Glucolipotoxicity and the Heart

Abstract

e. th ec li ni cs .c om Insulin resistance (IR) and type 2 diabetes mellitus are widely prevalent throughout the world and have reached epidemic proportions in both genders and in people of all racial and ethnic groups. IR has a metabolically complex and as yet incompletely understood etiology. Major driving forces for the rise of IR include obesity, sedentary lifestyle, excess caloric intake, and cigarette smoking, all of which have risen globally in prevalence. IR and diabetes mellitus (DM) increase the risk for all forms of atherosclerotic disease, heart failure, stroke, and microangiopathy, including proliferative retinopathy, nephropathy, and peripheral neuropathy. With over 340 million diabetic patients in the world, it is anticipated that this will result in a catastrophic rise in adult-onset blindness, end-stage renal disease, and need for dialysis, lower extremity amputation, as well as cardiovascular morbidity and premature mortality. Approximately 78% of diabetic patients will die of complications stemming from cardiovascular disease (CVD). The human, social, and economic costs of these clinical sequelae require urgent recognition and intervention. It has recently been estimated that up to twothirds of patients who present with myocardial infarction have either impaired glucose tolerance or DM. IR is frequently encountered in cardiology practice and it is important for cardiologists to have an indepth understanding of how IR adversely impacts cardiac structure, function, and metabolism. The term “glucolipotoxicity” is an apt descriptor for the overarching metabolic changes induced by IR. In this setting, systemic tissues do not internalize glucose appropriately in response to