Continuation of growth hormone (GH) therapy in GH-deficient patients during transition from childhood to adulthood: Impact on insulin sensitivity andsubstrate metabolism

The appropriate management of GH-deficient patients during transition from childhood to adulthood has not been reported in controlled trials, even tho ugh there is evidence to suggest that this phase is associated with specifi c problems in relation to GH sensitivity. An issue of particular interest i s the impact of GH substitution on insulin sensitivity, which normally decl ines during puberty. We, therefore, evaluated insulin sensitivity (euglycemic glucose clamp) and substrate metabolism in 18 GH-deficient patients (6 females and 12 males; age, 20 +/- 1 yr; body mass index, 25 +/- 1 kg/m(2)) in a placebo-controlle d, parallel study. Measurements were made at baseline, where all patients w ere on their regular GH replacement, after 12 months of either continued GH (0.018 +/- 0.001 mg/kg.day) or placebo, and finally after 12 months of ope n phase GH therapy (0.016 mg/kg.day). Before study entry GH deficiency was reconfirmed by a stimulation test. During the double-blind phase, insulin s ensitivity and fat mass tended to increase in the placebo group [Delta M-va lue (mg/kg.min), -0.7 +/- 1.1(GH) vs. 1.3 +/- 0.8 (placebo), P = 0.18; Delt a TBF (kg), 0.9 +/- 1.2 (GH) us. 4.4 +/- 1.6 (placebo), P = 0.1]. Rates of lipid oxidation decreased [Delta lipid oxidation (mg/kg.min), 0.02 +/- 0.14 (GH) vs. -0.32 +/- 0.13 (placebo), P < 0.05], whereas glucose oxidation in creased in the placebo-treated group (P < 0.05). In the open phase, a decre ase in insulin sensitivity was found in the former placebo group, although they lost body fat and increased fat-free mass [M-value (mg/kg.min), 5.1 +/ - 0.7 (placebo) vs. 3.4 +/- 1.0 (open), P = 0.09]. In the group randomized to continued GH treatment almost all hormonal and metabolic parameters rema ined unchanged during the study. In conclusion, 1) discontinuation of GH therapy for 1 yr in adolescent pati ents induces fat accumulation without compromising insulin sensitivity; and 2) the beneficial effects of continued GH treatment on body composition in terms of decrease in fat mass and increase in fat-free mass does not fully balance the direct insulin antagonistic effects.