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Newer Antidiabetics and Cardio-Metabolic Health: From Pathophysiology to Treatment
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Newer Antidiabetics and Cardio-Metabolic Health: From Pathophysiology to Treatment

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 March 2024) | Viewed by 10258

Special Issue Editors

Dr. Dimitrios Patoulias

E-Mail Website
Guest Editor
Outpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, Aristotle University of Thessaloniki, General Hospital “Hippokration”, 57001 Thessaloniki, Greece
Interests: type 2 diabetes mellitus; diabetic complications; cardiovascular disease; heart failure; chronic kidney disease
Special Issues, Collections and Topics in MDPI journals
Dr. Nikolaos Fragakis

E-Mail Website
Guest Editor
2nd Cardiology Department, Hippokration General Hospital, Aristotle University Medical School, Κonstantinoupoleos 49, 54642 Thessaloniki, PK, Greece
Interests: cardiology; electrophysiology; cardiometabolic medicine

Special Issue Information

Dear Colleagues,

Cardiometabolic Medicine is an emerging scientific field, attracting physicians across the spectrum of medical specialties, such as Internal Medicine, Cardiology, Endocrinology and Diabetology, and Nephrology. It is clear that type 2 diabetes mellitus constitutes the metabolic pandemic of the 21st century, with pessimistic projections regarding its prevalence. In addition, type 2 diabetes mellitus is associated with several comorbidities, such as hypertension, dyslipidemia, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, obesity, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, hyperuricemia, and several others. Some of them are coincident, while others are mostly complications of underlying diabetes mellitus. 

During the last decade, welcome novel classes of antidiabetic drugs have arrived, which have provided remarkable cardiorenal benefits for individuals with type 2 diabetes mellitus, revolutionizing its therapeutic approach. In addition, current treatment guedelines have widely adopted those drug classes across a wide spectrum of comorbidities, even in the absence of type 2 diabetes mellitus at baseline.

This Special Issue will publish high-quality original articles addressing the evolving role of newer antidiabetics in cardiometabolic health in type 2 diabetes mellitus, from pathophysiology to treatment, emphasizing molecular pathways and their therapeutic implications. In addition, narrative reviews and systematic reviews with or without meta-analyses will be considered for publication.

Dr. Dimitrios Patoulias
Dr. Nikolaos Fragakis
Guest Editors

Manuscript Submission Information

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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 mellitus
  • cardiovascular disease
  • chronic kidney disease
  • SGLT-2 inhibitor
  • GLP-1 receptor agonist
  • dual GLP-1/GIP receptor agonist
  • pathophysiology
  • treatment

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Published Papers (5 papers)

