Metabolic Therapy for Patients with Diabetes Mellitus and Coronary Artery Disease

Patients with diabetes mellitus and ischemic heart disease more frequently develop heart failure and have a greater amount of myocardial ischemia, often silent, compared with patients without diabetes. Furthermore, patients with coronary artery disease (CAD) and diabetes or insulin resistance have altered myocardial metabolism and accelerated and diffuse atherogenesis with involvement of distal coronary segments that causes chronic hypoperfusion and hibernation. Therefore, in patients with diabetes and CAD, the ischemic metabolic changes are heightened by the metabolic changes in patients with diabetes. An important metabolic alteration in patients with diabetes is the increase in free fatty acid (FFA) concentrations and the increased skeletal muscle and myocardial FFA uptake and oxidation. The increased uptake and utilization of FFA and the reduced utilization of glucose as a source of energy during stress and ischemia contribute to the increased susceptibility of diabetic hearts to myocardial ischemia and to a greater decrease of myocardial performance for a given amount of ischemia compared with nondiabetic hearts. A therapeutic approach aimed at an improvement in cardiac metabolism through manipulations of the use of metabolic substrates should result in an improvement in myocardial ischemia and left ventricular (LV) function. The inhibition of FFA oxidation with trimetazidine improves cardiac metabolism at rest, increases cardiac resistance to ischemia, and therefore reduces the decrease of LV function caused by chronic hypoperfusion and repetitive episodes of myocardial ischemia in patients with and without diabetes. Thus, modulation of myocardial FFA metabolism should be the key target for metabolic interventions in patients with CAD with and without diabetes. In patients with diabetes, the effects of modulation of FFA metabolism should be even greater compared with those observed in patients without diabetes. Because of its effect on cardiac metabolism at rest and its effects on myocardial ischemia and LV function, trimetazidine should always be considered for the treatment of patients with diabetes with CAD with or without LV dysfunction.