Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death

Abstract

More than 450 million people worldwide have diabetes mellitus (DM), a metabolic disorder characterized by an increase in blood glucose level (hyperglycemia) that arises from insufficient insulin secretion or resistance to insulin’s action. More than 70% of individuals with chronic DM will develop cardiovascular diseases (CVDs) including atherosclerosis and coronary artery diseases (CADs), hypertension, cardiac arrhythmias, cardiomyopathy (heart failure), stroke, and chronic kidney disease. A significant number of these individuals will also succumb to sudden cardiac death (SCD). SCD usually occurs in early morning from abnormal heart rhythms or arrhythmias and ventricular fibrillation. When the pumping action of the heart becomes erratic, a reduction in oxygenated blood to the brain leads to unconsciousness and brain damage. SCD is independent of age and sex and positively correlates with impairment in cardiac metabolism, muscle damage, fibrosis, apoptosis, hypertrophy, ischemia, and deranged cation signaling. This review centers on mechanisms by which intracellular cations (Na+, K+, and Ca2+) handling, inflammation, and oxidative and carbonyl stresses due to diabetes-induced hyperglycemia can lead to the deterioration of excitation/contraction coupling (ECC), impaired contractility, arrhythmias, and SCD in DM patients. It also discusses the beneficial effects of exercise training to attenuate the risk of SCD.