INSULIN-RESISTANCE IN CHRONIC HEART-FAILURE - RELATION TO SEVERITY AND ETIOLOGY OF HEART-FAILURE

Objectives. We attempted to assess insulin sensitivity in patients wit h chronic heart failure (CHF) and its relation to disease severity. Ba ckground. Peripheral muscular changes influence the progression of hea rt failure. This effect may be due to chronic disturbances of insulin and glucose metabolism that affect the energy status of skeletal and m yocardial muscle. Methods. We investigated insulin sensitivity in 79 m en-38 patients with CHF, 21 patients with angiographic evidence of cor onary artery disease without CHF and 20 healthy control subjects-and a ssessed its relation to disease severity, etiology and hormonal status (all subjects had a similar age and body mass index). Insulin sensiti vity was estimated by minimal modeling analysis of the glucose and ins ulin and profiles during a 0.5-g/kg body weight intravenous glucose to lerance test. Results. Compared with control subjects, patients with C HF had similar mean fasting glucose but increased insulin levels (67 v s. 29 pmol/liter, p < 0.002) and a 58% reduced mean insulin sensitivit y (2.01 vs. 4.84 min(-1)/pmol/ml x 10(5), p < 0.0001). Peak oxygen con sumption (Vo(2)) (r = 0.63), fasting triglycerides (r = -0.62) and age (r = -0.46, all p < 0.001) predicted insulin sensitivity independentl y. Rest norepinephrine and epinephrine levels, left ventricular ejecti on fraction and heart failure etiology were not related to insulin sen sitivity. Patients with coronary artery disease but no CHF had an inte rmediate 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 C HF due to ischemic heart disease]). In multivariate analyses of all 79 subjects, age (p = 0.0006), triglycerides (p = 0.0023), fasting insul in (p = 0.0037) and the presence of CHF (p = 0.018) were independent p redictors of impaired insulin sensitivity (adjusted joint R-2 = 0.53, p < 0.0001). Conclusions. CHF is associated with marked insulin resist ance, characterized by both fasting and stimulated hyperinsulinemia. A dvanced heart failure (in terms of reduced peak Vo,) is related to inc reased insulin resistance, but this is not directly mediated through v entricular dysfunction or increased catecholamine levels. (C) 1997 by the American College of Cardiology.