Simvastatin and bezafibrate increase cholesterol efflux in men with type 2 diabetes

BackgroundThe importance of functional properties of high-density lipoproteins (HDL) for atheroprotection is increasingly recognized. We determined the impact of lipid-lowering therapy on 3 key HDL functionalities in Type 2 diabetes mellitus (T2DM). Materials and methodsA placebo-controlled, randomized cross-over study (three 8-week treatment periods with simvastatin (40mg daily), bezafibrate (400mg daily), alone and in combination) was carried out in 14 men with T2DM. Cholesterol efflux was determined using human THP-1 monocyte-derived macrophages, HDL antioxidative capacity was measured as inhibition of low-density lipoprotein oxidation in vitro, and HDL anti-inflammatory capacity was assessed as suppression of thrombin-induced monocyte chemotactic protein 1 expression in human umbilical vein endothelial cells. Pre--HDL was assayed using crossed immunoelectrophoresis. ResultsWhile cholesterol efflux increased in response to simvatatin, bezafibrate and combination treatment (+12 to +23%; anova, P=0001), HDL antioxidative capacity (P=023) and HDL anti-inflammatory capacity (P=015) did not change significantly. Averaged changes in cellular cholesterol efflux during active treatment were correlated positively with changes in HDL cholesterol, apoA-I and pre--HDL (P<005 to P<0001). There were no inter-relationships between changes in the three HDL functionalities during treatment (P>010). Changes in HDL antioxidative capacity and anti-inflammatory capacity were also unrelated to changes in HDL cholesterol and apoA-I, while changes in HDL antioxidative capacity were related inversely to pre--HDL (P<005). ConclusionSimvastatin and bezafibrate increase cholesterol efflux, parallel to HDL cholesterol and apoA-I responses. The antioxidative and anti-inflammatory properties of HDL are not to an important extent affected by these therapeutic interventions.