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Effect of Glycemic Optimization on Electronegative Low-Density Lipoprotein in Diabetes: Relation to Nonenzymatic Glycosylation and Oxidative Modification¹

Departments of Biochemistry (J.L.S.-Q., S.B., J.O.-L.) and Endocrinology and Nutrition (A.P., A.C., M.R.), Hospital de la Santa Creu i Sant Pau, and Department of Biochemistry and Molecular Biology (J.O.-L.), Universitat Autónoma de Barcelona, Barcelona 08025, Spain

Address correspondence and requests for reprints to: Jordi Ordóñez-Llanos, M.D., Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, C/. Antoni María Claret 167, Barcelona 08025, Spain. E-mail: 2038{at}hsp santpau.es.

Abstract

The effect of insulin therapy on low-density lipoprotein (LDL) oxidizability, proportion of electronegative LDL [LDL(-)] and LDL composition was studied in 33 type 2 diabetic patients. Before glycemic control improvement, type 2 diabetic subjects presented higher triglyceride and very low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol than 25 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), contained 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 phopholipids. Lipoprotein profile improved after glycemic optimization but failed to change either LDL oxidizability (45.3 ± 6.2 min) or LDL(-) (17.9 ± 8.2%). These data suggest that oxidation rather than nonenzymatic glycosylation could be related to the high LDL(-) found in these patients and disagree 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%) decreased 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 observed on LDL(-) (from 17.3 ± 2.9% to 16.0 ± 4.3%). We conclude that nonenzymatic glycosylation, which appears as a determinant of the high proportion of LDL(-) in type 1 diabetes, does not play a major role in LDL(-) generation in type 2 diabetes.

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