Distribution of plasma levels of adiponectin and leptin in an adult Caucasian population

Objectives  Little is known regarding the distribution and the determinants of leptin and adiponectin levels in the general population.
Design  Cross-sectional study.
Patients  Women (3004) and men (2552) aged 35–74 living in Lausanne, Switzerland.
Measurements  Plasma levels of leptin and adiponectin (ELISA measurement).
Results  Women had higher leptin and adiponectin levels than men. In both genders, leptin and adiponectin levels increased with age. After adjusting for fat mass, leptin levels were significantly and negatively associated with age in women: 18·1 ± 0·3, 17·1 ± 0·3, 16·7 ± 0·3 and 15·5 ± 0·4 ng/ml (adjusted mean ± SE) for age groups [35–44], [45–54], [55–64] and [65–75], respectively, P  < 0·001. A similar but nonsignificant trend was also found in men. Conversely, the age-related increase of adiponectin was unrelated to body fat in both genders. Post-menopausal women had higher leptin and adiponectin levels than premenopausal women, independently of hormone replacement therapy. Although body fat mass was associated with leptin and adiponectin, the associations were stronger with body mass index (BMI), waist and hip in both genders. Finally, after adjusting for age and anthropometry, no relationships were found between leptin or adiponectin levels with alcohol, caffeine consumption and physical activity, whereas smoking and diabetes decreased leptin and adiponectin levels in women only.
Conclusions  The age-related increase in leptin levels is attributable to changes in fat mass in women and probably also in men. Leptin and adiponectin levels are more related to BMI than to body fat mass. The effects of smoking and diabetes appear to be gender-specific.     

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 adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies

Adiponectin is an adipocyte-secreted protein that circulates in high concentrations in the serum and acts to increase insulin sensitivity. Previous studies have shown that serum adiponectin is inversely associated with fat mass and insulin resistance in humans and that acute fasting decreases adipose tissue adiponectin mRNA expression in rodents. Whether acute energy deprivation, body fat distribution, or serum hormone levels are associated with circulating adiponectin in humans remains largely unknown. To identify predictors of serum adiponectin levels, we evaluated the association of adiponectin with several anthropometric, metabolic, and hormonal variables in a cross-sectional study of 121 women without a known history of diabetes. We also performed interventional studies to assess whether fasting for 48 h and/or leptin administration regulates serum adiponectin in healthy men and women. Our cross-sectional study shows that, in addition to overall obesity, central fat distribution is an independent negative predictor of serum adiponectin and suggests that adiponectin may represent a link between central obesity and insulin resistance. In addition, estradiol is negatively and independently associated with adiponectin, whereas there is no association between serum adiponectin and leptin, cortisol, or free testosterone levels. Our interventional studies demonstrate that neither fasting for 48 h, resulting in a low leptin state, nor leptin administration at physiological or pharmacological doses alters serum adiponectin levels. Further studies are needed to fully elucidate the physiology of adiponectin in humans and its role in the pathogenesis of insulin-resistant states.     

Serum adiponectin is associated with high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein particle size in young healthy men

The chromosomal localization of adiponectin has been found to be mapped to human chromosome 1q21.4-1q23, a region that was identified as a susceptibility locus for familial combined hyperlipidemia and polygenic type 2 diabetes. As these 2 disorders are associated with low high-density lipoprotein (HDL)-cholesterol, high triglycerides, and insulin resistance (IR), we examined the relation of serum adiponectin concentrations to serum lipid and lipoprotein profiles as well as IR in young healthy men. Serum adiponectin levels were positively associated with HDL-cholesterol, apolipoprotein (apo) A1, and low-density lipoprotein (LDL) particle size, and negatively associated with triglycerides and apo B. Negative associations were also found between adiponectin and body mass index (BMI), percent body fat, and IR,as determined by homeostasis model assessment (HOMA). However, after adjustment for BMI, no significant associations were found between adiponectin and LDL particle size and apo B. In a multiple regression analysis including all variables that showed significant univariate associations with adiponectin, associations of adiponectin with HDL-cholesterol (beta = 0.079, P =.0009), percent body fat (beta = -0.165, P =.002), and serum leptin (beta = -0.291, P =.01) were statistically significant. HDL-cholesterol (beta = 0.077, P =.001), percent body fat (beta = -0.078, P =.03), and LDL size (beta = 0.092, P =.03) emerged as significant and independent determinants of adiponectin after HOMA IR, fasting glucose, triglycerides, and systolic blood pressure (BP) were taken into account. Together, these variables explained 19% of adiponectin variability in the 2 models. HOMA IR did not emerge as a determinant of adiponectin in both models. These findings suggest that in young healthy men hypoadiponectinemia is more closely related to adiposity and dyslipidemia than IR.     

