Diabetic cardiomyopathy: is resistin a culprit?

Obesity, insulin resistance and their frequent complication of type 2 diabetes mellitus (T2DM) are major risk factors of cardiac dysfunction and heart failure (HF). The epidemic rise, in particular of T2DM, is alarming, especially considering the increased incidence of insulin resistance and diabetes in young adults and children (1,2). Cardiovascular disease, including HF, is the major cause of death in diabetic patients. A prominent contributing factor to HF in these patients is the development of diabetic cardiomyopathy (3)—a clinical myocardial condition distinguished by ventricular dysfunction that occurs independently of coronary artery disease (CAD) and hypertension. However, many diabetes-related comorbidities are now known to adversely affect the heart as diabetes progresses, including coronary atherosclerosis and microangiopathy, hypertension, autonomic dysfunction and neuro-hormonal abnormalities (4,5). The Framingham Heart Study was the first to quantify the increased risk of congestive HF experienced by patients with diabetes. Diabetic men have twice the risk of age-matched controls, and diabetic women experience a fivefold increased risk, which could not be explained by obesity, hyperlipidemia, hypertension or CAD (6). This observation was further confirmed by Rubler et al. who found fibrosis, hypertrophy, remodeling and other evidence of congestive HF in four diabetic patients without clinically significant CAD (3). Subsequently, extensive clinical data supported the concept of a diabetic cardiomyopathy in humans, and animal studies in both type 1 diabetes mellitus (T1DM) and T2DM models also demonstrate cardiac dysfunction worsened by diabetes (7-9). Diabetic cardiomyopathy usually manifests with diastolic dysfunction preceding systolic dysfunction, and has been observed in the context of both T1DM and T2DM. The development of diabetic cardiomyopathy and the cellular and molecular perturbations associated with the pathology are complex and multifactorial (7-9). Although considerable progress has been made, the molecular etiologies of diabetic cardiomyopathy remain poorly understood. Recently, a novel paradigm for the role of adipokines secretion and signaling in cardiac metabolism and function has emerged. Resistin, a newly discovered adipokine, has been proposed to be a link between obesity, insulin resistance and diabetes (10)