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Research

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11 pages, 1806 KiB  
Communication
Transfection of Vein Grafts with Early Growth Response Factor-1 Oligodeoxynucleotide Decoy: Effects on Stem-Cell Genes and Toll-like Receptor-Mediated Inflammation
by Konstantinos S. Mylonas, Michail Peroulis and Alkistis Kapelouzou
Int. J. Mol. Sci. 2023, 24(21), 15866; https://doi.org/10.3390/ijms242115866 - 1 Nov 2023
Cited by 1 | Viewed by 1025
Abstract
The long-term patency of vein grafts is challenged by intimal hyperplasia. We sought to explore the intricate relationships between the transcription factor Egr-1, toll-like receptors (TLRs), and stem cell genes and also assessed oligodeoxynucleotide decoys (ODNs) as a strategy to prevent vein graft [...] Read more.
The long-term patency of vein grafts is challenged by intimal hyperplasia. We sought to explore the intricate relationships between the transcription factor Egr-1, toll-like receptors (TLRs), and stem cell genes and also assessed oligodeoxynucleotide decoys (ODNs) as a strategy to prevent vein graft failures. A total of 42 New Zealand white rabbits were fed hyperlipidemic chow and classified into three groups. A double-stranded Egr-1 ODN was synthesized and infused in vein grafts prior to anastomosis with the common carotid artery. All vein grafts were retrieved at the conclusion of the predefined experimental period. Real-time quantitative polymerase chain reaction was performed to estimate expression patterns for several genes of interest. MYD88, TLR2-4, TLR8, NF-kB, TNF-α, IFNβ, and IFNγ; chemokines CCL4, CCL20, CCR2; numerous interleukins; and stem cell genes KFL4, NANOG, HOXA5, and HIF1α were universally downregulated in the ODN arm compared with the controls. By understanding these multifaceted interactions, our study offers actionable insights that may pave the way for innovative interventions in vascular reconstructions. Full article
(This article belongs to the Special Issue Newer Antidiabetics and Cardio-Metabolic Health: From Pathophysiology to Treatment)
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14 pages, 5612 KiB  
Article
Glucagon-like Peptide-1 Receptor Activation Reduces Pulmonary Vein Arrhythmogenesis and Regulates Calcium Homeostasis
by Chao-Shun Chan, Fong-Jhih Lin, Yao-Chang Chen, Yung-Kuo Lin, Satoshi Higa, Shih-Ann Chen and Yi-Jen Chen
Int. J. Mol. Sci. 2023, 24(17), 13100; https://doi.org/10.3390/ijms241713100 - 23 Aug 2023
Cited by 2 | Viewed by 1501
Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists are associated with reduced atrial fibrillation risk, but the mechanisms underlying this association remain unclear. The GLP-1 receptor agonist directly impacts cardiac Ca2+ homeostasis, which is crucial in pulmonary vein (PV, the initiator of atrial fibrillation) arrhythmogenesis. [...] Read more.
Glucagon-like peptide-1 (GLP-1) receptor agonists are associated with reduced atrial fibrillation risk, but the mechanisms underlying this association remain unclear. The GLP-1 receptor agonist directly impacts cardiac Ca2+ homeostasis, which is crucial in pulmonary vein (PV, the initiator of atrial fibrillation) arrhythmogenesis. This study investigated the effects of the GLP-1 receptor agonist on PV electrophysiology and Ca2+ homeostasis and elucidated the potential underlying mechanisms. Conventional microelectrodes and whole-cell patch clamp techniques were employed in rabbit PV tissues and single PV cardiomyocytes before and after GLP-1 (7-36) amide, a GLP-1 receptor agonist. Evaluations were conducted both with and without pretreatment with H89 (10 μM, an inhibitor of protein kinase A, PKA), KN93 (1 μM, an inhibitor of Ca2+/calmodulin-dependent protein kinase II, CaMKII), and KB-R7943 (10 μM, an inhibitor of Na+/Ca2+ exchanger, NCX). Results showed that GLP-1 (7-36) amide (at concentrations of 1, 10, and 100 nM) reduced PV spontaneous activity in a concentration-dependent manner without affecting sinoatrial node electrical activity. In single-cell experiments, GLP-1 (7-36) amide (at 10 nM) reduced L-type Ca2+ current, NCX current, and late Na+ current in PV cardiomyocytes without altering Na+ current. Additionally, GLP-1 (7-36) amide (at 10 nM) increased sarcoplasmic reticulum Ca2+ content in PV cardiomyocytes. Furthermore, the antiarrhythmic effects of GLP-1 (7-36) amide on PV automaticity were diminished when pretreated with H89, KN93, or KB-R7943. This suggests that the GLP-1 receptor agonist may exert its antiarrhythmic potential by regulating PKA, CaMKII, and NCX activity, as well as modulating intracellular Ca2+ homeostasis, thereby reducing PV arrhythmogenesis. Full article
(This article belongs to the Special Issue Newer Antidiabetics and Cardio-Metabolic Health: From Pathophysiology to Treatment)
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Review

