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

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.