Association between insulin resistance and the development of cardiovascular disease

Cardiovascular Diabetology, Journal Year: 2018, Volume and Issue: 17(1)

Published: Aug. 31, 2018

For many years, cardiovascular disease (CVD) has been the leading cause of death around world. Often associated with CVD are comorbidities such as obesity, abnormal lipid profiles and insulin resistance. Insulin is a key hormone that functions regulator cellular metabolism in tissues human body. resistance defined decrease tissue response to stimulation thus characterized by defects uptake oxidation glucose, glycogen synthesis, and, lesser extent, ability suppress oxidation. Literature widely suggests free fatty acids predominant substrate used adult myocardium for ATP production, however, cardiac metabolic network highly flexible can use other substrates, lactate or amino acids. During resistance, several alterations induce development disease. instance, an imbalance glucose generates chronic hyperglycemia, which turn triggers oxidative stress causes inflammatory leads cell damage. also alter systemic then dyslipidemia well-known triad: (1) high levels plasma triglycerides, (2) low high-density lipoprotein, (3) appearance small dense low-density lipoproteins. This triad, along endothelial dysfunction, be induced aberrant signaling, contribute atherosclerotic plaque formation. Regarding consequences alterations, it concluded damage at least three different mechanisms: signal transduction alteration, impaired regulation metabolism, altered delivery substrates myocardium. The aim this review discuss mechanisms CVD. New therapies focused on decreasing may both generation.

Language: Английский

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Diabetic Cardiomyopathy

Circulation Research, Journal Year: 2018, Volume and Issue: 122(4), P. 624 - 638

Published: Feb. 15, 2018

Heart failure and related morbidity mortality are increasing at an alarming rate, in large part, because of increases aging, obesity, diabetes mellitus. The clinical outcomes associated with heart considerably worse for patients mellitus than those without In people mellitus, the presence myocardial dysfunction absence overt coronary artery disease, valvular other conventional cardiovascular risk factors, such as hypertension dyslipidemia, has led to descriptive terminology, diabetic cardiomyopathy. prevalence cardiomyopathy is parallel increase Diabetic initially characterized by fibrosis, dysfunctional remodeling, diastolic dysfunction, later systolic eventually failure. Impaired cardiac insulin metabolic signaling, mitochondrial oxidative stress, reduced nitric oxide bioavailability, elevations advanced glycation end products collagen-based cardiomyocyte extracellular matrix stiffness, impaired calcium handling, inflammation, renin-angiotensin-aldosterone system activation, autonomic neuropathy, endoplasmic reticulum microvascular a myriad abnormalities have all been implicated development progression Molecular mechanisms linked underlying pathophysiological changes include AMP-activated protein kinase, peroxisome proliferator-activated receptors, O-linked N-acetylglucosamine, kinase C, microRNA, exosome pathways. aim this review provide contemporary view these instigators cardiomyopathy, well mechanistically based strategies prevention treatment

Language: Английский

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Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease

Diabetologia, Journal Year: 2017, Volume and Issue: 61(1), P. 21 - 28

Published: Aug. 3, 2017

Language: Английский

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Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence

Nature Reviews Cardiology, Journal Year: 2020, Volume and Issue: 17(9), P. 585 - 607

Published: Feb. 20, 2020

Language: Английский

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Heart Failure in Type 2 Diabetes Mellitus

Circulation Research, Journal Year: 2019, Volume and Issue: 124(1), P. 121 - 141

Published: Jan. 3, 2019

Patients with diabetes mellitus have >2× the risk for developing heart failure (HF; HF reduced ejection fraction and preserved fraction). Cardiovascular outcomes, hospitalization, prognosis are worse patients relative to those without. Beyond structural functional changes that characterize diabetic cardiomyopathy, a complex underlying, interrelated pathophysiology exists. Despite success of many commonly used antihyperglycemic therapies lower hyperglycemia in type 2 high prevalence persists. This, therefore, raises possibility additional factors beyond glycemia might contribute increased mellitus. This review summarizes state knowledge about impact existing on discusses potential mechanisms beneficial or deleterious effects. Second, we currently approved pharmacological evidence addresses their efficacy context Dysregulation cellular multiple models cardiomyopathy human hearts been described. These include oxidative stress, inflammation, endoplasmic reticulum aberrant insulin signaling, accumulation advanced glycated end-products, altered autophagy, myocardial substrate metabolism mitochondrial bioenergetics, lipotoxicity, signal transduction such as GRK (g-protein receptor kinase) renin angiotensin aldosterone signaling β-2 adrenergic signaling. pathophysiological pathways be amenable therapy reduce Successful targeting these could alter what is achieved using therapeutics.

