Effect of glycemic optimization on electronegative low-density lipoproteinin diabetes: Relation to nonenzymatic glycosylation and oxidative modification

The effect of insulin therapy on low-density lipoprotein (LDL) oxidizabilit y, proportion of electronegative LDL [LDL(-)] and LDL composition was studi ed in 33 type 2 diabetic patients. Before glycemic control improvement, typ e 2 diabetic subjects presented higher triglyceride and very low-density li poprotein cholesterol and lower high-density lipoprotein cholesterol than 2 5 healthy matched subjects. Furthermore, their LDL was more susceptible to oxidation (lag phase 45.9 +/- 5.4 min vs. 49.7 +/- 7.6 min, P < 0.05), cont ained a higher proportion of LDL(-) (19.0 +/- 8.7% vs. 14.3 +/- 5.5%, P < 0 .05), and was enriched in triglyceride and depleted in cholesterol and phop holipids. Lipoprotein profile improved after glycemic optimization but fail ed to change either LDL oxidizability (45.3 +/- 6.2 min) or LDL(-) (17.9 +/ - 8.2%). These data suggest that oxidation rather than nonenzymatic glycosy lation could be related to the high LDL(-) found in these patients and disa gree with results obtained in a previous study of type 1 diabetic patients. A second study was conducted in 10 type 1 and 10 type 2 diabetic subjects under insulin therapy, and the proportions of glycated LDL (gLDL) and LDL(- ) were determined. Basal gLDL (2.8 +/- 0.6%) and LDL(-) (20.7 +/- 6.1%) dec reased in type 1 diabetics after glycemic optimization (1.9 +/- 0.6% and 15 .4 +/- 3.4%, respectively; P < 0.05). In type 2 patients, even though gLDL decreased (from 2.2 +/- 0.6% to 1.6 +/- 0.6%, P < 0.05) no effect was obser ved on LDL(-) (from 17.3 +/- 2.9% to 16.0 +/- 4.3%). We conclude that nonen zymatic glycosylation, which appears as a determinant of the high proportio n of LDL(-) in type 1 diabetes, does not play a major role in LDL(-) genera tion in type 2 diabetes.