Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date.

ABSTRACT: The prevalence of type 2 diabetes (T2D) has increased worldwide and doubled over the last two decades. It features among the top 10 causes of mortality and morbidity in the world. Cardiovascular disease is the leading cause of complications in diabetes and within this, heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom. There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops. This review aims to give an overview of these mechanisms, with particular emphasis on metabolic inflexibility. T2D is associated with inefficient substrate utilisation, an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure. The review also gives a concise update on developments within clinical imaging, specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D. A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.

SUBMITTER: Athithan L

PROVIDER: S-EPMC6801309 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Role of micro-RNAs in pathophysiology of diabetic cardiomyopathy.

Project description:Diabetic cardiomyopathy (DCM), occurs independent of Hypertension, Coronary artery disease, or any other known cardiac disease and is characterized by myocardial fibrosis, myocytes loss and hypertrophy. The molecular mechanisms leading to these diseased cardiac phenotype are still being elucidated. A small number of studies have demonstrated that altered expression of several microRNAs are associated with ischemia , mechanical overload, or cardiovascular biology; however, much work is still required to identify individual or group of microRNAs and their role in the pathophysiology of diabetic cardiomyopathy. The aim of present study was to identify the expression of individual or group of microRNAs associated with myocytes hypertrophy and myocardial fibrosis during DCM. MicroRNAs expression profiles were studied in myocardium from High Fat diet and streptozotocin (STZ) induced diabetic (n=4) and non-diabetic (n=2) Wistar rats. All normalized and filtered microRNAs (n=780) processed for differential expression study using unpaired T-test in Gene spring in which unpaired comparison has been performed as test vs. control. After unpaired T-test, total 72 microRNAs were found to be significantly expressed with P-value ≤0.05. Differentially expression analysis was performed and at fold Change cut off ≥ 1.0, all 780 microRNA passed and 39 out of 780 microRNAs were differentially expressed on fold Change cut-off ≥1.5. These results indicate that during the development and progression of DCM, various microRNAs were differentially expressed and may participate in the regulation of various signaling pathways leading to myocytes hypertrophy, apoptosis and cardiac fibrosis.

2014-12-31 | GSE44179 | GEO

Diabetic Retinopathy: Pathophysiology and Treatments.

Project description:Diabetic retinopathy (DR) is the most common complication of diabetes mellitus (DM). It has long been recognized as a microvascular disease. The diagnosis of DR relies on the detection of microvascular lesions. The treatment of DR remains challenging. The advent of anti-vascular endothelial growth factor (VEGF) therapy demonstrated remarkable clinical benefits in DR patients; however, the majority of patients failed to achieve clinically-significant visual improvement. Therefore, there is an urgent need for the development of new treatments. Laboratory and clinical evidence showed that in addition to microvascular changes, inflammation and retinal neurodegeneration may contribute to diabetic retinal damage in the early stages of DR. Further investigation of the underlying molecular mechanisms may provide targets for the development of new early interventions. Here, we present a review of the current understanding and new insights into pathophysiology in DR, as well as clinical treatments for DR patients. Recent laboratory findings and related clinical trials are also reviewed.

| S-EPMC6032159 | biostudies-literature

Pathophysiology of the diabetic kidney.

Project description:Diabetes mellitus contributes greatly to morbidity, mortality, and overall health care costs. In major part, these outcomes derive from the high incidence of progressive kidney dysfunction in patients with diabetes making diabetic nephropathy a leading cause of end-stage renal disease. A better understanding of the molecular mechanism involved and of the early dysfunctions observed in the diabetic kidney may permit the development of new strategies to prevent diabetic nephropathy. Here we review the pathophysiological changes that occur in the kidney in response to hyperglycemia, including the cellular responses to high glucose and the responses in vascular, glomerular, podocyte, and tubular function. The molecular basis, characteristics, and consequences of the unique growth phenotypes observed in the diabetic kidney, including glomerular structures and tubular segments, are outlined. We delineate mechanisms of early diabetic glomerular hyperfiltration including primary vascular events as well as the primary role of tubular growth, hyperreabsorption, and tubuloglomerular communication as part of a "tubulocentric" concept of early diabetic kidney function. The latter also explains the "salt paradox" of the early diabetic kidney, that is, a unique and inverse relationship between glomerular filtration rate and dietary salt intake. The mechanisms and consequences of the intrarenal activation of the renin-angiotensin system and of diabetes-induced tubular glycogen accumulation are discussed. Moreover, we aim to link the changes that occur early in the diabetic kidney including the growth phenotype, oxidative stress, hypoxia, and formation of advanced glycation end products to mechanisms involved in progressive kidney disease.

| S-EPMC6029262 | biostudies-literature

Physical Exercise and Its Protective Effects on Diabetic Cardiomyopathy: What Is the Evidence?

