Relationship between carotid atherosclerosis and erythrocyte membrane cholesterol oxidation products in type 2 diabetic patients

Abstract 

Oxidative stress is well known to play a critical role in atherosclerosis. This study investigated an appropriate marker of in vivo oxidative stress and whether it could predict macroangiopathy in diabetes. The lipid composition of erythrocyte membranes was analyzed in 64 type 2 diabetic patients using gas chromatography–mass spectrometry (GC/MS). After 3,5,7-cholestatriene (a cholesterol oxidation product) was detected, the peak height ratio of 3,5,7-cholestatriene to cholesterol was calculated. Carotid artery intima-media thickness (IMT) was measured to evaluate atherosclerosis. The IMT was independently associated with 3,5,7-cholestatriene (P<0.0001), age (P=0.0001), and HbA_1c (P=0.05) by stepwise multiple regression analysis (R²=0.416, P<0.0001). When the subjects were divided into groups with or without carotid atherosclerosis, the 3,5,7-cholestatriene level was significantly higher in 37 subjects with atherosclerosis than in 27 subjects without it (0.41±0.22 vs. 0.16±0.16%, P<0.0001). Among 38 subjects with no clinical manifestations of macroangiopathy and long-term good glycemic control, the 3,5,7-cholestatriene level was also significantly higher in the patients with carotid atherosclerosis than in those without it (0.40±0.20 vs. 0.18±0.12%, P=0.0003). These data suggest that the 3,5,7-cholestatriene level in erythrocyte membrane lipids may be a useful predictor of subclinical atherosclerosis.

Keywords: Atherosclerosis, Oxidative stress, Cholesterol, Erythrocytes, Gas chromatography–mass spectrometry