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 involved in the regulation of GHBP in adiposity.


METHODS
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.


CONCLUSIONS
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.
Kratzsch
J
J
Department of Clinical Chemistry, University of Leipzig, Germany.
Dehmel
B
B
Pulzer
F
F
Keller
E
E
Englaro
P
P
Blum
W F
WF
Wabitsch
M
M
D000293:Adolescent; D000375:Aging / Q000097:blood* / Q000378:metabolism / Q000502:physiology; D001823:Body Composition; D001824:Body Constitution / Q000502:physiology; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood*; D002648:Child; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin; D016014:Linear Models; D008297:Male; D009765:Obesity / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism*; D011627:Puberty / Q000097:blood* / Q000378:metabolism / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss
D002352:Carrier Proteins; D007328:Insulin; D020738:Leptin; D011506:Proteins; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol; C051815:somatotropin-binding protein