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27 pages, 3294 KiB  
Review
The Renoprotective Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i)—A Narrative Review
by Liana Iordan, Laura Gaita, Romulus Timar, Vlad Avram, Adrian Sturza and Bogdan Timar
Int. J. Mol. Sci. 2024, 25(13), 7057; https://doi.org/10.3390/ijms25137057 - 27 Jun 2024
Viewed by 1221
Abstract
Chronic kidney disease (CKD) is a noncommunicable condition that has become a major healthcare burden across the globe, often underdiagnosed and associated with low awareness. The main cause that leads to the development of renal impairment is diabetes mellitus and, in contrast to [...] Read more.
Chronic kidney disease (CKD) is a noncommunicable condition that has become a major healthcare burden across the globe, often underdiagnosed and associated with low awareness. The main cause that leads to the development of renal impairment is diabetes mellitus and, in contrast to other chronic complications such as retinopathy or neuropathy, it has been suggested that intensive glycemic control is not sufficient in preventing the development of diabetic kidney disease. Nevertheless, a novel class of antidiabetic agents, the sodium-glucose cotransporter-2 inhibitors (SGLT2i), have shown multiple renoprotective properties that range from metabolic and hemodynamic to direct renal effects, with a major impact on reducing the risk of occurrence and progression of CKD. Thus, this review aims to summarize current knowledge regarding the renoprotective mechanisms of SGLT2i and to offer a new perspective on this innovative class of antihyperglycemic drugs with proven pleiotropic beneficial effects that, after decades of no significant progress in the prevention and in delaying the decline of renal function, start a new era in the management of patients with CKD. Full article
(This article belongs to the Special Issue Newer Antidiabetics and Cardio-Metabolic Health: From Pathophysiology to Treatment)
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18 pages, 1240 KiB  
Review
The Role of Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in Heart Failure
by Panagiotis Stachteas, Athina Nasoufidou, Dimitrios Patoulias, Paschalis Karakasis, Efstratios Karagiannidis, Michail-Angelos Mourtzos, Athanasios Samaras, Xanthi Apostolidou and Nikolaos Fragakis
Int. J. Mol. Sci. 2024, 25(6), 3122; https://doi.org/10.3390/ijms25063122 - 8 Mar 2024
Cited by 6 | Viewed by 2080
Abstract
Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF [...] Read more.
Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF and is associated with poor outcomes, only limited alternative pharmaceutical options are available in clinical practice. The objective of this narrative review is to provide a comprehensive analysis of the current evidence on the effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on diuretic resistance in HF patients. The primary emphasis is placed on clinical data that assess the impact of SGLT-2 inhibitors on fluid balance, symptom improvement, and clinical outcomes and secondarily on safety profile and potential adverse effects associated with SGLT-2 inhibitor use in acute decompensated HF. The current evidence on the efficacy of SGLT-2 on diuretic resistance remains controversial. Findings from observational and randomized studies are quite heterogenous; however, they converge on the notion that although SGLT-2 inhibitors show promise for mitigating diuretic resistance in HF, their diuretic effect may not be potent enough to be widely used to relieve objective signs of congestion in patients with HF. Importantly, the introduction of SGLT-2 inhibitors in HF treatment appears to be generally well tolerated, with manageable adverse effects. Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT-2 inhibitors on diuretic resistance in HF. Full article
(This article belongs to the Special Issue Newer Antidiabetics and Cardio-Metabolic Health: From Pathophysiology to Treatment)
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17 pages, 2537 KiB  
Review
The Impact of SGLT2 Inhibitors in the Heart and Kidneys Regardless of Diabetes Status
by Jennifer Matthews, Lakshini Herat, Markus P. Schlaich and Vance Matthews
Int. J. Mol. Sci. 2023, 24(18), 14243; https://doi.org/10.3390/ijms241814243 - 18 Sep 2023
Cited by 5 | Viewed by 3673
Abstract
Chronic Kidney Disease (CKD) and Cardiovascular Disease (CVD) are two devastating diseases that may occur in nondiabetics or individuals with diabetes and, when combined, it is referred to as cardiorenal disease. The impact of cardiorenal disease on society, the economy and the healthcare [...] Read more.
Chronic Kidney Disease (CKD) and Cardiovascular Disease (CVD) are two devastating diseases that may occur in nondiabetics or individuals with diabetes and, when combined, it is referred to as cardiorenal disease. The impact of cardiorenal disease on society, the economy and the healthcare system is enormous. Although there are numerous therapies for cardiorenal disease, one therapy showing a great deal of promise is sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The SGLT family member, SGLT2, is often implicated in the pathogenesis of a range of diseases, and the dysregulation of the activity of SGLT2 markedly effects the transport of glucose and sodium across the luminal membrane of renal cells. Inhibitors of SGLT2 were developed based on the antidiabetic action initiated by inhibiting renal glucose reabsorption, thereby increasing glucosuria. Of great medical significance, large-scale clinical trials utilizing a range of SGLT2 inhibitors have demonstrated both metabolic and biochemical benefits via numerous novel mechanisms, such as sympathoinhibition, which will be discussed in this review. In summary, SGLT2 inhibitors clearly exert cardio-renal protection in people with and without diabetes in both preclinical and clinical settings. This exciting class of inhibitors improve hyperglycemia, high blood pressure, hyperlipidemia and diabetic retinopathy via multiple mechanisms, of which many are yet to be elucidated. Full article
(This article belongs to the Special Issue Newer Antidiabetics and Cardio-Metabolic Health: From Pathophysiology to Treatment)
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