Metabolic energy metabolism in diabetes: therapeutic implications

Diabetic alterations of myocardial metabolism result mainly from malfunctio ns of acetyl-coenzyme A carboxylase, carnitine-palmitoyl-transferase-1 and pyruvate-dehydrogenase inducing an overshoot of fatty acid oxidation that i nhibits glucose oxidation, Gene expression of pyruvate-dehydrogenase and gl ucose transporters and depression of the third step of the mitochondrial re spiratory chain also contribute to the diabetic alterations of myocardial m etabolism, Ischaemic cardiovascular alterations are common and treatment is rarely successful in cases of diabetes since fatty acid oxidation is the c ostliest metabolic pathway for oxygen. Thus, in diabetes, aerobic glycolysi s gradually shifts to anaerobic glycolysis under ischaemia, with accumulati on of lactate and acid metabolites that in turn induce myocardial deteriora tion. Animal experiments have demonstrated that elective depression of acti vity of carnitine-palmitoyl-transferase-1 enzyme-activity promotes glucose oxidation and early rapid recovery of myocardial contractility, especially under diabetic conditions. To reduce diabetic alterations of myocardial met abolism, anti-diabetic treatment must be switched to insulin during the acu te ischaemic and post-ischaemic period of coronary diseases. Trimetazidine optimizes energy metabolism by selectively inhibiting action of the 3-ketoa cyl-coenzyme A thiolase enzyme involved in beta -oxidation and inhibiting t he overshoot of fatty oxidation, Trimetazidine, as the first 3-ketoacyl-coe nzyme A thiolase inhibitor, therefore provides permanent myocardial cytopro tection in stable angina pectoris, However, in our experience, this benefic ial anti-anginal effect is only observed in well-controlled situations. Cor on Artery Dis 12 (suppl 1):S29-S33 (C) 2001 Lippincott Williams and Wilkins .