Language: Английский

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Insulin resistance, cardiovascular stiffening and cardiovascular disease

Metabolism, Journal Year: 2021, Volume and Issue: 119, P. 154766 - 154766

Published: March 23, 2021

Language: Английский

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Triglyceride-glucose index as a marker in cardiovascular diseases: landscape and limitations

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: May 6, 2022

Abstract The triglyceride-glucose (TyG) index has been identified as a reliable alternative biomarker of insulin resistance (IR). Recently, considerable number studies have provided robust statistical evidence suggesting that the TyG is associated with development and prognosis cardiovascular disease (CVD). Nevertheless, application marker CVD not systemically evaluated, even less information exists regarding underlying mechanisms CVD. To this end, in review, we summarize history use surrogate for IR. We aimed to highlight value variety types explore potential limitations using predictor events improve its provide more extensive precise supporting evidence.

Language: Английский

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Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes

Circulation Research, Journal Year: 2016, Volume and Issue: 118(11), P. 1808 - 1829

Published: May 26, 2016

The clinical correlations linking diabetes mellitus with accelerated atherosclerosis, cardiomyopathy, and increased post-myocardial infarction fatality rates are increasingly understood in mechanistic terms. multiple mechanisms discussed this review seem to share a common element: prolonged increases reactive oxygen species (ROS) production diabetic cardiovascular cells. Intracellular hyperglycemia causes excessive ROS production. This activates nuclear poly(ADP-ribose) polymerase, which inhibits GAPDH, shunting early glycolytic intermediates into pathogenic signaling pathways. polymerase also reduce sirtuin, PGC-1α, AMP-activated protein kinase activity. These changes cause decreased mitochondrial biogenesis, production, disturbed circadian clock synchronization of glucose lipid metabolism. Excessive facilitates transport proatherogenic transcription factors, the neutrophil enzyme initiating NETosis, peptidylarginine deiminase 4, NOD-like receptor family, pyrin domain-containing 3 inflammasome. Insulin resistance cardiomyocyte by increasing fatty acid flux oxidation. stimulates overexpression PPARα translocation forkhead box O 1, cardiomyopathy. shift balance between fusion fission favor fission, reducing metabolic capacity efficiency electron chain ATP synthesis. Mitochondrial oxidative stress plays central role angiotensin II–induced gap junction remodeling arrhythmogenesis. contribute sudden death diabetics after myocardial post-translational modifications, ryanodine phosphorylation downregulation sarco-endoplasmic reticulum Ca ++ -ATPase transcription. Increased depress autonomic ganglion synaptic transmission oxidizing nAch α3 subunit, potentially contributing risk fatal cardiac arrhythmias associated neuropathy.

Language: Английский

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Basic Mechanisms of Diabetic Heart Disease

Circulation Research, Journal Year: 2020, Volume and Issue: 126(11), P. 1501 - 1525

Published: May 21, 2020

Diabetes mellitus predisposes affected individuals to a significant spectrum of cardiovascular complications, one the most debilitating in terms prognosis is heart failure. Indeed, increasing global prevalence diabetes and an aging population has given rise epidemic mellitus-induced Despite research attention this phenomenon, termed diabetic cardiomyopathy, received over several decades, understanding full potential contributing mechanisms, their relative contribution failure phenotype specific context mellitus, not yet been fully resolved. Key recent preclinical discoveries that comprise current state-of-the-art basic mechanisms complex phenotype, is, heart, form basis review. Abnormalities each cardiac metabolism, physiological pathophysiological signaling, mitochondrial compartment, addition oxidative stress, inflammation, myocardial cell death pathways, neurohumoral are addressed. Further, interactions between these how they align functional, morphological, structural impairments characterize considered light clinical context: from disease burden, its management clinic, where knowledge gaps remain. The need for continued interrogation (both known those be identified) essential only decipher why but also facilitate improved inroads into pervasive challenge.

Language: Английский

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Updated Cardiovascular Prevention Guideline of the Brazilian Society of Cardiology - 2019

Arquivos Brasileiros de Cardiologia, Journal Year: 2019, Volume and Issue: unknown

Published: Jan. 1, 2019

Introducao A doenca cardiovascular (DCV) e a principal causa de morte no Brasil mundo, determinando aumento da morbidade incapacidade ajustadas pelos anos vida. Embora as taxas mortalidade disability-adjusted life year (DALY) padronizadas por idade estejam diminuindo Brasil, possivelmente como resultado politicas saude bem-sucedidas, o numero total destas esta aumentando principalmente devido ao envelhecimento adoecimento populacao. presenca dos fatores risco classicos (hipertensao, dislipidemia, obesidade, sedentarismo, tabagismo, diabetes [...]

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