title: The impact of metabolic syndrome and CRP on vascular phenotype in type 2 diabetes mellitus.
abstract: 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).
  
  
  CONCLUSIONS
  MS and low-grade chronic inflammation have an independent impact on vascular phenotype including IMT in DM2.
authors.affiliation: Vascular Medicine, Department of General Internal Medicine & Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands. R.Alizadehdehnavi@lumc.nl
authors.forename: Reza
authors.initials: R
authors.lastname: Alizadeh Dehnavi
authors.forename: Edith D
authors.initials: ED
authors.lastname: Beishuizen
authors.forename: Marcel A
authors.initials: MA
authors.lastname: van de Ree
authors.forename: Saskia
authors.initials: S
authors.lastname: Le Cessie
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
authors.forename: Cornelis
authors.initials: C
authors.lastname: Kluft
authors.forename: Hans M G
authors.initials: HM
authors.lastname: Princen
authors.forename: Jouke T
authors.initials: JT
authors.lastname: Tamsma
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D019040:E-Selectin / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007249:Inflammation; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D008875:Middle Aged; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D018180:Thrombomodulin / Q000097:blood; D010959:Tissue Plasminogen Activator; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D005340:Fibrinogen; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator