Insulin Resistance in Chronic Heart Failure

Abstract

Insulin resistance is an important risk factor for the development of hypertension, atherosclerotic heart disease, left ventricular hypertrophy and dysfunction, and heart failure. It reflects a disturbance of glucose metabolism and potentially worsens metabolic efficiency of both skeletal muscle and cardiac muscle. The exact mechanisms of insulin resistance are not known, but the finding of significant insulin resistance occurring as a consequence of heart failure raises interesting possibilities as to its pathogenesis. While sympathetic nervous system overactivity can acutely reduce insulin sensitivity, it is not clear to what extent, in stable optimally treated chronic heart failure (CHF), the neurohormonal overactivity of this syndrome is the major cause of insulin resistance. Other potential mechanisms include the loss of skeletal muscle bulk, impaired endothelial function and reduced skeletal muscle blood flow, and a possible direct action of proinflammatory cytokines such as tumour necrosis factor-alpha. The consequences of insulin resistance in heart failure are not known, but the severity of the abnormality appears to parallel symptomatics and exercise limitation in this condition, and, in particular, be related to the impairment of gross skeletal muscle function. While specific therapies to correct insulin resistance in CHF have not been evaluated, there are several exciting possibilities on the horizon. Several nonpharmacological therapies have been shown to increase insulin sensitivity in patients with normal left ventricular function, and if these benefits could be duplicated in CHF, they may offer symptomatic benefit. These include weight reduction in the obese, regular exercise training and the use of dietary manipulation such as low-fat, high-fibre diets. Drug treatments with positive effects on insulin sensitivity include some angiotensin converting enzyme-inhibitors as well as newer drug groups, such as the glitazones and moxonidine, a centrally active agent with effects on the recently described imidazoline I-1 receptor that inhibits central sympathetic tone. The role of these agents in reversing the insulin resistance of chronic heart failure warrants further investigation.