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.     

Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus

The aim of the present study was to investigate the association of serum adiponectin concentration with regional adiposity and insulin resistance in subjects with type 2 diabetes mellitus. A total of 73 Japanese men with type 2 diabetes (aged 59 +/- 11 years and body mass index [BMI] 23.8 +/- 3.0 kg/m(2), mean +/- SD) were studied. Fasting serum adiponectin and leptin concentrations were determined by radioimmunoassay. Regional adiposity was measured by abdominal computed tomography (CT) at the umbilical level, and insulin resistance was estimated by homeostasis model assessment (HOMA-R). Univariate regression analysis showed that serum adiponectin levels were negatively correlated with subcutaneous and visceral fat areas. With multivariate regression analysis, visceral fat area was a predominant determinant of serum adiponectin levels. In contrast, subcutaneous fat area was strongly associated with serum leptin concentrations. Among subcutaneous and visceral fat areas, BMI, and serum leptin levels, both subcutaneous and visceral fat areas were independently associated with HOMA-R. In another model incorporating serum adiponectin levels, serum adiponectin levels were selected as an independent determinant of HOMA-R instead of visceral fat area. In conclusion, hypoadiponectinemia was associated with visceral fat accumulation rather than subcutaneous fat depot in Japanese men with type 2 diabetes mellitus. Both subcutaneous and visceral fat accumulation contribute to insulin resistance in these subjects, and the contribution of visceral fat may be mediated, in part, by hypoadiponectinemia.     

Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery

One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease (CHD) risk. A cross-sectional study was designed to randomly assign 79 morbidly obese subjects (27 men and 52 women; age: 30-45 years) either to a diet protocol (20 kcal per kg fat-free mass (FFM); 55% carbohydrates, 30% fat, and 15% proteins) or to malabsorptive surgery (biliopancreatic diversion). Fatness parameters, measured by dual-energy X-ray absorptiometry, lipid profile, insulin, leptin, sex steroid hormones and sex hormone-binding globulin (SHBG) levels were compared at baseline and 1 year after the beginning of the study. The data showed that plasma SHBG levels, but not testosterone levels, correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women. Total leptin levels were significantly lower (P<0.0001) in post-BPD subjects of both sexes compared to dietary treated obese subjects. The logarithm of plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG, but not insulin levels, were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients. The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness. Finally, in obese patients, SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis.     

Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01). This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.     

Sex-specific association of the androgen to oestrogen ratio with adipocytokine levels in older adults: the Rancho Bernardo Study

OBJECTIVE: Androgens and oestrogens have opposing effects on some adipocyte functions. Thus, the androgen to oestrogen balance may be as important as the individual hormones in determining the biological interaction between endogenous sex hormones and adipocyte-derived factors such as adiponectin and leptin. We tested this hypothesis by evaluating the sex-specific, cross-sectional association of sex hormones and androgen to oestrogen ratios with serum adiponectin and leptin in older men and postmenopausal women. DESIGN: Cross-sectional. PARTICIPANTS: A total of 1510 community dwelling men and postmenopausal women aged 50-92 years. MEASUREMENTS: Serum leptin, adiponectin and sex hormone levels. RESULTS: Adiponectin and leptin levels were higher in women than men (P < 0.001). In both sexes, adiponectin concentrations were lower, and leptin levels higher, with increasing BMI and waist girth (all P < 0.001). Although the ratio of total testosterone to total oestradiol was significantly associated with both adipocytokines in both sexes, the strongest and most consistent hormone-adipocytokine associations were observed when the androgen to oestrogen ratio was expressed as total testosterone to bioavailable oestradiol. In linear regressions, the testosterone to bioavailable oestradiol ratio was positively related to adiponectin and inversely related to leptin, with nearly identical standardized beta-coefficients for men and women (all P < 0.001). The strength of the hormone ratio-adipocytokine associations was reduced, but not eliminated, after adjustment for age, adiposity and cardiovascular disease risk factors, including insulin resistance. CONCLUSIONS: The striking similarity of the hormone ratio-adipocytokine associations for men and women, despite wide differences in sex hormone and adipocytokine levels, suggests these results reflect underlying physiological mechanisms common to both sexes.     

