Molecular Dysfunction and Phenotypic Derangement in Diabetic Cardiomyopathy.

Isabella Evangelista,Francesco Dotta,Alberto Palazzuoli,Tommaso Picchioni,Ranuccio Nuti

doi:10.3390/ijms20133264

Isabella Evangelista, Francesco Dotta + Show 3 more

Open Access

https://doi.org/10.3390/ijms20133264

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Abstract

The high incidence and poor prognosis of heart failure (HF) patients affected with diabetes (DM) is in part related to a specific cardiac remodeling currently recognized as diabetic cardiomyopathy (DCM). This cardiac frame occurs regardless of the presence of coronary artery diseases (CAD) and it can account for 15–20% of the total diabetic population. The pathogenesis of DCM remains controversial, and several molecular and cellular alterations including myocardial hypertrophy, interstitial fibrosis, oxidative stress and vascular inflammation, have been postulated. The main cardio-vascular alterations associated with hyperglycemia comprise endothelial dysfunction, adverse effects of circulating free fatty acids (FFA) and increased systemic inflammation. High glucose concentrations lead to a loss of mitochondrial networks, increased reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS) activation and a reduction in cGMP production related to protein kinase G (PKG) activity. Current mechanisms enhance the collagen deposition with subsequent increased myocardial stiffness. Several concerns regarding the exact role of DCM in HF development such as having an appearance as either dilated or as a concentric phenotype and whether diabetes could be considered a causal factor or a comorbidity in HF, remain to be clarified. In this review, we sought to explain the different DCM subtypes and the underlying pathophysiological mechanisms. Therefore, the traditional and new molecular and signal alterations and their relationship with macroscopic structural abnormalities are described.

Highlights

Diabetes mellitus (DM) is universally considered a traditional cardiovascular (CV) risk factor but its association with heart failure (HF) is undefined
The most important HF risk factor related to outcome in DM patients is a higher value of glycosylated hemoglobin (HbA1c), a strict glycemic control is not associated with a substantial decrease in CV events [6]
Due to the paucity of clinical trials, several questions are currently arising about the exact role of diabetes in HF development, its prevalence in HF patients, the different outcome in diabetic HF compared to non-diabetic patients, and the occurrence of dilated vs. concentric remodeling in diabetic cardiomyopathy (DCM) phenotypes

Summary

Introduction

Diabetes mellitus (DM) is universally considered a traditional cardiovascular (CV) risk factor but its association with heart failure (HF) is undefined. The most important HF risk factor related to outcome in DM patients is a higher value of glycosylated hemoglobin (HbA1c), a strict glycemic control is not associated with a substantial decrease in CV events [6]. These data underline the importance of cumulative glycemic burden, rather than glycemic control at a given point in time [7,8]. Whether diabetes could be considered a causal factor or a comorbidity in HF remains to be clarified Despite these data, a specific trial evaluating the impact of diabetes in HF and the incidence of DCM in the diabetic population does not exist

Epidemiology of Diabetes in Patients with Heart Failure

Impact of Diabetes on Heart Failure Occurrence

MicroRNA Signals in Diabetic Cardiomyopathy

Different Phenotypes in Diabetic Cardiomyopathy

Findings

Conclusions