The authors of a study published in the May 1, 2006 issue of the journal Arteriosclerosis, Thrombosis and Vascular Biology estimate that 43 percent of the increased cardiovascular mortality that occurs with type 2 diabetes (T2D) is due to inflammation and endothelial dysfunction, rather than conventional cardiovascular risk factors such as hypertension, obesity and disordered lipids.

Researchers in the Netherlands evaluated 631 participants in the Hoorn study, a study of glucose tolerance and cardiovascular disease in men and women aged 50 to 75. Subjects were examined upon enrollment and followed up for an average of 11.7 years during which the cause of any deaths was ascertained. Blood samples were tested for markers of endothelial dysfunction and low-grade inflammation as well as homocysteine, cholesterol, and triglycerides. Additionally, data on blood pressure, weight, height, smoking status, glucose tolerance and other factors was obtained. Participants were classified as having normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes.

Low-grade inflammation was associated with both type 2 diabetes and impaired glucose metabolism, while endothelial dysfunction was associated only with diabetes. Over the follow-up period, low-grade inflammation increased the risk of cardiovascular mortality by 43 percent. Among diabetics, the presence of endothelial dysfunction was associated with an 87 percent higher risk of cardiovascular mortality compared to those without the condition.

"T2D-associated endothelial dysfunction and low-grade inflammation can explain approximately 43% of the higher cardiovascular mortality risk conferred by T2D," the authors conclude. "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 in T2D, for which endothelial dysfunction is particularly ominous and for which both endothelial dysfunction and low-grade inflammation are highly prevalent."