Relationship of sex hormone-binding globulin to lipid, lipoprotein, glucose, and insulin concentrations in postmenopausal women.

Sex hormones play a major role in determining the risk of cardiovascular disease. While several studies have shown that reduced sex hormone-binding globulin (SHBG) is associated with increased insulin and triglyceride and decreased high-density lipoprotein cholesterol (HDLC) in premenopausal women, little data are available for postmenopausal women. We hypothesized that in postmenopausal women decreased SHBG would be associated with an atherogenic pattern of cardiovascular risk factors. We measured SHBG, lipids, lipoproteins, glucose, and insulin concentrations, and systolic and diastolic blood pressure in 101 postmenopausal women. SHBG was negatively associated with triglyceride (r = -.21) and insulin (r = -.47) concentrations and positively associated with HDLC concentrations (r = .47). After adjustment for overall adiposity (body mass index) and upper body adiposity (as measured by the ratio of waist to hip circumferences), SHBG was still associated with HDLC and insulin, but not with triglyceride. Sex hormones were not related to systolic and diastolic blood pressure. The results may help to explain an association of increased androgenicity, as measured by a lower SHBG concentration, with diabetes and risk of cardiovascular disease in older women.     

Implications of body fat distribution in an older twin population.

BACKGROUND: As people age, fat becomes preferentially deposited in the abdominal region over the periphery, and such changes are thought to be associated with adverse metabolic outcomes. We were interested in whether body mass index (BMI) and waist-hip ratio (WHR) are differentially associated with fasting insulin levels, triglycerides, and blood pressure (systolic and diastolic) in an older population. We were also interested in whether these associations change after controlling for genetic influences. METHODS: Data were obtained as part of the Swedish Adoption/Twin Study of Aging. All blood samples and anthropometric measures were assessed from 1989-1991 except insulin, which was assessed from 1986-1988. The sample contains 263 twin pairs (97 monozygotic and 166 dizygotic), 56% women, average age 65 years. RESULTS: In men and women, WHR and BMI were significantly associated with all the metabolic variables except for diastolic blood pressure. When BMI's association with the metabolic variables was assessed independent of WHR, it remained significantly associated with all metabolic variables except diastolic blood pressure in men and triglycerides in women. When WHR's association with the metabolic variables was assessed independent of BMI, it did not remain significantly associated with any of the metabolic variables in men and remained significantly associated with insulin and diastolic pressure in women. After controlling for genetic effects, the relationship between WHR and the metabolic variables became nonsignificant. However, BMI remained significantly associated with systolic blood pressure and triglycerides in men, independent of WHR. CONCLUSION: The results suggest that overall body fat is important to consider in relation to these metabolic parameters in older individuals. The results also suggest that BMI may share associations with blood pressure and triglycerides beyond those that can be attributed to familial influences.     

Hyperinsulinemia, upper body adiposity, and cardiovascular risk factors in non-diabetics

Previous studies have suggested that hyperinsulinemia and upper body adiposity are each separately associated with elevated BP and triglyceride (TG) levels, and with lower high density lipoprotein (HDL) cholesterol levels. The joint effect of hyperinsulinemia and upper body adiposity on lipids, lipoproteins, and BP, however, has not been previously studied. We hypothesized that the effect of body fat distribution on cardiovascular risk factors might be mediated through hyperinsulinemia. We measured BP, lipids and lipoproteins, HDL subfractions, and insulin and glucose concentrations as part of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors. Insulinemia and glycemia were assessed as the sum of the fasting, half-hour, one-hour, and two-hour insulin and glucose levels, respectively, measured during a standardized oral glucose tolerance test. Individuals who had diabetes according to National Diabetes Data Group criteria were excluded from the analyses. In univariate analyses, both hyperinsulinemia and waist-to-hip ratio (WHR), a measure of upper body adiposity, were positively associated with TG and negatively associated with total HDL and HDL2 cholesterol levels. However, when the effects of glycemia and insulinemia were controlled for by analysis of variance, WHR was no longer significantly related to TG levels. By contrast, WHR continued to be inversely related to total HDL and HDL2 cholesterol even after adjustment for glycemia and insulinemia. Hyperinsulinemia was only weakly related to HDL cholesterol. These results suggest that insulinemia and glycemia might mediate the effects of upper body adiposity on TG, although not on HDL and HDL2 cholesterol. Hyperinsulinemia was also positively associated with diastolic and systolic BP in men.     

