title: Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn Study.
abstract: OBJECTIVE
  The mechanisms responsible for the increased cardiovascular disease risk that accompanies type 2 diabetes (T2D) remain poorly understood. It is commonly held that endothelial dysfunction and low-grade inflammation can explain, at least in part, why deteriorating glucose tolerance is associated with cardiovascular disease. However, there is no direct evidence for this contention.
  
  
  RESULTS
  In this population-based study (n=631), T2D was cross-sectionally associated with both endothelial dysfunction and low-grade inflammation, whereas impaired glucose metabolism (IGM) was associated only with low-grade inflammation. These findings were independent of other risk factors that accompany T2D or IGM. During a follow-up of 11.7 years (median; range 0.5 to 13.2 years), low-grade inflammation was associated with a greater risk of cardiovascular mortality (hazard ratio, 1.43 [95% CI, 1.17 to 1.77] per 1 SD difference). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic (hazard ratio, 1.87 [95% CI, 1.43 to 2.45]) than in nondiabetic individuals (hazard ratio, 1.23 [95% CI, 0.86 to 1.75]; P interaction=0.06). Finally, T2D-associated endothelial dysfunction and low-grade inflammation explained approximately 43% of the increase in cardiovascular mortality risk conferred by T2D.
  
  
  CONCLUSIONS
  These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially for T2D patients.
authors.affiliation: Department of Internal Medicine, Bethesda General Hospital, Hoogeveen, The Netherlands.
authors.forename: Jolien
authors.initials: J
authors.lastname: de Jager
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
authors.forename: Adriaan
authors.initials: A
authors.lastname: Kooy
authors.forename: Piet J
authors.initials: PJ
authors.lastname: Kostense
authors.forename: Giel
authors.initials: G
authors.lastname: Nijpels
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Heine
authors.forename: Lex M
authors.initials: LM
authors.lastname: Bouter
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000382:microbiology*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000401:mortality*; D004730:Endothelium, Vascular / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D005947:Glucose