Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn Study.
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.
de Jager
Jolien
J
Department of Internal Medicine, Bethesda General Hospital, Hoogeveen, The Netherlands.
Dekker
Jacqueline M
JM
Kooy
Adriaan
A
Kostense
Piet J
PJ
Nijpels
Giel
G
Heine
Rob J
RJ
Bouter
Lex M
LM
Stehouwer
Coen D A
CD
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
D005947:Glucose