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.     

Increased upper body and overall adiposity is associated with decreased sex hormone binding globulin in postmenopausal women

An unfavorable body fat distribution is associated with many metabolic abnormalities including a high prevalence and incidence of noninsulin dependent diabetes mellitus and decreased high density lipoprotein cholesterol and increased triglyceride levels. One mechanism for the effect of body fat distribution on metabolic variables may be through sex hormones. We examined the relationship of body mass index (BMI), ratio of subscapular-to-triceps skinfold ratio (centrality index) and ratio of waist-to-hip ratio (WHR) to sex hormone binding globulin (SHBG) (an in vivo measure of androgenicity) in 101 postmenopausal Mexican-American and non-Hispanic white women from the San Antonio Heart Study, a population based study of diabetes and cardiovascular disease. SHBG was significantly correlated with BMI (r = -0.440, P less than 0.001), WHR (r = -0.255, P less than 0.01) and centrality index (r = -0.210, P less than 0.05). In a multiple linear regression analysis, SHBG remained significantly associated with BMI (P less than 0.001) and WHR (P less than 0.05) but not with age, ethnicity or centrality index. This work suggests that in postmenopausal women overall adiposity and an unfavorable body fat distribution are associated with increased androgenicity as measured by a lower SHBG concentration. Our finding may help to explain the association of body fat distribution with diabetes and cardiovascular risk factors in older women.     

Plasma sex hormone-binding globulin rather than corticosteroid-binding globulin is a marker of insulin resistance in obese adult males

Aim:  Plasma levels of corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG) may be regulated by insulin. The aim of this study was to test the hypothesis that these steroid-binding proteins are markers of insulin resistance and obesity in adult patients with the metabolic syndrome.
Methods:  Fasting blood samples were obtained from 108 male and 88 female overweight adult patients who had varying degrees of dyslipidaemia, adiposity and insulin resistance. We measured plasma levels of SHBG and CBG and investigated their correlation with insulin resistance [homeostasis model assessment (HOMA) % sensitivity] and anthropometric markers of adiposity.
Results:  In male patients, plasma SHBG correlated positively with HOMA (% sensitivity) and negatively with anthropometric measurements, including body mass index, waist circumference (cm) and percentage body fat. There was no correlation with CBG and any other parameter in the male patients. The female patients were treated as two groups, those not using oral contraceptives or hormone replacement therapy (n = 67) and those taking steroid medications (n = 21). Female patients using steroid medications had significantly higher SHBG levels but neither group showed any correlation between SHBG, insulin resistance and adiposity. Correlation studies of CBG with other parameters in the female subgroups did not reach statistical significance.
Conclusions:  We conclude that plasma SHBG is another surrogate marker for insulin resistance in obese males but not in obese females. It also appears that plasma CBG is not a useful marker of insulin resistance in patients with the metabolic syndrome.     

Associations between regional body fat distribution, fasting plasma free fatty acid levels and glucose tolerance in premenopausal women

The associations between total adiposity, body fat distribution measured by computed tomography (CT) and estimated by the waist-to-hip ratio (WHR), regional fat cell morphology, fasting plasma free fatty acid (FFA) levels and glucose tolerance were studied in a sample of 37 premenopausal women aged 35.3 +/- 4.6 years (mean +/- s.d.). Body fat mass, CT-derived abdominal and femoral fat areas, as well as the abdominal fat cell weight were all significantly associated with fasting plasma FFA levels (0.34 less than r less than 0.49, 0.005 less than P less than 0.05), and with the glucose and insulin areas during the oral glucose tolerance test (OGTT) (0.36 less than r less than 0.70, 0.0001 less than P less than 0.05). No associations were found between the WHR, the femoral fat cell weight and fasting plasma FFA levels or glucose area during the OGTT. However, the WHR and the femoral fat cell weight were positively associated with insulin area. Plasma FFA levels were positively correlated with the glucose area during the OGTT, whereas no association was found between plasma FFA levels and the insulin area. Covariance analysis indicated that this effect of plasma FFA levels on the magnitude of glucose response to OGTT was independent from that of total adiposity or regional body fat distribution variables. These results emphasize the importance of plasma FFA levels as a correlate of glucose tolerance and suggest that the associations previously reported between obesity, regional body fat distribution, fat cell size and glucose tolerance are, at least partly, mediated by variations in plasma FFA levels.     

