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Type 2 Diabetes and Cardiovascular Disease: Pathophysiological Mechanisms and Effects of SGLT-2i and GLP-1RAs

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 15757

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Special Issue Editors

Prof. Dr. Elena Succurro

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Guest Editor

Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy
Interests: prediabetes; type 2 diabetes; myocardial insulin resistance; cardiovascular organ damage; sex differences in prediabetes, type 2 diabetes and cardiovascular disease; mechanism of action of SGLT2i; gestational diabetes

Prof. Dr. Angela Sciacqua

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Guest Editor

1. Associate Professor of Internal Medicine, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
2. National Abilitation to Full Professor of Internal Medicine, 88100 Catanzaro, Italy
3. Director of Specialization School in Geriatrics, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
4. Director of Geriatric Division – Mater Domini University Hospital-Catanzaro, 88100 Catanzaro, Italy
Interests: cardiovascular and metabolic disease (chronic heart failure; arterial hypertension; insulin resistance; type 2 diabetes mellitus; cardiovascular biomarkers so as uric acid)

Special Issue Information

Dear Colleagues,

Type 2 diabetes (T2DM) is an independent risk factor for ischemic heart disease, stroke, and heart failure, and cardiovascular diseases (CVD) are the main cause of mortality and morbidity in patients with T2DM. It is estimated that the incidence of fatal and nonfatal coronary events in diabetic people is 1.5 to 3-4 times higher than in non-diabetic subjects of the same age. Moreover, increasing evidence suggests that the relative risk for CVD and mortality is higher in women than in men with diabetes.

Alterations in endothelial function and oxidative stress can contribute to the development of atherosclerotic lesion and may represent the mechanistic link between type 2 diabetes and cardiovascular diseases.

The prevention of cardiovascular events is a key goal in the management of patients with T2DM. Recent evidence from cardiovascular outcomes trials (CVOTs) demonstrated the benefits of the new classes of antihyperglycemic drugs—sodium-glucose-cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists—on the cardiovascular outcomes. However, the mechanisms through which treatments with SGLT-2i and GLP-1RAs are associated with an improvement in cardiovascular outcomes are not fully understood.

This Special Issue aims to publish original research and review articles concerning significant findings in the field of type 2 diabetes and CVD, in order to explore more processes that contribute to a better understanding of the pathophysiology of cardiovascular disease in patients with T2DM and to learn about new research on the CV protection mechanisms of SGLT-2i and GLP-1RAs.

Prof. Dr. Elena Succurro
Prof. Dr. Angela Sciacqua
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Type 2 diabetes
Cardiovascular disease
Sex differences in type 2 diabetes and cardiovascular disease
SGLT-2i
GLP-1RAs
Endothelial dysfunction
Oxidative stress
Atherosclerosis
Cardiovascular risk factors
Insulin resistance
Cardiovascular organ damage
Arterial stiffness
Prevention of cardiovascular disease
Heart failure

Published Papers (3 papers)

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Research

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19 pages, 3021 KiB

Open AccessArticle

Effect of Empagliflozin on Sphingolipid Catabolism in Diabetic and Hypertensive Rats

by Roxana Pérez-Villavicencio, Javier Flores-Estrada, Martha Franco, Bruno Escalante, Oscar Pérez-Méndez, Adriana Mercado and Rocio Bautista-Pérez

Int. J. Mol. Sci. 2022, 23(5), 2883; https://doi.org/10.3390/ijms23052883 - 07 Mar 2022

Cited by 5 | Viewed by 2413

Abstract

The profile of sphingomyelin and its metabolites shows changes in the plasma, organs, and tissues of patients with cardiovascular, renal, and metabolic diseases. The objective of this study was to investigate the effect of empagliflozin on the levels of sphingomyelin and its metabolites, as well as on the activity of acid and neutral sphingomyelinase (aSMase and nSMase) and neutral ceramidase (nCDase) in the plasma, kidney, heart, and liver of streptozotocin-induced diabetic and Angiotensin II (Ang II)-induced hypertension rats. Empagliflozin treatment decreased hyperglycemia in diabetic rats whereas blood pressure remained elevated in hypertensive rats. In diabetic rats, empagliflozin treatment decreased sphingomyelin in the plasma and liver, ceramide in the heart, sphingosine-1-phosphate (S1P) in the kidney, and nCDase activity in the plasma, heart, and liver. In hypertensive rats, empagliflozin treatment decreased sphingomyelin in the plasma, kidney, and liver; S1P in the plasma and kidney; aSMase in the heart, and nCDase activity in the plasma, kidney, and heart. Our results suggest that empagliflozin downregulates the interaction of the de novo pathway and the catabolic pathway of sphingolipid metabolism in the diabetes, whereas in Ang II-dependent hypertension, it only downregulates the sphingolipid catabolic pathway. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Cardiovascular Disease: Pathophysiological Mechanisms and Effects of SGLT-2i and GLP-1RAs)

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Review

Jump to: Research

18 pages, 1094 KiB

Open AccessReview

Glucagon-like Peptide-1 Receptor Agonists in the Management of Type 2 Diabetes Mellitus and Obesity: The Impact of Pharmacological Properties and Genetic Factors

by Jasna Klen and Vita Dolžan

Int. J. Mol. Sci. 2022, 23(7), 3451; https://doi.org/10.3390/ijms23073451 - 22 Mar 2022

Cited by 18 | Viewed by 4238

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of antihyperglycemic drugs that enhance appropriate pancreatic β-cell secretion, pancreatic α-cell (glucagon) suppression, decrease liver glucose production, increase satiety through their action on the central nervous system, slow gastric emptying time, and increase insulin action on peripheral tissue. They are effective in the management of type 2 diabetes mellitus and have a favorable effect on weight loss. Their cardiovascular and renal safety has been extensively investigated and confirmed in many clinical trials. Recently, evidence has shown that in addition to the existing approaches for the treatment of obesity, semaglutide in higher doses promotes weight loss and can be used as a drug to treat obesity. However, some T2DM and obese patients do not achieve a desired therapeutic effect of GLP-1 receptor agonists. This could be due to the multifactorial etiologies of T2DM and obesity, but genetic variability in the GLP-1 receptor or signaling pathways also needs to be considered in non-responders to GLP-1 receptor agonists. This review focuses on the pharmacological, clinical, and genetic factors that may influence the response to GLP-1 receptor agonists in the treatment of type 2 diabetes mellitus and obesity. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Cardiovascular Disease: Pathophysiological Mechanisms and Effects of SGLT-2i and GLP-1RAs)

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22 pages, 1776 KiB

Open AccessReview

Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

by Giuseppe Palmiero, Arturo Cesaro, Erica Vetrano, Pia Clara Pafundi, Raffaele Galiero, Alfredo Caturano, Elisabetta Moscarella, Felice Gragnano, Teresa Salvatore, Luca Rinaldi, Paolo Calabrò and Ferdinando Carlo Sasso

Int. J. Mol. Sci. 2021, 22(11), 5863; https://doi.org/10.3390/ijms22115863 - 30 May 2021

Cited by 51 | Viewed by 7999

Abstract

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events. Full article

(This article belongs to the Special Issue Type 2 Diabetes and Cardiovascular Disease: Pathophysiological Mechanisms and Effects of SGLT-2i and GLP-1RAs)

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