The complex phenotype of Diabetic Cardiomyopathy: clinical indicators and novel treatment targets

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Background

Diabetic cardiomyopathy is a clinical condition of heart dysfunction that develops in the absence of hypertension and coronary atherosclerosis in diabetic patients. The main characteristics of diabetic cardiomyopathy are myocardial fibrosis, cardiac stiffness, left ventricular hypertrophy and decreased left ventricular compliance. This eventually progresses to clinical heart failure with reduced ejection fraction. To detect changes in cardiac structure and function, such as fibrosis, several noninvasive techniques have been used. These include echocardiography, cinematic magnetic resonance imaging, and computed tomography. From a mechanistic perspective; oxidative stress, inflammation, enhanced production and deposition of advanced glycation end products (AGEs), mitochondrial dysfunction, impaired mitochondrial Ca2+ handling and function, and endoplasmic reticulum stress are observed. Furthermore activation of the sympathetic nervous system and renin-angiotensin system, microvascular dysfunction, and cardiac metabolic disorders are involved in the pathophysiology of this condition. Numerous proteins and signaling pathways, such as AMPK, FOXO1, SERCA2A, NF-kB, Nrf2, HO-1, MAPK, PKC, and PPARs, may be implicated in the development of diabetic cardiomyopathy. Additionally, increased levels of O-linked N-acetylglucosamine (O-GlcNAc), C-reactive protein, atrial natriuretic peptide, and, brain natriuretic peptide, among others, may also serve as clinical biomarkers to identify diabetic cardiomyopathy.



Lifestyle modifications including aerobic exercise, maintaining a healthy weight, and smoking cessation are beneficial treatment measures to avoid diabetic cardiomyopathy. It is significant to note that in people with diabetes mellitus; high blood glucose and systemic and cardiac insulin resistance, are independently correlated to the development and progression of cardiac dysfunction and heart failure. The prevalence of diabetic cardiomyopathy declines with sustained glycemic management. However, a formal definition for diabetic cardiomyopathy as a distinct clinical entity remains poorly defined due to a lack of accepted diagnostic criteria and knowledge of subclinical cardiovascular diseases at the early stages of diabetes mellitus. There is currently no distinct histological features, biochemical markers, or clinical manifestation that can be used to make a definitive diagnosis of diabetic cardiomyopathy. Additionally, there are no prospective clinical trials to back up the claim that high insulin or blood sugar levels alone, without additional risk factors like obesity, coronary heart disease, or high blood pressure, increase the likelihood of developing diabetic cardiomyopathy. To decipher the precise mechanisms behind the onset and progression of diabetic cardiomyopathy, and to develop novel strategies for reducing the risk of heart failure in people with diabetes, further research is necessary. Hence, more clinical observational studies are required to comprehend the unknown factors underlying diabetic cardiomyopathy, and to further investigate novel biomarkers that can be used for risk assessment, screening, and diagnosis. Early detection and early intervention are essential for preventing diabetic cardiomyopathy, which drives ongoing research to better understand and treat this condition.

This can be accomplished by utilizing cutting-edge methods built on the integration of multi-omics analysis, such as comparing and merging data from genomic, epigenetic, transcriptomic, proteomic, and metabolomic profiles. The use of data gathered by such high-throughput technologies may result in the development of a molecular framework for diabetic cardiomyopathy, which would then enable the identification of suitable and efficient diabetic cardiomyopathy biomarkers. The final objective is to use the new knowledge to develop precision medicine approach, leading to improving the clinical outcome of the disease.



The goal of this Research Topic is to shed light on the advances and new findings on diabetic cardiomyopathy progression and treatment. Submissions may address, but are not limited to, the following:

- Research progress of natural product and conventional drug therapy for diabetic cardiomyopathy

- Identification and validation of potential novel molecular biomarkers for the development, progression of diabetic cardiomyopathy

- Novel therapeutic drug targets for diabetic cardiomyopathy

- Cellular crosstalk in diabetic cardiomyopathy

- Metabolic complications and heart failure

The editors welcome original research, reviews, and other accepted article types.

Keywords: Diabetic Cardiomyopathy; Heart Failure; Metabolic Complications; Cellular Signaling

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