OP3: Oxidized LDL as residual lipid risk marker in type 2 diabetes

Abstract

Previous studies have revealed that the excess of cardiovascular events observed in patients with type 2 diabetes (T2D) and adequate control of low-density lipoprotein cholesterol (LDL) has been explained through the residual lipid risk. The atherogenic potential of diabetes could be associated with the modified proteins as the result of glycation and oxidation. The role of oxidized LDL (oxLDL) as a residual lipid risk marker is still unclarified. The aim of our study was to analyze the levels of oxLDL and their relationship with other standard lipid atherogenic risk factors as well as with insulin resistance (IR) in: T2D patients with coronary artery disease (CAD) (Group A, N=50), T2D patients without CAD (group B, N=45), and nondiabetic patients with CAD (group C, N=50). Patients were aged 40–70 years, matched by gender, duration of diabetes, smoking habit and hypertension. CAD was defined as the presence of any of the following: a) angina, b) myocardial infarction or c) positive angiography. In each patient, oxLDL levels were measured by ELISA methods (Mercodia), glycemic control by the glycated hemoglobin levels (HbA1c, measured by immuno-inhibition). Total cholesterol (TC), HDL and LDL cholesterol and triglycerides (Tg) were determined by enzymatic methods. IR was calculated using homeostatic model assessment insulin resistance (HOMA-IR) index. We found the highest levels of oxLDL in group A, being significantly higher than in groups B and C (A: 112.2±22.0, B: 95.9±10.2, C: 83.9±8. A vs B p<0.05 and A,B vs C p<0.01). We found significantly higher Tg levels in group A compared to group B (A: 3.39 ± 0.4, B: 2.49 ± 0.27 mmol/l, A vs B p<0.01) being significantly higher among diabetics in comparison to nondiabetics (C: 2.12±0.2 mmol/l, A,B vs C p<0.05). Simultaneously, there was no significant difference in the levels of TC, HDL and LDL between the groups. HbA1c level was higher in group A than in group B (A:7.87±0.23, B:6.92±0.13, C:4,9±0.18%; A vs B p<0.05; A, B vs C p<0.01). Similarly, the HOMA-IR values were higher in group A vs group B, and in both of the groups it was higher than in group C (A:10.4±1.4, B:8.5±1.2, C:7.9±0.7; A vs B p<0.01; B vs C p<0.05). In the groups of diabetic patients increased levels of oxLDL significantly correlated with Tg levels (r=0.628, p<0.01), and HOMA–IR (r=0.399, p<0.05) while oxLDL significantly correlated with HbA1c only in group A (r=0.697; p<0.001), but not in groups B and C (p=NS). Our results have demonstrated that in patients with T2D and CAD increased oxLDL levels could be good residual lipid risk marker. Atherogenic potential in T2D is associated predominantly with the increased oxLDL, higher IR and impairments in triglycerides metabolism but not with the levels of lipoproteins. Also, the results imply that in T2D patients LDL oxidation is significantly influenced by the impairments in glucose control.