Alterations in lipid transfers to HDL associated with the presence of coronary artery disease in patients with type 2 diabetes mellitus

Background: We previously showed that unesterified-cholesterol transfer to high-density lipoprotein ( HDL), a crucial step in cholesterol esterification and role in reverse cholesterol transport, was diminished in non-diabetic patients with coronary artery disease ( CAD). The aim was to investigate whether, in patients with type 2 diabetes mellitus ( T2DM), the occurrence of CAD was also associated with alterations in lipid transfers and other parameters of plasma lipid metabolism. Methods: Seventy-nine T2DM with CAD and 76 T2DM without CAD, confirmed by cineangiography, paired for sex, age ( 40-80 years), BMI and without statin use, were studied. In vitro transfer of four lipids to HDL was performed by incubating plasma of each patient with a donor emulsion containing radioactive lipids during 1 h at 37 degrees C. Lipids transferred to HDL were measured after chemical precipitation of non-HDL fractions and the emulsion. Results are expressed as % of total radioactivity of each lipid in HDL. Results: In T2DM + CAD, LDL-cholesterol and apo B were higher than in T2DM. T2DM + CAD also showed diminished transfer to HDL of unesterified cholesterol ( T2DM + CAD = 7.6 +/- 1.2; T2DM = 8.2 +/- 1.5 %, p < 0.01) and of cholesteryl-esters ( 4.0 +/- 0.6 vs 4.3 +/- 0.7, p < 0.01). Unesterified cholesterol in the non-HDL serum fraction was higher in T2DM + CAD ( 0.93 +/- 0.20 vs 0.85 +/- 0.15, p = 0.02) and CETP concentration was diminished ( 2.1 +/- 1.0 vs 2.5 +/- 1.1, p = 0.02). Lecithin-cholesterol acyltransferase activity, HDL size and lipid composition were equal. Conclusion: Reduction in T2DM + CAD of cholesterol transfer to HDL may impair cholesterol esterification and reverse cholesterol transport and altogether with simultaneous increased plasma unesterified cholesterol may facilitate CAD development in T2DM.