Reference values for serum leptin in healthy non-obese children and adolescents

Background: Adipokines are biologically active, low-molecular weight peptides, which play a major role in metabolic homeostasis in humans. Leptin has gained increasing attention in pediatrics as a biomarker for various metabolic pathologies. Yet, its usefulness is hampered by the relative lack of reference values from pediatric settings. Accordingly, this study aims to evaluate serum concentrations of leptin, soluble leptin receptor (sOB-R), and free leptin index (FLI) in healthy Danish schoolchildren aged 6-18 years and subsequently to establish reference intervals across sex and age groups.Methods: A total of 1193 healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6-18 years (median 11.9) were examined by trained medical staff. Serum leptin and sOB-R concentrations in venous fasting blood samples were quantitated by immunoassay. Percentile curves of leptin, sOB-R, and free leptin index were calculated using the General Additive Model for Location Scale and Shape (GAMLSS).Results: Significant age and sex-dependent differences in circulating leptin levels were found. In boys, the median leptin concentration for all ages combined was 3.35g/L (95%-interval: 0.71-22.47) and in girls, it was 9.89ng/L (95%-interval: 2.06-41.49). For SOB-R, no sex-specific difference was found, and the median sOB-R concentration was 8.24g/L (IQR: 3.58-23.74; range:< 1.56-744.15).Conclusion: We demonstrated an age-dependent correlation with both serum leptin concentration and free leptin index with a gradual and significant increase in girls throughout childhood and adolescence and a significantly higher leptin concentration and free leptin index bell-shaped peak in early adolescence in boys.