Protein, fat and glucose metabolism during treatment with recombinant human growth hormone in adults with growth hormone deficiency. Short-and long-term effects

Treatment of adults with growth hormone (GH) deficiency results in substantial changes in body composition with increased lean body mass and decreased fat mass. To gain more insight into the mechanisms of these changes we analysed the effects of recombinant human growth hormone (rhGH) on protein, fat and glucose metabolism after 1 and 6 months of treatment. Protein metabolism was investigated following intravenous bolus injection of 1-C-14 leucine, hepatic glucose production was assessed by injection of 3-H-3 glucose, and glucose and fat oxidation were calculated from indirect calorimetry. There was no significant change in lactate, pyruvate, glycerol or ketone body concentration. Glucagon levels did not change during treatment, but there was a significant increase in the insulin: glucagon ratio (P=0.048, P=0.028 at 1 and 6 months). rhGH treatment increased leucine metabolic clearance rate at 1 and 6 months (P=0.025, P=0.02) and non-oxidative leucine disposal, a measure of protein synthesis (P=0.056) after 1 month. There was no effect on leucine oxidation or on the relationship between energy expenditure and leucine appearance rate. Fat oxidation in relation to lean body mass (LBM) was higher after 1 month (P=0.01), whereas fat oxidation in relation to fat mass was increased after 1 and 6 months (P=0.002, for both). Glucose production rate increased after 1 month (P=0.02), but there was no significant effect when related to lean body mass. Glucose oxidation rate and glucose metabolic clearance rate were not changed by treatment with rhGH. The anabolic action of growth hormone is mediated by an increase in protein synthesis. The necessary energy requirements for this increase in protein synthesis may be provided by the lipolytic action of growth hormone. There was no effect of growth hormone treatment on glucose metabolism, but total glucose production rate increased after 1 month in relation to the increased lean body mass.