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Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants

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Abstract

Diabetic cardiomyopathy (DCM) is a diabetes mellitus–induced pathophysiological condition characterized by cardiac structural, functional, and metabolic changes that can result in heart failure (HF), in the absence of coronary artery disease, hypertension, and valvular heart disease. Metabolic alterations such as hyperglycemia, insulin resistance, hyperinsulinemia, and increased metabolism of free fatty acids result in oxidative stress, inflammation, advanced glycation end products formation, abnormalities in calcium homeostasis, and apoptosis that are responsible for structural remodeling. Cardiac stiffness, hypertrophy, and fibrosis eventually lead to dysfunction and HF with preserved ejection fraction and/or HF with reduced ejection fraction. In this review, we analyzed in detail the cellular and molecular mechanisms and the metabolic pathways involved in the pathophysiology of DCM. Different phenotypes are observed in DCM, and it is not clear yet if the restrictive and the dilated phenotypes are distinct or represent an evolution of the same disease. Phenotypic differences can be observed between T1DM and T2DM DCM, possibly explained by the different myocardial insulin action. Further studies are needed in order to better understand the underlying mechanisms of DCM and to identify appropriate therapeutic targets and novel strategies to prevent and reverse the progression toward heart failure in diabetic patients.

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Authors and Affiliations

  1. Division of Cardiology, University Hospital “Tor Vergata”, Rome, RM, Italy

    Francesca Romana Prandi, Domenico Sergi & Francesco Romeo

  2. Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria Alle Scotte Hospital, University of Siena, Siena, Italy

    Isabella Evangelista & Alberto Palazzuoli

  3. Unicamillus International University, Rome, RM, Italy

    Francesco Romeo

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  1. Francesca Romana Prandi
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  2. Isabella Evangelista
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Prandi, F.R., Evangelista, I., Sergi, D. et al. Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants. Heart Fail Rev 28, 597–606 (2023). https://doi.org/10.1007/s10741-021-10200-y

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