Short-term treatment with ezetimibe, simvastatin or their combination does not alter circulating adiponectin, resistin or leptin levels in healthy men

Objective Statin therapy decreases cardiovascular morbidity and mortality, and ezetimibe, a novel cholesterol absorption inhibitor has both lipid‐lowering and anti‐atherosclerotic effects in animal models. As several adipokines, that is, adiponectin, high molecular weight (HMW) adiponectin, leptin and/or possibly resistin are involved in the pathogenesis of insulin resistance (IR), dyslipidaemia and atherosclerosis, we investigated whether ezetimibe and/or statin treatment may modulate serum concentrations of these four major adipokines. Research design and methods One‐centre, randomized, parallel three‐group study in 72 healthy men [mean age 32 ± 9 years, mean body mass index (BMI) 25·7 ± 3·2 kg/m²]. Patients Seventy‐two healthy men. Each group of 24 subjects received a 14‐day treatment with either ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination. Blood was drawn before and after the 14‐day treatment period. Measurements Lipid levels, IR indices, serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Results Neither ezetimibe nor simvastatin or their combination had any effect on serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Baseline leptin levels correlated positively, while adiponectin and HMW adiponectin negatively, with BMI. Leptin concentrations correlated negatively while adiponectin and HMW adiponectin positively with plasma high‐density lipoprotein‐cholesterol concentrations. Resistin concentrations were not associated with BMI, lipid levels or indicators of IR. Conclusions Treatment with ezetimibe, simvastatin or their combination does not alter circulating levels of adiponectin, leptin or resistin in adult healthy men.     

Age-related changes in sex hormones affect the sex difference in serum leptin independently of changes in body fat

Serum leptin concentrations are highly correlated with body fatness, but there is considerable variability among individuals after adjusting for differences in body fatness. Theoretically, sex hormone levels may influence serum leptin, since the levels are higher in women than in men independently of body fat. Increasing old age is associated with decreases in serum sex hormone concentrations and changes in body fatness that may independently alter serum leptin concentrations. In a cross-sectional sample of 106 men and 166 women aged 62 to 98 years, serum leptin adjusted for total body fat had a significant positive association with age in men and a nonsignificant negative association with age in women. Serum testosterone had a significant negative association with serum leptin in men after adjusting for total body fat, the fasting insulin resistance index (FIRI), and sex hormone-binding globulin (SHBG). In a longitudinal sample of 22 elderly men and 52 women, serum leptin levels increased significantly over a 14-year period in men, but not in women. Increases in serum leptin were significantly associated with decreases in serum testosterone but not with changes in the body mass index (BMI) in men. In contrast, changes in leptin were associated with changes in the BMI but not with changes in serum estrone in women. These results suggest that differences among men and changes with age in serum leptin are associated with circulating levels of testosterone. Elderly men become progressively "hyperleptinemic" with age regardless of changes in body fatness, possibly due to decreasing testosterone levels.     

