Jørgensen J O, Flyvbjerg A, Lauritzen T, Alberti K G, Orskov H, Christiansen J S
Institute of Experimental Clinical Research, Second University Clinic of Internal Medicine, Kommunehospital, Aarhus, Denmark.
J Clin Endocrinol Metab. 1988 Jul;67(1):36-40. doi: 10.1210/jcem-67-1-36.
Increasing doses of biosynthetic human GH (R-hGH) were given sc to seven GH-deficient patients for three consecutive 14-day periods (2, 4, and 6 IU/day at 2000 h), followed by 14 days of no GH therapy. At the end of each period each patient was hospitalized for frequent blood sampling from 2000 to 1100 h the following day. A dose-dependent increase in serum GH and serum insulin-like growth factor I (IGF-I) levels occurred. However, the time course of the serum IGF-I concentrations was different on the four occasions; there was a significant fall in the evening when no therapy was given (P less than 0.01), a significant increase after injections of 2 IU R-hGH, and constant levels during treatment with 4 and 6 IU R-hGH. Plasma glucose levels were within the normal range, with a significantly lower fasting level (at 0400 h) when no GH was given. Breakfast induced a plasma glucose rise when GH was administered, but no rise without GH, and a postprandial serum insulin response that was GH dose dependent. GH therapy increased serum FFA (P less than 0.05) and blood 3-hydroxybutyrate levels, but had no effect on blood alanine or lactate or serum triglyceride and cholesterol levels. We conclude that the serum IGF-I response to GH is dose dependent, and that a GH replacement dose of 2 IU/day (equalling 1.5 IU/m2.day) is insufficient to maintain normal diurnal serum IGF-I levels. Furthermore, a GH-independent diurnal variation in serum IGF-I in these patients is suggested. This GH preparation also has diabetogenic and lipolytic actions.
连续三个14天期间（每天2000时皮下注射2、4和6国际单位），给7名生长激素缺乏患者注射递增剂量的生物合成人生长激素（重组人生长激素），随后14天不进行生长激素治疗。在每个阶段结束时，每位患者于次日2000时至1100时住院进行频繁采血。血清生长激素和血清胰岛素样生长因子I（IGF-I）水平呈剂量依赖性增加。然而，血清IGF-I浓度在这四次检测中的时间进程有所不同；未治疗的晚上显著下降（P<0.01），注射2国际单位重组人生长激素后显著增加，在使用4和6国际单位重组人生长激素治疗期间保持恒定水平。血浆葡萄糖水平在正常范围内，未给予生长激素时空腹水平（0400时）显著较低。给予生长激素时早餐可引起血浆葡萄糖升高，但未给予生长激素时则无升高，且餐后血清胰岛素反应呈生长激素剂量依赖性。生长激素治疗可增加血清游离脂肪酸（P<0.05）和血液3-羟基丁酸水平，但对血液丙氨酸或乳酸以及血清甘油三酯和胆固醇水平无影响。我们得出结论，血清IGF-I对生长激素的反应是剂量依赖性的，且每天2国际单位（相当于1.5国际单位/m²·天）的生长激素替代剂量不足以维持正常的昼夜血清IGF-I水平。此外，提示这些患者血清IGF-I存在不依赖生长激素的昼夜变化。这种生长激素制剂还具有致糖尿病和脂解作用。
