The impact of metabolic syndrome and CRP on vascular phenotype in type 2 diabetes mellitus.

Background: The burden of cardiovascular disease in diabetes mellitus type 2 (DM2) patients is variable. We hypothesize that metabolic syndrome (MS) and low-grade systemic inflammation modify the extent of atherosclerosis in DM2.

Methods: Vascular phenotype was determined using the following endothelium-related, hemostatic, and sonographic endpoints in 62 DM2 patients with mild dyslipidemia: sVCAM, sE-selectin, von Willebrand factor (VWF), fibrinogen, s-thrombomodulin (sTM), tPA, PAI-1, flow-mediated dilation (FMD), and intima media thickness (IMT). The impact of MS load (number of criteria present), MS components, and CRP on these parameters was assessed.

Results: Serum sVCAM, sTM, and tPA levels significantly increased with increasing MS load. IMT also significantly increased from 0.602+/-0.034 (one MS criterion) to 0.843+/-0.145 (four MS criteria, p=0.007). LogCRP significantly correlated with fibrinogen, PAI-1, and IMT. In a multiple regression (MR) model with age and gender as covariates, MS load predicted sVCAM and sTM; CRP predicted PAI-1 and fibrinogen; MS load and CRP simultaneously predicted tPA and IMT. For each MS criterion present, IMT significantly increased by 0.04 mm. An increase in CRP from 1 to 3 mg/L resulted in a significant increase of 0.04 mm. Patients with four MS criteria and inflammation (CRP >or=3 mg/L) are predicted to have a 0.21 mm thicker IMT than those without. A second stepwise MR analysis based on gender, traditional risk factors, diabetes-related parameters, renal function, individual MS criteria, and LogCRP as explanatory variables showed a significant effect of systolic and diastolic blood pressure, HDL, and LogCRP on IMT(r(2)=0.36, p<0.001).

Conclusion: MS and low-grade chronic inflammation have an independent impact on vascular phenotype including IMT in DM2.