Adipocytokines, fat distribution, and insulin resistance in elderly men and women

BACKGROUND: The aim of this study was to evaluate the relation between adiponectin and leptin, fat distribution, and insulin resistance in elderly men and women. METHODS: 68 elderly participants (28 men and 40 women) aged 66-77 years, with body mass index (BMI) ranging from 19.83 to 37.18 kg/m2, participated in the study. In all participants, we evaluated BMI, waist and hip circumferences, sagittal abdominal diameter (SAD), fat mass (FM) by dual energy X-ray absorptiometry, fasting and 2-hour glucose, insulin, homeostasis model assessment of insulin resistance (HOMA), leptin, and adiponectin. RESULTS: Elderly women had significantly higher circulating levels of adiponectin and leptin compared to men even after adjusting for age, FM, or waist circumference. In men and women, leptin was positively associated, whereas adiponectin was negatively associated, with BMI, indices of body fat distribution, as well as FM and FM%. Both fasting insulin and HOMA showed significant positive correlation with leptin and negative correlation with adiponectin in both sexes. In a step-wise multiple regression model with HOMA as the dependent variable and age, gender, waist circumference, FM, leptin, and adiponectin as independent variables, waist entered the regression first, explaining 19.7% of HOMA variance, leptin was second, and adiponectin was third, explaining each one an additional 10% of variance. In a multiple linear regression analysis, leptin and adiponectin alone explained up to 38% of HOMA variance. CONCLUSION: Leptin and adiponectin together seem to be strictly related to insulin resistance in elderly people, independently of body fat and body fat distribution.     

Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women

Whether the higher serum leptin levels in women are due to gender differences in fat mass or to other factors such as sex steroids remains unclear. In addition to sex steroids, serum insulin levels also appear to be related to leptin levels, although whether this effect is independent of the effects of body composition is unclear. The purpose of this study was to identify the major determinants of circulating serum leptin levels. We studied a large, population-based cohort of 345 men (23 to 90 years), 137 premenopausal women (21 to 54 years), and 212 postmenopausal women (34 to 94 years), including 47 women on hormone replacement therapy (HRT). Serum leptin levels were related to body composition as assessed by dual-energy x-ray absorptiometry (DEXA) and to circulating sex steroid and insulin levels. Serum leptin levels remained significantly higher in women versus men even after adjustment for fat mass, and leptin levels were significantly correlated with fat mass independently of age. By univariate analyses, logarithmically transformed serum leptin levels correlated positively with bioavailable estrogen ([E] estradiol plus estrone) in postmenopausal women not on HRT, and negatively with total and bioavailable testosterone (T) levels in men. Serum insulin levels were directly related to leptin levels regardless of gender and age. By multivariate analyses, fat mass, lean mass, and insulin levels were the strongest predictors of leptin levels in all groups. In addition, bioavailable E entered the model in the postmenopausal women not on HRT. These studies indicate that the fat mass, lean mass, and insulin level are the major determinants of the serum leptin level in adults. Moreover, after adjusting for these variables, bioavailable E also explains a significant proportion of the variance in leptin levels among postmenopausal women not on HRT.     

Associations of endogenous testosterone and SHBG with glycated haemoglobin in middle-aged and older men

Objective Low circulating levels of testosterone and sex‐hormone‐binding globulin (SHBG) are associated with increased cardiovascular risk in men. This association may be partially mediated through changes in glucose metabolism, but relatively few data are available on the relationship between sex hormones and markers of long‐term glycaemia. We assessed the associations of endogenous testosterone and SHBG with glycated haemoglobin (HbA_1c) in men. Design and subjects Cross‐sectional study of 1292 men from the Norfolk population of European Prospective Investigation into Cancer (EPIC‐Norfolk). Measurements Glycated haemoglobin, total testosterone (TT) and SHBG levels were measured, and free testosterone (FT) levels were calculated. Multiple linear regression models were used to assess the associations of TT, SHBG and FT with HbA_1c. Results Men with diabetes had lower testosterone and SHBG levels. In non‐diabetic men, HbA_1c levels were inversely associated with TT and calculated FT independently of age, body mass index, smoking, alcohol consumption and physical activity. The adjusted change in HbA_1c was 0·055 (95% CI 0·025; 0·085) per standard deviation (SD) decrease in TT and 0·041 (95% CI 0·010; 0·073) per SD decrease in calculated FT, respectively. SHBG levels were inversely associated with HbA_1c after multivariable adjustment (β = 0·038 per SD decrease (95% CI 0·004; 0·071)). Conclusions In middle‐aged and older men, low endogenous testosterone and SHBG levels are associated with glycaemia, even below the threshold for diabetes. Further studies are needed to determine the effects of interventions that raise testosterone levels in men having increased HbA_1c and subnormal testosterone levels.     

