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Diabetes & Metabolism Journal Mar 2021Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a... (Review)
Review
Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.
Topics: Animals; Diabetes Mellitus; Diabetic Cardiomyopathies; Heart Failure; Humans; Models, Animal; Oxidative Stress; Renin-Angiotensin System
PubMed: 33813812
DOI: 10.4093/dmj.2020.0285 -
Journal of Diabetes Research 2015Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by... (Review)
Review
Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by changes in energy substrates and occurs in the absence of atherothrombosis, hypertension, or other cardiomyopathies. Inflammation, hypertrophy, fibrosis, steatosis, and apoptosis in the myocardium have been studied in numerous diabetic experimental models in animals, mostly rodents. Type I and type II diabetes were induced by genetic manipulation, pancreatic toxins, and fat and sweet diets, and animals recapitulate the main features of human diabetes and related cardiomyopathy. In this review we update and discuss the main experimental models of diabetic cardiomyopathy, analysing the associated metabolic, structural, and functional abnormalities, and including current tools for detection of these responses. Also, novel experimental models based on genetic modifications of specific related genes have been discussed. The study of specific pathways or factors responsible for cardiac failures may be useful to design new pharmacological strategies for diabetic patients.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Disease Models, Animal; Heart; Myocardium
PubMed: 25973429
DOI: 10.1155/2015/656795 -
Cardiovascular Diabetology Feb 2015Diabetic cardiomyopathy is defined as ventricular dysfunction initiated by alterations in cardiac energy substrates in the absence of coronary artery disease and... (Review)
Review
Diabetic cardiomyopathy is defined as ventricular dysfunction initiated by alterations in cardiac energy substrates in the absence of coronary artery disease and hypertension. In addition to the demonstrated burden of cardiovascular events associated with diabetes, diabetic cardiomyopathy partly explains why diabetic patients are subject to a greater risk of heart failure and a worse outcome after myocardial ischemia. The raising prevalence and accumulating costs of cardiovascular disease in diabetic patients underscore the deficiencies of tertiary prevention and call for a shift in medical treatment. It is becoming increasingly clearer that the effective prevention and treatment of diabetic cardiomyopathy require measures to regulate the metabolic derangement occurring in the heart rather than merely restoring suitable systemic parameters. Recent research has provided deeper insight into the metabolic etiology of diabetic cardiomyopathy and numerous heart-specific targets that may substitute or reinforce current strategies. From both experimental and translational perspectives, in this review we first discuss the progress made with conventional therapies, and then focus on the need for prospective metabolic targets that may avert myocardial vulnerability and functional decline in next-generation diabetic care.
Topics: Animals; Diabetes Mellitus; Diabetic Cardiomyopathies; Drug Delivery Systems; Humans; Metabolic Diseases
PubMed: 25856422
DOI: 10.1186/s12933-015-0173-8 -
Heart Failure Reviews Jan 2014Diabetic cardiomyopathy (DCM) is defined as cardiac disease independent of vascular complications during diabetes. The number of new cases of DCM is rising at epidemic... (Review)
Review
Diabetic cardiomyopathy (DCM) is defined as cardiac disease independent of vascular complications during diabetes. The number of new cases of DCM is rising at epidemic rates in proportion to newly diagnosed cases of diabetes mellitus (DM) throughout the world. DCM is a heart failure syndrome found in diabetic patients that is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction, occurring in the absence of hypertension and coronary artery disease. DCM and other diabetic complications are caused in part by elevations in blood glucose and lipids, characteristic of DM. Although there are pathological consequences to hyperglycemia and hyperlipidemia, the combination of the two metabolic abnormalities potentiates the severity of diabetic complications. A natural competition exists between glucose and fatty acid metabolism in the heart that is regulated by allosteric and feedback control and transcriptional modulation of key limiting enzymes. Inhibition of these glycolytic enzymes not only controls flux of substrate through the glycolytic pathway, but also leads to the diversion of glycolytic intermediate substrate through pathological pathways, which mediate the onset of diabetic complications. The present review describes the limiting steps involved in the development of these pathological pathways and the factors involved in the regulation of these limiting steps. Additionally, therapeutic options with demonstrated or postulated effects on DCM are described.
Topics: Diabetic Cardiomyopathies; Energy Metabolism; Humans; Metabolic Diseases; Oxidative Stress; Prognosis; Ventricular Function
PubMed: 23443849
DOI: 10.1007/s10741-013-9377-8 -
Arquivos Brasileiros de Cardiologia Dec 2017
Topics: Brazil; Cardiovascular Diseases; Cholesterol, LDL; Diabetic Cardiomyopathies; Evidence-Based Medicine; Humans; Hypercholesterolemia; Risk Assessment; Risk Factors; Societies, Medical
PubMed: 29489927
DOI: 10.5935/abc.20170188 -
Heart Failure Reviews Mar 2013Since diabetic cardiomyopathy was first reported four decades ago, substantial information on its pathogenesis and clinical features has accumulated. In the heart,... (Review)
Review
Since diabetic cardiomyopathy was first reported four decades ago, substantial information on its pathogenesis and clinical features has accumulated. In the heart, diabetes enhances fatty acid metabolism, suppresses glucose oxidation, and modifies intracellular signaling, leading to impairments in multiple steps of excitation-contraction coupling, inefficient energy production, and increased susceptibility to ischemia/reperfusion injury. Loss of normal microvessels and remodeling of the extracellular matrix are also involved in contractile dysfunction of diabetic hearts. Use of sensitive echocardiographic techniques (tissue Doppler imaging and strain rate imaging) and magnetic resonance spectroscopy enables detection of diabetic cardiomyopathy at an early stage, and a combination of the modalities allows differentiation of this type of cardiomyopathy from other organic heart diseases. Circumstantial evidence to date indicates that diabetic cardiomyopathy is a common but frequently unrecognized pathological process in asymptomatic diabetic patients. However, a strategy for prevention or treatment of diabetic cardiomyopathy to improve its prognosis has not yet been established. Here, we review both basic and clinical studies on diabetic cardiomyopathy and summarize problems remaining to be solved for improving management of this type of cardiomyopathy.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Disease Management; Echocardiography, Doppler; Heart; Heart Failure; Humans; Signal Transduction
PubMed: 22453289
DOI: 10.1007/s10741-012-9313-3 -
International Journal of Molecular... Apr 2020Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is... (Review)
Review
Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. In addition, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.
Topics: Animals; Diabetes Mellitus; Diabetic Cardiomyopathies; Disease Management; Disease Susceptibility; Exercise; Humans; Ischemic Preconditioning; Metabolic Networks and Pathways; Myocardial Ischemia; Myocardial Reperfusion Injury
PubMed: 32326182
DOI: 10.3390/ijms21082896 -
Archives of Cardiovascular Diseases Nov 2021Diabetes mellitus is a metabolic disorder with a chronic hyperglycaemic state. Cardiovascular diseases are the primary cause of mortality in patients with diabetes.... (Review)
Review
Diabetes mellitus is a metabolic disorder with a chronic hyperglycaemic state. Cardiovascular diseases are the primary cause of mortality in patients with diabetes. Increasing evidence supports the existence of diabetic cardiomyopathy, a cardiac dysfunction with impaired cardiac contraction and relaxation, independent of coronary and/or valvular complications. Diabetic cardiomyopathy can lead to heart failure. Several preclinical and clinical studies have aimed to decipher the underlying mechanisms of diabetic cardiomyopathy. Among all the co-factors, hyperglycaemia seems to play an important role in this pathology. Hyperglycaemia has been shown to alter cardiac metabolism and function through several deleterious mechanisms, such as oxidative stress, inflammation, accumulation of advanced glycated end-products and upregulation of the hexosamine biosynthesis pathway. These mechanisms are responsible for the activation of hypertrophic pathways, epigenetic modifications, mitochondrial dysfunction, cell apoptosis, fibrosis and calcium mishandling, leading to cardiac stiffness, as well as contractile and relaxation dysfunction. This review aims to describe the hyperglycaemic-induced alterations that participate in diabetic cardiomyopathy, and their correlation with the severity of the disease and patient mortality, and to provide an overview of cardiac outcomes of glucose-lowering therapy.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Heart; Heart Failure; Humans; Hyperglycemia; Oxidative Stress
PubMed: 34627704
DOI: 10.1016/j.acvd.2021.08.004 -
JACC. Cardiovascular Imaging Jun 2017Type 2 diabetes mellitus (T2DM) and obesity are important contributors to nonischemic heart failure (HF) and atrial fibrillation. There is a 2- to 5-fold increase in HF... (Review)
Review
Type 2 diabetes mellitus (T2DM) and obesity are important contributors to nonischemic heart failure (HF) and atrial fibrillation. There is a 2- to 5-fold increase in HF associated with T2DM, and there is a 5% in HF risk in men and 7% increment in women for every unit increment in body mass index, after adjustment for traditional cardiovascular risk factors. Likewise, the risk of atrial fibrillation increases by about 6% per unit increase in body mass index. Metabolic cardiomyopathy leads to a number of changes in cardiac structure and function that can be recognized by imaging in the asymptomatic phase, and these parameters can be used for monitoring the progression of disease or the response to therapy. The purpose of this review is to familiarize clinicians with the potential benefits of early detection of preclinical myocardial abnormalities, as well as the mechanisms that might inform interventions to prevent disease progression in patients with T2DM and obesity.
Topics: Asymptomatic Diseases; Atrial Fibrillation; Biomarkers; Cardiac Imaging Techniques; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Early Diagnosis; Fibrosis; Heart Failure; Heart Rate; Humans; Myocardium; Obesity; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling
PubMed: 28595844
DOI: 10.1016/j.jcmg.2017.04.001 -
Diabetes & Vascular Disease Research 2023Over half a billion adults across the world have diabetes mellitus (DM). This has a wide-ranging impact on their health, including more than doubling their risk of major... (Review)
Review
Over half a billion adults across the world have diabetes mellitus (DM). This has a wide-ranging impact on their health, including more than doubling their risk of major cardiovascular events, in comparison to age-sex matched individuals without DM. Notably, the risk of heart failure is particularly increased, even when coronary artery disease and hypertension are not present. Macro- and micro-vascular complications related to endothelial cell (EC) dysfunction are a systemic feature of DM and can affect the heart. However, it remains unclear to what extent these and other factors underpin myocardial dysfunction and heart failure linked with DM. Use of unbiased 'omics approaches to profile the molecular environment of the heart offers an opportunity to identify novel drivers of cardiac dysfunction in DM. Multiple transcriptomics studies have characterised the whole myocardium or isolated cardiac ECs. We present a systematic summary of relevant studies, which identifies common themes including alterations in both myocardial fatty acid metabolism and inflammation. These findings prompt further research focussed on these processes to validate potentially causal factors for prioritisation into therapeutic development pipelines.
Topics: Adult; Humans; Myocardium; Diabetic Cardiomyopathies; Heart Failure; Diabetes Mellitus, Type 2; Gene Expression Profiling
PubMed: 38116627
DOI: 10.1177/14791641231205428