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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 Adults¹

Center for Clinical Pharmacology, Department of Pharmacology, Aarhus University (T.L.); Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital (C.H.G., J.O.L.J., J.S.C.), Kommunehospitalet; and Department of Clinical Biochemistry, Aarhus University Hospital (L.H.), Amtssygehuset, DK-8000 Aarhus C; and Novo Nordisk A/S (J.D., A.-M.K.), DK-2880 Bagsvaerd, Denmark

Address all correspondence and requests for reprints to: Dr. Torben Laursen, Ph.D., Center for Clinical Pharmacology, Department of Pharmacology, Aarhus University, Bartholin Building, DK-8000 Aarhus C, Denmark. E-mail: tl{at}farm.au.dk/torben.laursen@dadlnet.dk

It remains uncertain whether close imitation of the physiological pulsatile GH pattern determines the effects of GH treatment in humans. However, human studies have reported comparable metabolic responses to short-term constant and intermittent GH exposure. The aim of the study was to compare the metabolic effects of GH after continuous and intermittent sc delivery. In a parallel design, 14 GH-treated GH-deficient patients (mean age, 37 yr; mean body mass index, 27.4 kg/m²) were studied during steady state at the start 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 and during the study. Serum levels of insulin-like growth factor I (IGF-I) tended to increase in the patients switched to constant infusion (from 175 ± 36 to 209 ± 50 µg/L), but the differences obtained during the two regimens [+34.3 (inf) vs. -11.9 (inj)] were not significant (P = 0.34). Serum levels 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 unaffected by treatment regimen. Serum levels of free fatty acids, reflecting lipolysis, decreased significantly (16%) in the group switched to GH infusion (difference, -99.8 vs. +5 µmol/L; P < 0.03). The GH pattern did not influence insulin sensitivity (P = 0.71) or glucose effectiveness (P = 0.15) derived from Bergman’s minimal model. Similarly, the two treatment regimens had no differential impact on lipoprotein levels, bone metabolism, or body composition. In conclusion, continuous and intermittent administrations of GH for 6 months are comparable with respect to the IGF-IGFBP axis, whereas intermittent exposure may be of importance for the lipolytic effect of GH. The data on insulin sensitivity and lipoproteins suggest that constant GH exposure is as safe as intermittent GH administration.

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