Association between hormones and metabolic syndrome in older Italian men

OBJECTIVES: To determine whether low levels of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and dehydroepiandrosterone sulfate (DHEAS) and high levels of cortisol and leptin would be associated with metabolic syndrome (MS). DESIGN: Cross-sectional. SETTING: Population-based sample of older Italian men. PARTICIPANTS: Four hundred fifty-two men aged 65 and older enrolled in the Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS: Complete data on testosterone, cortisol, DHEAS, SHBG, fasting insulin, IGF-1 and leptin. MS was defined according to Adult Treatment Panel III criteria. RESULTS: MS was present in 73 men (15.8% of the sample). After adjusting for confounders, total testosterone (P < .05) and log (SHBG) (P < .001) were inversely associated, whereas log (leptin) was positively associated with MS (P < .001). Independent of age, log (SHBG) was positively associated with high-density lipoprotein cholesterol (P < .05) and negatively associated with abdominal obesity (P < .001) and triglycerides (P < .001). Log (leptin) was significantly associated with each component of MS. Cortisol, DHEAS, free and bioavailable testosterone, and IGF-1 were not associated with MS. Having three or more hormones in the lower (for hormones lower in MS) or the upper (for hormones higher in MS) quartile was associated with three times the risk of being affected by MS (odds ratio = 2.8, 95% confidence interval = 1.3-6.9) (P = .005), compared with not having this condition. CONCLUSION: Total testosterone and SHBG are negatively and leptin is positively associated with MS in older men. Whether specific patterns of hormonal dysregulation predict the development of MS should be tested in longitudinal studies.     

Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor,free leptin index,adiponectin, and resistin concentrations in healthy humans

The adipocyte-derived hormones leptin [which circulates in a free form and bound to a soluble leptin receptor (sOB-R)], adiponectin, and resistin play a key role in regulating energy homeostasis and metabolism. We assessed the association between body composition, total energy, and macronutrient intake and serum leptin, sOB-R, free leptin index, adiponectin, and resistin concentrations in 61 female and 53 male consecutively enrolled healthy Greek students. In this cross-sectional study, total energy and macronutrient intake were determined using 3-d food records. Body composition was assessed by bioelectrical impedance analysis; fasting blood samples were taken for the measurement of total leptin, sOB-R, adiponectin, and resistin; and the ratio leptin/sOB-R was used as an index of free leptin. Serum sOB-R concentrations were lower in the female subjects compared with the males (27.24 +/- 29.06 vs. 50.14 +/- 39.74 ng/ml, P < 0.001), whereas leptin, adiponectin, and resistin concentrations were significantly higher in females (leptin: 9.93 +/- 6.01 vs. 3.27 +/- 2.54 ng/ml, P < 0.001; adiponectin: 11.40 +/- 6.73 micro g/ml vs. 4.90 +/- 2.79 micro g/ml; P < 0.001; resistin: 16.86 +/- 5.39 ng/ml in females vs. 14.00 +/- 7.16 ng/ml in males, P < 0.02). Simple regression analysis showed that, in both genders, leptin, free leptin index, adiponectin, and resistin correlated positively with body fat mass and negatively with waist to hip ratio. sOB-R correlated negatively with body fat mass and positively with waist to hip ratio. Multiple regression analysis models controlling for gender, body fat, and total energy intake demonstrated that sOB-R is positively associated with energy intake from carbohydrates and negatively with energy intake from dietary fat, whereas free leptin index is negatively associated with energy intake from carbohydrates and positively with energy intake from dietary fat. No statistically significant correlations were observed between serum adiponectin or resistin concentrations and total energy or macronutrient intake. Thus, total energy intake and macronutrient composition of the diet are associated with sOB-R and free leptin index but do not play a role of comparable significance in predicting adiponectin and resistin concentrations in healthy young subjects.     

