DECREASED ABILITY OF HIGH-DENSITY-LIPOPROTEINS TO TRANSFER CHOLESTEROL ESTERS IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Esterified cholesterol transfer (ECT) from high density lipoproteins ( HDL) to very low (VLDL) and low density lipoproteins (LDL) may be abno rmal in situations at high risk for atherosclerosis. It has been shown to increase in insulin-dependent diabetes and to decrease in non-insu lin-dependent diabetes (NIDD). Since the net transfer of esterified ch olesterol (EC) results from a bidirectional exchange between HDL and V LDL/LDL, we developed a transfer assay specifically designed to measur e the unidirectional transfer of EC from HDL to lipid emulsions accord ing to first-order kinetics. Our results show that in NIDD the rate co nstant of HDL-dependent ECT is decreased by 30% by comparison with con trol subjects. Analysis of HDL composition revealed that, in both grou ps, HDL-dependent ECT was positively correlated with the free choleste rol/phospholipid ratio (r=0.94; P<0.001) and negatively correlated wit h the triglyceride/EC ratio (r=-0.85; P<0.001). It is concluded that, besides the known defect of acceptor lipoproteins, the abnormality of ECT in NIDD is also caused by a decreased ability of HDL to act as an EC donor, presumably because of a change in composition. In addition, our work shows that the amount of EC lost by HDL during the reaction t ransfer is counterbalanced by a reciprocal equimolar transfer of trigl ycerides.