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Clinical Science (London, England :... May 2017Diabetes increases the risk of heart failure approximately 2.5-fold, independent of coronary artery disease and other comorbidities. This process, termed diabetic... (Review)
Review
Diabetes increases the risk of heart failure approximately 2.5-fold, independent of coronary artery disease and other comorbidities. This process, termed diabetic cardiomyopathy, is characterized by initial impairment of left ventricular (LV) relaxation followed by LV contractile dysfunction. Post-mortem examination reveals that human diastolic dysfunction is closely associated with LV damage, including cardiomyocyte hypertrophy, apoptosis and fibrosis, with impaired coronary microvascular perfusion. The pathophysiological mechanisms underpinning the characteristic features of diabetic cardiomyopathy remain poorly understood, although multiple factors including altered lipid metabolism, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, as well as epigenetic changes, are implicated. Despite a recent rise in research interrogating these mechanisms and an increased understanding of the clinical importance of diabetic cardiomyopathy, there remains a lack of specific treatment strategies. How the chronic metabolic disturbances observed in diabetes lead to structural and functional changes remains a pertinent question, and it is hoped that recent advances, particularly in the area of epigenetics, among others, may provide some answers. This review hence explores the temporal onset of the pathological features of diabetic cardiomyopathy, and their relative contribution to the resultant disease phenotype, as well as both current and potential therapeutic options. The emergence of glucose-optimizing agents, namely glucagon-like peptide-1 (GLP-1) agonists and sodium/glucose co-transporter (SGLT)2 inhibitors that confer benefits on cardiovascular outcomes, together with novel experimental approaches, highlight a new and exciting era in diabetes research, which is likely to result in major clinical impact.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Humans
PubMed: 28473471
DOI: 10.1042/CS20160491 -
Journal of Cardiovascular Translational... Feb 2019Diabetic cardiomyopathy (DCM) or diabetes-induced cardiac dysfunction is a direct consequence of uncontrolled metabolic syndrome and occurs worldwide. However, the... (Review)
Review
Diabetic cardiomyopathy (DCM) or diabetes-induced cardiac dysfunction is a direct consequence of uncontrolled metabolic syndrome and occurs worldwide. However, the underlying cellular and molecular mechanisms remain poorly understood. Recently, exosomes have attracted considerable interest for their use as efficient, targeted, and non-immunogenic delivery systems for biological molecules or pharmacotherapies. This review will summarize the fast-developing field of the regulation and function of exosomes in DCM, affording valuable insights and therapeutic opportunities in combatting diabetes-related cardiac disorder for modern human health.
Topics: Animals; Cell Proliferation; Diabetic Cardiomyopathies; Exosomes; Humans; Myocytes, Cardiac; Recovery of Function; Regeneration; Signal Transduction; Stem Cell Transplantation
PubMed: 30251219
DOI: 10.1007/s12265-018-9825-x -
Life Sciences Mar 2013The incidence and prevalence of diabetes mellitus are both increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to... (Review)
Review
The incidence and prevalence of diabetes mellitus are both increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. However, the diabetic milieu is itself intrinsically noxious to the heart, and cardiomyopathy can develop independent of elevated blood pressure or coronary artery disease. This process, termed diabetic cardiomyopathy, is characterized by significant changes in the physiology, structure, and mechanical function of the heart. Presently, therapy for patients with diabetes focuses largely on glucose control, and attention to the heart commences with the onset of symptoms. When the latter develops, standard therapy for heart failure is applied. However, recent studies highlight that specific elements of the pathogenesis of diabetic heart disease are unique, raising the prospect of diabetes-specific therapeutic intervention. Here, we review recently unveiled insights into the pathogenesis of diabetic cardiomyopathy and associated metabolic remodeling with an eye toward identifying novel targets with therapeutic potential.
Topics: Diabetic Cardiomyopathies; Drug Delivery Systems; Humans; Ventricular Remodeling
PubMed: 23123443
DOI: 10.1016/j.lfs.2012.10.011 -
Cardiovascular Diabetology Apr 2024Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide...
BACKGROUND
Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known.
METHODS AND RESULTS
T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose.
