Background: Growth hormone deficiency is associated with increased morbidity and mortality from cardiovascular diseases, which might be related to changes in glucose and lipid metabolism.
Design: To assess the influence of long-term growth hormone replacement therapy (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 tolerance 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 significantly from a basal level of 75.9 +/- 18.9 to 200.8 +/- 31.0 microg L-1 after 12 months of therapy and remained stable, thereafter. GHRT did not affect fasting blood glucose, basal insulin, cholesterol, blood pressure and body weight. However, at 12 months, HbA1c (6.0 +/- 0.1 vs. 5.6 +/- 0.1% at basal, P < 0.05) and triglyceride (2.3 +/- 0.4 vs. 1.4 +/- 0.3 mmol L-1) significantly 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/(microU 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 and 18 months, total insulin secretion only after 12 months. SG (glucose effectiveness)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 after 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 of the increased insulin sensitivity in GHD patients to levels observed in body mass index-matched control subjects. This is accompanied by an increase in basal and total insulin secretion as well as in glucose effectiveness as a possible compensatory mechanism.