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Gender Differences of Adiponectin Levels Develop during the Progression of Puberty and Are Related to Serum Androgen Levels

University Hospital for Children and Adolescents (A.B., G.M., T.M.K., S.B., E.K., W.K.); Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnosis (J.K.); and Interdisciplinary Center for Clinical Research (M.B.), University of Leipzig, 04317 Leipzig, Germany

Address all correspondence and requests for reprints to: Dr. Antje Böttner, Research Laboratory, University Hospital for Children and Adolescents, University of Leipzig, Oststrasse 21–25, 04317 Leipzig, Germany. E-mail: antje.boettner{at}medizin.uni-leipzig.de.

Adiponectin is an adipocytokine with profound antidiabetic and antiatherogenic effects that is decreased in obesity. With the increasing prevalence of obesity and the emergence of related disorders, including type 2 diabetes in children, the regulation of adiponectin and its relationship to childhood obesity is of great interest. In this study we aimed to elucidate the impact of gender, pubertal development, and obesity on adiponectin levels in children. We investigated two phenotypically characterized cohorts of 200 normal weight and 135 obese children and adolescents covering a wide range of age (3.4–17.9 yr) and body mass index (–2.1 to +4.8 SD score). In healthy lean boys, adiponectin levels significantly declined in parallel with physical and pubertal development, subsequently leading to significantly reduced adiponectin levels in adolescent boys compared with girls (5.6 ± 0.5 vs. 7.1 ± 0.5 mg/liter; P = 0.03). This decline was inversely related to testosterone (r = –0.42; P < 0.0001) and dehydroepiandrosterone sulfate (r = –0.20; P = 0.0068) serum concentrations and may account for the gender differences seen in adults. Using a stepwise forward multiple regression model, pubertal stage was the strongest independent predictor of adiponectin (r² = 0.206; P < 0.0001), with additional influences of body mass index SD score and testosterone. Adiponectin levels were decreased in obese children and adolescents compared with lean peers of corresponding age and pubertal stage (5.18 vs. 7.13 mg/liter; P = 0.015). In obese children, adiponectin levels were closely associated with parameters related to the metabolic syndrome, such as insulin resistance, hyperinsulinemia, blood pressure, and uric acid, in univariate and multivariate analyses, with the insulin sensitivity index being the strongest independent parameter identified by stepwise forward multiple regression (r² = 0.226; P < 0.0001). Hence, there is a strong association of adiponectin serum concentrations with obesity, pubertal development, and metabolic parameters in children indicating epidemiological and pathophysiological relevance already in childhood.

This work was supported by grants from the German Diabetes Society (to A.B. and J.K.) and the Interdisciplinary Center for Clinical Research at the University of Leipzig [to A.B. (B21), J.K. (B15), and W.K.].

Abbreviations: BMI, Body mass index; BP, blood pressure; DHEA-S, dehydroepiandrosterone sulfate; FPI, fasting plasma insulin; HDL, high-density lipoprotein; HOMA, homeostasis model assessment; ISI, insulin sensitivity index; Ob-BP, leptin-binding protein, also termed soluble leptin receptor; oGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; SDS, SD score; WHR, waist to hip ratio.

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