Background: In chronic heart failure (CHF) skeletal muscle insulin resistance occurs independently of etiology and contributes to impaired energy metabolism. GLUT4, the predominant glucose transporter in the skeletal muscle promotes the rate-limiting step of glucose utilization in skeletal muscle. The significance of skeletal muscle GLUT4 in patients with CHF has not been studied in detail. Methods: In patients with CHF and free of diabetes mellitus (n = 29; mean NYHA class 2.3 ± 0.1, peak VO2 18.8 ± 1.1 mL/kg/min) and healthy control subjects of similar age (n = 7), GLUT4 protein was assessed from percutaneous skeletal muscle biopsies. Skeletal muscle insulin sensitivity was assessed by intravenous glucose tolerance testing using a minimal modeling technique. Body composition was analyzed by dual energy X-ray absorptiometry (DEXA) scanning. Results: Skeletal muscle GLUT4 was lower in CHF patients than in controls (0.75 ± 0.07 vs 1.24 ± 0.19 density units, P <0.01) and decreased in parallel to severity of CHF, being lowest in NYHA III/IV (0.596 ± 0.08, ANOVA P <0.01 vs controls). GLUT4 was lower in patients with an ischemic etiology compared to dilated cardiomyopathy and controls (ANOVA P <0.01). Patients and controls were similar for global parameters of body composition (weight: 78 ± 4 vs 76 ± 4 kg, BMI 25.5 ± 0.8 vs 25.8 ± 1.5 kg/m2), and total tissue amount and regional distribution of fat and lean tissue (all P > 0.2). Low GLUT4 predicted impaired insulin sensitivity, i.e. insulin resistance (r = 0.55, P <0.01). In multivariate analysis, GLUT4 levels predicted insulin sensitivity independently of age and parameters of body composition (including weight, BMI, and total and regional fat and lean tissue distribution). Conclusion: In non-diabetic patients with CHF, skeletal muscle GLUT4 transport protein is reduced in parallel to disease severity, independently of body composition. Low skeletal muscle GLUT4 contributes to insulin resistance in CHF.
- Chronic heart failure
- Insulin resistance
- Skeletal muscle
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine