Journal ArticleDOI
Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction.
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TLDR
The role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption is discussed and the unexpected logic of inhibiting SGLTs in the diabetic kidney is outlined.Abstract:
Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.read more
Citations
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Journal ArticleDOI
SGLT2 Inhibitors: Emerging Roles in the Protection Against Cardiovascular and Kidney Disease Among Diabetic Patients
TL;DR: SGLT2 inhibitors are novel antidiabetic medications with immense utility in the management of patients with T2DM as they confer protection against cardiovascular/renal death and improve all-cause mortality.
Journal ArticleDOI
Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure.
Mieczysław Dutka,Rafał Bobiński,Izabela Ulman-Włodarz,Maciej Hajduga,Jan Bujok,Celina Pająk,Michał Ćwiertnia +6 more
TL;DR: The current state of knowledge about the mechanisms of action of SGLT2is developed for the treatment of diabetes and which, thanks to their cardioprotective effects, may, in the future, become a treatment for patients with HF are presented.
Journal ArticleDOI
Impact of Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitors on Arterial Stiffness and Vascular Aging—What Do We Know So Far? (A Narrative Review)
TL;DR: Clinical studies have demonstrated the active role of vascular endothelium in the onset of cardiovascular diseases and sodium–glucose cotransporter 2 inhibitors decrease arterial stiffness and vascular resistance.
Journal ArticleDOI
The controversial role of glucose in the diabetic kidney.
TL;DR: In this article, the role of glycogen in the storage of glucose in the kidney and its accumulation in the cells has been investigated, providing new information on the link between diabetes and diabetic kidney disease.
Journal ArticleDOI
The antioxidative effects of empagliflozin on high glucose‑induced epithelial-mesenchymal transition in peritoneal mesothelial cells via the Nrf2/HO-1 signaling
Huaying Shen,Pedro Pereira +1 more
TL;DR: Wang et al. as discussed by the authors investigated whether empagliflozin could inhibit high glucose (HG)-induced epithelial-mesenchymal transition (EMT) and oxidative stress via activating the Nrf2/HO-1 signaling pathway.
References
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Journal ArticleDOI
Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030
TL;DR: Findings indicate that the "diabetes epidemic" will continue even if levels of obesity remain constant, and given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.
Journal ArticleDOI
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
Piotr Ponikowski,Adriaan A. Voors,Stefan D. Anker,Héctor Bueno,John G.F. Cleland,Andrew J.S. Coats,Volkmar Falk,José Ramón González-Juanatey,Veli-Pekka Harjola,Ewa A. Jankowska,Mariell Jessup,Cecilia Linde,Petros Nihoyannopoulos,John Parissis,Burkert Pieske,Jillian P. Riley,Giuseppe M.C. Rosano,Luis M. Ruilope,Frank Ruschitzka,Frans H. Rutten,Peter van der Meer,Gerasimos Filippatos,John J.V. McMurray,Victor Aboyans,Stephan Achenbach,Stefan Agewall,Nawwar Al-Attar,John Atherton,Johann Bauersachs,A. John Camm,Scipione Carerj,Claudio Ceconi,Antonio Coca,Perry M. Elliott,Çetin Erol,Justin A. Ezekowitz,Covadonga Fernández-Golfín,Donna Fitzsimons,Marco Guazzi,Maxime Guenoun,Gerd Hasenfuss,Gerhard Hindricks,Arno W. Hoes,Bernard Iung,Tiny Jaarsma,Paulus Kirchhof,Juhani Knuuti,Philippe Kolh,Stavros Konstantinides,Mitja Lainscak,Patrizio Lancellotti,Gregory Y.H. Lip,Francesco Maisano,Christian Mueller,Mark C. Petrie,Massimo F Piepoli,Silvia G. Priori,Adam Torbicki,Hiroyuki Tsutsui,Dirk J. van Veldhuisen,Stephan Windecker,Clyde W. Yancy,José Luis Zamorano +62 more
TL;DR: Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chair person) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK)
Journal ArticleDOI
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.
Bernard Zinman,Christoph Wanner,John M. Lachin,David Fitchett,Erich Bluhmki,Stefan Hantel,Michaela Mattheus,Theresa Devins,Odd Erik Johansen,Hans-Juergen Woerle,Uli C. Broedl,Silvio E. Inzucchi +11 more
TL;DR: Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.
Journal ArticleDOI
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
Piotr Ponikowski,Adriaan A. Voors,Stefan D. Anker,Héctor Bueno,John G.F. Cleland,Andrew J.S. Coats,Volkmar Falk,José Ramón González-Juanatey,Veli-Pekka Harjola,Ewa A. Jankowska,Mariell Jessup,Cecilia Linde,Petros Nihoyannopoulos,John Parissis,Burkert Pieske,Jillian P. Riley,Giuseppe M.C. Rosano,Luis M. Ruilope,Frank Ruschitzka,Frans H. Rutten,Peter van der Meer +20 more
TL;DR: ACCF/AHAIAI: angiotensin-converting enzyme inhibitor as discussed by the authors, angio-catabolizing enzyme inhibitor inhibitor inhibitor (ACS inhibitor) is a drug that is used to prevent atrial fibrillation.
Journal ArticleDOI
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
Piotr Ponikowski,Adriaan A. Voors,Stefan D. Anker,Héctor Bueno,John G.F. Cleland,Andrew J.S. Coats,Volkmar Falk,José Ramón González-Juanatey,Veli-Pekka Harjola,Ewa A. Jankowska,Mariell Jessup,Cecilia Linde,Petros Nihoyannopoulos,John Parissis,Burkert Pieske,Jillian P. Riley,Giuseppe M.C. Rosano,Luis M. Ruilope,Frank Ruschitzka,Frans H. Rutten,Peter van der Meer +20 more
TL;DR: Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chair person) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK)