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Anadolu Kardiyoloji Dergisi : AKD = the... Dec 2011Diabetic individuals are at significantly greater risk of developing heart failure (HF) independent from other risk factors such as coronary artery disease (CAD) and... (Review)
Review
Diabetic individuals are at significantly greater risk of developing heart failure (HF) independent from other risk factors such as coronary artery disease (CAD) and hypertension. Diabetic cardiomyopathy (DCP) is defined as ventricular dysfunction in the absence of hypertension, coronary artery and valvular heart disease, which increases the risk of HF. Due to better understanding of its pathophysiology and clinical importance, DCP is more frequently recognized in daily practice. The most important mechanisms of DCP are hyperglycemia, insulin resistance/hyperinsulinemia, abnormal fatty acid metabolism, increased apoptosis, cardiac autonomic neuropathy and local renin-angiotensin-aldosterone system (RAAS) overactivation. Echocardiography is the most frequently used diagnostic method for the detection of this pathology. Currently, although there is no specific treatment for DCP, strict glycemic and concomitant risk factor controls seems to be the most important target strategy for prevention of the progression and treatment of DCP. In this article, we aim to provide an extensive review on the pathophysiology, diagnosis, management of DCP.
Topics: Diabetic Cardiomyopathies; Echocardiography; Humans
PubMed: 22137942
DOI: 10.5152/akd.2011.196 -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2022Histone methylation is one of the key post-translational modifications that plays a critical role in various heart diseases, including diabetic cardiomyopathy. A great... (Review)
Review
Histone methylation is one of the key post-translational modifications that plays a critical role in various heart diseases, including diabetic cardiomyopathy. A great deal of evidence has shown that histone methylation is closely related to hyperglycemia, insulin resistance, lipid and advanced glycation end products deposition, inflammatory and oxidative stress, endoplasmic reticulum stress and cell apoptosis, and these pathological factors play an important role in the pathogenesis of diabetic cardiomyopathy. In order to provide a novel theoretical basis and potential targets for the treatment of diabetic cardiomyopathy from the perspective of epigenetics, this review discussed and elucidated the association between histone methylation and the pathogenesis of diabetic cardiomyopathy in details.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Histones; Humans; Methylation; Oxidative Stress; Protein Processing, Post-Translational
PubMed: 35770643
DOI: No ID Found -
Acta Diabetologica Sep 2011Diabetic cardiomyopathy has been defined as "a distinct entity characterized by the presence of abnormal myocardial performance or structure in the absence of epicardial... (Review)
Review
Diabetic cardiomyopathy has been defined as "a distinct entity characterized by the presence of abnormal myocardial performance or structure in the absence of epicardial coronary artery disease, hypertension, and significant valvular disease". The diagnosis stems from the detection of myocardial abnormalities and the exclusion of other contributory causes of cardiomyopathy. It rests on non-invasive imaging techniques which can demonstrate myocardial dysfunction across the spectra of clinical presentation. The presence of diabetes is associated with an increased risk of developing heart failure, and the 75% of patients with unexplained idiopathic dilated cardiomyopathy were found to be diabetic. Diabetic patients with microvascular complications show the strongest association between diabetes and cardiomyopathy, an association that parallels the duration and severity of hyperglycemia. Metabolic abnormalities (that is hyperglycemia, hyperinsulinemia, and hyperlipemia) can lead to the cellular alterations characterizing diabetic cardiomyopathy (that is myocardial fibrosis and/or myocardial hypertrophy) directly or indirectly (that is by means of renin-angiotensin system activation, cardiac autonomic neuropathy, alterations in calcium homeostasis). Moreover, metabolic abnormalities represent, on a clinical ground, the main therapeutic target in the patients with diabetes since the diagnosis of diabetes is made. Since diabetic cardiomyopathy is highly prevalent in the asymptomatic type 2 diabetic patients, screening for its presence at the earliest stage of development can lead to prevent the progression to chronic heart failure. The most sensitive test is standard echocardiogram, while a less expensive pre-screening method is the detection of microalbuminuria.
