Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes

Area of Science:

• Cardiology
• Endocrinology
• Pathophysiology

Background:

• Diabetes mellitus-related cardiomyopathy (DMCMP) was initially characterized by a dilated left ventricle (LV) and systolic dysfunction.
• Recent studies highlight a restrictive phenotype with concentric LV remodeling and diastolic dysfunction as a primary presentation of DMCMP.
• These two phenotypes, restrictive/HFPEF and dilated/HFREF, represent independent pathways rather than sequential stages of the disease.

Purpose of the Study:

• To elucidate the distinct pathophysiological mechanisms underlying the restrictive and dilated phenotypes of DMCMP.
• To differentiate the roles of metabolic derangements and autoimmunity in the development of specific DMCMP phenotypes.
• To clarify diagnostic criteria and treatment strategies for the different DMCMP presentations.

Main Methods:

• Review of clinical studies and proposed pathophysiological mechanisms for DMCMP.
• Analysis of the association between diabetes mellitus (DM) type, metabolic factors, autoimmunity, and specific cardiomyopathy phenotypes.
• Comparison of diagnostic requirements and treatment approaches for restrictive/HFPEF and dilated/HFREF phenotypes.

Main Results:

• Phenotype-specific mechanisms involve endothelial dysfunction in restrictive/HFPEF and cardiomyocyte cell death in dilated/HFREF.
• Metabolic derangements (hyperglycemia, lipotoxicity) favor restrictive/HFPEF, prevalent in obese type 2 DM patients.
• Autoimmunity predisposes to dilated/HFREF, more common in autoimmune-prone type 1 DM patients.
• Coronary microvascular rarefaction and advanced glycation end-products are implicated in both phenotypes.

Conclusions:

• DMCMP evolves into distinct restrictive/HFPEF or dilated/HFREF phenotypes driven by specific pathophysiological pathways.
• Patient-specific factors, including metabolic status and autoimmune predisposition, dictate the DMCMP phenotype.
• Accurate diagnosis and phenotype-specific management are crucial for improving outcomes in patients with DMCMP.