Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men

Objective: The relationships between adipocytokines, sex steroids and the GH/IGF-I axis is poorly studied and subject to controversy in healthy elderly male subjects. We investigated the association between both adiponectin and leptin, and the metabolic syndrome (MetS), lipid parameters, insulin sensitivity, sex steroids and IGF-I in healthy non-diabetic Lebanese men. Design and methods: In this cross-sectional study, a total of 153 healthy non-diabetic men aged 50 and above (mean age 59.3±7 years) had a detailed clinical and biological evaluation. Subjects were classified according to the National Cholesterol Education Program criteria of the MetS. Insulin sensitivity was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI). Results: Subjects with the MetS had lower adiponectin and higher leptin levels (P<0.0001 for both variables) compared with individuals without the MetS. Adiponectin was significantly correlated with waist size, triglycerides, high-density lipoprotein (HDL) cholesterol and QUICKI (r=−0.33, −0.26, 0.45 and 0.36 respectively, P<0.0001 for all variables). The relation between adiponectin and HDL cholesterol, triglycerides and QUICKI remained significant after adjustment for age and body mass index (BMI). Also, leptin was strongly correlated with waist size and QUICKI (r=0.63 and −0.63 respectively, P<0.001 for both variables). However, its relation to the lipid profile was weak (for cholesterol r=0.16, P<0.05; for triglycerides r=0.17, P<0.05) and disappeared after adjustment for BMI. Adiponectin was positively correlated with sex hormone-binding globulin (SHBG) (r=0.39, P<0.001) and inversely correlated with free-androgen index (r=−0.24, P<0.01), estradiol and dehydroepiandrosterone sulfate (r=−0.165, P<0.05; r=−0.21, P<0.01 respectively). This difference remained significant for SHBG after adjustment for age and BMI (r=0.20, P<0.005). Finally, leptin was inversely correlated with total testosterone and SHBG (r=−0.44, P<0.001; r=−0.30, P<0.001 respectively); the relation with testosterone remained significant after adjustment for BMI. No significant relationship of either adiponectin or leptin with GH or IGF-I values was observed. In a stepwise multiple regression analysis, the independent predictors of adiponectin were HDL cholesterol, QUICKI, age and BMI (P<0.0001, P=0.005, P=0.002 and P=0.047 respectively) while for leptin, it was QUICKI, waist size and testosterone (P<0.0001, P<0.0001 and P= 0.004 respectively). The adjusted R2 values were 0.34 and 0.55. Conclusion: Our results show that in a healthy elderly male population, both adiponectin and leptin are related to insulin sensitivity, independent of age and BMI. While adiponectin is independently related to triglycerides and HDL cholesterol, the weak relationship of leptin to the lipid profile is completely mediated by BMI. In addition, and more interestingly, both adipocytokines are strongly associated with sex steroids. We speculate that SHBG is regulated by adiponectin and that there is an inhibitory effect of testosterone on the adiponectin gene. Further studies are needed to fully elucidate these relationships.