Effect of glycemic optimization on electronegative low-density lipoprotein in diabetes: relation to nonenzymatic glycosylation and oxidative modification.
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.
Sánchez-Quesada
J L
JL
Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Barcelona 08025, Spain.
Pérez
A
A
Caixàs
A
A
Rigla
M
M
Payés
A
A
Benítez
S
S
Ordóñez-Llanos
J
J
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004563:Electrochemistry; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006031:Glycosylation; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D006442:Glycated Hemoglobin; D007328:Insulin; D008077:Lipoproteins, LDL; D014280:Triglycerides