生长激素可增加短肠综合征患者的去脂体重和谷氨酰胺可用性：一项辅助性双盲随机交叉研究。

Growth hormone enhances fat-free mass and glutamine availability in patients with short-bowel syndrome: an ancillary double-blind, randomized crossover study.

作者信息

Seguy David, Darmaun Dominique, Duhamel Alain, Thuillier François, Cynober Luc, Cortot Antoine, Gottrand Frédéric, Messing Bernard

机构信息

From the Service de Nutrition Lille, France (DS); the Institut National de la Santé et de la Recherche Médicale, Lille, Unité U995, Université Lille Nord de France, Lille, France (DS and FG); the Département de Biostatistiques, Equipe d'Accueil EA2694, Lille, France (AD); the Centre Hospitalier Régional Universitaire de Lille, Université Lille Nord de France, Lille, France (DS, AD, AC, and FG); the Institut National de la Recherche Agronomique Unité Mixte de Recherche 1280, Centre de Recherche en Nutrition Humaine, Université de Nantes, Nantes, France (DD); the Laboratoire de Biochimie, Centre Hospitalier, Meaux, France (FT); the Service Interhospitalier de Biochimie Cochin, Assistance Publique-Hôpitaux de Paris et Equipe d'Accueil EA4466, Faculté de Pharmacie, Université Paris Descartes, Paris, France (LC); and the Université Paris 7 Denis Diderot, Paris, France (BM).

出版信息

Am J Clin Nutr. 2014 Sep;100(3):850-8. doi: 10.3945/ajcn.113.071845. Epub 2014 Jul 30.

DOI:10.3945/ajcn.113.071845

PMID:25080462

Abstract

BACKGROUND

Benefits of recombinant human growth hormone (rhGH) alone or combined with glutamine in patients with intestinal failure because of short-bowel syndrome remain controversial.

OBJECTIVE

We explored effects of rhGH on whole-body protein metabolism in patients with short-bowel syndrome with intestinal failure (SBS-IF) to gain insight into its mechanism of action.

DESIGN

Eight stable hyperphagic patients with severe SBS-IF received, in a double-blind, randomized crossover study, low-dose rhGH (0.05 mg · kg⁻¹ · d⁻¹) and a placebo for two 3-wk periods. Leucine and glutamine kinetics under fasting and fed conditions, fat-free mass (FFM), and serum insulin were determined on the final day of each treatment.

RESULTS

rhGH increased FFM and nonoxidative leucine disposal (NOLD; an index of protein synthesis) (P < 0.02), whereas FFM and NOLD were correlated in the fed state (r = 0.81, P = 0.015). With rhGH administration, leucine release from protein breakdown (an index of proteolysis) decreased in the fed compared with fasting states (P = 0.012), which was not observed with the placebo. However, the fast-to-fed difference in leucine release from protein breakdown was not significantly different between rhGH and placebo (P = 0.093). With rhGH, the intestinal absorption of leucine and glutamine increased (P = 0.036) and correlated with serum insulin (r = 0.91, P = 0.002). rhGH increased glutamine de novo synthesis (P < 0.02) and plasma concentrations (P < 0.03) in both fasting and fed states.

CONCLUSIONS

In SBS-IF patients, feeding fails to decrease proteolysis in contrast to what is physiologically observed in healthy subjects. rhGH enhances FFM through the stimulation of protein synthesis and might decrease proteolysis in response to feeding. Improvements in de novo synthesis and intestinal absorption increase glutamine availability over the physiologic range, suggesting that beneficial effects of rhGH in hyperphagic patients might be achieved without glutamine supplementation.

摘要

背景

重组人生长激素（rhGH）单独使用或与谷氨酰胺联合使用对短肠综合征所致肠衰竭患者的益处仍存在争议。

目的

我们探讨了rhGH对短肠综合征伴肠衰竭（SBS - IF）患者全身蛋白质代谢的影响，以深入了解其作用机制。

设计

在一项双盲、随机交叉研究中，8例病情稳定、食欲亢进的重度SBS - IF患者接受了两个为期3周的治疗阶段，分别给予低剂量rhGH（0.05 mg·kg⁻¹·d⁻¹）和安慰剂。在每个治疗阶段的最后一天，测定禁食和进食状态下的亮氨酸和谷氨酰胺动力学、去脂体重（FFM）以及血清胰岛素水平。

结果

rhGH增加了FFM和非氧化亮氨酸处置（NOLD；蛋白质合成指标）（P < 0.02），且在进食状态下FFM与NOLD相关（r = 0.81，P = 0.015）。给予rhGH后，与禁食状态相比，进食状态下蛋白质分解产生的亮氨酸释放量（蛋白水解指标）减少（P = 0.012），而给予安慰剂时未观察到这种情况。然而，rhGH组与安慰剂组在进食与禁食状态下蛋白质分解产生的亮氨酸释放量差异无统计学意义（P = 0.093）。使用rhGH后，亮氨酸和谷氨酰胺的肠道吸收增加（P = 0.036），且与血清胰岛素相关（r = 0.91，P = 0.002）。rhGH在禁食和进食状态下均增加了谷氨酰胺的从头合成（P < 0.02）和血浆浓度（P < 0.03）。