Increased serum GHBP levels in obese pubertal children and adolescents: relationship to body composition, leptin and indicators of metabolic disturbances

Abstract

OBJECTIVE: The serum concentration of the high-affinity growth hormone-binding protein (GHBP) is increased in obesity but the mechanisms are poorly understood. This study assessed the physiological mechanisms involved in the regulation of GHBP in adiposity.

SUBJECTS AND MEASUREMENTS: We tested a number of obesity specific parameters for their association with GHBP. In this study, 199 normal or overweight children and adolescents (101 boys, 98 girls, aged (mean±s.d.): 13.7±2.3 y) underwent an anthropometric evaluation (circumference measurements and bioimpedance analysis) combined with blood withdrawal for the measurement of insulin-like growth factor-I (IGF-I), insulin, leptin and GHBP (by specific RIA), uric acid, triglycerides and cholesterol.

RESULTS: By linear regression analysis GHBP correlated significantly (P<0.001) with percent body fat mass (r=0.71), waist (r=0.73) and hip (r=0.69) circumference, weight (r=0.61), waist hip ratio (WHR) (r=0.54), as well as with the serum concentrations of leptin (r=0.64), uric acid (r=0.54), insulin (r=0.45), LDL-cholesterol (r==0.43), cholesterol (r=0.33), LDL/HDL ratio (r=0.47), triglycerides (r=0.30) and with height standard deviations scores (SDS) (r=0.23). Age, gender and pubertal stage had no impact on GHBP. In a multiple regression analysis containing age and gender, as well as the anthropometric variables, percent fat mass and waist circumference, as independent variables, associations between GHBP and leptin (P<0.001), cholesterol (P<0.01), LDL-cholesterol (P=0.01), LDL/HDL ratio (P=0.02), triglycerides (P=0.01) remained significant. In a final model using the stepwise analysis involving age, gender and all the independent predictors of GHBP, waist circumference (P<0.001) accounted for 49.5% of the 60.0% total variability in GHBP, while the implication of leptin (P<0.001), age (P<0.01) and cholesterol(P<0.05) increased the predicted variability for 7.5%, 1.9%, and 1.0%, respectively. Serum GHBP was significantly reduced in a subgroup of 104 overweight or obese patients during a diet-induced weight loss programme, the coefficient of correlation between GHBP and leptin after (r=0.45, P<0.001) and before weight reduction (r=0.41, P<0.001) were comparable.

CONCLUSION: Waist circumference, an indicator of abdominal body fat mass, is a major determinant of GHBP levels during childhood, while leptin may be one candidate for a signal linking adipocytes to the growth hormone receptor related GHBP release. Additionally, elevated serum levels of GHBP may reflect metabolic disturbances of adiposity.