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Diabetes sglt2

Michael J Jurczak, Saumya Saini, Simona Ioja, Diana K Costa, Nnamdi Udeh, Xiaojian Zhao, Jean M Whaley, Richard G Kibbey
Inhibition of the sodium-glucose co-transporter type 2 (SGLT2) has received growing acceptance as a novel, safe and effective means to improve glycemic control in patients with type 2 diabetes. Inhibition of SGLT2 lowers the renal glucose threshold and reduces plasma glucose by promoting glucose excretion in urine. Both animal studies and clinical trials in man suggest that SGLT2 inhibition has the potential to improve pancreatic β-cell function by reducing glucose toxicity. However, there is limited data exploring how reducing glucotoxicity via SGLT2 inhibition affects rates of β-cell proliferation and death throughout life in the context of insulin resistance and type 2 diabetes...
August 17, 2018: Islets
Benedetta Maria Bonora, Roberta Cappellari, Mattia Albiero, Angelo Avogaro, Gian Paolo Fadini
Context: Reduction in the levels of circulating stem cells (CSCs) and endothelial progenitor cells (EPCs) predicts development or progression of micro- and macroangiopathy in patients with type 2 diabetes (T2D). Objective: We tested whether treatment with sodium glucose cotransporter-2 (SGLT2) inhibitors affected the levels of CSCs and EPCs. Design: A randomized trial of dapagliflozin versus placebo with open-label extension, and an open-label observational study of empagliflozin treatment...
August 2, 2018: Journal of Clinical Endocrinology and Metabolism
Sachiya Ikeda, Yasuki Takano, Dietmar Schwab, Agnes Portron, Nahoko Kasahara-Ito, Tomohisa Saito, Satofumi Iida
PURPOSE: Tofogliflozin is an orally available selective inhibitor of sodium-glucose co-transporter 2 for treatment of type 2 diabetes mellitus (T2DM). Two studies were conducted to evaluate the effect of renal impairment on pharmacokinetics and pharmacodynamics of tofogliflozin. METHODS: The studies were: 1) single dose study in T2DM patients with normal renal function and mild, moderate and severe renal impairment, and 2) multiple dose study for 24 weeks in T2DM patients with normal renal function and moderate renal impairment...
August 13, 2018: Drug Research
Yoshiaki Kubota, Takeshi Yamamoto, Shuhei Tara, Yukichi Tokita, Kenji Yodogawa, Yuki Iwasaki, Hitoshi Takano, Yayoi Tsukada, Kuniya Asai, Masaaki Miyamoto, Yasushi Miyauchi, Eitaro Kodani, Naoki Sato, Jun Tanabe, Wataru Shimizu
INTRODUCTION: Protection from lethal ventricular arrhythmias leading to sudden cardiac death is one of the most important problems after myocardial infarction. Cardiac sympathetic hyperactivity is related to poor prognosis and fatal arrhythmias and can be non-invasively assessed with heart rate variability, heart rate turbulence, T-wave alternans, late potentials, and 123 I-meta-iodobenzylguanide (123 I-MIBG) scintigraphy. Sodium glucose cotransporter 2 (SGLT2) inhibitors potentially reduce sympathetic nervous system activity that is augmented in part due to the stimulatory effect of hyperglycemia...
August 10, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Hao Li, Fang-Hong Shi, Shi-Ying Huang, Shun-Guo Zhang, Zhi-Chun Gu
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral antidiabetic drugs, which mainly increase urinary glucose excretion through reducing renal glucose reabsorption. There is still a concern about the overall safety profile of SGLT2 inhibitors. In this systematic review and meta-analysis, we will assess the clinical adverse effects of SGLT2 inhibitors in type 2 diabetes mellitus. METHODS: This systemic review and meta-analysis described in this protocol will be conducted to follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline...
August 2018: Medicine (Baltimore)
Jasper Sung, Suja Padmanabhan, Seema Gurung, Sally Inglis, Mauro Vicaretti, Lindy Begg, N Wah Cheung, Christian M Girgis
No abstract text is available yet for this article.
September 2018: Journal of Clinical & Translational Endocrinology
Ningning Wan, Asadur Rahman, Hirofumi Hitomi, Akira Nishiyama
The EMPA-REG OUTCOME study revealed that a sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, can remarkably reduce cardiovascular (CV) mortality and heart failure in patients with high-risk type 2 diabetes. Recently, the CANVAS program also showed that canagliflozin, another SGLT2 inhibitor, induces a lower risk of CV events. However, the precise mechanism by which an SGLT2 inhibitor elicits CV protective effects is still unclear. Possible sympathoinhibitory effects of SGLT2 inhibitor have been suggested, as significant blood pressure (BP) reduction, following treatment with an SGLT2 inhibitor, did not induce compensatory changes in heart rate (HR)...
