Introduction: Metabolic inflexibility was first described as a failure of skeletal muscle of diabetic subjects to appropriately move between use of lipid in the fasting state and use of carbohydrate in the insulin-stimulated prandial state. Metabolically healthy hearts have a well developed capacity to switch between lipid and carbohydrate fuels, depending on hormone levels and substrate availability in the circulation, but it is assumed that this flexibility is lost in the maladapted diabetic heart.
Objectives: We show in this short review that chronic treatment with lipid-lowering drugs, as well as acute administration of insulin and glucose, modulate the substrate flux in the diabetic heart. We also show that such interventions have functional implications in terms of improved cardiac efficiency and tolerance to ischemic stress.