Growth hormone treatment in adolescent males with idiopathic short stature: changes in body composition, protein, fat, and glucose metabolism.

@article{citeulike:2208598, abstract = {CONTEXT: Cross-sectional observations show an inverse relationship between pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin resistance may be mediated by GH. OBJECTIVE: Our objective was to assess longitudinally the effects of short-term GH supplementation in adolescent males with non-GH-deficient idiopathic short stature (ISS) on body composition, substrate metabolism, and insulin sensitivity. Children with ISS were studied to simulate the pubertal increase in GH secretion. PARTICIPANTS AND SETTING: Eight males with ISS (10.8-16.5 yr) were recruited from pediatric endocrinology clinics at an academic medical center. STUDY DESIGN: Participants were evaluated in the General Clinical Research Center before and after 4 months of GH supplementation (0.3 mg/kg.wk). Body composition was assessed with dual-energy x-ray absorptiometry. Whole-body glucose, protein, and fat turnover were measured using stable isotopes. In vivo insulin action was assessed during a 3-h hyperinsulinemic (40 mU/m(2).min) euglycemic clamp. RESULTS: GH supplementation led to 1) increase in hepatic glucose production and fasting insulin levels, 2) increase in lean body mass and decrease in fat mass, and 3) improvement in cardiovascular lipid risk profile. Plasma IGF-I levels correlated positively with insulin levels. CONCLUSIONS: Four months of GH supplementation in adolescent males with ISS is associated with significant body composition changes and hepatic insulin resistance.}, address = {Division of Pediatric Endocrinology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. tamara.hannon@chp.edu}, author = {Hannon, T. S. and Danadian, K. and Suprasongsin, C. and Arslanian, S. A. }, citeulike-article-id = {2208598}, comment = {While the main intent of GH treatment of short, non-GHD children is to increase their growth velocity and adult height, the GH doses used are typically higher and may simulate the 2-3 fold GH increase that occurs with puberty. Hannon et al. from Children’s Hospital of Pittsburgh set out to examine the effect of GH “supplementation” on carbohydrate, protein, and lipid metabolism and body composition. Using stable isotopes of glucose, leucine, and glycerol, they were able to measure or calculate hepatic glucose production, insulin sensitivity, protein turnover, and lipolysis in 8 boys (most in early puberty) with ISS before and after 4 months of GH treatment. Using DEXA, they found a significant decrease in percent body fat (22.8\% to 15.4\%) accompanied by an average 4.3 kg increase in fat-free (lean) mass. Hepatic glucose production increased, while hepatic insulin sensitivity decreased; however, fasting glucose levels were not different, as fasting insulin levels were increased. Serum lipid profiles showed lower total cholesterol and LDL cholesterol (118 decreased to 84 mg/dL). As there was no significant change in testosterone levels over the 4 mo treatment period, the investigators concluded that the physiologic insulin resistance seen with puberty is most likely not mediated by sex steroids, but rather it is more likely a result of the 2-3 fold increase in GH production. Supporting this conclusion was a positive correlation between serum IGF-1 levels and fasting insulin levels. Although there are some limitations of this study (small sample size, early puberty in most patients), this finding makes sense, as insulin resistance improves after puberty is complete, in the face of similar or rising sex steroids, but falling GH levels. Even more impressive are the changes in lean and fat mass with GH treatment, which one might expect to be attenuated in GH sufficient children (as compared to GH treatment of GHD children). This is a wonderful study, not easy to carry out in children; one hopes that the investigators will continue to follow these children so that they can report longer-term effects of GH on metabolism and body composition in non-GHD patients. SteveLaFranchi, MD }, doi = {http://dx.doi.org/10.1210/jc.2007-0308}, issn = {0021-972X}, journal = {J Clin Endocrinol Metab}, keywords = {growth, insulinresistance, metabolism, r-gh}, month = {August}, number = {8}, pages = {3033--3039}, posted-at = {2008-01-08 19:19:54}, priority = {2}, title = {Growth hormone treatment in adolescent males with idiopathic short stature: changes in body composition, protein, fat, and glucose metabolism.}, url = {http://dx.doi.org/10.1210/jc.2007-0308}, volume = {92}, year = {2007} }

