慢性心力衰竭患者全身蛋白质周转、肌肉代谢及代谢激素水平的异常

Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure.

作者信息

Nørrelund H, Wiggers H, Halbirk M, Frystyk J, Flyvbjerg A, Bøtker H E, Schmitz O, Jørgensen J O L, Christiansen J S, Møller N

机构信息

Medical Department M (Endocrinology and Diabetes), Aarhus Universitets-Hospital, Aarhus, Denmark.

出版信息

J Intern Med. 2006 Jul;260(1):11-21. doi: 10.1111/j.1365-2796.2006.01663.x.

DOI:10.1111/j.1365-2796.2006.01663.x

PMID:16789974

Abstract

OBJECTIVE

It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism.

DESIGN

We studied eight nondiabetic patients with CHF (ejection fraction 30 +/- 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise.

RESULTS

Our data confirm that CHF patients have a decreased lean body mass. CHF patients are characterised by (i) decreased glucose oxidation [glucose oxidation (mg kg(-1) min(-1)): 1.25 +/- 0.09 (patients) vs. 1.55 +/- 0.09 (controls), P < 0.01] and muscle glucose uptake [a - v diff(glucose) (micromol L(-1)): -10 +/- 25 (patients) vs. 70 +/- 22 (controls), P < 0.01], (ii) elevated levels of free fatty acids (FFA) [FFA (mmol L(-1)): 0.72 +/- 0.05 (patients) vs. 0.48 +/- 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and signs of elevated fat oxidation and muscle fat utilization [a - v diff(FFA) (mmol L(-1)): 0.12 +/- 0.02 (patients) vs. 0.05 +/- 0.01 (controls), P < 0.05] and (iii) elevated protein turnover and protein breakdown [phenylalanine flux (micromol kg(-1) h(-1)): 36.4 +/- 1.5 (patients) vs. 29.6 +/- 1.3 (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise.

CONCLUSIONS

In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention.

摘要

目的

众所周知，慢性心力衰竭（CHF）与胰岛素抵抗和恶病质有关，但对其潜在的底物代谢了解甚少。本研究旨在确定基础葡萄糖、脂质和蛋白质代谢的紊乱情况。

设计

我们研究了8例非糖尿病CHF患者（射血分数30±4%）和8例健康对照者。采用同位素分析法测定蛋白质代谢（全身和局部肌肉通量）和总葡萄糖周转率。通过间接测热法获得底物氧化情况。通过自行车测力计运动研究运动的代谢反应。

结果

我们的数据证实CHF患者的瘦体重降低。CHF患者的特征为：（i）葡萄糖氧化减少[葡萄糖氧化（mg·kg⁻¹·min⁻¹）：1.25±0.09（患者）对1.55±0.09（对照），P<0.01]和肌肉葡萄糖摄取减少[a-v葡萄糖差值（μmol·L⁻¹）：-10±25（患者）对70±22（对照），P<0.01]；（ii）游离脂肪酸（FFA）水平升高[FFA（mmol·L⁻¹）：0.72±0.05（患者）对0.48±0.03（对照），P<0.01]以及3-羟基丁酸水平升高，且脂肪氧化和肌肉脂肪利用增加的迹象[a-v FFA差值（mmol·L⁻¹）：0.12±0.02（患者）对0.05±0.01（对照），P<0.05]；（iii）蛋白质周转率和蛋白质分解增加[苯丙氨酸通量（μmol·kg⁻¹·h⁻¹）：36.4±1.5（患者）对29.6±1.3（对照），P<0.01]。患者循环中的去甲肾上腺素、胰高血糖素和脂联素水平较高，而胃饥饿素水平较低。在短期运动期间，我们未观察到对照者和患者之间的代谢反应有任何差异。