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Sodium cotransporter

Purva Sharma, Yash Jobanputra, Karen Lewin, Stuart Bagatell, Daniel Lichtstein
BACKGROUND: Diabetic ketoacidosis (DKA) is a serious complication of diabetes seen commonly in autoimmune Type 1 diabetes mellitus (DM), however patients with Type 2 diabetes are also at risk. Diabetic ketoacidosis may be precipitated by the catabolic stress of acute illness such as trauma, surgery, or infections. Recent studies have suggested that sodium glucose cotransporter-2 (SGLT-2) inhibitors precipitate DKA in Type 2 diabetes. We present a case series of four patients on SGLT-2 inhibitors who presented with DKA...
March 13, 2018: Reviews on Recent Clinical Trials
Kazuaki Negishi
We are now entering the very exciting era of treatment and management of diabetes mellitus (DM) with the emergence of new therapeutic agents, including sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP-4i). From a cardiology and echocardiography perspective, the existence of diabetic cardiomyopathy has been proven through over four decades of discussion. DM is highly prevalent in patients with heart failure (HF). Independent associations are found after adjusting for hypertension (HTN) and coronary artery disease (CAD)...
February 2018: Cardiovascular Diagnosis and Therapy
Mikhail Kosiborod, Carolyn S P Lam, Shun Kohsaka, Dae Jung Kim, Avraham Karasik, Jonathan Shaw, Navdeep Tangri, Su-Yen Goh, Marcus Thuresson, Hungta Chen, Filip Surmont, Niklas Hammar, Peter Fenici
BACKGROUND: Randomized trials demonstrated lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high CV risk. Prior real-world data suggested similar SGLT-2i effects in T2D patients with broader risk profile, but focused on heart failure and death, and were limited to US and Europe. OBJECTIVES: To examine a broad range of CV outcomes in patients initiated on SGLT-2i vs. other glucose lowering drugs (oGLD) across six countries in Asia Pacific, Middle East and North America (NCT02993614)...
March 7, 2018: Journal of the American College of Cardiology
Laura Van den Mooter, Simon Caerels, Chantal Mathieu
There is a clear unmet clinical need in people with Type 1 diabetes (T1DM) considering present day insulin therapy. New insulin analogues and novel technologies allowing more tailored insulin administration have improved the quality of life of people with T1DM, but issues like hypoglycemia, weight gain and variability in glucose profiles remain problematic. Areas covered: In this review, the clinical efficacy, safety and tolerability of dapagliflozin, a sodium-glucose cotransporter type 2 inhibitor, in type 1 diabetes (T1DM) is described based on a review of phase 2 and 3 studies to date...
March 14, 2018: Expert Opinion on Pharmacotherapy
Sanjay Kalra, Jubbin Jacob, Manash P Baruah
Salutogenesis is an accepted approach for chronic disease management. Calorie restriction and exercise are two evidence based salutogenic interventions in diabetes treatment. Calorie restriction mimetics and exercise mimetics may be used as pharmacological tools to help manage diabetes in a sulutogenic manner. This article discusses the biochemical basis and pharmacology of metformin and sodium glucose cotransporter 2 inhibitors. It describes how a combination of these drugs can be used as a calories restriction and exercise mimetic, to help improve diabetes control...
January 2018: Indian Journal of Endocrinology and Metabolism
Se Hee Min, Jeong-Hwa Yoon, Sun Joon Moon, Seokyung Hahn, Young Min Cho
Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline...
March 13, 2018: Scientific Reports
Karin Rådholm, Gemma Figtree, Vlado Perkovic, Scott D Solomon, Kenneth W Mahaffey, Dick de Zeeuw, Greg Fulcher, Terrance D Barrett, Wayne Shaw, Mehul Desai, David R Matthews, Bruce Neal
BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure and cardiovascular death overall, in those with and without a baseline history of heart failure, and in other participant subgroups. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks...
March 11, 2018: Circulation
Vladimir Kepe, Claudio Scafoglio, Jie Liu, William H Yong, Marvin Bergsneider, Sung-Cheng Huang, Jorge R Barrio, Ernest M Wright
A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects...
March 10, 2018: Journal of Neuro-oncology
Milton Packer, Dalane W Kitzman
Obesity-related heart failure with a preserved ejection fraction (HFpEF) is an important phenotype prevalent in the community, especially in people with metabolic disorders (e.g., dyslipidemia, diabetes). These individuals exhibit a marked expansion of plasma volume, but ventricular distensibility is limited, most likely as a result of cardiac microvascular rarefaction acting in concert with myocardial and pericardial fibrosis. Consequently, the increase in plasma volume causes a disproportionate increase in cardiac filling pressures, leading to heart failure, even though systolic ejection is not impaired...
March 7, 2018: JACC. Heart Failure
Shiori Ito, Toshio Hosaka, Wataru Yano, Takahiro Itou, Misako Yasumura, Yukari Shimizu, Hideyuki Kobayashi, Takashi Nakagawa, Keisuke Inoue, Sohei Tanabe, Takuma Kondo, Hitoshi Ishida
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert their antidiabetic effects by promoting urinary glucose excretion. Nutrition therapy is obviously important, but little is known about the interactions between SGLT2i agents and carbohydrate restriction. Therefore, we studied these interactions using an obese diabetic animal model. KK-Ay mice were pair-fed normal chow [NC; carbohydrate: fat: protein = 65:15:20], low carbohydrate [LC; 43:42:15] or severely carbohydrate restricted diets [SR; 12:45:43] for 12 weeks...