Topics: Animals; Cardiovascular System; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Disease Models, Animal; Humans
PubMed: 20198391
DOI: 10.1007/s00592-010-0180-x -
Redox Biology Feb 2024Ketone bodies are considered as an alternative energy source for diabetic cardiomyopathy (DCM) and can improve the energy supply of the heart muscle, suggesting that it...
Ketone bodies are considered as an alternative energy source for diabetic cardiomyopathy (DCM) and can improve the energy supply of the heart muscle, suggesting that it may be an important area of research and development as a therapeutic target for DCM. Cumulative cardiovascular trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in diabetic populations. Whether SGLT2 inhibitors improve DCM by enhancing ketone body metabolism remains and whether they help prevent oxidative damage remains to be clarified. Here, we present the combined results of nine GSE datasets for diabetic cardiomyopathy (GSE215979, GSE161931, GSE145294, GSE161052, GSE173384, GSE123975, GSE161827, GSE210612, and GSE5606). We found significant up-regulated gene 3-hydroxymethylglutaryl CoA synthetase 2 (HMGCS2) and down-regulated gene 3-hydroxybutyrate dehydrogenase (BDH1) and 3-oxoacid CoA-transferase1 (OXCT1), respectively. Based on the analysis of the constructed protein interaction network, it was found that HMGCS2 was in the core position of the interaction network. In addition, Gene ontology (GO) enrichment analysis mainly focused on redox process, acyl-CoA metabolic process, catalytic activity, redox enzyme activity and mitochondria. The activity of HMGCS2 in DCM heart was increased, while the expression of ketolysis enzymes BDH1 and OXCT1 was inhibited. In vivo, Empagliflozin (Emp) treated DCM group significantly decreased ventricular weight, myocardial cell cross-sectional area, and myocardial fibrosis. In addition, Emp further promoted the activity of BDH1 and OXCT1, increased the utilization of ketone bodies, further promoted the activity of HMGCS2 in DCM, and increased the synthesis of ketone bodies, prevented mitochondrial breakage and dysfunction, increased myocardial ATP to provide sufficient energy, inhibited oxidative stress and apoptosis of cardiac cells ex vivo, and improved the myocardial dysfunction of DCM. Emp can improve mitochondrial dysfunction in diabetic cardiomyopathy by regulating ketone body metabolism and oxidative stress. These findings provide a theoretical basis for evaluating Emp as a treatment for DCM.
Topics: Humans; Diabetic Cardiomyopathies; Oxidative Stress; Myocytes, Cardiac; Ketone Bodies; Mitochondrial Diseases; Diabetes Mellitus; Benzhydryl Compounds; Glucosides
PubMed: 38160540
DOI: 10.1016/j.redox.2023.103010 -
Cardiovascular Diabetology Feb 2017Diabetic cardiomyopathy (DCM) is a cardiac dysfunction which affects approximately 12% of diabetic patients, leading to overt heart failure and death. However, there is... (Review)
Review
Diabetic cardiomyopathy (DCM) is a cardiac dysfunction which affects approximately 12% of diabetic patients, leading to overt heart failure and death. However, there is not an efficient and specific methodology for DCM diagnosis, possibly because molecular mechanisms are not fully elucidated, and it remains asymptomatic for many years. Also, DCM frequently coexists with other comorbidities such as hypertension, obesity, dyslipidemia, and vasculopathies. Thus, human DCM is not specifically identified after heart failure is established. In this sense, echocardiography has been traditionally considered the gold standard imaging test to evaluate the presence of cardiac dysfunction, although other techniques may cover earlier DCM detection by quantification of altered myocardial metabolism and strain. In this sense, Phase-Magnetic Resonance Imaging and 2D/3D-Speckle Tracking Echocardiography may potentially diagnose and stratify diabetic patients. Additionally, this information could be completed with a quantification of specific plasma biomarkers related to related to initial stages of the disease. Cardiotrophin-1, activin A, insulin-like growth factor binding protein-7 (IGFBP-7) and Heart fatty-acid binding protein have demonstrated a stable positive correlation with cardiac hypertrophy, contractibility and steatosis responses. Thus, we suggest a combination of minimally-invasive diagnosis tools for human DCM recognition based on imaging techniques and measurements of related plasma biomarkers.
