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)     

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.     

Truncal fat in relation to total body fat: influences of age, sex, ethnicity and fatness

OBJECTIVE: To investigate the influence of age, sex, ethnicity and total fatness on central obesity in four ethnic populations. DESIGN: Cross-sectional analysis of study subjects enrolled from 1993 to 2005. SUBJECTS: A multi-ethnic (Caucasian (CA), African-American (AA), Hispanic-American (HA) and Asian (As)) convenience sample of 604 men and 1192 women (aged 18-96 years, body mass index 15.93-45.80 kg/m(2)). MEASUREMENTS: Total body fat (TBF) and truncal fat were measured by dual-energy X-ray absorptiometry. General linear regression models were used to test for independent associations with log(10)-transformed truncal fat. RESULTS: For all ethnicities, men had a lower percent body fat and more truncal fat than women. Log(10-)transformed truncal fat increased with TBF approximately as a square root function. At older ages, there was a greater amount of truncal fat in CA, HA and As men (approximately 0.20-0.25 kg/decade) with the effect more pronounced in AA men ( approximately 0.33 kg/decade). For women, the increment of truncal fat per decade was reduced in CA and AA women (approximately 0.07 kg) compared with As and HA women (approximately 0.33 kg). Adjusted for mean values of covariates in our sample, AA had less truncal fat than As. CONCLUSION: The accumulation of truncal fat is strongly related to age, ethnicity and total fatness in both men and women.     

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.     

Relationship of adiponectin to body fat distribution,insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex

AIMS/HYPOTHESIS: Increased intra-abdominal fat is associated with insulin resistance and an atherogenic lipoprotein profile. Circulating concentrations of adiponectin, an adipocyte-derived protein, are decreased with insulin resistance. We investigated the relationships between adiponectin and leptin, body fat distribution, insulin sensitivity and lipoproteins. METHODS: We measured plasma adiponectin, leptin and lipid concentrations, intra-abdominal and subcutaneous fat areas by CT scan, and insulin sensitivity index (S(I)) in 182 subjects (76 M/106F). RESULTS: Adiponectin concentrations were higher in women than in men (7.4+/-2.9 vs 5.4+/-2.3 micro g/ml, p<0.0001) as were leptin concentrations (19.1+/-13.7 vs 6.9+/-5.1 ng/ml, p<0.0001). Women were more insulin sensitive (S(I): 6.8+/-3.9 vs 5.9+/-4.4 x 10(-5) min(-1)/(pmol/l), p<0.01) and had more subcutaneous (240+/-133 vs 187+/-90 cm(2), p<0.01), but less intra-abdominal fat (82+/-57 vs 124+/-68 cm(2), p<0.0001). By simple regression, adiponectin was positively correlated with age ( r=0.227, p<0.01) and S(I) ( r=0.375, p<0.0001), and negatively correlated with BMI ( r=-0.333, p<0.0001), subcutaneous ( r=-0.168, p<0.05) and intra-abdominal fat ( r=-0.35, p<0.0001). Adiponectin was negatively correlated with triglycerides ( r=-0.281, p<0.001) and positively correlated with HDL cholesterol ( r=0.605, p<0.0001) and Rf, a measure of LDL particle buoyancy ( r=0.474, p<0.0001). By multiple regression analysis, adiponectin was related to age ( p<0.0001), sex ( p<0.005) and intra-abdominal fat ( p<0.01). S(I) was related to intra-abdominal fat ( p<0.0001) and adiponectin ( p<0.0005). Both intra-abdominal fat and adiponectin contributed independently to triglycerides, HDL cholesterol and Rf. CONCLUSION/INTERPRETATION: These data suggest that adiponectin concentrations are determined by intra-abdominal fat mass, with additional independent effects of age and sex. Adiponectin could link intra-abdominal fat with insulin resistance and an atherogenic lipoprotein profile.     

性别、年龄及体脂参数与静息能量消耗的关系

目的　研究中国人性别、年龄及体脂参数与静息能量消耗的关系。方法　对体重指数为14 .1～ 41.7kg/m2 的 15 6例正常糖耐量者 ,应用生物电阻抗法测总体脂、核磁共振方法测局部体脂、应用间接测热法测静息能量消耗。结果　 (1)校正脂肪重量 (FM)、去脂肪块重量 (FFM )后见到每公斤体重静息能量消耗 (REE/kg)在女性较男性显著降低 (P <0 .0 0 1) ;(2 )校正性别、FM及FFM后在 40～ 5 9岁及≥ 60岁年龄组的REE/kg较 <40岁组显著降低 (P <0 .0 0 1) ;(3 )年龄、BMI、腹内脂肪面积 (VA)都是REE/kg的独立相关因素 ,表现为两者之间的负性影响 ,女性尚见到腹部皮下脂肪面积 (SA)的参与。结论　 (1)性别对REE/kg有独立影响 ,女性REE/kg低于男性 ;(2 )年龄是REE/kg的独立影响因素 ,中年及老年人REE/kg降低 ;(3 )体脂 (总体脂和局部体脂 )增加与REE/kg的下降相关。     

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.     