March 2018: Physiological Reports
B Chacko, M Whitley, U Beckmann, K Murray, M Rowley
Sodium-glucose cotransporter 2 inhibitor (SGLT2i)-associated euglycaemic diabetic ketoacidosis (euDKA) is a serious and increasingly recognised complication of treatment with this class of oral hypoglycaemic agents and can present a diagnostic challenge, resulting in delayed recognition, inappropriate treatment and potentially life-threatening acidosis. We present two cases of patients developing SGLT2i-associated euDKA in the early postoperative period. We support ceasing SGLT2i for 72 hours preoperatively and would suggest continuing to withhold the medication until oral intake is restored, and recommend a wider awareness of SGLT2i-associated diabetic ketoacidosis (DKA) amongst patients and their healthcare providers with an emphasis on checking ketone levels irrespective of blood glucose levels in the postoperative setting...
March 2018: Anaesthesia and Intensive Care
R Kerridge, I Whyte, F Prior, J Luu, D A Story
No abstract text is available yet for this article.
March 2018: Anaesthesia and Intensive Care
Annas Al-Sharea, Andrew J Murphy, L A Huggins, Y Hu, Ira J Goldberg, Prabhakara R Nagareddy
BACKGROUND AND AIMS: Leukocytosis, particularly monocytosis, has been shown to promote atherosclerosis in both diabetic and non-diabetic mouse models. We previously showed that hyperglycemia independently promotes monocytosis and impairs the resolution of atherosclerosis. Since patients with chronic diabetes often develop dyslipidemia and also have increased risk for atherosclerosis, we sought to examine how controlling blood glucose affects atherosclerosis development in the presence of severe hyperlipidemia...
March 2, 2018: Atherosclerosis
Liping Meng, Hiroyasu Uzui, Hangyuan Guo, Hiroshi Tada
Cardiac fibrosis is a major pathological manifestation of diabetic cardiomyopathy (DCM), which leads to cardiac remodeling, dilated cardiomyopathy and congestive heart failure. Human cardiac fibroblasts (HCF) constitute the predominant cell type in the heart and matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are also involved in cardiac fibrosis. However, it is unclear whether high glucose levels affect the expression of MMPs and TIMPs in HCF. Sodium‑glucose cotransporter (SGLT) inhibitors have been developed as therapeutic agents and the anti‑DCM effect of SGLT inhibitors has been demonstrated by previous studies...
March 6, 2018: Molecular Medicine Reports
Hiroko Hashimoto, Naohiro Nomura, Wakana Shoda, Kiyoshi Isobe, Hiroaki Kikuchi, Kouhei Yamamoto, Takuya Fujimaru, Fumiaki Ando, Takayasu Mori, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
OBJECTIVE: Metformin is an antidiabetic drug that is widely used to treat patients with diabetes mellitus. Recent studies have reported that treatment with metformin not only improved blood glucose levels but also reduced blood pressure. However, it remains unclear how metformin reduces blood pressure. We hypothesized that metformin affects sodium reabsorption in the kidneys. METHODS: Urinary sodium excretion and expression of renal sodium transporters were examined in 8-week-old male C57BL/6 mice with acute and chronic treatment of metformin...
March 3, 2018: Metabolism: Clinical and Experimental
Yochai Birnbaum, Mandeep Bajaj, Hsiu-Chiung Yang, Yumei Ye
BACGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors (DPP4I) are used to treat type 2 diabetes (T2DM). DPP4 inhibitors (DPP4) attenuate Nlrp3 inflammasome activation in the kidney. SGLT2 inhibition reduces inflammation and attenuates the progression of diabetic nephropathy (DN). The effects of dapagliflozin (Dapa) on the activation of the Nlrp3 inflammasome and the combined effect of SGLT2 and DPP4 on T2DM-induced inflammasome activation and progression of DN have not been previously studied...
March 5, 2018: Cardiovascular Drugs and Therapy
Shinji Kamei, Masahiro Iwamoto, Miyuki Kameyama, Masashi Shimoda, Tomoe Kinoshita, Atsushi Obata, Tomohiko Kimura, Hidenori Hirukawa, Fuminori Tatsumi, Kenji Kohara, Shuhei Nakanishi, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
Sodium-glucose cotransporter 2 inhibitor tofogliflozin is a new type of antidiabetic drug for individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to examine in which type of individuals and/or under which conditions tofogliflozin could exert more beneficial effects on body composition and/or glycemic control in Japanese individuals with T2DM. We retrospectively evaluated the effects of tofogliflozin on body composition and/or glycemic control in individuals with T2DM who newly started taking tofogliflozin...
2018: Journal of Diabetes Research
Hiroki Nakajima, Sadanori Okada, Takako Mohri, Eiichiro Kanda, Naoyuki Inaba, Yoko Hirasawa, Hiroaki Seino, Hisamoto Kuroda, Toru Hiyoshi, Tetsuji Niiya, Hitoshi Ishii
Background: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents...
2018: Diabetology & Metabolic Syndrome
Kevin W Huynh, Jiansen Jiang, Natalia Abuladze, Kirill Tsirulnikov, Liyo Kao, Xuesi Shao, Debra Newman, Rustam Azimov, Alexander Pushkin, Z Hong Zhou, Ira Kurtz
Na+ -coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na+ -coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3...
March 2, 2018: Nature Communications
Adriana Mihaela Ilieșiu, Andreea Simona Hodorogea
Heart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic problem affecting more than half of the patients with heart failure (HF). HFpEF has a significant morbidity and mortality and so far no treatment has been clearly demonstrated to improve the outcomes in HFpEF, in contrast to the efficacy of treatment in heart failure with reduced ejection fraction (HFrEF).The failure of proven beneficial drugs in HFrEF to influence the outcome of patients with HFpEF could be related to the heterogeneity of the disease, its various phenotypes and multifactorial pathophysiology, incompletely elucidated yet...
March 2, 2018: Advances in Experimental Medicine and Biology
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