Long-term effects of continuous subcutaneous infusion versus daily subcutaneous injections of growth hormone (GH) on the insulin-like growth factor system, insulin sensitivity, body composition, and bone and lipoprotein metabolism in GH-deficient adults

It remains uncertain whether close imitation of the physiological pulsatile GH pattern determines the effects of GH treatment in humans. However, huma n studies have reported comparable metabolic responses to short-term consta nt and intermittent GH exposure. The aim of the study was to compare the me tabolic effects of GH after continuous and intermittent sc delivery. In a p arallel design, 14 GH-treated GH-deficient patients (mean age, 37 yr; mean body mass index, 27.4 kg/m(2)) were studied during steady state at the star t of the study and after 6 months. Seven patients received daily injections (inj) in the evening as usual, and 7 received a continuous infusion (inf) of GH by means of a portable pump. The GH dose was kept unchanged before an d during the study. Serum levels of insulin-like growth factor I(IGF-I) ten ded to increase in the patients switched to constant infusion (from 175 +/- 36 to 209 +/- 50 mug/L), but the differences obtained during the two regim ens [+34.3 (inf) vs. -11.9 (inj)] were not significant (P = 0.34). Serum le vels of IGF-II (P = 0.71) and IGF-binding protein (IGFBP)-3 (P = 0.75) were identical during the two modes of treatment. Serum levels of IGFBP-1 (P = 0.72), IGFBP-2 (P = 0.34), and GH-binding protein (P = 0.75) were unaffecte d by treatment regimen. Serum levels of free fatty acids, reflecting lipoly sis, decreased significantly (16%) in the group switched to GH infusion (di fference, -99.8 vs. +5 mu mol/L; P < 0.03). The GH pattern did not influenc e insulin sensitivity (P = 0.71) or glucose effectiveness (P = 0.15) derive d from Bergman's minimal model. Similarly, the two treatment regimens had n o differential impact on lipoprotein levels, bone metabolism, or body compo sition. In conclusion, continuous and intermittent administrations of GH fo r 6 months are comparable with respect to the IGF-IGFBP axis, whereas inter mittent exposure may be of importance for the lipolytic effect of GH. The d ata on insulin sensitivity and lipoproteins suggest that constant GH exposu re is as safe as intermittent GH administration.