Global awareness has made us cognizant that people with diabetes are susceptible to various disorders involving eye, kidney or nervous system and blood circulation affecting the limbs in the long run. Along these lines, type 2 diabetic patients are more likely to develop heart disease and have a greater incidence of heart attack. According to American Heart Association (AHA), diabetes is one of the major contributing factors for cardiovascular disease and accounts for at least 68 percent of diabetic population of age 65 or older to die from some form of heart disease.
Diabetic heart disease (DHD) is a broader term used to explain heart problems in patients who have diabetes. DHD may include conditions like coronary heart disease, where plaque accumulating in your arteries reduces the blood flow to the heart eventually leading to heart failure, a condition where your heart cannot pump enough blood to meet your body’s requirements. Another consequence of diabetes can be diabetic cardiomyopathy where the damage is extended to the structure and function of the heart. Patients with diabetic cardiomyopathy are more predisposed to develop irregular heartbeat disorders called arrhythmias.
Arrhythmias are conditions in which there is a problem with the rate or rhythm of your heartbeat. It is observed when the electrical signals to the heart that coordinate heartbeats do not function properly. This leads to increase in heart rate (basal rate of more than 100bpm), a condition called trachycardia or decrease in heart rate (basal rate less than 60bpm), called bradycardia. The detailed illustration of these conditions can be found at AHA website. While these conditions can have serious complications in patients, the condition becomes far worse in patients with DHD.
Under normal conditions, mitochondrias which are the energy sources of the cell, give rise to dangerous chemicals known as reactive oxygen species (ROS), byproducts of aerobic metabolism. Oxidative stress occurs when there is excessive production of ROS and if these chemicals are not removed, they possess damage to proteins, tissues and genetic material of the heart cells. However, mitochondria have antioxidant defense systems which decrease ROS production. Under pathological conditions such as diabetes, glucose fluctuations far exceed the ROS production than the oxidative defense systems are capable of cleaning and thus the problem becomes far more intense.
At this year’s Scientific Sessions, one of my colleagues presented his work establishing an interesting link between oxidative stress and arrhythmias. His project focused on protein which is a key enabler of ROS- mediated cardiac arrhythmias, known as mitochondrial translator protein (TSPO). TSPO is an outer mitochondrial membrane protein, previously described as peripheral benzodiazepine receptor, a secondary binding site for diazepam. It’s primarily associated with cholesterol transport to inside the cell, while the group explains its potential role in mitochondrial instability during arrhythmias by mechanism, where excess ROS generated in diabetic patient positively up-regulates its own levels – a process called ROS induced ROS-release (RIRR). Thus, TSPO can be a potential therapeutic target against arrhythmias in diabetic patients. Preliminary data by the group confirmed the increased levels of TPSO in hearts of diabetic rats, which might be responsible for increased propensity of diabetic hearts to arrhythmic events. While TPSO is probably upregulated as compensatory mechanism during type 2 diabetes, its global gene silencing may interfere with essential homeostatic function including cholesterol import and mitochondrial biogenesis. In relation to that, the group is further looking into avenues for targeted and specific TSPO inhibition in the areas affected after heart attack.
Personally, I am not only proud of his work but also hopeful that research studies like his help us to identify potential targets for curing serious conditions like DHD.
References:
Ilkan Z, Akar FG. The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart.Front Physiol. 2018;26;9:1518
Ilkan Z, Strauss B, Akar FG. Reversal of TSPO Upregulation in the Diabetic Heart by Chronic TSPO Gene Silencing Causes Metabolic Sink via an Increase in ROMK Expression. Circulation. 2018;138:A16826.