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.     

Effect of age, gender, and body fat distribution on serum leptin concentrations

The aim of this study was to clarify the relationship between serum leptin concentration and age, gender and body fat distribution. Serum leptin concentrations were determined 267 subjects (138 men and 129 women), aged 30 to 91. The thicknesses of the preperitoneal fat layer (Pmax) and subcutaneous fat layer (Smin) in the abdomen were measured by ultrasonography. Fat mass and percent fat were measured by the bioelectrical impedance analysis method. Women had higher leptin and leptin/fat mass values than men in all BMI groups (BMI < 20, 20-23.9, 24-25.9, > or = 26). The leptin concentration correlated significantly with BMI, fat mass, percent fat, waist, hip, waist/hip ratio (W/H), Pmax, Smin and serum Cr in both men and women. The leptin concentration correlated significantly with age in men only and P/S in female only. Leptin/fat mass values significantly correlated with age, fat mass, and percent fat, but not with BMI, waist, hip, W/H, Pmax, Smin and P/S in men. In women, leptin/fat mass values significantly correlated with BMI, fat mass, percent fat, waist, hip, Pmax, Smin and P/S, but not with age or W/H. Multiple regression analysis showed that fat mass and serum creatinine were significant determinants of the leptin and leptin/fat mass values both in men and women, but that age was a significant determinant of these values only in men. These results suggest that the influence of aging on serum leptin concentration exists only in men.     

Studies in the distribution of body fat. II. Longitudinal effects of change in weight

Information on the effects of age, sex, obesity and weight change on the fat distribution pattern has not been systematically reported. As an index of body fat distribution, the waist hip circumference ratio (WHR) was computed in 370 men and 177 women aged 22-86 years, participants of the Baltimore Longitudinal Study of Aging. For cross-sectional analysis, initial data on the participants were analyzed; for longitudinal study, the changes in the measurements related to weight change during a 5-year follow-up were analyzed. From cross-sectional analysis: (1) waist circumference is larger in men than in women and increases progressively with age; (2) hip circumference shows no consistent age or sex differences; (3) thus, the well known sex differences in WHR are totally attributable to differences in waist circumference; (4) increases in WHR with age occur in both men and women. From longitudinal analysis of weight change: (1) changes in waist and hip circumferences are correlated directly with changes in weight in both sexes, but there are large differential sex effects; (2) in men, waist changes dominate; (3) in women, waist and hip changes are nearly the same; (4) thus, weight changes in men have large effects on the WHR, while in women changes in WHR are very small. Men, as a group, have a more dangerous fat distribution pattern than women, but men as a group will show a more beneficial pattern of change in WHR with weight control than women.     

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.     

Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age.

The relationships of body composition and physical fitness [maximal aerobic capacity (VO2max)] to the decline in insulin sensitivity with age were examined in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older men with normal glucose tolerance (OGTT), glucose disposal rates (M) during hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar relationships existed in the 36 older men with a spectrum of OGTT responses; however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free mass.min) was not different from that in the young men (8.56 +/- 0.47; P = NS). Furthermore, in older and young men with normal OGTT matched for WHR, percent fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals during the clamp and in its relationship to insulin concentrations at the tissue level (multicompartmental analysis). In contrast, despite higher steady state plasma insulin levels during the clamp, M was significantly lower in the older men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus, in healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max.     

Effects of fat mass and body fat distribution on resting metabolic rate in the elderly

The aim of the present study was to investigate the relationship between resting metabolic rate (RMR) and fat-free mass, fat mass, and body fat distribution in 164 women (age 60 to 85 years; body mass index [BMI], 18.5 to 35.6 kg/m(2)) and 98 men (age 60 to 85 years; BMI, 18.3 to 36.5 kg/m(2)). After an overnight fast, RMR was assessed by indirect calorimetry and body composition by bioelectrical impedance analysis. Waist-to-hip ratio (WHR) was used to determine fat distribution. Results from linear regression analysis showed that most of the variance in RMR could be attributed to fat-free mass in women (R(2) = 0.54) and men (R(2) = 0.44), respectively. Fat mass explained an additional 3% and 2% of the variability in RMR in women and men, respectively. In stepwise multiple regression analysis, considering body composition and fat distribution, only fat-free mass and WHR were significant predictors of RMR in both sexes. In addition to fat-free mass, in women 6% and in men 8% of the variability in RMR was attributable to WHR. Grouping subjects according to their WHR, RMR, and RMR adjusted for fat-free mass and fat mass showed a significant increase with increasing WHR in both sexes. Results indicate that RMR not only depends on fat-free mass but also is influenced by fat mass, especially by fat distribution. These findings support our hypothesis of an elevated RMR with increasing abdominal body fat as a direct consequence of its greater metabolic activity.     

