A. M. Hetherton

Irish endocrine society

LDL oxidation has been implicated as an important atherogenic factor. We have previously shown that the LDL estetified/free cholesterol ratio is different in diabetes. This study examines the effect ofLDL glycosylation on the susceptibility of LDL to in vitro oxidation. In particular it examines whether there is a relationship between LDL cholesterol esterification, LDL glycosylation and the susceptibility to oxidation. LDL was isolated by sequential ultracentrifugation from normoc holesternlaemic (n=l 0, serum cholesterol 5.30-+0.18mmol/ 1 ) and hypercholesterolaemic diabetic patients(n=7 serum cholesterol 7.18_+0.2mmol/1) and normocholesterolaemic control subjects (n=10, serum cholesterol 5.14_+0.28mmo1/1). LDL glycosylation was determined using aminophenylborate gel chromatography and LDL composition was determined. The susceptibility of LDL to oxidation in the presence of CuS04 was assessed by measuring thiobarbituric reactive substances (TBARS) LDL from the hypercholesterolaemic diabetic patients was more rapidly oxidised, TBARS at 1, 2, 3 and 4 hours being 12.6+3.7, 24.5+3.3, 38.4+2.3, and 40.0_+2.1 nmol/mg LDL protein compared with 4.8_+0.6,16.0+2.5, 24.5+9.5, and 32.4+2.1 for LDL from control subjects (p<0.05). Oxidation of LDL from the normocholeslerolaemic diabetic patients of 6.3_+0.7, 18.4=[_,0.3, 34.0+2.4 and 37.2+2.1, nmol/mg LDL protein, was also significantly greater than that from controls (p<0.05). The esterified/free cholesterol ratio correlated positively with the susceptibility of the LDL to oxidation (p<0.05) which was also related positively to the degree of LDL glycosylation (p<0.01). These results suggest a mechanism which would account for the increased accumulation of cholesterol in the atherosclerotic plaque of the normocholesterolaemic diabetic patient.