Metabolic remodelling in diabetic cardiomyopathy

AbstractDiabetes is a risk factor for heart failure and cardiovascular mortality with specific changes to myocardial metabolism, energetics, structure, and function. The gradual impairment of insulin production and signalling in diabetes is associated with elevated plasma fatty acids and increased myocardial free fatty acid uptake and activation of the transcription factor PPARα. The increased free fatty acid uptake results in accumulation of toxic metabolites, such as ceramide and diacylglycerol, activation of protein kinase C, and elevation of uncoupling protein-3. Insulin signalling and glucose uptake/oxidation become further impaired, and mitochondrial function and ATP production become compromised. Increased oxidative stress also impairs mitochondrial function and disrupts metabolic pathways. The diabetic heart relies on free fatty acids (FFA) as the major substrate for oxidative phosphorylation and is unable to increase glucose oxidation during ischaemia or hypoxia, thereby increasing myocardial injury, especially in ageing female diabetic animals. Pharmacological activation of PPARγ in adipose tissue may lower plasma FFA and improve recovery from myocardial ischaemic injury in diabetes. Not only is the diabetic heart energetically-impaired, it also has early diastolic dysfunction and concentric remodelling. The contractile function of the diabetic myocardium negatively correlates with epicardial adipose tissue, which secretes proinflammatory cytokines, resu...
Source: Cardiovascular Research - Category: Cardiology Source Type: research

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CONCLUSION: Our results indicate the potential role of immediate (5 min) or early (15 min) acquisition in replacement of standardized 240 minutes acquisition in PD patients, but this result is not confirmed in HF patients, in which the acquisition at 240 min is confirmed as the most affordable timing for image interpretation, emphasizing the different pathophysiology that underlies these two pathologies. PMID: 31985388 [PubMed - as supplied by publisher]
Source: Current Radiopharmaceuticals - Category: Radiology Tags: Curr Radiopharm Source Type: research
ConclusionThe CAPACITY HFpEF trial will provide data on short-term safety and efficacy of praliciguat on peak exercise capacity, as well as multiple secondary endpoints of submaximal functional capacity, patient-reported outcomes, and biomarkers.
Source: American Heart Journal - Category: Cardiology Source Type: research
Diabetes mellitus type 2 (DM2) is a risk factor for developing heart failure but there is no specific therapy for diabetic heart disease. Sodium glucose transporter 2 inhibitors (SGLT2I) are recently developed...
Source: Cardiovascular Diabetology - Category: Cardiology Authors: Tags: Original investigation Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31845331 [PubMed - as supplied by publisher]
Source: The Journal of Physiology - Category: Physiology Authors: Tags: J Physiol Source Type: research
We examined the association between HR obtained at admission at Day 4 and at discharge and long ‐term mortality in a cohort of 672 patients discharge from hospital after management of acute HF.Methods and resultsAll patients examined were in sinus rhythm. HR was derived from electrocardiogram and was defined as the first reported HR in the medical record. At 1  year follow up, 60 patients died. Median HR was 86 ± 17 b.p.m. (first tertile: 75 b.p.m., third tertile: 97 b.p.m.) at admission, 76 ± 14 b.p.m. (first tertile: 67 b.p.m., third tertile 85 b.p.m....
Source: ESC Heart Failure - Category: Cardiology Authors: Tags: Short Communication Source Type: research
Glucagon-like peptide-1 (GLP-1) reduces cardiovascular events in diabetic patients; however, its counter-protective effects have also been suggested in patients with heart failure and the clear explanation for...
Source: Cardiovascular Diabetology - Category: Cardiology Authors: Tags: Original investigation Source Type: research
Publication date: Available online 25 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Xianxiu Wan, KarryAnne Belanger, Steven G. Widen, Muge N. Kuyumcu-Martinez, Nisha J. GargAbstractAberrations in the cGMP-PKG-Ca2+ pathway are implicated in cardiovascular complications of diverse etiologies, though involved molecular mechanisms are not understood. We performed RNA-Seq analysis to profile global changes in gene expression and exon splicing in Chagas disease (ChD) murine myocardium. Ingenuity-Pathway-Analysis of transcriptome dataset identified 26 differentially expressed gene...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
This study demonstrates for the first time that senescent cells secrete functional LTs, significantly contributing to the LTs pool known to cause or exacerbate idiopathic pulmonary fibrosis. Against Senolytics There is no consensus in science that is so strong as to have no heretics. So here we have an interview with a naysayer on the matter of senolytic treatments, who argues that the loss of senescent cells in aged tissues will cause more harm to long-term health than the damage they will do by remaining. To be clear, I think this to be a ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The increasing burden of heart failure globally can be partly attributed to the increased prevalence of diabetes, and the subsequent development of a distinct form of heart failure known as diabetic cardiomyopathy. Despite this, effective treatment options have remained elusive, due partly to the lack of an experimental model that adequately mimics human disease. In the current study, we combined three consecutive daily injections of low-dose streptozotocin with high-fat diet, in order to recapitulate the long-term complications of diabetes, with a specific focus on the diabetic heart. At 26 weeks of diabetes, several meta...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Recent data indicate that optimal cardiovascular (CV) risk management negates most of the increased CV risk associated with diabetes mellitus.1 However, there was a persistent increased risk of heart failure (HF). Recent studies showing the beneficial effect of SGLT2 inhibitors in reducing incident HF highlights the need for new ways of identifying those at highest risk of HF and personalizing therapeutic interventions to this group.2 As the onset of HF is mediated by the development of a cardiomyopathy, the use of natriuretic peptide (NP) screening might highlight those at higher risk.
Source: Journal of Cardiac Failure - Category: Cardiology Authors: Tags: Research Letter Source Type: research
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