PLASMA-LIPOPROTEINS FROM PATIENTS WITH POORLY CONTROLLED DIABETES-MELLITUS AND IN-VITRO GLYCATION OF LIPOPROTEINS ENHANCE THE TRANSFER RATEOF CHOLESTERYL ESTER FROM HDL TO APO-B-CONTAINING LIPOPROTEINS

Alterations in the reverse cholesterol transport system have been desc ribed in diabetic mellitus patients in several but not all studies. Fu rthermore, recently published investigations suggest that a faster ''i n vitro'' transfer rate of cholesteryl ester from high density lipopro teins to apoB-containing lipoproteins could be solely ascribed to vari ation of the plasma lipoprotein composition and concentration in the d iabetic state, The present study analysed the influence of lipoprotein glycation on the cholesteryl ester transfer protein-mediated transfer of esterified cholesterol from high density lipoprotein and its subfr actions to lighter density lipoproteins. For this purpose two sets of ''in vitro'' experiments were carried out utilizing:1) plasma lipoprot eins drawn from diabetic and from normal subjects and; 2) normal lipop roteins or partially purified cholesteryl ester transfer protein submi tted to ''in vitro'' glycation. The transfer rate of C-14-cholesteryl ester labelled HDL subfractions to low or very low density lipoprotein s was measured in all experiments. After incubations with plasma d > 1 .21 g/ml or with purified cholesteryl eater transfer protein, apoB-con taining lipoproteins were precipitated with a dextran sulfate/MgCl2 so lution. The ''in vitro'' glycation of the partially purified cholester yl ester transfer protein markedly impaired its activity. However, gre ater transfer rates were observed when lipoproteins from diabetic indi viduals or the ''in vitro'' glycated lipoproteins were utilized. This effect was attributed to glycation of the protein component of HDL. In conclusion, lipoprotein glycation elicits an enrichment of the apoB-c ontaining lipoproteins with cholesteryl ester that is likely related t o the premature atherosclerosis in patients with poorly controlled dia betes.