Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
Diabetologia. 2010 Jul;53(7):1304-13. doi: 10.1007/s00125-010-1738-4. Epub 2010 Apr 6.
AIMS/HYPOTHESIS: Growth hormone-deficient patients show deterioration of insulin sensitivity and beta cell function. High-dose growth hormone treatment often induces further impairment of insulin sensitivity, leading to an increase in insulin and glucose levels or even, in cases of preexisting beta cell defect, to overt diabetes. However, low-dose treatment may improve insulin sensitivity, although data in humans with detailed metabolic phenotyping are as yet not available. We postulated that long-term low-dose growth hormone replacement, restoring IGF-1 to the low-normal range, might beneficially affect glucose metabolism.
We studied prospectively the metabolic responses to 24 and 48 weeks of growth hormone treatment in a small group of six adults with severe growth hormone deficiency (four men, two women; age 40-59 years; BMI 30.2 +/- 1 kg/m(2); mean growth hormone dose 0.3 +/- 0.04 mg/day). All participants underwent an oral glucose tolerance test, euglycaemic-hyperinsulinaemic clamp and hyperglycaemic-hyperinsulinaemic clamp plus i.v. L: -arginine on three occasions. Insulin sensitivity was measured by calculating the M value during the steady state of the euglycaemic-hyperinsulinaemic clamp. Insulin secretion and clearance were estimated from AUC(C-peptide), AUC(insulin) and their ratio at each phase of the hyperglycaemic-hyperinsulinaemic clamp.
Growth hormone significantly improved insulin sensitivity (M value 13.8 +/- 2.6 [baseline] vs 19.6 +/- 2.6 [24 weeks] and 23.7 +/- 1.9 [48 weeks] micromol kg(-1) min(-1); p < 0.01). Although the insulin response to glucose and arginine decreased slightly, the disposition index, integrating insulin sensitivity and secretion, significantly increased (p < 0.01), indicating an improvement in whole-body glucose metabolism. Insulin clearance was not affected during treatment (p > 0.05).
CONCLUSIONS/INTERPRETATION: Our data indicate that long-term low-dose growth hormone treatment may improve insulin sensitivity and whole-body glucose metabolism in adults with severe growth hormone-deficiency.
目的/假设：生长激素缺乏症患者的胰岛素敏感性和β细胞功能恶化。大剂量生长激素治疗常导致胰岛素敏感性进一步受损，导致胰岛素和血糖水平升高，甚至在存在β细胞缺陷的情况下导致显性糖尿病。然而，低剂量治疗可能会改善胰岛素敏感性，尽管在具有详细代谢表型的人类中尚无数据。我们假设，长期低剂量生长激素替代治疗，将 IGF-1 恢复到正常低水平，可能有益于葡萄糖代谢。
我们前瞻性地研究了六名严重生长激素缺乏症成年人（四名男性，两名女性；年龄 40-59 岁；BMI 30.2±1kg/m2；平均生长激素剂量 0.3±0.04mg/天）接受 24 周和 48 周生长激素治疗后的代谢反应。所有参与者均接受了口服葡萄糖耐量试验、正常血糖高胰岛素钳夹和高血糖高胰岛素钳夹加静脉内 L：-精氨酸试验。稳态时通过计算正常血糖高胰岛素钳夹的 M 值来测量胰岛素敏感性。通过计算高血糖高胰岛素钳夹期间 AUC(C-肽)、AUC(胰岛素)及其比值来估计胰岛素分泌和清除率。
生长激素显著改善了胰岛素敏感性（M 值分别为 13.8±2.6[基线]、19.6±2.6[24 周]和 23.7±1.9[48 周]µmol/kg/min；p<0.01）。尽管葡萄糖和精氨酸的胰岛素反应略有下降，但整体葡萄糖代谢的处置指数（综合胰岛素敏感性和分泌）显著增加（p<0.01），表明改善。治疗期间胰岛素清除率不受影响（p>0.05）。
结论/解释：我们的数据表明，长期低剂量生长激素治疗可能改善严重生长激素缺乏症成年人的胰岛素敏感性和整体葡萄糖代谢。
