Associations between body mass, leptin, IGF-1 and circulating adrenal androgens in children with obesity and premature adrenarche

Objective: To explain why adrenal androgens rise with increasing adiposity during childhood, the role of body mass index (BMI), leptin and IGF-I was studied. We also tested whether these parameters contribute to inducing premature adrenarche (PA). Design: In a cross-sectional study, 26 prepubertal obese children were compared with a group of 26 prepubertal children of normal weight, and 3 0 children under observation for PA were compared with 30 healthy children, matched for gender, bone age and BMI. Methods: Relative contributions of BMI standard deviation scores (SDS) and height SDS, as well as unbound leptin and IGF-I, to the levels of androgens, dehydroepiandrosterone sulfate (DHEAS) and Delta4-androstenedione (AD) were investigated by means of stepwise regression models. Logarithms of all hormones were standardised for age using residuals of a simple regression analysis, labelled by the suffix '(res)'. Results: In the obese children, height SDS, IGF-I-res, DHEAS(res) (all P < 0.05), leptin(res) (P < 0.01), and AD(res) (P = 0.07) were higher than in the controls, and covariates were correlated with each other (leptinres versus BMI SDS r = 0.71, IGF-I-res versus height SDS r = 0.61). In the stepwise regression analysis of control and obese children, BMI SDS explained 26% and leptin(res) explained 12% of the variability of DHEAS(res) but this percentage remained at 26% when both variables were simultaneously introduced into the model. In contrast, IGF-I-res and BMI SDS alone each accounted for 15% of the variability of AD, and their joint influence accumulated to explain 28% of the variability of AD(res). In PA, neither BMI SDS nor leptin(res) were correlated with the increased androgens. Conclusion: Before the onset of gonadal activity in obese and control children, DHEAS levels, to some extent, are explained by BMI and leptin, while IGF-I in addition to BMI in part accounts for AD levels. Enhanced adrenal androgen secretion in children with PA, however, may be explained by parameters other than leptin or BMI.