2018: Frontiers in Endocrinology
R Herring, D Russell-Jones
Despite advances in insulin analogues and monitoring, and changes in insulin delivery, Type 1 diabetes is still difficult to control. It can result in significant short- and long-term adverse health effects including renal failure, blindness, early cardiovascular disease and foot ulceration. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have potential benefit as an adjunct treatment in people not achieving adequate glycaemic control with insulin alone. This article is protected by copyright. All rights reserved...
August 8, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Clifford J Bailey, Nikolaus Marx
This review examines recent randomised controlled cardiovascular (CV) outcome trials with glucose-lowering therapies in type 2 diabetes and their impact on the treatment of patients with type 2 diabetes. The trials were designed to comply with regulatory requirements to confirm that major adverse cardiac events (MACE) are not detrimrntally affected by such therapies. Trials involving dipeptidyl peptidase-4 (DPP4) inhibitors did not alter a composite MACE comprising CV deaths, nonfatal myocardial infarction (MI) and non-fatal stroke...
August 8, 2018: Diabetes, Obesity & Metabolism
Paola Cassis, Monica Locatelli, Domenico Cerullo, Daniela Corna, Simona Buelli, Cristina Zanchi, Sebastian Villa, Marina Morigi, Giuseppe Remuzzi, Ariela Benigni, Carlamaria Zoja
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have pleiotropic properties beyond blood glucose-lowering effects and modify important nonglycemic pathways, leading to end-organ protection. SGLT2 inhibitors display renoprotective effects in diabetic kidney disease, which creates a rationale for testing the therapeutic potential of this drug class in nondiabetic chronic kidney disease. Here, we have shown that dapagliflozin provided glomerular protection in mice with protein-overload proteinuria induced by bovine serum albumin (BSA), to a similar extent as an ACE inhibitor used as standard therapy for comparison...
August 9, 2018: JCI Insight
Habib Yaribeygi, Niki Katsiki, Alexandra E Butler, Amirhossein Sahebkar
Inflammatory responses have a pivotal role in the development of diabetic nephropathy (DN). The nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is a newly recognized and potent inflammatory mediator that induces inflammatory responses in several disorders, including DN. The suppression of procytokine release and inflammatory response is integral to the prevention of complications arising from the inflammatory process. In this review, we discuss the role of the NLRP3 inflammasome in the pathogenesis of DN, focusing on its effects on interleukin (IL)-1β and IL-18...
August 4, 2018: Drug Discovery Today
A G Obrezan, N V Kulikov
In this article we present data of scientific studies of prevalence of diabetes mellitus (DM) among patients with chronic heart failure (CHF), pathogenetic and risk factors of CHF development patients with DM (hyperglycemia, elevated body mass index, age, ischemic heart disease, nephropathy, proteinuria, DM duration, etc.). The article also contains results of analysis of mortality of patients with and without DM in dependence of ejection fraction value. After characterization of drugs for treatment of CHF in general and specifically in patients with DM we make focus on perspective directions in treatment of this group of patients...
July 2018: Kardiologiia
M Joubert, A Manrique, B Cariou, X Prieur
Type 2 diabetes (T2D) is a major risk factor for heart failure (HF). Although the number of cases of myocardial infarction in the T2D population has been reduced by 25% over the last 10 years, the incidence of HF is continuously increasing, making it the most worrying diabetes complication. This strongly reinforces the urgent need for innovative therapeutic interventions to prevent cardiac dysfunction in T2D patients. To this end, epidemiological, imaging and animal studies have aimed to highlight the mechanisms involved in the development of diabetic cardiomyopathy...
July 23, 2018: Diabetes & Metabolism
Francesco Prattichizzo, Valeria De Nigris, Stefano Micheloni, Lucia La Sala, Antonio Ceriello
Recent clinical trials have demonstrated a strong cardiovascular (CV) protective effect of sodium/glucose cotransporter (SGLT) 2 inhibitors, a recently introduced class of hypoglycaemic agents. The improvement of glycated haemoglobin and other conventional risk factors explains only a portion of the observed CV risk reduction. A relevant feature of SGLT2-inhibitor-treated diabetic patients is the increase in circulating levels of ketone bodies, which has been proposed to mediate part of the beneficial effects of this class of drugs, mainly through their bioenergetic properties...
