Endothelial dysfunction plays a key role in increasing cardiovascular risk in type 2 diabetes: the Hoorn study.
In the pathogenesis of cardiovascular events, interaction between risk factors has seldom been identified. However, endothelial dysfunction on the one hand and type 2 diabetes mellitus, impaired glucose metabolism (IGM), and insulin resistance on the other may act synergistically (ie, interact) in the development of cardiovascular disease. We therefore investigated the interaction between endothelial dysfunction and type 2 diabetes mellitus, IGM, and insulin resistance with regard to risk of cardiovascular events. In a prospective population-based cohort (n=445; 69 years; 55% women; 23% type 2 diabetes mellitus, 28% IGM [by design]), endothelial dysfunction (brachial artery flow-mediated dilatation), glucose tolerance (oral glucose tolerance test), and insulin sensitivity (homeostasis model assessment for insulin resistance [HOMA2-IR]) were determined. After a median follow-up of 7.6 years, 106 participants had had a cardiovascular event. After adjustments, 1 SD less flow-mediated dilatation was associated with cardiovascular events in type 2 diabetes mellitus (hazard ratio 1.69 [95% confidence interval, 1.14-2.52]) and IGM (1.50 [0.95-2.37]) and among those in the highest HOMA2-IR tertile (1.92 [1.42-2.60]), but not in normal glucose metabolism (0.85 [0.63-1.16]) or among those in the lower 2 HOMA2-IR tertiles combined (0.85 [0.65-1.12]). Interaction between flow-mediated dilatation and type 2 diabetes mellitus, IGM, or insulin resistance was present on an additive (relative excess risk caused by interaction>0) and on a multiplicative scale (P interaction<0.05). Endothelial dysfunction and type 2 diabetes mellitus, IGM, or insulin resistance synergistically increase cardiovascular event risk. This identifies endothelial dysfunction as a key therapeutic target in these individuals.
['van Sloten|Thomas T|TT|', 'Henry|Ronald M A|RM|', 'Dekker|Jacqueline M|JM|', 'Nijpels|Giel|G|', 'Unger|Thomas|T|', 'Schram|Miranda T|MT|', 'Stehouwer|Coen D A|CD|']
D000368:Aged D001786:Blood Glucose D001916:Brachial Artery D002318:Cardiovascular Diseases D003924:Diabetes Mellitus, Type 2 D004730:Endothelium, Vascular D005260:Female D005500:Follow-Up Studies D006801:Humans D015994:Incidence D007333:Insulin Resistance D008297:Male D009426:Netherlands D011159:Population Surveillance D011446:Prospective Studies D012307:Risk Factors D013997:Time Factors D014655:Vascular Resistance D014664:Vasodilation
type 2 diabetes mellitus insulin resistance cardiovascular diseases endothelium epidemiology prospective studies