Effect of Irbesartan on Insulin Sensitivity in Chronic Heart Failure

• Insulin sensitivity assessment using intravenous glucose tolerance testing [ Time Frame: 3 months ]
  

• Assessment of body composition using dual energy x-ray absorptiometry [ Time Frame: 3 months ]
  
• Assessment of exercise capacity on a treadmill including respiratory gas analysis [ Time Frame: 3 months ]
  

Drug: Irbesartan
up-titration over 4 weeks to target dose 300 mg od

In CHF impaired insulin sensitivity is a common finding characterised by elevated fasting insulin levels and impaired effectiveness of insulin to utilise glucose in peripheral tissues, mainly in skeletal muscle tissue. Additionally, impaired insulin sensitivity, i.e. insulin resistance, progresses in parallel to severity of CHF and relates to major clinical symptoms such as reduced exercise capacity and muscle fatigue. In survival analyses, insulin resistance is a significant predictor of mortality, independently of and additionally to other established prognostic markers such as age, NYHA class, peak oxygen consumption, or LVEF. These findings indicate that insulin resistance is involved in CHF pathophysiology. Importantly, insulin resistance in CHF occurs independently of ischemic etiology. In ischaemic heart disease, however, insulin resistance as part of the metabolic syndrome is also an important prerequisite for the development of arteriosclerosis. Accordingly insulin resistance was found worst in CHF patients with ischemic etiology compared to patients with CHF due to dilated cardiomyopathy and those with ischaemic heart disease without heart failure. On the basis of these findings we hypothesise that therapeutically improving insulin sensitivity may have additional beneficial effects on energy utilisation and therefore improve clinical symptoms such as reduced exercise capacity and muscle fatigue.