Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure
J W Swan1, S D Anker, C Walton
1Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College, London, England, United Kingdom.
Insights
Chronic heart failure (CHF) is linked to significant insulin resistance, with impaired insulin sensitivity correlating with reduced peak oxygen consumption. This suggests metabolic disturbances contribute to heart failure progression.
Area of Science:
- Cardiology
- Metabolic Medicine
- Physiology
Background:
- Peripheral muscular changes in heart failure progression may stem from disturbed insulin and glucose metabolism.
- These metabolic disturbances can impact the energy status of skeletal and myocardial muscle.
Purpose of the Study:
- To assess insulin sensitivity in patients with chronic heart failure (CHF).
- To investigate the relationship between insulin sensitivity and CHF severity, etiology, and hormonal status.
Main Methods:
- Insulin sensitivity was evaluated in 79 men (38 with CHF, 21 with coronary artery disease without CHF, 20 healthy controls) using minimal modeling analysis of glucose and insulin profiles during an intravenous glucose tolerance test.
- Relationships between insulin sensitivity and clinical parameters (peak oxygen consumption, fasting triglycerides, age, hormonal status, left ventricular ejection fraction) were assessed.
Main Results:
- Patients with CHF exhibited significantly reduced insulin sensitivity (58% lower) and higher fasting insulin levels compared to controls.
- Peak oxygen consumption, fasting triglycerides, and age independently predicted insulin sensitivity.
- In multivariate analyses, age, triglycerides, fasting insulin, and the presence of CHF were independent predictors of impaired insulin sensitivity.
Conclusions:
- Chronic heart failure is associated with marked insulin resistance, including hyperinsulinemia.
- Advanced heart failure, indicated by reduced peak oxygen consumption, correlates with increased insulin resistance.
- Ventricular dysfunction or elevated catecholamine levels do not appear to be the direct mediators of this insulin resistance.
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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