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Insulin-Like Growth Factor I and Growth Hormone (GH) Treatment in GH-Deficient Humans: Differential Effects on Protein, Glucose, Lipid, and Calcium Metabolism¹

Division of Endocrinology, Nemours Children’s Clinic and Research Programs (N.M., S.W., A.R.), and Baptist Medical Center Physical Therapy Department (K.H.), Jacksonville, Florida 32207; The Johns Hopkins School of Public Health and Hygiene (K.O.O.), Baltimore, Maryland 21205-2179; and National Institutes of Health (N.E.V., A.L.Y.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Nelly Mauras, M.D., Nemours Children’s Clinic, 807 Nira Street, Jacksonville, Florida 32207. E-mail: nmauras{at}nemours.org

We examined the effects of recombinant human (rh) insulin-like growth factor I (IGF-I) vs. rhGH in a variety of metabolic paths in a group of eight severely GH-deficient young adults using an array of contemporary tools. Protein, glucose, and calcium metabolism were studied using stable labeled tracer infusions of L-[1-¹³C]leucine, [6,6-²H₂]glucose, and ⁴²Ca and ⁴⁴Ca; substrate oxidation rates were assessed using indirect calorimetry; muscle strength was determined by isokinetic and isometric dynamometry of the anterior quadriceps, as well as growth factors, hormones, glucose, and lipid concentrations in plasma before and after 8 weeks of rhIGF-I (60 µg/kg, sc, twice daily), followed by 4 weeks of washout, then 8 weeks of rhGH (12.5 µg/kg·day, sc); the treatment order was randomized.

In the doses administered, rhIGF-I and rhGH both increased fat-free mass and decreased the percent fat mass, with a more robust decrease in the percent fat mass after rhGH; both were associated with an increase in whole body protein synthesis rates and a decrease in protein oxidation. Neither hormone affected isokinetic or isometric measures of skeletal muscle strength. However, rhGH was more potent than rhIGF-I at increasing lipid oxidation rates and improving plasma lipid profiles. Both hormones increased hepatic glucose output, but rhGH treatment was also associated with decreased carbohydrate oxidation and increased glucose and insulin concentrations, indicating subtle insulin resistance. Neither hormone significantly affected bone calcium fluxes, supporting the concept that these hormones, by themselves, are not pivotal in bone calcium metabolism. In conclusion, rhIGF-I and rhGH share common effects on protein, muscle, and calcium metabolism, yet have divergent effects on lipid and carbohydrate metabolism in the GH-deficient state. These differences may allow for better selection of treatment modalities depending on the choice of desired effects in hypopituitarism.

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