Glycosylated low density lipoprotein is more sensitive to oxidation: implications for the diabetic patient?

Abstract

Oxidised low density lipoprotein (LDL) is considered to be atherogenic. This study examined the relationship between glycosylation and oxidation of LDL from 10 normocholesterolaemic Type 2 diabetic patients, 10 hypercholesterolaemic Type 2 diabetic patients, and 10 normocholesterolaemic non-diabetic subjects. LDL was isolated by sequential ultracentrifugation and susceptibility to oxidation assessed by measuring thiobarbituric reactive substances (TBARS) during a 4-h oxidation period. LDL glycosylation was measured by aminophenylborate gel chromatography. Results demonstrated an increased susceptibility to oxidation in LDL from both diabetic groups, the mean 3-h TBARS values being 35.2 ± 2.1 and 36.4 ± 2.6 nmol MDA/mg LDL protein for normocholesterolaemic and hypercholesterolaemic diabetic patients compared with 24.5 ± 2.5 nmol MDA/mg LDL protein for control subjects. LDL glycosylation of 2.20% ± 0.11% and 2.89% ± 0.46% for normocholesterolaemic and hypercholesterolaemic diabetic LDL was significantly higher than that for the non-diabetic control subjects of 1.60% ± 0.12%, ( P < 0.02). There was a significant positive correlation ( P < 0.005) between LDL glycosylation and LDL oxidation. The esterified/free cholesterol ratio which correlated positively with oxidation ( P < 0.01) was significantly higher in LDL from both diabetic groups compared with LDL from control subjects ( P < 0.01). Thus the increased incidence of atherosclerosis in diabetes may be related to glycosylation of LDL through its increased susceptibility to oxidation.