Post-heparin lipolytic enzyme activities, sex hormones and sex hormone-binding globulin (SHBG) in men and women: The HERITAGE Family Study

We tested the hypothesis that androgen, estrogen, and sex hormone-binding globulin (SHBG) levels would be significantly related to post-heparin hepatic lipase (HL) and lipoprotein lipase (LPL) activities in a sample of Caucasian men (n = 233) and women (n = 235) aged 17-64 years from the HERITAGE Family Study. Body composition (hydrostatic weighing), abdominal adipose tissue distribution (computed tomography), plasma lipid-lipoprotein and hormone levels, and post-heparin lipases activities were measured. HL activity was significantly higher in males, whereas LPL activity was higher in women (P < 0.005). In women only, HL activity was positively associated with body fat mass (r = 0.17, P < 0.05) and intra-abdominal adipose tissue area (r = 0.18, P < 0.05). Significant associations were also found between fasting insulin and LPL activity (r = -0.16, P < 0.05 and r = -0.18, P < 0.005) as well as HL activity (r = 0.22, P < 0.005, and r = 0.27, P < 0.0001) in men and women, respectively. A positive association between total testosterone and HL activity was noted in men (r = 0.13, P = 0.05). In women, plasma SHBG levels were negatively associated with HL activity (r = -0.48, P < 0.0001), and statistical adjustment for body fat mass, visceral adipose tissue area, and fasting insulin did not attenuate this correlation. In multivariate analyses with models including adiposity variables and measurements of the hormonal profile, insulin, and testosterone levels were both independent positive predictors of HL activity in men. In women, hormone use was a significant positive predictor, and SHBG level a strong negative predictor of HL activity, independent of plasma estradiol and testosterone concentrations. Fasting insulin was the only significant predictor of LPL activity in men (negative association), whereas menstrual status, fasting insulin (negative associations), and plasma SHBG levels (positive association) were all independent predictors of LPL activity in women. These results suggest that the postulated sensitivity of lipolytic enzymes to androgens and estrogens is reflected by a strong negative association between SHBG levels and HL, and a lower magnitude positive association of this hormonal parameter to LPL activity in women. These associations appear to be independent from concomitant variation in total adiposity or body fat distribution.     

Relation between androgens and cardiovascular risk factors in a young population

Objective The relationship between androgens and blood pressure, insulin resistance, lipid profile, adiponectin and hs‐CRP in a young Middle‐Eastern population has not been examined previously. We studied this relationship in a randomly selected population of Lebanese students. Methods Three hundred and sixty‐eight subjects (201 men and 167 women) aged 18–30 years were included in the study. Anthropometric and biological parameters [waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP), triglycerides, total cholesterol, HDL cholesterol, homeostasis model assessment of insulin resistance (HOMA‐IR), total testosterone (TT), dehydroepiandrostenedione sulphate (DHEAS), sex hormone‐binding globulin (SHBG), adiponectin (ADP) and hs‐CRP] were measured. Results In men, there were inverse associations of both TT and SHBG with body mass index (BMI), WC, HOMA‐IR, triglycerides and hs‐CRP. After adjustment for major confounders (BMI, WC, age and smoking), associations disappeared except for those between TT and hs‐CRP, and for SHBG HOMA‐IR, hs‐CRP and triglycerides. In women, only SHBG was inversely associated with BMI, WC, HOMA‐IR and hs‐CRP and positively correlated with adiponectin. Except for the association between SHBG and adiponectin, these correlations disappeared after adjustment for confounders. Although DHEAS appeared to correlate negatively with blood pressure in men, this relationship disappeared after adjustment for confounders, while a relationship between DHEAS and triglycerides in women persisted after such adjustment. In multivariate regression analysis, SHBG was an independent predictor of hs‐CRP, triglycerides and HOMA‐IR in men and of adiponectin in women. Conclusion Our results suggest that SHBG is independently associated with HOMA‐IR, adiponectin, hs‐CRP and triglycerides. A gender difference in these associations is observed. Further studies are needed to elucidate these findings.     

Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: a population study

It has been suggested that a low grade inflammatory state could predispose for developing insulin resistance and contribute to the development of obesity and type 2 diabetes. Corticosteroid-binding globulin (CBG), the main plasma protein transport for cortisol, has been shown to be negatively regulated by insulin and IL-6, at least in vitro, suggesting that insulin resistance and inflammation may both contribute to decreasing CBG levels. In the present study we measured CBG concentrations in a human healthy population and investigated the relationships of CBG with anthropometric and biochemical markers for inflammation and/or insulin resistance. The data showed that the mean serum CBG level was significantly lower in males (n = 151) than in females (n = 113; 32.5 +/- 9.1 vs. 39.2 +/- 13.9 mg/liter; P < 0.0001). In both sexes serum CBG levels were correlated negatively with age (r = -0.12; P = 0.04), body mass index (r = -0.31; P < 0.0001), waist to hip ratio (WHR; r = -0.39; P < 0.0001), systolic (r = -0.15; P < 0.01) and diastolic (r = -0.15; P = 0.01) blood pressures, and HOMA, an index of insulin resistance (r = -0.12; P = 0.04). In addition, the CBG concentration was negatively associated with serum IL-6 concentrations (r = -0.23; P = 0.017) and with the soluble fraction of TNFalpha receptors, soluble TNF receptor 1 (sTNFR1; r = -0.35; P < 0.0001), and sTNFR2 (r = -0.56; P < 0.0001) in women. A stepwise regression analysis using CBG as an independent variable showed that sex (P < 0.00001), body mass index (P = 0.0002), and HOMA (P = 0.0005), but not systolic blood pressure, diastolic blood pressure, IL-6, sTNFR1, or sTNFR2, constituted significant independent factors that explained 21% of the CBG variance (14%, 2%, and 5%, respectively). In a subsample of 120 men and 68 women, fasting serum free cortisol (calculated as the ratio fasting cortisol/CBG) was significantly associated with WHR (r = 0.24; P = 0.001), systolic (r = 0.18; P = 0.01) and diastolic (r = 0.19; P = 0.007) blood pressures, and HOMA value (r = 0.20; P = 0.005), but not with BMI or age. BMI (P < 0.0001), free cortisol (P = 0.003), and CBG (P = 0.009), but not WHR and age, contributed to 20%, 6%, and 8%, respectively, of HOMA variance in women in a multiple regression analysis. In this model only BMI (P < 0.0001) independently contributed to HOMA variance in men. These findings support the hypothesis that the CBG level is an interesting indicator for both insulin resistance and low grade inflammation. Whether the decrease in CBG levels is genetic by nature or directly associated to increased insulin and/or IL-6 merits further investigation. Nevertheless, because CBG has been shown to be expressed by the adipose tissue, decreased CBG could create locally increased cortisol disposal, with no change in circulating cortisol, and facilitate fat accumulation, insulin resistance, and type 2 diabetes.     

Are Body Mass or Insulin Resistance Independently Associated with Cardiovascular Risk Factors in Non-diabetic Elderly Nigerians?

The aim was to establish whether risk factors for cardiovascular disease (CVD) are positively and independently associated with fasting insulin and/or body mass and waist–hip ratio in healthy elderly Nigerian subjects. Fasting plasma glucose, insulin, total cholesterol, triglycerides, blood pressure, and basal insulin resistance (HOMA method) were measured in 500 healthy elderly (≥55 years) Nigerian volunteers (295 men, 205 women). Associations between blood pressure, triglycerides or cholesterol and fasting insulin, HOMA, body mass index (BMI) or waist–hip ratio were examined using linear regression. Age was controlled for in all analyses. In men, diastolic and systolic blood pressure were strongly associated with BMI, while there was no evidence of an independent relationship with fasting insulin or HOMA. Triglycerides were strongly associated with waist–hip ratio, with a weaker independent association with HOMA but not fasting insulin; fasting insulin and HOMA showed strong independent associations with total cholesterol. In women diastolic and systolic blood pressure were also strongly associated with BMI, but there was an independent relationship with fasting insulin for diastolic blood pressure and a less significant (p = 0.057) one for systolic blood pressure. Triglycerides were significantly associated with BMI but none of the other variables; there were no significant associations with cholesterol. There was no evidence of interaction between fasting insulin or HOMA and BMI or waist–hip ratio. The results suggest the hypotheses that in this population BMI or waist–hip ratio are stronger determinants of blood pressure and triglyceride levels than fasting insulin or HOMA, and that where insulin does play a role its effects are separate and additive.     