CONCLUSION
This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
Topics: Humans; Animals; Mice; Diabetic Cardiomyopathies; Sirtuin 1; Fibronectins; Diabetes Mellitus, Type 1; Ferroptosis; Tumor Suppressor Protein p53; Myocytes, Cardiac
PubMed: 38566123
DOI: 10.1186/s12933-024-02183-5 -
Revista Da Associacao Medica Brasileira... Jan 2019Although long ago described, there is no established consensus regarding the real existence of Diabetic Cardiomyopathy (CMPDM). Due to its complex pathophysiology, it... (Review)
Review
Although long ago described, there is no established consensus regarding the real existence of Diabetic Cardiomyopathy (CMPDM). Due to its complex pathophysiology, it has been difficult for clinical and experimental research to establish clear connections between diabetes mellitus (DM) and heart failure (HF), as well as to solve the mechanisms of the underlying myocardial disease. However, the epidemiological evidence of the relationship of these conditions is undisputed. The interest in understanding this disease has intensified due to the recent results of clinical trials evaluating new glucose-lowering drugs, such as sodium-glucose transporter inhibitors 2, which demonstrated favorable responses considering the prevention and treatment of HF in patients with DM. In this review we cover aspects of the epidemiology of CMPDM and its possible pathogenic mechanisms, as well as, present the main cardiac phenotypes of CMPDM (HF with preserved and reduced ejection fraction) and implications of the therapeutic management of this disease.
Topics: Diabetic Cardiomyopathies; Echocardiography; Evidence-Based Medicine; Humans; Phenotype; Risk Factors
PubMed: 30758422
DOI: 10.1590/1806-9282.65.1.69 -
Experimental Physiology Feb 2024Diabetic cardiomyopathy (DCM) is a significant cause of heart failure in patients with diabetes, and its pathogenesis is closely related to myocardial mitochondrial... (Review)
Review
Diabetic cardiomyopathy (DCM) is a significant cause of heart failure in patients with diabetes, and its pathogenesis is closely related to myocardial mitochondrial injury and functional disability. Studies have shown that the development of diabetic cardiomyopathy is related to disorders in mitochondrial metabolic substrates, changes in mitochondrial dynamics, an imbalance in mitochondrial Ca regulation, defects in the regulation of microRNAs, and mitochondrial oxidative stress. Physical activity may play a role in resistance to the development of diabetic cardiomyopathy by improving myocardial mitochondrial biogenesis, the level of autophagy and dynamic changes in fusion and division; enhancing the ability to cope with oxidative stress; and optimising the metabolic substrates of the myocardium. This paper puts forward a new idea for further understanding the specific mitochondrial mechanism of the occurrence and development of diabetic cardiomyopathy and clarifying the role of exercise-mediated myocardial mitochondrial changes in the prevention and treatment of diabetic cardiomyopathy. This is expected to provide a new theoretical basis for exercise to reduce diabetic cardiomyopathy symptoms.
Topics: Humans; Diabetic Cardiomyopathies; Mitochondria, Heart; Myocardium; Exercise; Oxidative Stress; Diabetes Mellitus
PubMed: 37845840
DOI: 10.1113/EP091309 -
Minerva Cardiology and Angiology Jun 2022Diabetic patients are prone to suffer from cardiovascular disease, specifically from ischemic heart disease and diabetic cardiomyopathy, which have a huge impact on... (Review)
Review
Diabetic patients are prone to suffer from cardiovascular disease, specifically from ischemic heart disease and diabetic cardiomyopathy, which have a huge impact on morbidity and mortality worldwide. Cardiac fibrosis due to alteration of the extracellular matrix (ECM) remodeling is often observed in diabetes and myocardial fibrosis is an important part of cardiac remodeling that leads to heart failure and death. At single-cell level, the ECM govern, metabolism, motility, orientation, and proliferation. However, in pathological condition such as diabetes, changes in ECM lead to fibrosis and subsequently cardiac stiffness and cardiomyocytes dysfunction. Antidiabetic drugs, particularly sodium-glucose cotransporter-2 (SGLT2) inhibitors have antifibrotic effects and may promote ECM reverse remodeling. In this review, the mechanisms, and the role of ECM remodeling and reverse remodeling as a potential therapeutic target for diabetic cardiomyopathy are discussed.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Extracellular Matrix; Fibrosis; Heart Failure; Humans; Myocytes, Cardiac
PubMed: 34713679
DOI: 10.23736/S2724-5683.21.05794-X -
Frontiers in Endocrinology 2021The global burden of diabetes mellitus and its complications are currently increasing. Diabetic cardiomyopathy (DCM) is the main cause of diabetes mellitus associated... (Review)
Review
The global burden of diabetes mellitus and its complications are currently increasing. Diabetic cardiomyopathy (DCM) is the main cause of diabetes mellitus associated morbidity and mortality; therefore, a comprehensive understanding of DCM development is required for more effective treatment. A disorder of epigenetic posttranscriptional modification of histones in chromatin has been reported to be associated with the pathology of DCM. Recent studies have implicated that histone deacetylases could regulate cardiovascular and metabolic diseases in cellular processes including cardiac fibrosis, hypertrophy, oxidative stress and inflammation. Therefore in this review, we summarized the roles of histone deacetylases in the pathogenesis of DCM, aiming to provide insights into exploring potential preventative and therapeutic strategies of DCM.
