In vivo glycated low-density lipoprotein is not more susceptible to oxidation than nonglycated low-density lipoprotein in type 1 diabetes.
It has been suggested that low-density lipoprotein (LDL) modified by glycation may be more susceptible to oxidation and thus, enhance its atherogenicity. Using affinity chromatography, LDL glycated in vivo (G-LDL) and relatively nonglycated. (N-LDL) subfractions can be isolated from the same individual. The extent of and susceptibility to oxidation of N-LDL compared with G-LDL was determined in 15 type 1 diabetic patients. Total LDL was isolated and separated by boronate affinity chromatography into relatively glycated (G-) and nonglycated (N-) subfractions. The extent of glycation, glycoxidation, and lipoxidation, lipid soluble antioxidant content, susceptibility to in vitro oxidation, and nuclear magnetic resonance (NMR)-determined particle size and subclass distribution were determined for each subfraction. Glycation, (fructose-lysine) was higher in G-LDL versus N-LDL, (0.28 +/- 0.08 v 0.13 +/- 0.04 mmol/mol lysine, P < .0001). However, levels of glycoxidation/lipoxidation products and of antioxidants were similar or lower in G-LDL compared with N-LDL and were inversely correlated with fructose-lysine (FL) concentrations in G-LDL, but positively correlated in N-LDL. In vitro LDL (CuCl2) oxidation demonstrated a longer lag time for oxidation of G-LDL than N-LDL (50 +/- 0.16 v 37 +/- 0.15 min, P < .01), but there was no difference in the rate or extent of lipid oxidation, nor in any aspect of protein oxidation. Mean LDL particle size and subclass distribution did not differ between G-LDL and N-LDL. Thus, G-LDL from well-controlled type 1 diabetic patients is not more modified by oxidation, more susceptible to oxidation, or smaller than relatively N-LDL, suggesting alternative factors may contribute to the atherogenicity of LDL from type 1 diabetic patients.
Jenkins
Alicia J
AJ
Division of Endocrinology-Diabetes-Medical Genetics, Medical University of South Carolina, Charleston 29403, USA.
Thorpe
Suzanne R
SR
Alderson
Nathan L
NL
Hermayer
Kathie L
KL
Lyons
Timothy J
TJ
King
Lowrey P
LP
Chassereau
Charlyne N
CN
Klein
Richard L
RL
D000328:Adult; D000975:Antioxidants / Q000737:chemistry; D001786:Blood Glucose / Q000737:chemistry / Q000378:metabolism; D002846:Chromatography, Affinity; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000737:chemistry; D006023:Glycoproteins / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology
D000975:Antioxidants; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D006023:Glycoproteins; D008077:Lipoproteins, LDL