Invited review
Metabolic management of diabetic patients with ischaemic heart disease

Diabetic patients with ischaemic heart disease have a greater rate of myocardial ischaemia, often silent, compared with patients without diabetes. Furthermore, patients with coronary artery disease (CAD) and diabetes 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 ischaemic metabolic changes are heightened by the metabolic changes related to diabetes. Metabolic changes during diabetes and myocardial ischaemia include an increase in free fatty acid (FFA) concentrations with increased skeletal muscle and myocardial FFA uptake and oxidation, and reduced utilization of glucose as a source of energy during stress. This contributes to the increased susceptibility of diabetic hearts to myocardial ischaemia and to a greater decrease of myocardial performance for a given amount of ischaemia compared with non-diabetic hearts. The metabolic approach, including strict glycaemic control and inhibition of FFA oxidation, aims to obtain an improvement in myocardial metabolism, relief of ischaemia and recovery of left ventricular function. The inhibition of FFA oxidation with trimetazidine improves cardiac metabolism at rest, increases cardiac resistance to ischaemia, and therefore reduces the decrease of LV function caused by chronic hypoperfusion and episodes of myocardial ischaemia 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 than those observed in patients without diabetes. Because of its effect on cardiac metabolism at rest and its effects on myocardial ischaemia and LV function, metabolic agents should always be considered for the treatment of patients with diabetes with CAD with or without LV dysfunction.