Molecular insights into diabetic cardiomyopathy

Chayanika Barman, Rajesh Pandey, Jasbir Singh, Kuldip S. Sodhi


Diabetes mellitus affects the heart in 3 ways: (1) coronary artery disease (CAD) due to accelerated atherosclerosis; (2) cardiac autonomic neuropathy (CAN); and (3) diabetic cardiomyopathy (DbCM). Although there is high awareness among clinicians about the first two entities, DbCM is poorly recognized by most physicians and diabetologists. DbCM, first described by Rubler et al. in 1972, is defined as myocardial dysfunction occurring in patients with diabetes in the absence of CAD, hypertension, or valvular heart disease. The development of DbCM is multi-factorial including autonomic dysfunction, metabolic derangements, abnormalities in ion homeostasis, alteration in structural proteins, and interstitial fibrosis. Chronic hyperglycemia is thought to play a central role in the development of DbCM. The main metabolic abnormalities in diabetes are hyperglycemia, hyperlipidemia and inflammation, all of which stimulate generation of reactive oxygen/nitrogen species which result in reduction of myocardial contractility and acceleration of fibrosis besides cellular DNA damage and cardiomyocyte apoptosis. In addition, advanced glycation end products (AGEs) indirectly exert their detrimental effect on the myocardium by interacting and up-regulating their receptors, including receptors of AGE and galectin-3. This results in activation of transcription factors, such as nuclear factor-kB (NF-kB). The NF-kB dependent genes, in turn, trigger several pathways that induce production of pro-inflammatory cytokines and cause myocardial damage. All these molecular events are potential therapeutic targets in DbCM.



Diabetic cardiomyopathy, Insulin, Genes, Apoptosis, Fibrosis, Therapy

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