cohorts: adult males (n greater than or equal to 204), adult females (n greater than or equal to 184), boys and male adolescents (n greater than or equal to 282), and girls and female adolescents (n greater than or equal to 257). None of these subjects were grossly obese or had known metabolic disorders. Percent body fat from underwater weighing, subcutaneous fat from 6 skinfold measurements, trunk fat (3 skinfolds) and extremity fat (3 skinfolds) were considered in the analysis. Although a few significant associations were encountered, the lack of consistency across samples suggested that they were probably random and biologically not meaningful. The same negative findings were found for the ratio of trunk subcutaneous fat to extremity subcutaneous fat and the ratio of subcutaneous fat (6 skinfolds) to total fat mass. Earlier reports indicating a significant association between high body fat content and antigens B18, Bw35 or Cw4 were not supported by the results of this study. It was concluded that no consistent pattern of association emerged between genotypes or alleles of the HLA system and percent body fat, subcutaneous fat or fat distribution in children and adults of both sexes.     

Relationship of sex hormone binding globulin to overall adiposity and body fat distribution in a biethnic population

Previous data have indicated that decreased sex hormone binding globulin (SHBG) is associated with increased overall and upper body adiposity and higher levels of glucose, insulin and triglyceride (TG) and decreased levels of high-density lipoprotein (HDL) cholesterol. Since Mexican Americans have greater overall and upper body adiposity, higher rates of non-insulin-dependent diabetes mellitus, higher TG and lower HDL levels than non-Hispanic whites, we postulated that they would also have lower levels of SHBG. We measured total testosterone and total estradiol using a commercial radioimmunoassy and SHBG using a dextran-coated charcoal technique in premenopausal women (61 Mexican American and 39 non-Hispanic white) as part of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors. There were no significant ethnic differences in total testosterone or total estradiol. SHBG, however, was lower in Mexican American (0.285 micrograms/dl) than in non-Hispanic white women (0.429 micrograms/dl) (P = 0.009). After adjustment for body mass index (BMI), ratio of waist-to-hip circumference (WHR) and ratio of subscapular-to-triceps skinfolds (centrality index), SHBG remained lower in Mexican Americans (0.307 micrograms/dl) than in non-Hispanic whites (0.396 micrograms/dl), although this difference was no longer statistically significant (P = 0.083). BMI, WHR and centrality index were all negatively associated with SHBG (P less than 0.01). The lower levels of SHBG in premenopausal Mexican American women compared to non-Hispanic white women may reflect greater in-vivo androgenicity and may be related to a variety of metabolic abnormalities seen in this ethnic group.