Associations of abdominal adiposity, fasting insulin, sex hormone binding globulin, and estrone with lipids and lipoproteins in post-menopausal women

The associations of abdominal adiposity, fasting serum levels of insulin, and sex hormones with blood lipids, lipoproteins, and apolipoproteins A-I and B were studied cross-sectionally in 75 healthy, postmenopausal white women. In univariate analyses, abdominal adiposity (increased waist-to-hip girth ratio) and fasting insulin concentrations were negatively and significantly associated (P less than 0.05) with plasma high density lipoprotein cholesterol (r = -0.47 and -0.38, respectively) and apolipoprotein A-I (r = -0.37 and -0.36), and positively associated with log triglycerides (r = 0.54 and 0.33) and apolipoprotein B (r = 0.43 and 0.22). Sex hormone binding globulin was positively and significantly associated with high density lipoprotein cholesterol (r = 0.32) and negatively associated with log triglyceride (r = -0.45) and apolipoprotein B (r = -0.36). Estrone was positively and significantly associated with high density lipoprotein cholesterol (r = 0.27), apolipoprotein A-I (r = 0.23) and negatively associated with low density lipoprotein cholesterol (r = -0.24) and apolipoprotein B (r = -0.25). Total estradiol, free estradiol, free testosterone, and total testosterone were more weakly associated with the lipid measures. In multivariate analyses, abdominal adiposity remained significantly associated with high density lipoprotein cholesterol, log triglycerides, apolipoproteins A-I and B after adjustment for sex hormone binding globulin, estrone, and insulin concentrations. Insulin remained associated only with apolipoprotein A-I after adjustment for abdominal adiposity, estrone, and sex hormone binding globulin. Sex hormone binding globulin remained marginally associated with log triglyceride (P = 0.07) after adjustment for the remaining three factors. Estrone remained significantly associated with high density lipoprotein cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose tolerance and hyperinsulinaemia in obese women: role of adipose tissue distribution, muscle fibre characteristics and androgens

The separate independent statistical contribution of abdominal distribution of fat, hyperandrogenicity and muscle morphology to glucose intolerance and hyperinsulinaemia was analysed in 88 obese women. In univariate analyses the waist/hip circumference ratio (WHR), body fat and lean body mass were all positively associated, and SHBG levels were negatively associated with insulin and glucose values. Muscle fibre areas were positively correlated with insulin but not with glucose concentrations. Adjustment for other variables did not remove the positive association between WHR and fasting insulin and glucose concentrations. SHBG, free testosterone and type IIb fibre areas were, however, significant confounding factors in the relationship between WHR and summed insulin and glucose concentrations. We conclude that fat distribution in obese women is associated with fasting hyperglycaemia and hyperinsulinaemia, independently of androgens and muscle fibre morphology, but that reduced SHBG concentrations and increased type IIb fibre areas may partly explain increased glucose and insulin responses to an oral glucose load in abdominally obese women.     

Body fat and C-reactive protein levels in healthy non-obese men

BACKGROUND AND AIM: The relationships between C-reactive protein (CRP) levels, adipose tissue and metabolic alterations have not been clearly established in healthy non-obese subjects. We investigated the relationships between body fat, CRP levels and metabolic variables in healthy, non-obese sons of patients affected by metabolic syndrome (MS). METHODS AND RESULTS: Age, CRP and interleukin 6 (IL-6) levels, anthropometric measures (body mass index, BMI; waist circumference and waist-to-hip ratio, WHR), total and regional fat content (as determined by means of dual X-ray absorptiometry, DXA), total and LDL cholesterol, and the metabolic variables related to MS (HDL-cholesterol, triglyceride, glucose and insulin levels; the fasting insulin resistance index, FIRI; blood pressure) were evaluated in 85 healthy non-obese sons of MS patients. Linear and multiple regression analyses were used to evaluate the relationships between body fat, metabolic variables and CRP levels, and to investigate whether the association between body fat content and metabolic variables persists after adjustment for CRP levels. Body fat was associated with all of the investigated variables. CRP levels were associated with total and regional body fat, the anthropometric index of weight, age, and with some metabolic alterations (HDL-cholesterol and triglyceride levels, systolic blood pressure, and fasting insulin and LDL-cholesterol levels). The associations between total body fat and the metabolic variables did not change after adjustment for CRP levels. Total body fat was the best predictor of CRP levels (p<0.0001). CONCLUSIONS: In healthy, non-obese sons of MS patients, total body fat is the best predictor of CRP levels, and remains closely associated with metabolic abnormalities after adjustment for CRP levels. These findings strongly support the hypothesis that body fat is the main determinant of metabolic abnormalities and a low inflammatory state, at least in healthy subjects.     

