Insulin-like growth factor I and growth hormone (GH) treatment in GH-deficient humans: Differential effects on protein, glucose, lipid, and calcium metabolism

We examined the effects of recombinant human (rh) insulin-like growth facto r I(IGF-I) vs. rhGH in a variety of metabolic paths in a group of eight sev erely GH-deficient young adults using an array of contemporary tools. Prote in, glucose, and calcium metabolism were studied using stable labeled trace r infusions of L-[1-C-13]leucine, [6,6-H-2(2)]glucose, and Ca-42 and Ca-44; substrate oxidation rates were assessed using indirect calorimetry; muscle strength was determined by isokinetic and isometric dynamometry of the ant erior quadriceps, as well as growth factors, hormones, glucose, and lipid c oncentrations in plasma before and alter 8 weeks of rhIGF-I(60 mu g/kg, sc, twice daily), followed by 4 weeks of washout, then 8 weeks of rhGH(12.5 mu g/kg day, sc); the treatment order was randomized. In the doses administered, rhIGF-I and rhGH both increased fat-free mass an d decreased the percent fat mass, with a more robust decrease in the percen t fat mass after rhGH; both were associated with an increase in whole body protein synthesis rates and a decrease in protein oxidation. Neither hormon e affected isokinetic or isometric measures of skeletal muscle strength. Ho wever, rhGH was more potent than rhIGF-I at increasing lipid oxidation rate s and improving plasma lipid profiles. Both hormones increased hepatic gluc ose output, but rhGH treatment was also associated with decreased carbohydr ate oxidation and increased glucose and insulin concentrations, indicating subtle insulin resistance. Neither hormone significantly affected hone calc ium fluxes, supporting the concept that these hormones, by themselves, are not pivotal in bone calcium metabolism. In conclusion, rhIGF-I and rhGH sha re common effects on protein, muscle, and calcium metabolism, yet have dive rgent effects on lipid and carbohydrate metabolism in the GH-deficient stat e. These differences may allow for better selection of treatment modalities depending on the choice of desired effects in hypopituitarism.