Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure

Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College, London, England, United Kingdom.

OBJECTIVES: We attempted to assess insulin sensitivity in patients with chronic heart failure (CHF) and its relation to disease severity. BACKGROUND: Peripheral muscular changes influence the progression of heart failure. This effect may be due to chronic disturbances of insulin and glucose metabolism that affect the energy status of skeletal and myocardial muscle. METHODS: We investigated insulin sensitivity in 79 men-38 patients with CHF, 21 patients with angiographic evidence of coronary artery disease without CHF and 20 healthy control subjects-and assessed its relation to disease severity, etiology and hormonal status (all subjects had a similar age and body mass index). Insulin sensitivity was estimated by minimal modeling analysis of the glucose and insulin and profiles during a 0.5 g/kg body weight intravenous glucose tolerance test. RESULTS: Compared with control subjects, patients with CHF had similar mean fasting glucose but increased insulin levels (67 vs. 29 pmol/liter, p < 0.002) and a 58% reduced mean insulin sensitivity (2.01 vs. 4.84 min-1/pmol/ml x 10(5), p < 0.0001). Peak oxygen consumption (VO2) (r = 0.63), fasting triglycerides (r = -0.62) and age (r = -0.46, all p < 0.001) predicted insulin sensitivity independently. Rest norepinephrine and epinephrine levels, left ventricular ejection fraction and heart failure etiology were not related to insulin sensitivity. Patients with coronary artery disease but no CHF had an intermediate mean insulin sensitivity (3.30 min-1/pmol/ml x 10(5) [-32%, p = 0.042 vs. control subjects; +113%, p = 0.0023 vs. patients with CHF due to ischemic heart disease]). In multivariate analyses of all 79 subjects, age (p = 0.0006), triglycerides (p = 0.0023), fasting insulin (p = 0.0037) and the presence of CHF (p = 0.018) were independent predictors of impaired insulin sensitivity (adjusted joint R2 = 0.53, p < 0.0001). CONCLUSIONS: CHF is associated with marked insulin resistance, characterized by both fasting and stimulated hyperinsulinemia. Advanced heart failure (in terms of reduced peak VO2) is related to increased insulin resistance, but this is not directly mediated through ventricular dysfunction or increased catecholamine levels.

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				J. A. Houmard, D. S. O'Neill, D. Zheng, M. S. Hickey, and G. L. Dohm Impact of hyperinsulinemia on myosin heavy chain gene regulation J Appl Physiol, June 1, 1999; 86(6): 1828 - 1832. [Abstract] [Full Text] [PDF]

				S. D. Anker and M. Rauchhaus Heart failure as a metabolic problem Eur J Heart Fail, June 1, 1999; 1(2): 127 - 131. [Abstract] [Full Text] [PDF]

				J. Niebauer, C.-D. Pflaum, A. L. Clark, C. J. Strasburger, J. Hooper, P. A. Poole-Wilson, A. J. S. Coats, and S. D. Anker Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation J. Am. Coll. Cardiol., August 1, 1998; 32(2): 393 - 397. [Abstract] [Full Text] [PDF]

				P. Dreifuss, S. D. Anker, and A. J.S. Coats Growth Hormone in Chronic Heart Failure • Response Circulation, April 28, 1998; 97(16): 1650 - 1651. [Full Text] [PDF]