Glucose tolerance in women: the effects of age, body composition, and sex hormones.

OBJECTIVE: To determine the separate and interactive effects of age, phase of the menstrual cycle, menopausal hormone status, body fat mass, and regional fat distribution on glucose tolerance in healthy women. DESIGN: Retrospective study. SETTING: The Baltimore Longitudinal Study of Aging. PATIENTS: Two hundred sixty healthy women aged 22-89 years. MEASUREMENTS: Plasma levels of estradiol and progesterone, body mass index (BMI), waist-to-hip ratio (WHR), and plasma glucose values in the fasting state (FPG) as well as 120 minutes after 40 gm/m2 of oral glucose (G120) were measured for each participant. RESULTS: We found a progressive decline in oral glucose tolerance of 0.4 mM (6.7 mg/dL)/decade at G120) in women from early to late adult years, with no relationship to phase of the menstrual cycle and no abrupt change associated with the menopause. Multiple regression analysis revealed significant, independent effects of BMI and WHR on FPG and G120. The influence of age (P less than 0.01) on G120 was stronger than that of the BMI or WHR (P less than 0.05). There was no significant relationship between the levels of endogenous sex hormones and glucose tolerance after adjustments for age, BMI, and WHR. However, women taking oral contraceptives, but not those receiving postmenopausal replacement therapy, did exhibit mildly elevated G120 values. CONCLUSIONS: Age per se, and to a lesser extent BMI and WHR, but not levels of endogenous sex steroids, contribute to the physiological decline in glucose tolerance in older women.     

The effect of sex, age and race on estimating percentage body fat from body mass index: The Heritage Family Study

OBJECTIVE: To study the effects of sex, age and race on the relation between body mass index (BMI) and measured percent body fat (%fat). DESIGN: Cross-sectional validation study of sedentary individuals. SUBJECTS: The Heritage Family Study cohort of 665 black and white men and women who ranged in age from 17 to 65 y. MEASUREMENTS: Body density determined from hydrostatic weighing. Percentage body fat determined with gender and race-specific, two-compartment models. BMI determined from height and weight, and sex and race in dummy coded form. RESULTS: Polynomial regression showed that the relationship between %fat and BMI was quadratic for both men and women. A natural log transformation of BMI adjusted for the non-linearity. Test for homogeneity of log transformed BMI and gender showed that the male-female slopes were within random variance, but the intercepts differed. For the same BMI, the %fat of females was 10.4% higher than that of males. General linear models analysis of the women's data showed that age, race and race-by-BMI interaction were independently related to %fat. The same analysis applied to the men's data showed that %fat was not just a function of BMI, but also age and age-by-BMI interaction. Multiple regression analyses provided models that defined the bias. CONCLUSIONS: These data and results published in the literature show that BMI and %fat relationship are not independent of age and gender. These data showed a race effect for women, but not men. The failure to adjust for these sources of bias resulted in substantial differences in the proportion of subjects defined as obese by measured %fat.     

Sex differences of body fat distribution and cardiovascular dysmetabolic factors in old age

BACKGROUND: The relationship between sexual differences of body fat distribution and cardiovascular dysmetabolic factors in old people is controversial. OBJECTIVES: To use centrality index-derived body fat distribution to clarify its relationship with glucose tolerance status, blood pressure and lipid profile. DESIGN: Cross-sectional survey in a tertiary-care medical centre in Tainan, Taiwan. SUBJECTS: 114 men and 101 women, aged > or = 60 years. METHODS: We measured total % body fat and body fat distribution (reflected as centrality index) by dual energy x-ray absorptiometry, and plasma glucose, glycosylated haemoglobin, blood pressure, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol and atherogenic index (total cholesterol/HDL cholesterol). RESULTS: Centrality index showed better linear correlation with cardiovascular dysmetabolic factors than body mass index, total % body fat and waist-to-hip ratio, except in systolic blood pressure. Women had higher total % body fat, but the % abdominal fat and centrality index were both higher in men. Subjects with diabetes mellitus had the highest centrality index compared with those with impaired or normal glucose tolerance. After adjustment for age and total % body fat, men still had higher diastolic blood pressure, triglyceride levels and atherogenic indices, but lower HDL cholesterol levels than women. However, when further adjusted for centrality index, the sex differences in cardiovascular dysmetabolic factors were statistically insignificant. CONCLUSIONS: Centrality index is a useful method for assessing body fat distribution in older people. Body fat distribution is an important factor in sex differences of cardiovascular dysmetabolic factors in old people.