Topics: Diabetic Cardiomyopathies; Echocardiography; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon
PubMed: 28231848
DOI: 10.1186/s12933-017-0506-x -
Nature Reviews. Cardiology Apr 2021Diabesity is a term used to describe the combined adverse health effects of obesity and diabetes mellitus. The worldwide dual epidemic of obesity and type 2 diabetes is... (Review)
Review
Diabesity is a term used to describe the combined adverse health effects of obesity and diabetes mellitus. The worldwide dual epidemic of obesity and type 2 diabetes is an important public health issue. Projections estimate a sixfold increase in the number of adults with obesity in 40 years and an increase in the number of individuals with diabetes to 642 million by 2040. Increased adiposity is the strongest risk factor for developing diabetes. Early detection of the effects of diabesity on the cardiovascular system would enable the optimal implementation of effective therapies that prevent atherosclerosis progression, cardiac remodelling, and the resulting ischaemic heart disease and heart failure. Beyond conventional imaging techniques, such as echocardiography, CT and cardiac magnetic resonance, novel post-processing tools and techniques provide information on the biological processes that underlie metabolic heart disease. In this Review, we summarize the effects of obesity and diabetes on myocardial structure and function and illustrate the use of state-of-the-art multimodality cardiac imaging to elucidate the pathophysiology of myocardial dysfunction, prognosticate long-term clinical outcomes and potentially guide treatment strategies.
Topics: Adult; Child; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Heart Diseases; Humans; Myocardium; Obesity; United States
PubMed: 33188304
DOI: 10.1038/s41569-020-00465-5 -
Acta Diabetologica Aug 2021Growing interest has been accumulated in the definition of worsening effects of diabetes in the cardiovascular system. This is associated with epidemiological data... (Review)
Review
Growing interest has been accumulated in the definition of worsening effects of diabetes in the cardiovascular system. This is associated with epidemiological data regarding the high incidence of heart failure (HF) in diabetic patients. To investigate the detrimental effects both of hyperglycemia and insulin resistance, a lot of preclinical models were developed. However, the evidence of pathogenic and histological alterations of the so-called diabetic cardiomyopathy (DCM) is still poorly understood in humans. Here, we provide a stringent literature analysis to investigate unique data regarding human DCM. This approach established that lipotoxic-related events might play a central role in the initiation and progression of human DCM. The major limitation in the acquisition of human data is due to the fact of heart specimen availability. Postmortem analysis revealed the end stage of the disease; thus, we need to gain knowledge on the pathogenic events from the early stages until cardiac fibrosis underlying the end-stage HF.
Topics: Diabetes Mellitus; Diabetic Cardiomyopathies; Disease Progression; Heart; Heart Failure; Humans; Hyperglycemia; Insulin Resistance; Myocardium
PubMed: 33791873
DOI: 10.1007/s00592-021-01705-x -
Cardiovascular Diabetology Aug 2023Myocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and...
BACKGROUND
Myocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and trigger of myocardial microvascular disease. Mitochondrial calcium homeostasis plays an important role in maintaining the normal function, survival and death of endothelial cells. Considering that mitochondrial calcium uptake 1 (MICU1) is a key molecule in mitochondrial calcium regulation, this study aimed to investigate the role of MICU1 in CMECs and explore its underlying mechanisms.
METHODS
To examine the role of endothelial MICU1 in diabetic cardiomyopathy (DCM), we used endothelial-specific MICU1 mice to establish a diabetic mouse model and evaluate the cardiac function. In addition, MICU1 overexpression was conducted by injecting adeno-associated virus 9 carrying MICU1 (AAV9-MICU1). Transcriptome sequencing technology was used to explore underlying molecular mechanisms.
