Parsonage William, Hetmanski David, Cowley Alan
University of Nottingham, Nottingham, United Kingdom.
Am J Cardiol. 2002 Mar 15;89(6):696-703. doi: 10.1016/s0002-9149(01)02342-6.
Chronic heart failure (HF) is associated with insulin resistance. Putative mechanisms of insulin resistance are abnormal skeletal muscle blood flow and antagonism of insulin action due to sympathetic nervous system activation. We measured insulin sensitivity, the vasoactive properties of insulin, and the association between insulin resistance and markers of neurohormonal activation in 10 patients with chronic HF and in 9 healthy controls. Noninvasive hemodynamic measurements and an hyperinsulinemic, euglycemic clamp were used. Patients were insulin resistant compared with the controls (p <0.05 for area under insulin dose-response curve). Insulin infusion led to a selective increase in forearm blood flow accompanied by a decrease in mean arterial pressure and superior mesenteric blood flow. Heart rate decreased in patients but not in controls; however, when baseline measurements were controlled for, there was no difference in the overall hemodynamic response to insulin infusion between the study groups. In univariate analysis, age, serum creatinine, fasting insulin, and triglyceride levels correlated inversely with insulin sensitivity (p <0.05 for all). Cardiac output had a significant correlation with insulin sensitivity (p <0.05). On stepwise multiple linear regression analysis, only age and fasting plasma insulin emerged as significant predictors of insulin sensitivity (R(2) 0.613, p = 0.001). In particular, we found no evidence of a relation between insulin sensitivity and plasma noradrenaline. Patients with chronic HF exhibit significant metabolic insulin resistance. Insulin resistance is not secondary to failure of insulin-mediated vasodilatation or sympathetic nervous system activation and is likely due to abnormalities at the level of the skeletal myocyte.
慢性心力衰竭（HF）与胰岛素抵抗相关。胰岛素抵抗的可能机制是骨骼肌血流异常以及交感神经系统激活导致的胰岛素作用拮抗。我们在10例慢性HF患者和9例健康对照者中测量了胰岛素敏感性、胰岛素的血管活性特性以及胰岛素抵抗与神经激素激活标志物之间的关联。采用了非侵入性血流动力学测量和高胰岛素-正葡萄糖钳夹技术。与对照组相比，患者存在胰岛素抵抗（胰岛素剂量-反应曲线下面积，p<0.05）。输注胰岛素导致前臂血流选择性增加，同时平均动脉压和肠系膜上动脉血流减少。患者的心率下降，而对照组未下降；然而，在对基线测量进行校正后，研究组之间对胰岛素输注的总体血流动力学反应没有差异。在单变量分析中，年龄、血清肌酐、空腹胰岛素和甘油三酯水平与胰岛素敏感性呈负相关（均p<0.05）。心输出量与胰岛素敏感性显著相关（p<0.05）。在逐步多元线性回归分析中，只有年龄和空腹血浆胰岛素是胰岛素敏感性的显著预测因子（R² 0.613，p = 0.001）。特别是，我们没有发现胰岛素敏感性与血浆去甲肾上腺素之间存在关联的证据。慢性HF患者表现出显著的代谢性胰岛素抵抗。胰岛素抵抗并非继发于胰岛素介导的血管舒张功能衰竭或交感神经系统激活，可能是由于骨骼肌细胞水平的异常所致。
