Evaluating the metabolic approach to treatment of diabetic coronary patients

Diabetic patients with coronary artery disease have an altered myocardial metabolism of glucose and free fatty acids (FFA) and accelerated and diffuse atherogenesis with involvement of peripheral coronary segments that causes chronic hypoperfusion and hibernation. Therefore, in coronary diabetic patients the ischaemic metabolic changes that occur as a consequence of the mismatch between blood supply and cardiac metabolic requirements are heightened by the diabetic metabolic alterations. Important metabolic alterations in diabetic patients are the decreased utilization of glucose and the increase in muscular and myocardial FFA uptake and oxidation. These metabolic changes are responsible for the increased susceptibility of the diabetic heart to myocardial ischaemia and to a greater decrease of myocardial performance for a given amount of ischaemia compared to non diabetic hearts. A therapeutic approach aimed at an improvement of cardiac metabolism through manipulations of the utilization of metabolic substrates should result in an improvement of myocardial ischaemia and of left ventricular function. The inhibition of FFA oxidation improves cardiac metabolism at rest, increases the cardiac resistance to ischaemia and therefore reduces the decline of left ventricular function due to chronic hypoperfusion and repetitive episodes of myocardial ischaemia in patients with and without diabetes. Modulation of myocardial FFA metabolism should be the key target for metabolic interventions in diabetic patients with coronary artery disease