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

The aim of the present study was to evaluate the long-term (30 months) meta bolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 mu g/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 i v (frequently sampled iv glucose tolerance test) glucose tolerance test, an d body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body compositio n, 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 signific antly, and three patients developed impaired glucose tolerance. Fasting ins ulin level (P < 0.003) and the, homeostasis model assessment insulin resist ance score increased significantly, indicating a deterioration in insulin s ensitivity; whereas the insulin sensitivity index, calculated from the freq uently sampled iv glucose tolerance test, only decreased slightly. The clea rance of C-peptide and insulin increased 100% and 60%, respectively, and th e prehepatic insulin secretion was tripled during rhGH treatment; but relat ed to the impairment in glucose tolerance, <beta>-cell response was still i nappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound c hanges in kinetics of C-peptide, and insulin and prehepatic insulin secreti on, despite an increase in lean body mass and a reduction of fat mass. Ther efore, rhGH treatment may precipitate diabetes in some patients already sus ceptible to the disorder.