Diabetes is a major risk factor for the development of
cardiovascular disease via contributing and/or triggering significant cellular signaling and metabolic and structural alterations at the level of the heart and the whole body. The main cause of mortality and morbidity in diabetic patients is
cardiovascular disease including
diabetic cardiomyopathy. Therefore, understanding how diabetes increases the incidence of
diabetic cardiomyopathy and how it mediates the major perturbations in cell signaling and energy metabolism should help in the development of
therapeutics to prevent these perturbations. One of the significant metabolic alterations in diabetes is a marked increase in cardiac
fatty acid oxidation rates and the domination of
fatty acids as the major energy source in the heart. This increased reliance of the heart on
fatty acids in the diabetic has a negative impact on cardiac function and structure through a number of mechanisms. It also has a detrimental effect on cardiac efficiency and worsens the energy status in diabetes, mainly through inhibiting cardiac
glucose oxidation. Furthermore, accelerated cardiac
fatty acid oxidation rates in diabetes also make the heart more vulnerable to ischemic injury. In this review, we discuss how cardiac energy metabolism is altered in
diabetic cardiomyopathy and the impact of cardiac
insulin resistance on the contribution of
glucose and
fatty acid to overall cardiac
ATP production and cardiac efficiency. Furthermore, how diabetes influences the susceptibility of the myocardium to
ischemia/reperfusion injury and the role of the changes in
glucose and
fatty acid oxidation in mediating these effects are also discussed.