The increased insulin sensitivity in growth hormone-deficient adults is reduced by growth hormone replacement therapy

Background Growth hormone deficiency is associated with increased morbidity and mortality from cardiovascular diseases, which might be related to chan ges in glucose and lipid metabolism. Design To assess the influence of long-term growth hormone replacement ther apy (GHRT) on glucose metabolism we examined eight growth hormone-deficient (GHD) adults (seven female/one male; age, 46 +/- 3 years; body mass index, 31 +/- 2 kg m(-2)) over a period of 18 months in comparison to an adequate control group consisting of eight obese subjects matched for age, sex, and body mass index. We performed frequently sampled intravenous glucose toler ance tests (FSIGT) with minimal model analysis before the study, and after 12 and 18 months. Results Following GHRT, insulin-like growth factor-1 (IGF-1) increased sign ificantly from a basal level of 75.9 +/- 18.9 to 200.8 +/- 31.0 mu g L-1 af ter 12 months of therapy and remained stable, thereafter. GHRT did not affe ct fasting blood glucose, basal insulin, cholesterol, blood pressure and bo dy weight. However, at 12 months, HbA1c (6.0 +/- 0.1 vs. 5.6 +/- 0.1% at ba sal, P<0.05) and triglyceride (2.3 +/- 0.4 vs. 1.4 +/- 0.3 mmol L-1) signif icantly increased but returned to pretreatment values at 18 months. Insulin sensitivity was higher in GHD (8.2 +/- 3.1) compared to controls (3.6 +/- 0.53 x 10(-4) min(-1)/(mu U mL(-1)), P = 0.06) and decreased significantly after 18 months of GHRT to 5.1+/- 2.6, P<0.05. Basal insulin secretion was similar to that in the control group and increased significantly after 12 a nd 18 months, total insulin secretion only after 12 months. SG (glucose eff ectiveness)was lower in GHD patients (0.0095 +/- 0.001 min(-1)) compared to controls (0.020 +/- 0.003 min(-1), P<0.05) and increased significantly aft er 12 and 18 months of GHRT (0.016 +/- 0.002, and 0.015 +/- 0.001 min(-1), P<0.05), respectively. Hepatic insulin extraction rate was similar in both groups and remained unchanged following GHRT. Conclusion We conclude that long-term GHRT induces a significant decrease o f the increased insulin sensitivity in GHD patients to levels observed in b ody mass index-matched control subjects. This is accompanied by an increase in basal and total insulin secretion as well as in glucose effectiveness a s a possible compensatory mechanism.