ISOLATION, CHARACTERIZATION, AND METABOLISM OF THE GLYCATED AND NONGLYCATED SUBFRACTIONS OF LOW-DENSITY LIPOPROTEINS ISOLATED FROM TYPE-I DIABETIC-PATIENTS AND NONDIABETIC SUBJECTS

The total low-density lipoprotein (LDL) fraction was isolated from 21 patients with type I diabetes and 7 nondiabetic normolipemic subjects. The LDL was separated into two subfractions, one glycated (G-LDL) and one nonglycated (N-LDL), using affinity chromatography. G-LDL comprised 21.1 +/- 3.6 and 5.2 +/- 0.6% of the total LDL in diabetic patients and normal subjects, respectively. G-LDL isolated from both diabetic patients and normal subjects was significantly more glycated than N-LDL isolated from the same subject. G-LDL isolated from both diabetic patients and normal subjects was enriched in triglycerides. The metabolism of N-LDL and G-LDL was investigated in human fibroblasts, which express only the classical LDL receptor, and in human monocyte-derived macrophages, which also express a receptor for G-LDL. In fibroblasts, the rates of receptor-mediated accumulation of N-LDL isolated from normal subjects and diabetic patients were significantly greater (P < 0.01) than those of G-LDL. In contrast, when the same LDL subfractions were incubated with human monocyte-derived macrophages, the rates of receptor-mediated accumulation of G-LDL isolated from both groups were significantly greater (P < 0.01) than those of N-LDL. Rates of degradation of G-LDL by human macrophages were not significantly different hom those of N-LDL during short-term incubations but reached statistical significance (P < 0.05) when LDL subfractions were incubated with cells for 24 h. G-LDL stimulated cholesteryl ester synthesis rates in human macrophages significantly (P < 0.05) more than N-LDL from the same subject and thus may contribute to the increased prevalence of atherosclerosis in diabetic patients.