Abstract 4080: Impact of LDL Particle Size on Carotid Intima-Media Thickness in Patients With Type 2 Diabetes Regardless of Medication
Background: Small LDL particles and modifications to LDL such as glycation and oxidation have been linked to the pathogenesis of atherosclerosis in patients with diabetes mellitus. We investigated whether LDL particle size, or the levels of glycated LDL or malondialdehyde-modified LDL (MDA-LDL), one oxidized form of LDL, are associated with carotid intima-media thickness (IMT), a powerful predictor of future cardiovascular disease (CVD) events in patients with type 2 diabetes.
Methods: In this study, 172 patients with type 2 diabetes (age, 66.8±10.3 years) were enrolled. The patients had received antidiabetic treatment (insulin therapy 26, oral antidiabetic agents 49; total 70) and lipid-lowering agents (statins 80, fibrates 5; total 85). We measured carotid IMT using high-resolution ultrasound. We determined LDL particle size using gradient gel electrophoresis, and serum glycated LDL and MDA-LDL levels using sandwich enzyme-linked immunosorbent assays.
Results: The three variables were significantly correlated with one another (LDL particle size and glycated LDL, r=−0.163; LDL particle size and MDA-LDL, r=−0.161; glycated LDL and MDA-LDL, r=0.179; P<0.05 for all). Univariate analyses defined statistically significant correlations of carotid IMT with LDL particle-size, HbA1c, glycated LDL, MDA-LDL, HDL cholesterol, and age. The strongest association of IMT was with LDL particle size (r=−0.406, P<0.0001), followed by that with HDL cholesterol (r=−0.225, P=0.0037). A stepwise multiple logistic regression analysis revealed that LDL particle size and HDL cholesterol are independent predictors of carotid IMT (total R2=0.165). Neither glycated LDL nor MDA-LDL had a significant independent contribution to the severity of carotid IMT in the multivariate model.
Conclusions: LDL particle size, but not the glycated LDL or MDA-LDL level, was independently associated with carotid IMT in patients with type 2 diabetes regardless of antidiabetic and lipid-lowering medication. These results suggest that the measurement of LDL particle size may be more useful than quantification of modified LDLs for assessing the risk of CVD in patients with type 2 diabetes. Small LDL particles may be the most important predictor for the risk of CVD in diabetic patients.