Insulin Resistance: A New Target in Heart Failure

There is increasing evidence of a reciprocal interrelationship between chronic heart failure (CHF) and insulin resistance (IR). Studies have shown that patients with CHF have IR and that the degree of IR is associated with reduced exercise capacity and peak oxygen consumption (VO2).

IR has also been linked to decreased exercise capacity in patients with diabetes mellitus and other chronic disease states, as well as in healthy subjects confirming that IR is independently linked to exercise intolerance studies have shown that IR is pathophysiologically linked with CHF and is implicated in the disease progression in CHF. This is likely because IR is associated with endothelial dysfunction, inflammation, increased oxidative stress and myocardial remodelling; processes that accelerate the progression of disease in CHF. Therefore, the IR has now emerged as a potential target for intervention in improving the symptoms and outcome in patients with CHF.

However, there are still some key unanswered questions. Firstly, what is the prevalence of IR in the cohort of CHF patients in Tayside? Previous studies outside the UK examining prevalence of IR in CHF were conducted in the pre-B-blocker era. However, B-blockers, which may worsen metabolic control, are now widely used in the treatment of CHF. It is likely that the prevalence might be higher in our present cohort of patients with CHF. Secondly, what are the potential contributory factors to IR in CHF?The exact mechanisms of IR in CHF are not known. Sympathetic over-activity in CHF can acutely reduce insulin sensitivity and it also decreases the release of insulin from the pancreatic beta cells, and increases hepatic glucose production. Other mediators include cytokines and adiponectin and leptin. The loss of skeletal muscle bulk and impaired endothelial function with reduced skeletal muscle blood flow may also contribute to IR in CHF. Determining the relative importance of these various factors may help identify therapeutic strategies in overcoming IR in CHF. Finally, what is the mechanism for the impaired exercise capacity and reduced peak VO2 in CHF? Exercise VO2 measures the total body's oxygen consumption which reflects both cardiac output and peripheral utilization of oxygen. We do not know whether the problem is due to a worsening of the reduced cardiac output in CHF and/or decreased peripheral utilization. To determine this, we plan to measure the cardiac output at the same as the measurement of VO2.

The aims and objectives of the study are:

Primary objectives