Lack of concordance between plasma markers of cardiovascular risk and intima-media thickness in patients with type 2 diabetes

Aim: Endothelial dysfunction, oxidative stress and systemic inflammation play an important role in the enhanced cardiovascular risk in diabetes. Carotid intima-media thickness (IMT), a widely accepted marker of subclinical atherosclerosis, is known to be increased in patients with type 2 diabetes. The relationships between plasma markers of cardiac risk and carotid IMT are not well known. We therefore studied a group of patients with type 2 diabetes to evaluate the relationships between plasma markers of cardiac risk and carotid IMT. Design and patients: We measured carotid IMT and the levels of soluble endothelial adhesion molecules [sE-selectin, intercellular cell adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1)], C-reactive protein (CRP) and 8-isoprostane in 40 patients with type 2 diabetes without clinical macrovascular complications (HbA(1c) < 10%, duration of diabetes < 12 years) and 25 healthy subjects. We then examined the correlations between these plasma markers, carotid IMT and various clinical and biochemical parameters. Results: Diabetic patients had higher plasma sE-selectin (p = 0.03), sICAM-1 (p = 0.05), CRP (p = 0.047) and 8-isoprostane (p = 0.001) concentrations than control subjects. Mean IMT values were identical (0.63 +/- 0.02 mm) in diabetic (range, 0.40-0.92 mm) and healthy subjects (range, 0.45-0.85 mm). In diabetic patients, stepwise multivariate analysis showed that HbA(1c) and plasma glucose were independent predictors of sE-selectin (r(2) = 0.19 and r(2) = 0.17, p < 0.01, respectively), whereas waist circumference and body mass index (BMI) were predictors of sICAM-1 (r(2) = 0.27, p = 0.001 and r(2) = 0.22, p = 0.002, respectively). Waist circumference was the only predictor of CRP (r(2) = 0.2, p < 0.01), and systolic blood pressure was the only predictor of 8-isoprostane (r(2) = 0.19, p = 0.006). In control subjects, similar analysis showed that plasma glucose and waist circumference were predictors of sE-selectin and sICAM-1, respectively (r(2) = 0.2, p < 0.05). Conclusions: These results indicate that some well-controlled type 2 diabetic patients free of clinical macrovascular complications have elevated plasma markers of cardiovascular risk without having increased IMT. The elevation of plasma markers of endothelial cell activation (sE-selectin and s-ICAM-1) or inflammation (CRP) and oxidative stress (8-isoprostane) in diabetics vs. controls is distinct from and cannot be explained simply by differences in the burden of atherosclerosis as assessed by carotid IMT.