Abstract
OBJECTIVES: The aim of the study was to examine insulin homeostasis during growth hormone (GH) therapy, and to investigate the effect of GH treatment on insulin and leptin concentration in obese children.
SUBJECTS: Nineteen obese children (8 with Prader-Willi Syndrome (PWS)) were treated with GH 0.1 IU/kg/day dose for 3 months and were compared with 29 non-treated age and sex matched obese children (9 PWS) and 49 GH treated non-obese short children. Mean age of the children was 10.3±1.8 (6.7–13.8) y, with body mass index of 23.6±10.4 (11.5–47) kg/m2.
RESULTS: Leptin concentration decreased and was correlated inversely with initial leptin value (r2=−0.374, P<0.001) and decreased body mass (r2=0.338, P=0.001). Insulin sensitivity index was not significantly changed during therapy. Leptin decrease after 3 months of GH administration was correlated inversely with the increase in first phase insulin response to intravenous glucose tolerance test (IVGTT) (r2=−0.595, P<0.001). Results of long-term follow-up of treated patients demonstrated a decrease in insulin concentration after cessation of therapy. In GH-treated subjects, the glucose increase in response to glucose load appeared to be higher than in untreated subjects.
CONCLUSION: The high insulin response to glucose load seen in GH-treated subjects was appropriate to their glucose concentration and the insulin sensitivity index was unchanged relative to the pretreatment period. Increased insulin dosage in our patients did not induce an increase in leptin concentrations as had been hypothesised.
International Journal of Obesity (2001) 25, 538–542
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References
Brobeck JR . Food intake as mechanism of temperature regulation Yale J Biol Med 1948 20: 545–552.
Kennedy JC . Role of depot fat in hypothalamic control of food intake in rat Proc Roy Soc London B 1953 140: 578–592.
Zhang Y, Procena R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue Nature 1994 372: 425–432.
Halaas JL, Gajiwala KD, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RC, Burley SK, Friedman JM . Weight reducing effects of the plasma protein encoded by the obese gene Science 1995 269: 543–546.
Considine RV, Shinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Maro CC, Mckee LJ, Bauer TL, Caro JS . Serum immunoreactive leptin concentrations in normal weight and obese humans New Eng J Med 1995 334: 292–295.
Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, Kern PA, Friedman JM . Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight reduced subjects Nature Med 1995 1: 1155–1161.
Skaggs SR, Christ DM . Exogenous human growth hormone reduces body fat in obese women Horm Res 1991 35: 19–24.
Karlsson C, Stenlof K, Johannsson G, Marin P, Bjorntorp P, Bengtsson BA, Carlsson B, Carlsson LM, Sjostrom L . Effects of growth hormone treatment on the leptin system and on energy expenditure in abdominally obese men Eur J Endocrinol 1998 138: 408–414.
Carrel AL, Myers SE, Whiteman BY, Allen DB . Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: a controlled study J Pediatr 1999 134: 215–221.
Davis PSW, Evans S, Broomhead S, Clough H, Day JME, Laidlow A, Barnes ND . Effect of GH on height, weight and body composition in Prader Willi syndrome Arch Dis Child 1998 78: 474–476.
Sherwin RS, Shulman GA, Hendler R, Walesky M, Belous A, Tamborlane W . Effect of growth hormone on oral glucose tolerance and circulating metabolic fuels in man Diabetologia 1983 24: 155–161.
MacDougald OA, Hwang C, Fan H, Lane MD . Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes Proc Natl Acad Sci USA 1995 92: 9034–9037.
Cassidy SD . Prader-Willi syndrome Curr Prob Pediatr 1984 14: 1–55.
Zadik Z, Chalew SA, McCarter RJ Jr, Meistas M, Kowarski AA . The influence of age on the 24 h integrated concentration of growth hormone in normal individuals J Clin Endocrinol Metab 1985 60: 513–518.
Zadik Z, Chalew S, Kowarski A . Assessment of growth hormone secretion in normal stature children using 24-h integrated concentration of growth hormone and pharmacological stimulation J Clin Endocrinol Metab 1990 71: 932–936.
Azcue M, Fried M, Pencharz PB . Use of bioelectrical impedance analysis to measure body water in patients with cystic fibrosis J Pediatr Gastroenterol Nut 1993 16: 440–445.