Project description:As one of the most serious complications of diabetes, diabetic cardiomyopathy (DCM) imposes a huge burden on individuals and society, and represents a major public health problem. It has long been recognized that physical exercise has important health benefits for patients with type 2 diabetes, and regular physical exercise can delay or prevent the complications of diabetes. Current studies show that physical exercise has been regarded as an importantly non-pharmacological treatment for diabetes and DCM, with high efficacy and low adverse events. It can inhibit the pathological processes of myocardial apoptosis, myocardial fibrosis, and myocardial microvascular diseases through improving myocardial metabolism, enhancing the regulation of Ca2+, and protecting the function of mitochondria. Eventually, it can alleviate the occurrence and development of diabetic complications. Describing the mechanisms of physical exercise on DCM may provide a new theory for alleviating, or even reversing the development of DCM, and prevent it from developing to heart failure.

| S-EPMC6286969 | biostudies-literature

Pathophysiology and therapeutics of arrhythmogenic right ventricular cardiomyopathy 5

Project description:Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited cardiac disease characterized by fibro-fatty replacement of the myocardium that causes heart failure and sudden cardiac death. The most aggressive subtype of ARVC is ARVC type 5 (ARVC5), caused by a p.S358L mutation in TMEM43. The function and localization of TMEM43 and the mechanism by which the p.S358L mutation causes the disease, are unknown.

2019-07-12 | GSE101301 | GEO

Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets.

Project description:Diabetes is a worldwide epidemic that has led to a rise in diabetic kidney disease (DKD). Over the past two decades, there has been significant clarification of the various pathways implicated in the pathogenesis of DKD. Nonetheless, very little has changed in the way clinicians manage patients with this disorder. Indeed, treatment is primarily centered on controlling hyperglycemia and hypertension and inhibiting the renin-angiotensin system. The purpose of this review is to describe the current understanding of how the hemodynamic, metabolic, inflammatory, and alternative pathways are all entangled in pathogenesis of DKD and detail the various therapeutic targets that may one day play a role in quelling this epidemic.

| S-EPMC4430644 | biostudies-other

Venetoclax: evidence to date and clinical potential.

Project description:The emergence of targeted therapy for patients with hematological diseases has permanently altered the therapeutic landscape. Immunochemotherapy regimes are now more and more being replaced by targeted therapies due to superior efficacy and better safety profiles. However, evolution and selection of subclones with continuous treatment leads to disease relapse and resistance toward these novel drugs. Venetoclax, the highly selective BCL-2 inhibitor (ABT-199), has an acceptable safety profile. To date, it has been approved for the treatment of first-line and relapsed/refractory chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, extension of indications can be expected in monotherapy and in combination regimens with promising outcomes in other hematological diseases. In this article, we describe the mechanism of action that stands behind the efficacy of venetoclax and provide a summary of available results from clinical trials.

| S-EPMC6788387 | biostudies-literature

Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats.

Project description:Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ?+?SPR) or saline (STZ?+?NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-?1, TNF-?, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ?+?NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.

| S-EPMC6204188 | biostudies-literature

Non-Invasive Imaging in Diabetic Cardiomyopathy.

Project description:There is increasing recognition of a specific diabetic cardiomyopathy beyond ischemic cardiomyopathy, which leads to structural and functional myocardial abnormalities. The aim of this review is to summarize the recent literature on diagnostic findings and prognostic significance of non-invasive imaging including echocardiography, nuclear imaging, computed tomography and cardiovascular magnetic resonance in diabetic cardiomyopathy.

| S-EPMC6617232 | biostudies-literature

Pathophysiology of Diabetic Retinopathy: The Old and the New.

Project description:Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities-including hyperpermeability, hypoperfusion, and neoangiogenesis-that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.

| S-EPMC6202564 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data