Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria

Journal of Diabetes and its Complications, Elsevier, ISSN 1873-460X

Volume 30, 2, 2016

DOI:10.1016/j.jdiacomp.2015.11.005, Dimensions: pub.1043010171, PMID: 26651261,



  1. (1) Steno Diabetes Center, grid.419658.7, Capital Region
  2. (2) Maastricht University Medical Centre, grid.412966.e
  3. (3) Rigshospitalet, grid.475435.4, Capital Region
  4. (4) University of Copenhagen, grid.5254.6, KU
  5. (5) Aarhus University, grid.7048.b, AU







BACKGROUND: We evaluated markers of inflammation and endothelial dysfunction and their associations with incident cardiovascular disease (CVD), all-cause mortality and progression of coronary artery calcium (CAC) in patients with type 2 diabetes (T2D) and microalbuminuria but without known coronary artery disease (CAD). METHODS: Prospective study including 200 patients receiving multifactorial treatment. Markers of inflammation (TNF-ɑ, sICAM-1, sICAM-3, hsCRP, SAA, IL-1β, IL-6, IL-8) and endothelial dysfunction (thrombomodulin, sVCAM-1, sICAM-1, sICAM-3, sE-selectin, sP-selectin) were measured at baseline. Adjustment included traditional CVD risk factors, and full adjustment additionally NT-proBNP and CAC. The "SQRT method" assessed CAC progression after 5.8years, and cut-point was an annualised difference >2.5. RESULTS: Occurrence of CVD (n=40) and all-cause mortality (n=26) was traced after 6.1years. In adjusted and fully adjusted Cox models, TNF-ɑ was a determinant of CVD and all-cause mortality (p≤0.007). Further, in adjusted and fully adjusted logistic regression, TNF-ɑ was related to CAC progression (p≤0.042). Of the other biomarkers, sICAM-3 and thrombomodulin were also associated with both endpoints (p≤0.046), IL-1β with CVD endpoints (p=0.021), and sVCAM-1 and sICAM-1 with all-cause mortality (p≤0.005). Higher composite z-scores including all markers of inflammation and endothelial dysfunction were associated with CVD and all-cause mortality (p≤0.008). CONCLUSIONS: In patients with T2D and microalbuminuria without known CAD and receiving multifactorial treatment, biomarkers of inflammation and endothelial dysfunction were independently associated with CVD, all-cause mortality and CAC progression. Especially TNF-ɑ was a robust determinant, even after adjusting for NT-proBNP and CAC.

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Times Cited: 35

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