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The Effect of 30 Months of Low-Dose Replacement Therapy with Recombinant Human Growth Hormone (rhGH) on Insulin and C-Peptide Kinetics, Insulin Secretion, Insulin Sensitivity, Glucose Effectiveness, and Body Composition in GH-Deficient Adults

Department of Internal Medicine and Endocrinology (A.M.R., S.M., J.H., S.M.), Hvidovre University Hospital, Copenhagen 2650 Hvidovre; Department of Endocrinology M (S.F., J.O.L.J., J.S.C.), Aarhus University Hospital 8000 Aarhus C; and Novo Nordisk A/S (A.V.), 2880 Bagsværd, Denmark

Address all correspondence and requests for reprints to: Anne Mette Rosenfalck, M.D., Department of Internal Medicine and Endocrinology 541, Hvidovre University Hospital, Kettegaard Alle 30, DK 2650 Hvidovre, Denmark. E-mail: amro{at}dadlnet.dk

The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 µg/kg·day (= 1.6 IU/day), in 11 patients with adult GH deficiency.

Glucose metabolism was evaluated by an oral glucose tolerance test and an iv (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry.

Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P < 0.001) and a 12% reduction of fat mass (P < 0.002); however, the glucose tolerance deteriorated significantly, and three patients developed impaired glucose tolerance. Fasting insulin level (P < 0.003) and the homeostasis model assessment insulin resistance score increased significantly, indicating a deterioration in insulin sensitivity; whereas the insulin sensitivity index, calculated from the frequently sampled iv glucose tolerance test, only decreased slightly. The clearance of C-peptide and insulin increased 100% and 60%, respectively, and the prehepatic insulin secretion was tripled during rhGH treatment; but related to the impairment in glucose tolerance, ß-cell response was still inappropriate.

Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite an increase in lean body mass and a reduction of fat mass. Therefore, rhGH treatment may precipitate diabetes in some patients already susceptible to the disorder.

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