title: The role of inflammation on atherosclerosis, intermediate and clinical cardiovascular endpoints in type 2 diabetes mellitus.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular morbidity and mortality. Sub-clinical systemic inflammation is often present in T2DM patients. Systemic inflammation has also been implicated in the pathophysiology of atherosclerosis. This review investigates the direct evidence present in literature for the effect of inflammation on atherosclerosis, specifically in the setting of T2DM. Special emphasis is given to the pathogenesis of atherosclerosis as well as intermediate and clinical cardiovascular endpoints. The important role of deteriorated endothelial function in T2DM was excluded from the analysis.
  
  
  METHODS
  Extensive literature searches were performed using the PubMed and Web of Science databases. Articles were identified, retrieved and accepted or excluded based on predefined criteria.
  
  
  RESULTS
  Substantial evidence was found for an important inflammatory component in the pathogenesis of atherosclerosis in T2DM, demonstrated by inflammatory changes in plaque characteristics and macrophage infiltration. Most epidemiologic studies found a correlation between inflammation markers and intermediate cardiovascular endpoints, especially intima-media thickness. Several, but not all clinical trials in T2DM found that reducing sub-clinical inflammation had a beneficial effect on intermediate endpoints. When regarding cardiovascular events however, current literature consistently indicates a strong relationship between inflammation and clinical endpoints in subjects with T2DM.
  
  
  CONCLUSIONS
  Current literature provides direct evidence for a contribution of inflammatory responses to the pathogenesis of atherosclerosis in T2DM. The most consistent relation was observed between inflammation and clinical endpoints.
authors.affiliation: Vascular Medicine, Department of General Internal Medicine & Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands. A.Ray@lumc.nl
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authors.initials: A
authors.lastname: Ray
authors.forename: M V
authors.initials: MV
authors.lastname: Huisman
authors.forename: J T
authors.initials: JT
authors.lastname: Tamsma
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authors.lastname: van Asten
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authors.lastname: Bingen
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authors.lastname: Hoogeveen
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authors.initials: VA
authors.lastname: Kwee
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authors.lastname: Laman
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authors.forename: M
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authors.lastname: Mohammadi
authors.forename: M
authors.initials: M
authors.lastname: Nijenhuis
authors.forename: M
authors.initials: M
authors.lastname: Rijkée
authors.forename: M M
authors.initials: MM
authors.lastname: van Tellingen
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authors.lastname: de Vries
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology