Recent Advances in Understanding the Pathophysiology and Biomarkers of Diabetic Cardiomyopathy in Diabetes Mellitus: A Review.

Diabetic cardiomyopathy (DCM) is a complex and progressive disorder associated with diabetes (DM), which is a consequence of the impaired cardiac function in the absence of any evidence of coronary artery disease or hypertension. DCM pathophysiology is multifactorial and includes hyperglycaemia, insulin resistance, oxidative stress, and metabolic dysfunction. In the early stages, significant alterations occur in the structure and functions of the adipose tissue, including cardiomyocyte hypertrophy, myocardial fibrosis, and diastolic dysfunction. The disease develops up to heart failure, both systolic and diastolic. The leading roles in the process of cardiovascular disease pathologies are played by the enhancement of insulin levels, cardiomyocyte apoptosis, activation of the renin-angiotensin-aldosterone system (RAAS), and the production of inflammatory cytokines, which include TNF-α and IL-6. Pro-fibrotic signaling pathways, especially transforming growth factor-beta (TGF-β), play a key role in the development of myocardial fibrosis. In addition, impaired calcium handling contributes to disturbances in cardiac rhythm. Despite many drugs that help control blood glucose and lipid levels, there are very few pharmacological treatments that directly target cardiac tissue damage. Common cardiac biomarkers such as natriuretic peptides and troponins are also not sensitive for early detection of diabetic cardiomyopathy (DCM), which highlights the need to identify more specific and reliable biomarkers. Recent studies point out IGFBP7, TGF- beta, and galectin-3 as the potential biomarkers of early DCM and DCM progression. The high rate of DM in the world, especially type 2 diabetes, has indicated the need to screen early and use novel therapies to reduce cardiovascular risks. A clear understanding of the complex pathogenic mechanisms underlying diabetic cardiomyopathy (DCM) will be pivotal for the development of targeted therapeutics aimed at reversing disease progression and improving the prognosis of patients with diabetes.