Effects of four years' treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH‐deficient adults

OBJECTIVE To study the effects of long-term growth hormone (GH) treatment on lipid metabolism and carbohydrate tolerance in GH-deficient adults. DESIGN Open trial of GH treatment for 4 years. GH dose was (median, range) 0.025 (0.010–0.050) IU/kg daily. PATIENTS Thirteen GH-deficient hypopituitary adults (seven men, six women), aged (median, range) 47 (24–65) years were followed for 4 years. MEASUREMENTS Fasting lipids, lipoproteins, apolipoproteins, glucose and insulin concen_trations were measured at yearly intervals during GH therapy. A 75-g oral glucose tolerance test (OGTT) was also performed yearly, during which circulating glucose and insulin were measured at 30-minute intervals for 3 h. RESULTS Fasting total and low density lipoprotein (LDL) cholesterol concen_trations decreased on GH therapy, but no change was observed in fasting triglyceride or high density lipoprotein (HDL) concen_trations. Compared to pretreatment values, total and LDL cholesterol levels were significantly lower at 1 year (mean ± SEM) (6.39 ± 0.46 vs. 5.71 ± 0.38 mmol/l, P < 0.05; 4.46 ± 0.36 vs. 3.24 ± 0.20 mmol/l, P < 0.01, respectively) and the reductions were maintained for the 4 years. Apolipoproteins A-1 and B did not differ significantly from the pretreatment levels. Fasting plasma glucose increased significantly at the first year (4.9 ± 0.1 vs. 5.3 ± 0.1 mmol/l, P < 0.05) but it returned to the pretreatment value in the following years. Fasting plasma insulin increased significantly at 1 year (4.3 (1.0–13.6) vs. 11.9 (1.2–26.9) mU/l, P < 0.05) and showed a progressive downward trend but remained significantly raised throughout the subsequent years. The 3-h area under the glucose curve (AUC) during the OGTT tended to be increased at the first year (P = 0.07) and it returned to the pretreatment level in the following years. The AUC of plasma insulin was significantly raised at 1 year (P = 0.024) and it returned to the pretreatment level in the following years. CONCLUSIONS Four years of GH therapy in GH-deficient adults resulted in a sustained improvement in total and LDL cholesterol concen_trations. Mild fasting hyperinsulinaemia persisted, although an initial deterioration in glucose tolerance, associated with post-glucose hyperinsulinaemia, was not sustained.