Endothelial Dysfunction and Low-Grade Inflammation Explain Much of the Excess Cardiovascular Mortality in Individuals With Type 2 Diabetes

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. Methods and 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 w... Endothelial dysfunction and low-grade inflammation may explain, at least in part, the increased cardiovascular disease risk in type 2 diabetes (T2D). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic than in nondiabetic individuals (P interaction=0.06). T2D-associated endothelial dysfunction and low-grade inflammation explained ≈43% of the increase in cardiovascular mortality risk conferred by T2D.