Topics: Diabetic Cardiomyopathies; Epigenesis, Genetic; Histone Deacetylases; Humans; Myocardium; Oxidative Stress
PubMed: 34367065
DOI: 10.3389/fendo.2021.679655 -
Pharmacology & Therapeutics Jul 2015Diabetes is a global health problem with more than 550 million people predicted to be diabetic by 2030. A major complication of diabetes is cardiovascular disease, which... (Review)
Review
Diabetes is a global health problem with more than 550 million people predicted to be diabetic by 2030. A major complication of diabetes is cardiovascular disease, which accounts for over two-thirds of mortality and morbidity in diabetic patients. This increased risk has led to the definition of a diabetic cardiomyopathy phenotype characterised by early left ventricular dysfunction with normal ejection fraction. Here we review the aetiology of diabetic cardiomyopathy and explore the involvement of the protein caveolin-3 (Cav3). Cav3 forms part of a complex mechanism regulating insulin signalling and glucose uptake, processes that are impaired in diabetes. Further, Cav3 is key for stabilisation and trafficking of cardiac ion channels to the plasma membrane and so contributes to the cardiac action potential shape and duration. In addition, Cav3 has direct and indirect interactions with proteins involved in excitation-contraction coupling and so has the potential to influence cardiac contractility. Significantly, both impaired contractility and rhythm disturbances are hallmarks of diabetic cardiomyopathy. We review here how changes to Cav3 expression levels and altered relationships with interacting partners may be contributory factors to several of the pathological features identified in diabetic cardiomyopathy. Finally, the review concludes by considering ways in which levels of Cav3 may be manipulated in order to develop novel therapeutic approaches for treating diabetic cardiomyopathy.
Topics: Animals; Caveolin 1; Caveolin 3; Diabetic Cardiomyopathies; Genetic Therapy; Glucose; Humans; Insulin; MicroRNAs; Molecular Targeted Therapy; Myocardial Contraction; Myocardium; Nitric Oxide Synthase; Oxidative Stress; Protein Processing, Post-Translational; Signal Transduction
PubMed: 25779609
DOI: 10.1016/j.pharmthera.2015.03.002 -
Advances in Experimental Medicine and... 2018Patients with type 1 and type 2 diabetes mellitus (T1D and T2D) show an increased incidence of heart failure (HF) even after adjustment for well established risk factors... (Review)
Review
Patients with type 1 and type 2 diabetes mellitus (T1D and T2D) show an increased incidence of heart failure (HF) even after adjustment for well established risk factors for HF such as hypertension and ischaemic heart disease. The resulting specific form of cardiomyopathy is known as diabetic cardiomyopathy" (DCM). Pathogenetic mechanisms underlying DCM are likely to be multifactorial, from altered myocardial metabolism (hyperglycaemia, hyperinsulinaemia, increased circulating fatty acids and trglycerides) to microvascular disease, autonomic neuropathy, and altered myocardial structure with fibrosis. Current medical treatment recommendations from scientific societies on HF in patients with diabetes mellitus (DM) do not differ from those for patients without DM. Regarding the effect of different hypoglycaemic drugs on HF in patients with DM, and considering the best available current evidence, the sodium-glucose-co-transporter 2 inhibitors and metformin seem to be especially advantageous regarding the effects in patients with T2D and HF.
Topics: Diabetic Cardiomyopathies; Heart Failure; Humans; Prevalence
PubMed: 28980272
DOI: 10.1007/5584_2017_105