Insulin resistance and progression of heart failure in the older adult

Abstract

Heart failure is a disease of advancing age. Despite the advent of effective therapies, the overall outcome among the elderly has not been altered significantly. Aging is also associated with whole body and myocardial insulin resistance. Insulin resistance is accompanied by increased sympathetic nervous system activation and increased nonesterified fatty acid (NEFA) uptake in excess of NEFA oxidation, leading to NEFA accumulation within cardiac myocytes and mitochondria. Myocardial mitochondria demonstrate increased reactive oxygen species and calcium sequestration and decreased protein expression leading to impaired energetic reserves. Although these alterations in myocardial mitochondrial function lead to an accelerated course of heart failure, these changes can be modified and protect against exacerbation of heart failure. In particular, glucagon-like peptide-1, a naturally occurring incretin, has been shown to improve left ventricular ejection fraction and functional status in patients. Further investigation must be pursued for this promising novel therapeutic target for heart failure.