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在I型(胰岛素依赖型)糖尿病患者中,使用生长抑素抑制内源性生长激素分泌后外源性生长激素的半衰期。

Half-life of exogenous growth hormone following suppression of endogenous growth hormone secretion with somatostatin in type I (insulin-dependent) diabetes mellitus.

作者信息

Mullis P E, Pal B R, Matthews D R, Hindmarsh P C, Phillips P E, Dunger D B

机构信息

Department of Paediatrics, John Radcliffe Hospital, Oxford, UK.

出版信息

Clin Endocrinol (Oxf). 1992 Mar;36(3):255-63. doi: 10.1111/j.1365-2265.1992.tb01441.x.

Abstract

OBJECTIVE

To estimate the half-life of growth hormone in young adult patients with type I (insulin-dependent) diabetes mellitus following bolus injection and prolonged exposure for the purpose of deconvolution analysis of plasma growth hormone profiles to determine growth hormone secretory rates.

DESIGN

In the bolus study, an intravenous bolus injection of 100 mU of biosynthetic human growth hormone was given while endogenous growth hormone was suppressed by a continuous infusion of somatostatin under three different glucose clamp conditions: normoglycaemia (5 mmol/l) with normoinsulinaemia (65 pmol/l); hyperglycaemia (12 mmol/l) with normoinsulinaemia; and normoglycaemia with hyperinsulinaemia (360 pmol/l). In the infusion study, the effect of prolonged and repeated growth hormone exposure upon the growth hormone half-life was estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two hours apart under euglycaemic somatostatin suppression were applied.

PATIENTS

Six young adult patients with type I (insulin-dependent) diabetes mellitus were studied in both the bolus and the infusion study.

RESULTS

Mean GH half-lives by mono-exponential analysis were not significantly different remaining unaltered by the short-term metabolic changes of hyperglycaemia and hyperinsulinaemia. Data were therefore pooled yielding an overall mean GH half-life of 13.6 minutes (range 11.9-19.4). Applying a bi-exponential model mean GH half-lives were 3.1 minutes (range 2.5-5.9) for the rapid phase of distribution of the hormone and 13.8 minutes (range 9.6-16.9) for the decay of GH from the circulation. The GH half-life during the infusions studies did not vary with repeated exposure but was significantly longer (mean half-life of 25.7 minutes; range 19.4-37.1) than during the bolus studies (P less than 0.001).

CONCLUSIONS

The half-life of exogenous r-hGH is not affected by glucose or insulin concentrations but increases after prolonged GH exposure in young adults with type I (insulin-dependent) diabetes mellitus.

摘要

目的

估计I型(胰岛素依赖型)糖尿病青年成年患者静脉推注生长激素并长时间暴露后的半衰期,以便对血浆生长激素谱进行去卷积分析,从而确定生长激素分泌率。

设计

在推注研究中,在三种不同的葡萄糖钳夹条件下,通过持续输注生长抑素抑制内源性生长激素的同时,静脉推注100 mU生物合成人生长激素:正常血糖(5 mmol/l)伴正常胰岛素血症(65 pmol/l);高血糖(12 mmol/l)伴正常胰岛素血症;正常血糖伴高胰岛素血症(360 pmol/l)。在输注研究中,评估生长激素长时间重复暴露对其半衰期的影响。在正常血糖且生长抑素抑制的情况下,每隔两小时进行三次60分钟的生长激素输注脉冲(6 mU/kg/脉冲)。

患者

六名I型(胰岛素依赖型)糖尿病青年成年患者参与了推注研究和输注研究。

结果

通过单指数分析得出的平均生长激素半衰期无显著差异,不受高血糖和高胰岛素血症短期代谢变化的影响。因此,将数据合并后得出总体平均生长激素半衰期为13.6分钟(范围11.9 - 19.4)。应用双指数模型,激素快速分布阶段的平均生长激素半衰期为3.1分钟(范围2.5 - 5.9),生长激素从循环中衰减阶段的半衰期为13.8分钟(范围9.6 - 16.9)。输注研究期间的生长激素半衰期不会因重复暴露而变化,但明显长于推注研究期间(平均半衰期为25.7分钟;范围为19.4 - 37.1)(P < 0.001)。

结论

外源性重组人生长激素的半衰期不受葡萄糖或胰岛素浓度的影响,但在I型(胰岛素依赖型)糖尿病青年成年患者中,生长激素长时间暴露后半衰期会延长。

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