短期给予低剂量重组人生长激素对肥胖症和库欣综合征患者胰岛素样生长因子-I水平的影响：对生长激素敏感性的间接评估

Effects of short-term administration of low-dose rhGH on IGF-I levels in obesity and Cushing's syndrome: indirect evaluation of sensitivity to GH.

作者信息

Maccario M, Tassone F, Gauna C, Oleandri S E, Aimaretti G, Procopio M, Grottoli S, Pflaum C D, Strasburger C J, Ghigo E

机构信息

Division of Endocrinology, Department of Internal Medicine, University of Turin, Italy.

出版信息

Eur J Endocrinol. 2001 Mar;144(3):251-6. doi: 10.1530/eje.0.1440251.

DOI:10.1530/eje.0.1440251

PMID:11248744

Abstract

OBJECTIVE

To verify the hypothesis of an increased sensitivity to GH in obesity (OB) and Cushing's syndrome (CS).

DESIGN

We studied the effects of short-term administration of low-dose rhGH on circulating IGF-I levels in patients with simple OB or CS and in normal subjects (NS).

METHODS

Nineteen women with abdominal OB aged (mean +/- s.e.m.) 38.2+/-3.1 years, body mass index 40.7+/-2.5 kg/m(2), waist to hip ratio 0.86+/-0.02, ten with CS (50.4+/-4.2 years, 29.7 +/- 3.3 kg/m(2)) and 11 NS (35.0+/-3.6 years, 20.5+/-0.5 kg/m(2)) underwent s.c. administration of 5 microg/kg per day rhGH at 2200 h for four days. Serum IGF-I, IGF-binding protein-3 (IGFBP-3), GH-binding protein (GHBP), insulin and glucose levels were determined at baseline and 12 h after the first and the last rhGH administration.

RESULTS

Basal IGF-I levels in NS (239.3+/-22.9 microg/l) were similar to those in OB (181.5+/-13.7 microg/l) and CS (229.0+/-29.1 microg/l). Basal IGFBP-3, GHBP and glucose levels in NS, OB and CS were similar while insulin levels in NS were lower (P<0.01) than those in OB and CS. In NS, the low rhGH dose induced a sustained rise of IGF-I levels (279.0+/-19.5 microg/l, P<0.001), a non-significant IGFBP-3 increase and no change in GHBP, insulin and glucose levels. In OB and CS, the IGF-I response to rhGH showed progressive increase (246.2+/-17.2 and 311.0+/-30.4 microg/l respectively, P<0.01 vs baseline). Adjusting by ANCOVA for basal values, rhGH-induced IGF-I levels in CS (299.4 microg/l) were higher than in OB (279.1 microg/l, P<0.01), which, in turn, were higher (P<0.05) than in NS (257.7 microg/l). In OB, but not in CS, IGFBP-3 and insulin levels showed slight but significant (P<0.05) increases during rhGH treatment, which did not modify glucose levels in any group; thus, in the OB patient group a significant fall in glucose/insulin ratio was observed.

CONCLUSIONS

Short-term treatment with low-dose rhGH has enhanced stimulatory effect on IGF-I levels in OB and, particularly, in hypercortisolemic patients. These findings support the hypothesis that hyperinsulinism and hypercortisolism enhance the sensitivity to GH in humans.

摘要

目的

验证肥胖（OB）和库欣综合征（CS）患者对生长激素（GH）敏感性增加的假说。

设计

我们研究了短期给予低剂量重组人生长激素（rhGH）对单纯性OB患者、CS患者及正常受试者（NS）循环中胰岛素样生长因子-I（IGF-I）水平的影响。

方法

19名腹部肥胖女性，年龄（均值±标准误）为38.2±3.1岁，体重指数40.7±2.5kg/m²，腰臀比0.86±0.02；10名CS患者（50.4±4.2岁，29.7±3.3kg/m²）；11名NS（35.0±3.6岁，20.5±0.5kg/m²）。于22:00皮下注射5μg/kg每日的rhGH，共4天。在基线时以及首次和末次rhGH给药后12小时测定血清IGF-I、胰岛素样生长因子结合蛋白-3（IGFBP-3）、生长激素结合蛋白（GHBP）、胰岛素和葡萄糖水平。

结果

NS组的基础IGF-I水平（239.3±22.9μg/l）与OB组（181.5±13.7μg/l）和CS组（229.0±29.1μg/l）相似。NS组、OB组和CS组的基础IGFBP-3、GHBP和葡萄糖水平相似，而NS组的胰岛素水平低于OB组和CS组（P<0.01）。在NS组，低剂量rhGH导致IGF-I水平持续升高（279.0±19.5μg/l，P<0.001），IGFBP-3有不显著升高，GHBP、胰岛素和葡萄糖水平无变化。在OB组和CS组，对rhGH的IGF-I反应呈逐渐增加（分别为246.2±17.2和311.0±30.4μg/l，与基线相比P<0.01）。经协方差分析校正基础值后，CS组rhGH诱导的IGF-I水平（299.4μg/l）高于OB组（279.1μg/l，P<0.01），而OB组又高于NS组（257.7μg/l，P<0.05）。在OB组而非CS组，rhGH治疗期间IGFBP-3和胰岛素水平有轻微但显著（P<0.05）升高，各组葡萄糖水平均未改变；因此，在OB患者组观察到葡萄糖/胰岛素比值显著下降。