Circulating levels of adipokines and IGF-1 are associated with skeletal muscle strength of young and old healthy subjects

It is known that adipose tissue mass increases with age, and that a number of hormones, collectively called adipokines, are produced by adipose tissue. For most of them it is not known whether their plasmatic levels change with age. Moreover, it is known that adipose tissue infiltration in skeletal muscle is related to sarcopenia and loss of muscle strength. In this study we investigated the age-related changes of representative adipokines and insulin-like growth factor (IGF)-1 and their effect on muscle strength. We studied the association between circulating levels of adiponectin, leptin, resistin and IGF-1 and muscle strength. This cross-sectional study included 412 subjects of different age (152 subjects aged 18–30 years and 260 subjects aged 69–81 years) recruited within the framework of the European research network project “Myoage”. The levels of adiponectin (both in male and female subjects) and leptin (only in males) were significantly higher in old subjects compared to young, while those of IGF-1 were lower in old subjects. In old subjects adiponectin, resistin and the resistin/IGF-1 ratio (but not IGF-1 alone) were inversely associated with quadriceps torque, while only adiponectin was inversely associated with handgrip strength independently from percentage of fat mass, height, age, gender and geographical origin. The ratio of leptin to adiponectin was directly associated with handgrip strength in both young and old subjects. These results suggest that in humans the age-associated loss of strength is associated with the levels of representative adipokines and IGF-1.     

Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study

OBJECTIVE: To test the hypothesis that lower endogenous testosterone levels are associated with higher blood pressure, left ventricular mass, and left ventricular hypertrophy. DESIGN: Population-based cross-sectional study. METHODS: Sex hormone levels, measured by immunoassay, anthropometric measurements and resting blood pressure were studied in 1548 men aged 25-84 Years; echocardiography was completed in 1264 of these men. Partial correlations and multiple regressions were used to estimate the associations between sex hormones, blood pressure and left ventricular mass by height. Analyses of variance and covariance were used to compare men with categorical hypertension and left ventricular hypertrophy. RESULTS: In age-adjusted partial correlations, total testosterone and sex hormone-binding globulin (SHBG) were each inversely associated with systolic blood pressure (SBP) (P<0.001). Men with categorical hypertension (SBP> or =140 or diastolic blood pressure (DBP)> or =90 mmHg) had lower levels of total and free testosterone and SHBG before (P<0.001, P=0.011 and P<0.001, respectively) and after (P<0.001, P=0.035 and P=0.002, respectively) adjusting for body mass index (BMI). Total testosterone and SHBG were each inversely associated with left ventricular mass (P<0.001), and men with left ventricular hypertrophy had significantly lower levels of total testosterone (P=0.042) and SHBG (P=0.006); these associations were no longer significant after adjusting for BMI. CONCLUSION: The results of the present study are consistent with the hypothesis that lower levels of testosterone in men are associated with higher blood pressure, left ventricular mass, and left ventricular hypertrophy. The reduced associations after adjusting for BMI suggest that the association of low testosterone levels with blood pressure and left ventricular mass is mediated by obesity.     

Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.     

Diet and sex hormone-binding globulin

The serum concentration of sex hormone-binding globulin (SHBG) is inversely related to weight and in animal studies is inversely related to protein intake. As SHBG can affect the biological activity of testosterone and estradiol, we wished to determine the role of protein intake on SHBG levels in men. Using data from the Massachusetts Male Aging Study we examined cross-sectional relationships between dietary components and SHBG levels in 1552 men (aged 40-70 yr) for whom these factors were known. Analyzed by multiple regression, controlling for testosterone and estradiol levels, age (P<0.001) and fiber intake (P = 0.02) were positively correlated to SHBG concentration, whereas body mass index (P<0.001) and protein intake (P<0.03) were negatively correlated to SHBG concentration. The intakes of calories, fat (animal or vegetable), and carbohydrate were not related to SHBG concentration. We conclude that age and body mass index are major determinants of SHBG concentrations in older men, and fiber and protein intake are also significant contributors to SHBG levels, but total caloric intake and the intake of carbohydrate or fat are not significant. Thus, diets low in protein in elderly men may lead to elevated SHBG levels and decreased testosterone bioactivity. The decrease in bioavailable testosterone can then result in declines in sexual function and muscle and red cell mass, and contribute to the loss of bone density.