Relationship between GH-induced metabolic changes and changes in body composition: A dose and time course study in GH-deficient adults

Objective: Although growth hormone (GH)-induced changes in fat and protein metabolism are likely to underlie changes in body composition, the relationship has not been clearly defined. The aim was to study the effects of dose and time course on substrate metabolism and relate to body compositional changes during GH treatment. Design: In an open randomised-controlled study, 16 GH-deficient adults were randomised to treatment with GH 3 mu g/kg/d (low dose, n = 6) or 6 mu g/kg/d (higher dose, n = 10) for 12 weeks. Changes in whole body protein metabolism, estimated using the leucine turnover technique, and resting energy expenditure (REE) were assessed after short-term GH (two weeks) and longer-term GH (12 weeks). Changes in lean body mass (LBM) and fat mass (FM) over 12 weeks were assessed by DXA. Results: The maximal changes in leucine oxidation (Lox) (-3.9 :L 1.1 versus +0.8 +/- 1.8 mu mol/min, p = 0.03) and REE (+132 +/- 36 versus -28 +/- 41 kcal/d, p = 0.01) were significantly greater in the higher, than the low dose group. FM fell (-1.4 +/- 0.4 kg, p = 0.005) and LBM increased (+2.2 +/- 0.7 kg, p = 0.01) significantly in the higher dose group only. The acute reduction in Lox at two weeks in the higher dose group was no longer significant after 12 weeks. The change in Lox after two (r = -0.53, p = 0.035), but not 12, weeks was significantly correlated with the change in LBM. Conclusions: GH-induced changes in protein metabolism were influenced by the dose and duration of GH treatment. Suppression of protein oxidation occured soon after initiation of GH in the higher dose group and predicted a later gain in LBM. Early assessment of whole body protein metabolism may allow prediction of the anabolic potential of GH. (c) 2007 Elsevier Ltd. All rights reserved.