Increased Lipid Peroxidation in LDL from Type-2 Diabetic Patients

Increased oxidative stress is associated with type-2 diabetes and related cardiovascular diseases, but oxidative modification of LDL has been partially characterized. Our aim was to compare the lipid and fatty acid composition as well as the redox status of LDL from diabetic patients and healthy subjects. First, to ensure that isolation of LDL by sequential ultracentrifugation did not result in lipid modifications, lipid composition and peroxide content were determined in LDL isolated either by ultracentrifugation or fast-protein liquid chromatography. Both methods resulted in similar concentrations of lipids, fatty acids, hydroxy-octadecadienoic acid (HODE) and malondialdehyde (MDA). Then, LDLs were isolated by ultracentrifugation from eight type-2 diabetic patients and eight control subjects. Compared to control LDL, diabetic LDL contained decreased cholesteryl esters and increased triglyceride concentrations. Ethanolamine plasmalogens decreased by 49%. Proportions of linoleic acid decreased in all lipid classes, while proportions of arachidonic acid increased in cholesteryl esters. Total HODE concentrations increased by 56%, 12- and 15-hydroxy-eicosatetraenoic acid by 161 and 86%, respectively, and MDA levels increased by twofold. α-Tocopherol concentrations, expressed relative to triglycerides, were lower in LDL from patients compared to controls, while γ-tocopherol did not differ. Overall, LDL from type-2 diabetic patients displayed increased oxidative stress. Determination of hydroxylated fatty acids and ethanolamine plasmalogen depletion could be especially relevant in diabetes.