TY - JOUR ID - citeulike:2208598 L3 - citeulike-article-id:2208598 TI - Growth hormone treatment in adolescent males with idiopathic short stature: changes in body composition, protein, fat, and glucose metabolism. JF - J Clin Endocrinol Metab VL - 92 IS - 8 SP - 3033 EP - 3039 AD - Division of Pediatric Endocrinology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. tamara.hannon@chp.edu SN - 0021-972X N2 - CONTEXT: Cross-sectional observations show an inverse relationship between pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin resistance may be mediated by GH. OBJECTIVE: Our objective was to assess longitudinally the effects of short-term GH supplementation in adolescent males with non-GH-deficient idiopathic short stature (ISS) on body composition, substrate metabolism, and insulin sensitivity. Children with ISS were studied to simulate the pubertal increase in GH secretion. PARTICIPANTS AND SETTING: Eight males with ISS (10.8-16.5 yr) were recruited from pediatric endocrinology clinics at an academic medical center. STUDY DESIGN: Participants were evaluated in the General Clinical Research Center before and after 4 months of GH supplementation (0.3 mg/kg.wk). Body composition was assessed with dual-energy x-ray absorptiometry. Whole-body glucose, protein, and fat turnover were measured using stable isotopes. In vivo insulin action was assessed during a 3-h hyperinsulinemic (40 mU/m(2).min) euglycemic clamp. RESULTS: GH supplementation led to 1) increase in hepatic glucose production and fasting insulin levels, 2) increase in lean body mass and decrease in fat mass, and 3) improvement in cardiovascular lipid risk profile. Plasma IGF-I levels correlated positively with insulin levels. CONCLUSIONS: Four months of GH supplementation in adolescent males with ISS is associated with significant body composition changes and hepatic insulin resistance. KW - growth KW - insulinresistance KW - metabolism KW - r-gh N1 - While the main intent of GH treatment of short, non-GHD children is to increase their growth velocity and adult height, the GH doses used are typically higher and may simulate the 2-3 fold GH increase that occurs with puberty. Hannon et al. from Children’s Hospital of Pittsburgh set out to examine the effect of GH “supplementation” on carbohydrate, protein, and lipid metabolism and body composition. Using stable isotopes of glucose, leucine, and glycerol, they were able to measure or calculate hepatic glucose production, insulin sensitivity, protein turnover, and lipolysis in 8 boys (most in early puberty) with ISS before and after 4 months of GH treatment. Using DEXA, they found a significant decrease in percent body fat (22.8% to 15.4%) accompanied by an average 4.3 kg increase in fat-free (lean) mass. Hepatic glucose production increased, while hepatic insulin sensitivity decreased; however, fasting glucose levels were not different, as fasting insulin levels were increased. Serum lipid profiles showed lower total cholesterol and LDL cholesterol (118 decreased to 84 mg/dL). As there was no significant change in testosterone levels over the 4 mo treatment period, the investigators concluded that the physiologic insulin resistance seen with puberty is most likely not mediated by sex steroids, but rather it is more likely a result of the 2-3 fold increase in GH production. Supporting this conclusion was a positive correlation between serum IGF-1 levels and fasting insulin levels. Although there are some limitations of this study (small sample size, early puberty in most patients), this finding makes sense, as insulin resistance improves after puberty is complete, in the face of similar or rising sex steroids, but falling GH levels. Even more impressive are the changes in lean and fat mass with GH treatment, which one might expect to be attenuated in GH sufficient children (as compared to GH treatment of GHD children). This is a wonderful study, not easy to carry out in children; one hopes that the investigators will continue to follow these children so that they can report longer-term effects of GH on metabolism and body composition in non-GHD patients. SteveLaFranchi, MD AU - Hannon, TS AU - Danadian, K AU - Suprasongsin, C AU - Arslanian, SA PY - 2007/08// UR - http://dx.doi.org/10.1210/jc.2007-0308 ER -