Changes in body composition and leptin levels during growth hormone (GH) treatment in short children with various GH secretory capacities

Abstract

Objective: The aim of this study was to follow changes in body composition, estimated by dual-energy Xray absorptiometry (DXA), in relation to changes in leptin during the first year of GH therapy in order to test the hypothesis that leptin is a metabolic signal involved in the regulation of GH secretion in children. Design and Methods: In total, 33 prepubertal children were investigated. Their mean (S.D.) chronological age at the start of GH treatment was 11.5 (1.6) years, and their mean height was ¹ 2.33 (0.38) S.D. scores (SDS). GH was administered subcutaneously at a daily dose of 0.1 (n ¼ 26) or 0.2 (n ¼ 7) IU/kg body weight. Ten children were in the Swedish National Registry for children with GH deficiency, and twenty-three children were involved in trials of GH treatment for idiopathic short stature. Spontaneous 24-h GH secretion was studied in 32 of the children. In the 24-h GH profiles, the maximum level of GH was determined and the secretion rate estimated by deconvolution analysis (GH t ). Serum leptin levels were measured at the start of GH treatment and after 10 and 30 days and 3, 6 and 12 months of treatment. Body composition measurements, by DXA, were performed at baseline and 12 months after the onset of GH treatment. Results: After 12 months of GH treatment, mean height increased from ¹ 2.33 to ¹ 1.73 SDS and total body fat decreased significantly by 3.0 (3.3)%. Serum leptin levels were decreased significantly at all time points studied compared with baseline. There was a significant correlation between the change in total body fat and the change in serum leptin levels during the 12 months of GH treatment, whereas the leptin concentration per unit fat mass did not change. In a multiple stepwise linear regression analysis with 12 month change in leptin levels as the dependent variable, the percentage change in fat over 12 months, the baseline fat mass (%) of body mass and GH t accounted for 24.0%, 11.5% and 12.2% of the variability respectively. Conclusions: There are significant correlations between changes in leptin and fat and endogenous GH secretion in short children with various GH secretory capacities. Leptin may be the messenger by which the adipose tissue affects hypothalamic regulation of GH secretion.

Altered ghrelin levels in boys with autism: a novel finding associated with hormonal dysregulation

“…Leptin levels were reduced after GH replacement therapy, and this effect was thought to be secondary to reduction in fat mass32. In contrast, another study found that leptin levels were significantly increased after a single dose of GH and subsequently dropped below the baseline; this observation indicates that GH has a direct regulatory effect on leptin gene expression33.…”

Serum leptin and IGF-I during growth hormone treatment in chronic renal failure

“…These observations illustrate that serum leptin responds differently to hGH in children with CRF, who are GH/IGF-I insensitive but not GH deficient. Indeed, in short children with various GH secretory capacities, the magnitude of decrease in serum leptin during 12 months of hGH treatment has been shown to correlate inversely with endogenous GH secretion [2]. This study suggests that, unlike GHD, basal leptin levels cannot be used as a predictor of response to hGH treatment over the 1st year in children with CRF.…”

“…The decrease in serum leptin in GHD has been proposed as a predictor of the growth response to hGH [1,2,3]. In addition to high circulating GH, low GH-binding protein, low-normal insulin-like growth factor-I (IGF-I), reduced free IGF-I, high-normal IGF-II, high IGF-binding protein levels [4,5,6] and elevated serum leptin levels have been reported in children with chronic renal failure (CRF) [7].…”

Response to IGF-1 Generation Test in Short Prepubertal Children Born Very Preterm or at Term

“…While this is in contrast to the results of an IGF-1 stimulation test using one dose of rhGH [41], it is consistent with findings using longer courses of rhGH. Leptin concentrations were reduced by 20% after 10 days of GH therapy in short children [42], and by 60% after 3 months of rhGH treatment in children with Prader-Willi syndrome, independently of changes in body composition [43]. Higher circulating leptin concentrations have been found in preterm infants on day 1 of life compared to control infants, with a rapid decline after birth, suggesting a physiological advantage by limiting body energy expenditure for subsequent growth [44].…”

“…However, there are contradictory results in the literature. Some studies have reported a decrease in leptin levels in short children with [45,46] and without [42] GH deficiency after 1 year of GH therapy. Conversely, Meazza et al [47] have detected a significant increase in leptin levels after 1 year of GH treatment in children with GH deficiency.…”