INCREASED SERUM GHBP LEVELS IN OBESE PUBERTAL CHILDREN AND ADOLESCENTS - RELATIONSHIP TO BODY-COMPOSITION, LEPTIN AND INDICATORS OF METABOLIC DISTURBANCES

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 i nvolved in the regulation of GHBP in adiposity. SUBJECTS AND MEASUREME NTS: We tested a number of obesity specific parameters for their assoc iation with GHBP. In this study, 199 normal or overweight children and adolescents (101 boys, 98 girls, aged [mean+/-s.d.): 13.7+/-2.3y) und erwent an anthropometric evaluation (circumference measurements and bi oimpedance analysis) combined with blood withdrawal for the measuremen t of insulin-like growth factor-I (IGF-I), insulin, leptin and GHBP (b y 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), a s 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 pu bertal stage had no impact on GHBP. In a multiple regression analysis containing age and gender, as well as the anthropometric variables, pe rcent fat mass and waist circumference, as independent variables, asso ciations 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 analy sis 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 variabil ity for 7.5%, 1.9%, and 1.0%, respectively. Serum GHBP was significant ly reduced in a subgroup of 104 overweight or obese patients during a diet-induced weight loss programme, the coefficient of correlation bet ween GHBP and leptin after (r= 0.45, Pt 0.001) and before weight reduc tion (r= 0.41, P ( 0.001) were comparable. CONCLUSION: Waist circumfer ence, 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 GH BP release. Additionally, elevated serum levels of GHBP may reflect me tabolic disturbances of adiposity.