Persons with type 2 diabetes develop diffuse atherosclerosis and consequent organ damage. In patients with atherosclerotic disease as well as in patients with type 2 diabetes there is an increased production and increased blood levels of the cytokine TNF-?. In the surroundings of atherosclerotic plaques there is accumulation of TNF- ?, especially around culprit lesions. Atherosclerotic plaques are attached to the endothelium, which is the innermost layer of the vessels. Among other functions the endothelium helps to maintain a relaxed vascular tone by producing nitric oxide (NO). It has been shown that TNF-? impairs the intracellular signal that is initiated when insulin binds to its receptors, what results in insulin resistance. Since one of the endpoints of the insulin signal in endothelial cells is the activation of eNOS, that catalyzes NO production, it is reasonable to believe that TNF-? has a substantial role in the development of atherosclerosis in insulin-resistant states. The purpose of the studies described in this book is to contribute to the clarification of this role.

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