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[Metabolic considerations in the treatment of coronary disease in diabetic patients]
1Service de Cardiologie B, Hôpital A. de Villeneuve, CHU de Montpellier, 371, avenue du Doyen G. Giraud, 34295 Montpellier. c-piot@chu-montpellier.fr
Insights
Diabetic hearts have impaired energy metabolism, increasing coronary heart disease severity and reperfusion injury. Therapies like glucose-insulin-potassium infusion and trimetazidine improve outcomes by targeting metabolic disturbances.
Area of Science:
- Cardiology
- Metabolic Disorders
- Biochemistry
Context:
- Coronary heart disease (CHD) is the leading cause of mortality in diabetic patients.
- Diabetic hearts exhibit altered myocardial energy metabolism, worsening ischemic and reperfusion injury.
- Key metabolic abnormalities include impaired glucose metabolism and increased fatty acid oxidation.
Purpose:
- To review the metabolic derangements in the diabetic heart during ischemia and reperfusion.
- To discuss therapeutic strategies aimed at correcting these metabolic abnormalities.
- To highlight the role of glucose-insulin-potassium infusion and trimetazidine in improving outcomes.
Summary:
- Diabetic hearts show reduced glucose uptake, glycolysis, and oxidation, alongside increased fatty acid oxidation.
- During ischemia, impaired glucose oxidation shifts ATP production to anaerobic glycolysis, causing lactate accumulation and acidosis.
- Reperfusion recovery is significantly delayed in diabetic hearts due to slow restoration of intracellular homeostasis.
- Glucose-insulin-potassium infusion reduces mortality in diabetic patients with acute myocardial infarction.
- Trimetazidine offers a metabolic, non-hemodynamic approach to complement standard CHD treatments.
Impact:
- Understanding diabetic heart metabolism is crucial for developing effective treatments for ischemic heart disease.
- Metabolic interventions can significantly improve outcomes for diabetic patients suffering from myocardial ischemia and infarction.
- Targeting specific metabolic pathways offers a promising strategy to enhance myocardial protection and recovery.
Abstract:
Coronary heart disease represents the first cause of death in diabetic patients. The poor outcome of this ischemic disease is multifactorial. The abnormalities in myocardial energy metabolism encountered by the diabetic heart explain both the ischemic severity and the worsening of reperfusion lesions. The metabolic abnormalities in diabetic heart consist in both an impairment of glucose metabolism (diminished glucose uptake, reduced glycolysis, decreased glucose oxidation...) and an increase in fatty acid oxidation. During ischemia, glucose oxidation is reduced and anaerobic glycolysis becomes the main ATP substrate. Lactate accumulate in myocardial cells, inducing both a metabolic acidosis and an intracellular calcium overload. During reperfusion, intracellular homeostasis is restored very slowly in diabetic heart. Several therapeutic approaches are used to correct these metabolic disturbances. Glucose--insulin--potassium infusion in acute myocardial infarction leads to a significant reduction in the mortality relative risk in diabetic patients (ECLA and DIGAMI studies). The benefit is greater in diabetic patients who where non-insulin-treated prior to ischemia followed by myocardial reperfusion therapy. Others more direct pharmacological approaches improve glucose oxidation during myocardial ischaemia and myocardial reperfusion. The reference drug remains trimetazidine for which one of the fundamental mechanism of action was discovered recently. This specific metabolic, non haemodynamic approach, complete the gold-standard treatment of coronary heart disease in diabetic patients (e.g. aspirin, beta-blockers, ACE inhibitors and statins).
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