Amit T, Barkey RJ, Yudaim MBH, Hochberg Z . A new convenient assay of growth hormone binding protein activity in human serum J Clin Endocrinol 1990 71: 474–479.
Pacini G, Bergman RN . MINIMOD: a computer program to calculate insulin sensitivity and pancreatic responsitivity from the frequently sampled intravenous glucose tolerance test Comput Methods Programs Biomed 1986 23: 113–122.
Richelson B, Pederson SB, Borglum JD, Moller-Pederson T, Jorgenson J, Jorgenson JO . Growth hormone treatment of obese women for 5 weeks: effect on body composition and adipose tissue LPL activity Am J Physiol 1994 266: E211–216.
Clemmons DR, Snyder DK, Williams R, Underwood LE . Growth hormone administration conserves lean body mass during dietary restriction in obese subjects J Clin Endocrinol Metab 1987 64: 878–883.
Korlaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF . Response of leptin to short term and prolonged overfeeding in humans J Clin Endocrinol Metab 1996 81: 4162–4165.
Hassink SG, Sheslow DV, de Lancey E, Opemntanova I, Considine RV, Caro JF . Serum leptin in children with obesity relationship to gender and development Pediatrics 1996 98: 201–203.
Beck-Nielsen H, Pederson O, Lindskow HO . Normalization of the insulin sensitivity and the cellular binding during treatment of obese diabetics for one year Acta Endocrinol 1979 90: 103–112.
Kolaczynski JW, Nyce MR, Considine RV, Baden G, Nolan JJ, Henry R, Nudallar SR, Olefsky J, Caro JF . Acute and chronic effect of insulin on leptin production in humans: studies in vivo and in vitro Diabetes 1996 45: 699–701.
Utriainen T, Malmstrom R, Makimattila S, Yki-Jarvinen H . Supraphysiological hyperinsulinemia increases plasma leptin concentrations after 4 h in normal subjects Diabetes 1996 45: 1364–1366.
Malmstrom R, Taskinen MR, Karonen SL, Yki-Jarvinen H . Insulin increases plasma leptin concentrations in normal subjects and patients with NIDDM Diabetologia 1996 39: 993–996.
Cohen B, Novick D, Rubinstein M . Modulation of insulin activities by leptin Science 1996 274: 1185–1188.
Schwartz MW, Prigeon RL, Kahn SE, Nicolson M, Moore J, Morawiecki A, Boyko EJ, Porte D Jr . Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms Diabetes Care 1997 20: 1476–1481.
Brismar K, Fernquist-Forbs E, Wahren J, Hall K . Effect of insulin on the hepatic production of insulin like growth factor binding protein-1 (IGF-BP-1) IGF-BP3 and IGF-I in insulin dependent diabetes J Clin Endocrinol Metab 1994 79: 872–878.
Paolisso G, Ammendola S, Del Buono A, Gambardella A, Riondino M, Tagliamonte MR, Risso AM, Carella C, Varricchio M . Serum levels of insulin like growth factor-I (IGF-I) and IGF-BP3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function J Clin Endocrinol Metab 1997 82: 2204–2209.
Ymer SI, Herrington AC . Evidence for the specific binding of growth hormone to a receptor like protein in rabbit serum Endocrinol 1985 42: 153–161.
Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WJ, Barnard R, Waters MJ, Wood WI . Growth hormone receptor and serum-binding protein: purification, cloning and expression Nature 1987 330: 537–543.
Hochberg Z, Hertz P, Colin V, Ish-Shalom S, Yeshurun D, Yudim MBH, Amit T . The distal axis of growth hormone (GH) in nutritional disorders: GH binding protein, insulin like growth factor I and IGF-I receptors in obesity and anorexia nervosa Metabolism 1992 41: 106–112.
Golden NH, Kritzer P, Jacobson MS, Chaslow FI, Schebendach J, Freedman SM, Shenker IR . Disturbances in growth hormone secretion in adolescents with anorexia nervosa J Pediatr 1994 125: 655–660.
Zadik Z, Zung A, Altman Y, Chen M . The effect of exogenous and endogenous growth hormone on plasma growth hormone binding activity in prepubertal children Horm Res 1993 40: 161–167.
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Zadik, Z., Wittenberg, I., Segal, N. et al. Interrelationship between insulin, leptin and growth hormone in growth hormone-treated children. Int J Obes 25, 538–542 (2001). https://doi.org/10.1038/sj.ijo.0801601
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