Composition of LDL as determinant of its susceptibility to in vitro oxidation in patients with well-controlled type 2 diabetes.

Abstract

There is increasing evidence that oxidation of low-density lipoprotein (LDL) in the vascular wall plays an important role in the development of atherosclerosis. The present study was undertaken to characterise how different constituents of LDL contribute to its in vitro oxidisability. The LDL composition, i.e. lipids, antioxidants, fatty acids, plasmenylcholines, and baseline level of conjugated dienes (CD) of 94 well-controlled and normolipidaemic type 2 diabetic patients was measured. Two oxidisability indices were determined: the lag time, reflecting the resistance of LDL to copper-induced oxidation, and the amount of conjugated dienes formed during oxidation of LDL. The lag time was not related to the total level of saturated, monounsaturated, and polyunsaturated fatty acids, but a strong inverse relationship was observed with fatty acids with three or more double bonds (r = -0.56, p < 0.001). In addition, an inverse relation was observed between the lag time and LDL-plasmenylcholine (r = -0.35, p < 0.001). Although not related to lag time in univariate analysis, alpha-tocopherol was a significant determinant in multiple regression analysis. A multiple linear regression model with LDL polyunsaturated fatty acids with three or more double bonds, alpha-tocopherol, monounsaturated fatty acids, and plasmenylcholines as determinants explained 47% of the variation in lag time. CD production was negatively correlated to oleic acid and positively to linoleic acid (r = -0.45 and r = 0.73, respectively; p<0.001). Fatty acids with three or more double bonds were the most important predictor of LDL lag time, whereas oleic acid and linoleic acid were major determinants of the amount of CD formed during oxidation of LDL.