August 2, 2018: Diabetes, Obesity & Metabolism
Eugene Han, Eugene Shin, Gyuri Kim, Ji-Yeon Lee, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
Although both sodium glucose co-transporter 2 inhibition by dapagliflozin and thiazolidinedione, pioglitazone have glucose-lowering and anti-inflammatory effects, the therapeutic efficacy of their combination on diabetic nephropathy has not been investigated. 9-week-old male db/db mice were randomly assigned to 4 groups and administrated with (1) vehicle, (2) dapagliflozin, (3) pioglitazone, or (4) dapagliflozin and pioglitazone combination. Human proximal tubule (HK-2) cells were treated with glucose or palmitate acid in the presence of medium, dapagliflozin, pioglitazone, or both...
2018: Frontiers in Endocrinology
Alexandre Lugat, Michael Joubert, Bertrand Cariou, Xavier Prieur
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). T2DM is associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload. However, the relative contribution of these two parameters remains unclear. In order to get new insight into the mechanism involved in diabetic cardiomyopathy, the cardiac phenotype of a unique T2DM mice model has been performed: the seipin knockout mice (SKO). Cardiac phenotyping revealed a diastolic dysfunction associated with hyperglycemia in these mice with a chronic activation of the hexosamine biosynthetic pathway (HBP), suggesting a glucose overload...
June 2018: Médecine Sciences: M/S
David León Jiménez, David Z I Cherney, Petter Bjornstad, Luis Castilla Guerra, José Pablo Miramontes González
While SGLT2 inhibitors have been use for the routine management of type 2 diabetes for several years, it is perhaps their natriuretic effects that are most important clinically. This natriuresis activates tubuloglomerular feedback, resulting in reduced glomerular hypertension and proteinuria, leading to renal protective effects in the EMPA-REG OUTCOME and CANVAS Program trials. In the cardiovascular system, it is likely that plasma volume contraction due to natriuresis in response to SGLT2 inhibition is at least in part responsible for the reduction in the risk of heart failure observed in these trials...
August 1, 2018: American Journal of Physiology. Renal Physiology
Annayya R Aroor, Nitin A Das, Andrea J Carpenter, Javad Habibi, Guanghong Jia, Francisco I Ramirez-Perez, Luis Martinez-Lemus, Camila M Manrique-Acevedo, Melvin R Hayden, Cornel Duta, Ravi Nistala, Eric Mayoux, Jaume Padilla, Bysani Chandrasekar, Vincent G DeMarco
BACKGROUND: Arterial stiffness is emerging as an independent risk factor for the development of chronic kidney disease. The sodium glucose co-transporter 2 (SGLT2) inhibitors, which lower serum glucose by inhibiting SGLT2-mediated glucose reabsorption in renal proximal tubules, have shown promise in reducing arterial stiffness and the risk of cardiovascular and kidney disease in individuals with type 2 diabetes mellitus. Since hyperglycemia contributes to arterial stiffness, we hypothesized that the SGLT2 inhibitor empagliflozin (EMPA) would improve endothelial function, reduce aortic stiffness, and attenuate kidney disease by lowering hyperglycemia in type 2 diabetic female mice (db/db)...
July 30, 2018: Cardiovascular Diabetology
Yoshio Sumida, Kenta Murotani, Miyoko Saito, Atsuko Tamasawa, Yusuke Osonoi, Masashi Yoneda, Takeshi Osonoi
AIMS: No pharmacological therapies are approved for nonalcoholic fatty liver disease (NAFLD). Luseogliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been developed for the treatment of adults with type 2 diabetes (T2DM). The aim of this prospective, single arm study is to evaluate the efficacy of luseogliflozin on hepatic fat content and HbA1c in T2DM patients with NAFLD. METHODS: Forty T2DM patients with NAFLD were treated with luseogliflozin 2...
July 27, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Bettina Hartmann, Peter Bramlage, Stefanie Lanzinger, Thomas Danne, Michael Hummel, Matthias Kaltheuner, Dirk Raddatz, Wolfgang Rathmann, Hans-Martin Reuter, Jochen Seufert, Reinhard W Holl
AIMS: Based on the DIVE (Diabetes Versorgungs-Evaluation) and DPV (Diabetes-Patienten-Verlaufsdokumentation) datasets we aimed to explore the impact of differences in treatment modalities on outcomes in Germany and put these into a global context. METHODS: The 2014-2016 DIVE and DPV databases were combined and a total of 127,838 patients 18 years and older was analyzed with respect to demographics, cardiovascular risk factors, comorbidities, treatments and outcomes, separately for each German state...
July 26, 2018: Diabetes/metabolism Research and Reviews
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