Impaired serum capacity to induce cholesterol efflux is associated with endothelial dysfunction in type 2 diabetes mellitus

Objective: Reverse cholesterol transport (RCT) plays a protective role against atherosclerosis and cholesterol efflux from cells is an early step in the RCT pathway. We investigated whether the capacity of serum to induce cholesterol efflux was associated with endothelial dysfunction in type 2 diabetes. Methods: Endothelium-dependent and-independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound and serum cholesterol efflux capacity was determined by measuring the transfer of [3H] cholesterol from Fu5AH cells to serum in 137 patients with type 2 diabetes and 75 controls. Results: Serum cholesterol efflux capacity was lower in diabetic patients than in the controls (13.6+/-2.5% vs. 14.6+/-3.4%, respectively, p=0.02), and both endothelium-dependent vasodilation (4.9+/-2.2% vs. 8.8+/-4.1%, respectively, p<0.01) and endothelium-independent vasodilation were impaired (13.4+/-4.3% vs. 16.3+/-5.5%. respectively, p<0.01). Endothelium-dependent vasodilation correlated with serum cholesterol efflux capacity (r=0.26, p=0.003) in diabetic patients and controls (r=0.24, p=0.037). On general linear model analysis, the presence of diabetes, brachial artery diameter and serum cholesterol efflux capacity were significant independent determinants of endothelium-dependent vasodilation. Conclusion: Impaired serum cholesterol efflux capacity was associated with endothelial dysfunction independent of other cardiovascular risk factors.