Reference Values for Serum Leptin Levels in Children, Adolescents, and Adults With Normal Weight, Overweight, and Obesity

Background: Interpretation of blood leptin concentration in clinical practice and research is limited by a lack of comprehensive reference values. We aimed to establish reference ranges across the age and weight spectrum, taking into consideration important covariates age (0-75 years), pubertal status, and body weight status (normal to extreme obesity). Method: Data from 12 629 individuals across 16 European cohorts were pooled and extracted for weight, height, Tanner stage (TS), and serum leptin concentration via ELISA (Leptin ELISA kit). Generalized additive models for location, shape, and scale were used to render reference curves stratified by sex, TS, and weight status. Results: In boys, serum leptin concentrations increased between ages 6 and 12, followed by a decline after age 12, while girls showed an increase until age 15, with body mass index (BMI) SD score (SDS) dependent trajectories thereafter. Leptin concentrations were generally higher in girls than boys, except in boys aged 9 to 15 years with a BMI-SDS of > 3. In adults, women consistently had higher leptin concentrations across all BMI categories. In men, leptin concentrations decreased until the mid-20s for a BMI of 30 kg/m² and until age 50 for a BMI of 40 kg/m², stabilizing thereafter. Conclusion: We present the first reference curves for leptin concentrations across the entire age and weight range. An online tool and an R package for calculating leptin z-scores that are specific to age, sex, TS, and BMI (or BMI-SDS) are now available for clinical and research use at https://leptin.science.