Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death

Diabetes mellitus (DM) is a major global metabolic disorder characterized by an increase in blood glucose level (hyperglycemia). It is caused by inadequate insulin secretion or insulin resistance. More than 450 million people worldwide have DM and this number is expected to reach 650 million by 2030. More than 70% of DM patients 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 them will succumb to sudden cardiac death (SCD). SCD occurs in most cases in the early morning, and it is caused by abnormal heart rhythms or arrhythmias resulting in ventricular fibrillation. The pumping action of the heart becomes erratic as impulse conduction from the sinoatrial node to the atria and the ventricles becomes disorganized. As such, the heart is unable to pump oxygenated blood to the vital organs of the body including the brain, leading to unconsciousness and brain damage. SCD can occur in any person irrespective of age, ethnicity, gender, religion, and other demographics, and it is closely linked to changes in cardiac metabolism and muscle damage, fibrosis, apoptosis, hypertrophy, ischaemia, and deranged cation signaling. This review is related to the mechanisms by which intracellular cations (Na+, K+, and Ca2+) handling, inflammation, and oxidative and carbonyl stresses due to diabetesinduced hyperglycemia can lead to the deterioration of excitation/contraction coupling (ECC), impaired contractility, arrhythmias, and SCD in DM patients. A brief outline is also done on the beneficial effect of exercise training to prevent SCD.