Effects of Losartan on Insulin Resistance in Patients With Heart Failure

Chronic heart failure (CHF) is associated with marked insulin resistance, characterized by both fasting and stimulated hyperinsulinemia. Furthermore, insulin resistance is a predictor of CHF and associated with more severe disease and a worse prognosis in patients with CHF. In CHF patients, therefore, insulin resistance is not merely a function of adiposity and may have implications in the pathophysiology of CHF disease progression. Angiotensin II negatively modulates insulin-mediated actions by regulating multiple levels of the insulin signaling cascade such as the insulin receptor, IRS, and PI3-kinase. Furthermore, both ACE inhibitors and angiotensin II receptor blockers (ARB) improve glycemic status not only in patients with type II diabetes but also in patients with hypertension and the metabolic syndrome. On the other hand, it is well known that some cytokines, such as TNF-α, are involved with pathophysiology of insulin resistance and CHF. However, it is still unclear whether the ARB improves insulin resistance in CHF patients already treated with ACE inhibitors and whether there is the relationship between insulin resistance and inflammatory cytokines in CHF patients already treated with ACE inhibitors. Therefore, the purpose of this study is to evaluate the effects of losartan, an ARB, on glucose metabolism and inflammatory cytokines in CHF patients treated with ACE inhibitors.