Riedl M, Ludvik B, Pacini G, Clodi M, Kotzmann H, Wagner O, Kautzky-Willer A, Prager R, Luger A
University of Vienna, Vienna, Austria; Institute of Systems Science and Biomedical Engineering (LADSEB-CNR), Padova, Italy.
Eur J Clin Invest. 2000 Sep;30(9):771-8. doi: 10.1046/j.1365-2362.2000.00695.x.
Growth hormone deficiency is associated with increased morbidity and mortality from cardiovascular diseases, which might be related to changes in glucose and lipid metabolism.
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.
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.
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.
生长激素缺乏与心血管疾病的发病率和死亡率增加有关，这可能与糖脂代谢变化有关。
为评估长期生长激素替代疗法（GHRT）对糖代谢的影响，我们对8名生长激素缺乏（GHD）成年人（7名女性/1名男性；年龄46±3岁；体重指数31±2 kg/m²）进行了为期18个月的研究，并与由8名年龄、性别和体重指数匹配的肥胖受试者组成的适当对照组进行比较。在研究前、12个月和18个月后，我们进行了频繁采样的静脉葡萄糖耐量试验（FSIGT）并进行最小模型分析。
GHRT治疗后，胰岛素样生长因子-1（IGF-1）从基础水平75.9±18.9显著增加至治疗12个月后的200.8±31.0 μg/L，并在此后保持稳定。GHRT不影响空腹血糖、基础胰岛素、胆固醇、血压和体重。然而，在12个月时，糖化血红蛋白（HbA1c）（6.0±0.1% vs. 基础值5.6±0.1%，P<0.05）和甘油三酯（2.3±0.4 vs. 1.4±0.3 mmol/L）显著增加，但在18个月时恢复到治疗前值。GHD患者的胰岛素敏感性（8.2±3.1）高于对照组（3.6±0.53×10⁻⁴ min⁻¹/(μU/mL)，P = 0.06），GHRT治疗18个月后显著降低至5.1±2.6，P<0.05。基础胰岛素分泌与对照组相似，在12个月和18个月后显著增加，总胰岛素分泌仅在12个月后增加。GHD患者的SG（葡萄糖效能）（0.0095±0.001 min⁻¹）低于对照组（0.020±0.003 min⁻¹，P<0.05），GHRT治疗12个月和18个月后分别显著增加（0.016±0.002和0.015±0.001 min⁻¹，P<0.05）。两组的肝脏胰岛素提取率相似，GHRT治疗后保持不变。
我们得出结论，长期GHRT可使GHD患者增加的胰岛素敏感性显著降低至体重指数匹配的对照受试者所观察到的水平。这伴随着基础和总胰岛素分泌以及葡萄糖效能的增加，作为一种可能的代偿机制。