Relationships of plasma estradiol, testosterone, and sex hormone-binding globulin with lipoproteins, apolipoproteins, and high density lipoprotein subfractions in men

Plasma estradiol, testosterone, and sex hormone-binding globulin (SHBG) were studied in relation to plasma lipoproteins, high density lipoprotein (HDL) subfractions, and apolipoproteins in 73 healthy but sedentary middle-aged men. Among potentially confounding variables, a strong positive association was found between estradiol levels and cigarette use, while testosterone and SHBG correlated negatively with percent body fat and alcohol intake. After adjustment for smoking, percent body fat, and alcohol, plasma estradiol levels correlated negatively with total cholesterol and low density lipoprotein cholesterol, and testosterone levels correlated positively with apolipoprotein B, while SHBG levels correlated positively with HDL2 mass and apolipoprotein A-I. SHBG was also strongly associated with the waist to hip girth ratio (WHR). Adjustment for WHR eliminated the significant associations of SHBG with triglycerides, HDL2 mass, and apolipoprotein A-I. SHBG levels and WHR may reflect tissue sensitivity and the impact of exposure to fluctuating levels of sex hormones for a period of days, or longer. These variables may provide more insight into the role of sex hormones in lipoprotein metabolism than do single samples of circulating hormones. It is also suggested that long term effects of sex hormones on adipose tissue distribution may at least partially underlie sex-related differences in lipoprotein metabolism.     

Sex hormone-binding globulin at the crossroad of body composition, somatotropic axis and insulin/glucose homeostasis in young healthy men

Objectives Sex hormone–binding globulin (SHBG) modulates the bioavailability of sex steroids at tissue level. Genetic, hormonal and lifestyle‐related factors determine the SHBG levels, and low SHBG levels are a known risk factor for the development of the metabolic syndrome, diabetes and cardiovascular diseases. We investigated to what extent different determinants contribute to the variation in SHBG levels in healthy young men. Design and patients Healthy male siblings (n = 677) aged 25–45 year were recruited in a cross‐sectional, population‐based study. Measurements Lean and fat mass were measured using dual‐energy X‐ray absorptiometry (DXA), and immunoassays were used to determine the serum hormonal levels. Additional information about smoking and physical activity was obtained using questionnaires. Carriers of two SHBG polymorphisms, the Asp327Asn polymorphism and the (TAAAA)_n repeat polymorphism, were identified. Results Weight, BMI, whole body fat mass and truncal fat mass were negatively associated with SHBG levels. Body composition characteristics did not differ between SHBG genotype groups, indicating that body composition controls SHBG levels rather than the other way around. The associations may be mediated by adipokines because leptin and adiponectin were, respectively, inversely and positively associated with SHBG levels. Insulin and glucose were negatively associated with SHBG levels, as well as IGF‐1 and IGF‐BP3, while no associations were found with free thyroid hormone status. Conclusions In conclusion, we found that fat mass, insulin and IGF‐1 levels are important negative determinants of SHBG levels in young healthy men. The association with fat mass could be mediated by the effects of adiponectin and/or leptin on SHBG synthesis.     

Association of sex hormone-binding globulin and insulin resistance among Japanese-American subjects

An association between sex hormone-binding globulin (SHBG) and insulin resistance expressed by the homeostasis model (HOMA-R), and the significance of both variables as risk factors for the development of type 2 diabetes were investigated in 483 Japanese-American subjects. The serum SHBG level was significantly higher in women (68.7 nmol/l) than in men (45.1 nmol/l). This difference was also significant independently of age, body mass index (BMI), waist to hip ratio (WHR), and HOMA-R. When multiple regression analysis was performed after adjustment for age and BMI, SHBG was not correlated with HOMA-R in men. In women, SHBG was not significantly correlated with HOMA-R after adjustment for age, BMI, and WHR. In a 3-year prospective analysis, HOMA-R was significantly higher in converters to type 2 diabetes than non-converters in both men and women which was independent of age, BMI and WHR. However, after adjusting these variables, SHBG was not a significant risk factor either in men or women. These results indicate that SHBG might be related to insulin resistance secondarily via BMI and/or WHR in both men and women among Japanese-Americans. HOMA-R is a useful index for both men and women as a risk factor of type 2 diabetes when only fasting blood samples can be obtained.     

