title: C-reactive protein and incident diabetes in patients with arterial disease.
abstract: BACKGROUND
  Systemic low-grade inflammation, as measured by high-sensitive C-reactive protein (hsCRP), may contribute to the risk of type 2 diabetes in patients with manifest arterial disease.
  
  
  METHODS
  Cohort study in 4072 patients with manifest arterial disease without diabetes. The relation between quartiles of hsCRP and type 2 diabetes was assessed with Cox regression analyses, taking age, smoking and blood pressure-lowering medication and lipid-lowering medication into account. Insulin resistance was estimated with homeostasis model of insulin resistance (HOMA-IR). In exploratory models, adjustments were performed for body mass index (BMI) and visceral and subcutaneous adipose tissue thickness.
  
  
  RESULTS
  During a median follow-up of 5·0 (IQR 2·5-8·2) years, 288 subjects developed diabetes. High hsCRP was independently associated with incident diabetes (Q4 vs. Q1 males: HR 1·62; 95% CI 1·06-2·48; females: HR 3·12; 95% CI 1·57-6·21). HOMA-IR at baseline is related to hsCRP plasma levels (Q4 vs. Q1: males: β 0·27; 95% CI 0·19-0·36; females: β 0·35; 95% CI 0·22-0·48). The risk of diabetes associated with hsCRP was abolished in males (Q4 vs. 1 HR 1·23; 95% CI 0·80-1·88) and attenuated in females (Q4 vs. 1 HR 2·32; 95% CI 1·14-4·75) after adding BMI to the model, but not modified by statin use (P for interaction: 0·61).
  
  
  CONCLUSIONS
  Patients with manifest arterial disease with high hsCRP plasma levels are at increased risk to develop type 2 diabetes and are more insulin resistant as compared to those with low hsCRP levels. This increase in risk is more pronounced in females than in males and is not modified by statin use.
authors.affiliation: Department of Vascular Medicine, University Medical Centre Utrecht (UMC Utrecht), Utrecht, The Netherlands.
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Verhagen
authors.forename: Annemarie M J
authors.initials: AM
authors.lastname: Wassink
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D017544:Aortic Aneurysm, Abdominal / Q000209:etiology; D001158:Arteries; D002097:C-Reactive Protein / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000209:etiology; D003327:Coronary Disease / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000209:etiology; D011446:Prospective Studies; D012307:Risk Factors; D014652:Vascular Diseases / Q000150:complications*
chemical_list: D002097:C-Reactive Protein
keywords: HsCRP; inflammation; insulin resistance; manifest vascular disease; obesity; type 2 diabetes