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

Abstract

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 30 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 D4-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 ðP , 0:01Þ; and AD res ðP ¼ 0:07Þ were higher than in the controls, and covariates were correlated with each other (leptin res versus BMI SDS r ¼ 0:71; IGF-I res versus height SDS r ¼ 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.

Pubertal development in obese children and adolescents

“…DHEAS levels were increased in almost all age groups. Increased DHEAS levels in obese children have been reported earlier by L'Allemand et al 39 DHEAS is a marker for adrenal activity and adrenarche. The mechanisms by which adrenal androgen secretion is activated are incompletely understood and likely involve intraadrenal changes in the activity of adrenal steroidogenic enzymes stimulated by insulin and IGF-1.…”

“…This finding is in line with earlier observations that obesity is associated with hyperandrogenemia in pubertal girls. 39,43 In contrast, obese boys showed impaired mean testosterone levels compared to mean reference values in age group 8-10 years and between 12 and 18 years of age.…”

Reference values for leptin and adiponectin in children below the age of 10 based on the IDEFICS cohort

“…There are some studies in healthy children on the national level, [8][9][10]20 but their comparability with our results is limited mostly because of either a different age distribution of the sample or due to incomparable laboratory analyses. Pre-analytical (for example, serum vs plasma) and analytical factors (laboratory method) can significantly affect measured concentrations of leptin and adiponectin.…”

“…21 In addition, not only total, but also either free or bound leptin concentrations have been reported. L'Allemand et al, 10 for instance, specifically measured free leptin. In a Greek study, 9 the enzyme-linked immunosorbent assay method was used to examine the serum leptin concentration of 294 children (154 boys).…”

“…2,7 According to a literature review, normative values of leptin and adiponectin for children are mainly based on small national study populations. [8][9][10][11] European reference standards from unselected populations are missing. Therefore, the main objective of this paper is to establish age-and sex-specific reference values for leptin and adiponectin, based on a European sample of normalweight children aged 3.0-8.9 years from eight European countries who participated in the baseline examinations of the IDEFICS (Identification and prevention of Dietary-and lifestyle-induced health Effects in Children and infantS) study.…”