RESULTS
Here, we found that MICU1 expression is decreased in CMECs of diabetic mice. Moreover, we demonstrated that endothelial cell MICU1 knockout exacerbated the levels of cardiac hypertrophy and interstitial myocardial fibrosis and led to a further reduction in left ventricular function in diabetic mice. Notably, we found that AAV9-MICU1 specifically upregulated the expression of MICU1 in CMECs of diabetic mice, which inhibited nitrification stress, inflammatory reaction, and apoptosis of the CMECs, ameliorated myocardial hypertrophy and fibrosis, and promoted cardiac function. Further mechanistic analysis suggested that MICU1 deficiency result in excessive mitochondrial calcium uptake and homeostasis imbalance which caused nitrification stress-induced endothelial damage and inflammation that disrupted myocardial microvascular endothelial barrier function and ultimately promoted DCM progression.
CONCLUSIONS
Our findings demonstrate that MICU1 expression was downregulated in the CMECs of diabetic mice. Overexpression of endothelial MICU1 reduced nitrification stress induced apoptosis and inflammation by inhibiting mitochondrial calcium uptake, which improved myocardial microvascular function and inhibited DCM progression. Our findings suggest that endothelial MICU1 is a molecular intervention target for the potential treatment of DCM.
Topics: Animals; Mice; Calcium; Calcium-Binding Proteins; Dependovirus; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Endothelial Cells; Inflammation; Mitochondrial Membrane Transport Proteins
PubMed: 37592255
DOI: 10.1186/s12933-023-01941-1 -
ESC Heart Failure Apr 2023Diabetes mellitus (DM) is a serious epidemic around the globe, and cardiovascular diseases account for the majority of deaths in patients with DM. Diabetic... (Review)
Review
Diabetes mellitus (DM) is a serious epidemic around the globe, and cardiovascular diseases account for the majority of deaths in patients with DM. Diabetic cardiomyopathy (DCM) is defined as a cardiac dysfunction derived from DM without the presence of coronary artery diseases and hypertension. Patients with either type 1 or type 2 DM are at high risk of developing DCM and even heart failure. Metabolic disorders of obesity and insulin resistance in type 2 diabetic environments result in dyslipidaemia and subsequent lipid-induced toxicity (lipotoxicity) in organs including the heart. Although various mechanisms have been proposed underlying DCM, it remains incompletely understood how lipotoxicity alters cardiac function and how DM induces clinical heart syndrome. With recent progress, we here summarize the latest discoveries on lipid-induced cardiac toxicity in diabetic hearts and discuss the underlying therapies and controversies in clinical DCM.
Topics: Humans; Diabetic Cardiomyopathies; Heart Failure; Diabetes Mellitus, Type 2; Insulin Resistance; Lipids
PubMed: 36369594
DOI: 10.1002/ehf2.14224 -
Hamostaseologie 2015Cardiovascular disease is the major cause of morbidity and mortality in subjects suffering from diabetes mellitus. While coronary artery disease is the leading cause of... (Review)
Review
Cardiovascular disease is the major cause of morbidity and mortality in subjects suffering from diabetes mellitus. While coronary artery disease is the leading cause of cardiac complications in diabetics, it is widely recognized that diabetes increases the risk for the development of heart failure independently of coronary heart disease and hypertension. This increased susceptibility of the diabetic heart to develop structural and functional impairment is termed diabetic cardiomyopathy. The number of different mechanisms proposed to contribute to diabetic cardiomyopathy is steadily increasing and underlines the complexity of this cardiac entity. In this review the mechanisms that account for the increased myocardial vulnerability in diabetic cardiomyopathy are discussed.
Topics: Animals; Cytokines; Diabetic Cardiomyopathies; Heart; Humans; Models, Cardiovascular; Oxidative Stress; Reactive Oxygen Species; Ventricular Dysfunction, Left
PubMed: 25408270
DOI: 10.5482/HAMO-14-09-0038