A study in the relationships between leptin, insulin, and body fat in Asian subjects

OBJECTIVE: To study the relationship of leptin concentrations with indices of obesity, fasting insulin, insulin resistance and lipid profiles (total cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)- cholesterol and triglyceride) in an Asian cohort. DESIGN: Cross sectional study. SUBJECTS: A total of 133 healthy volunteers were enrolled (64 female: age: 25-61 y, body mass index (BMI): 18.7-45.1 kg/m2 and 69 male: age: 25-61 y, BMI: 19.3-35.0 kg/m2). MEASUREMENTS: Weight, height, waist and hip circumferences, blood pressure, lean body mass (by bioelectric impedence analysis (BIA)), plasma leptin and lipid profiles were taken after a 10 h fast. RESULTS: Percentage of body fat measured by bioelectric impedance was the strongest determinant of plasma leptin (r = 0.844, P < 0.0001). Females had higher leptin concentrations than males for the same fat mass. In a multiple linear regression model, body fat percentage, (percentage body fat* gender), hip circumference and fasting insulin were significant determinants of leptin concentration (r = 0.882, P < 0.0001). CONCLUSION: Leptin concentration correlated closely with percentage body fat in Asian subjects. Hip circumference as a corollary for peripheral obesity, was better associated with leptin than waist circumference or waist-to-hip ratio (WHR). Distribution of fat in females tended to be peripheral and may partly explain the gender difference. Fasting insulin level and central obesity were correlated with HDL-cholesterol, triglyceride and blood pressure, while fasting leptin had little correlation with these metabolic parameters. Therefore, insulin resistance was a better guide to cardiovascular risk assessment than plasma leptin.     

Effect of fat distribution on endothelial-dependent and endothelial-independent vasodilatation in healthy humans

AIM: The present study aims to explore the relationship between inflammatory cytokines, plasma lipids, insulin, blood pressure (BP), total adiposity/markers of fat distribution and endothelial function in healthy people across a wide range of body fatness. METHODS: Seventy-three healthy people (44 women; age range: 24-64 years) with body mass index (BMI) range of 18.6-73.1 kg/m2 were recruited. All participants underwent assessment of conduit artery endothelial-dependent vasodilatation by using flow-mediated vasodilatation (FMD) of the brachial artery and endothelial-independent vasodilatation to sublingual GTN. They had blood taken for measurement of plasma markers of glucose homeostasis (fasting insulin and glucose), systemic inflammation (interleukin-6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor-alpha receptor 2 (TNF-alpha R2)) and lipids (low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides). Morphometric assessment (waist circumference, BMI and waist-to-hip ratio (WHR)) and systolic and diastolic arterial pressure were also measured. RESULTS: Markers of total body fat/fat distribution (waist circumference, BMI and WHR), inflammation (IL-6, CRP and TNF-alpha R2), metabolism (fasting insulin, HDL, LDL and triglycerides) and BP (systolic and diastolic) correlated with FMD. Among these measurements, WHR was the only independent predictor of FMD (r2 = 0.30; p = 0.0001). CONCLUSIONS: WHR is an important marker of endothelial dysfunction in healthy people across a wide range of body fatness.     

Relationship of body fat distribution to the metabolic clearance of insulin in premenopausal women

The effects of body fat distribution on the metabolic clearance rate of insulin (MCR) and its relationship to peripheral insulin sensitivity (M/I) and androgenic activity were assessed in six nonobese and 20 obese premenopausal women with varying waist-to-hip girth ratio (WHR). As an index of androgenic activity, plasma levels of the sex hormone binding globulin (SHBG) and percentage free testosterone (%FT) were determined. The mean MCR in the obese and nonobese groups were similar (571 +/- 29 vs 578 +/- 31 ml/min/m2). Within the obese group, MCR varied between 401 and 822 ml/min/m2 and was inversely correlated with the WHR (r = -0.50, P less than 0.05). The reduction in MCR with upper body fat localization was observed at both sub- and supra-maximal plasma insulin levels. MCR correlated negatively with fasting and postglucose challenge plasma insulin levels and positively with M/I. MCR also correlated with plasma SHBG and %FT levels. We conclude that upper body fat localization is associated with diminished insulin clearance. This diminution is closely aligned with the degree of peripheral insulinemia and insulin sensitivity. The increase in androgenic activity may contribute to the aberrant insulin clearance observed in upper body obese subjects.