Myocardial metabolism in diabetic cardiomyopathy: potential therapeutic targets.

SIGNIFICANCE: Cardiovascular complications in diabetes are particularly serious and represent the primary cause of morbidity and mortality in diabetic patients. Despite early observations of cardiac dysfunction in diabetic humans, cardiomyopathy unique to diabetes has only recently been recognized. RECENT ADVANCES: Research has focused on understanding the pathogenic mechanisms underlying the initiation and development of diabetic cardiomyopathy. Emerging data highlight the importance of altered mitochondrial function as a major contributor to cardiac dysfunction in diabetes. Mitochondrial dysfunction occurs by several mechanisms involving altered cardiac substrate metabolism, lipotoxicity, impaired cardiac insulin and glucose homeostasis, impaired cellular and mitochondrial calcium handling, oxidative stress, and mitochondrial uncoupling. CRITICAL ISSUES: Currently, treatment is not specifically tailored for diabetic patients with cardiac dysfunction. Given the multifactorial development and progression of diabetic cardiomyopathy, traditional treatments such as anti-diabetic agents, as well as cellular and mitochondrial fatty acid uptake inhibitors aimed at shifting the balance of cardiac metabolism from utilizing fat to glucose may not adequately target all aspects of this condition. Thus, an alternative treatment such as resveratrol, which targets multiple facets of diabetes, may represent a safe and promising supplement to currently recommended clinical therapy and lifestyle changes. FUTURE DIRECTIONS: Elucidation of the mechanisms underlying the initiation and progression of diabetic cardiomyopathy is essential for development of effective and targeted treatment strategies. Of particular interest is the investigation of alternative therapies such as resveratrol, which can function as both preventative and mitigating agents in the management of diabetic cardiomyopathy.