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René Rodriguez-Gutierrez, Victor M Montori
No abstract text is available yet for this article.
March 20, 2018: Annals of Internal Medicine
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
Gian Paolo Fadini, Giancarlo Zatti, Ileana Baldi, Daniele Bottigliengo, Agostino Consoli, Andrea Giaccari, Giorgio Sesti, Angelo Avogaro
In randomized controlled trials (RCTs), SGLT-2 inhibitors (SGLT2i) showed glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) was a multicenter retrospective study designed to evaluate baseline characteristics of patients receiving dapagliflozin versus selected comparators (DPP-4 inhibitors, gliclazide, or GLP-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281,217 patients, the analysis included 17,285 initiating dapagliflozin or comparator glucose lowering medications (GLM), 6751 of whom had a follow-up examination...
March 8, 2018: Diabetes, Obesity & Metabolism
Wathik Alsalim, Margaretha Persson, Bo Ahrén
AIMS: Previous studies have shown that dipeptidyl peptidase (DPP)-4 inhibition lowers whereas sodium-glucose co-transporter 2 (SGLT-2) inhibition increases glucagon levels. This study evaluated the extent of these opposite effects in a direct comparative head-to-head study. METHODS: In a single-centre, randomized study with a cross-over design, 28 metformin-treated patients with type 2 diabetes (T2D; mean age 63 years, baseline HbA1c 6.8%) were treated with vildagliptin (50 mg twice daily) or dapagliflozin (10 mg once daily) for two weeks with a four week wash out period in between...
March 2, 2018: Diabetes, Obesity & Metabolism
Lovic Dragan, Manolis Kallistratos, Constantinos Tsioufis, Charalampos Grassos, Dragan Djordjevic, Ivan Tasic, Athanasios Manolis, Andreas Pittaras
BACKGROUND: The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease related death and cardiovacular events associated with HbA1c levels of greater than 7 % compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion...
February 26, 2018: Cardiovascular & Hematological Disorders Drug Targets
Robert Puckrin, Marie-Philippe Saltiel, Pauline Reynier, Laurent Azoulay, Oriana H Y Yu, Kristian B Filion
AIMS: There is concern about the infection-related safety profile of sodium-glucose co-transporter 2 (SGLT-2) inhibitors. We aimed to determine the effect of SGLT-2 inhibitors on genitourinary and other infections via systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We conducted a systematic search of Medline, EMBASE, Cochrane Central Register of Controlled Trials, and to identify double-blinded RCTs enrolling ≥ 50 patients with type 2 diabetes which compared an SGLT-2 inhibitor to placebo or active comparator...
February 27, 2018: Acta Diabetologica
Yi-Hsin Lin
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the newest class of oral antidiabetic drugs (OADs), approved to be a second-line OAD for type 2 diabetes in Taiwan since 2016. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) had both released statements associating the use of SGLT-2 inhibitors may increase the risk of eu-glycemic diabetic ketoacidosis (euDKA). This review reveals the possible pathophysiology with a chain of metabolic adaptions to decrease plasma glucose and increase plasma ketone bodies through pancreas, kidney, liver and adipose tissue...
February 21, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
B M Mishriky, R J Tanenberg, K A Sewell, D M Cummings
AIMS: Our aim was to compare Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) to Dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy to metformin. METHODS: We searched for randomized trials comparing SGLT-2i to DPP-4i as add-on therapy to metformin in Type 2 diabetes.We pooled trials reporting outcomes between 12 and 26 weeks together while trials reporting results ≥52 weeks were pooled together. The primary outcomes were the change in haemoglobin A1c (A1c) at ≤26 and ≥52 weeks...
February 7, 2018: Diabetes & Metabolism
Tetsushi Hamaguchi, Yushi Hirota, Takehito Takeuchi, Yasushi Nakagawa, Atsuko Matsuoka, Masaaki Matsumoto, Hiroyuki Awano, Kazumoto Iijima, Pei Chieng Cha, Wataru Satake, Tatsushi Toda, Wataru Ogawa
A Japanese woman in her late 30s with severe insulin resistance and bodily features including a triangular face, prominent forehead, small chin, large and low-set ears, and ocular depression was investigated. A similar phenotype was not observed in other family members with the exception of her son, suggesting that the condition was caused by a de novo mutation that was transmitted from mother to son. Exome analysis revealed the presence in the proband and her son of a c.1945C>T mutation in PIK3R1, a common mutation associated with SHORT syndrome...
February 24, 2018: Journal of Diabetes Investigation
Charles Khouri, Jean-Luc Cracowski, Matthieu Roustit
OBJECTIVE: Inhibitors of the sodium-glucose co-transporter-2 (SGLT-2) are a novel class of glucose lowering agents showing promising results. However, the use of canagliflozin has been associated with an increased risk of lower-limb amputation. Whether this risk concerns other SGLT-2 inhibitors is unclear. METHODS: We performed a disproportionality analysis using the WHO global database of individual case safety reports (VigiBase®) to address this issue. RESULTS: Among the 8,293,886 reports available between January 2013 and December 2017, we identified 79 reports of lower-limb amputations associated with SGLT-2 inhibitors...
February 12, 2018: Diabetes, Obesity & Metabolism
Miyajima Katsuhiro, Soon Hui Teoh, Hideaki Yamashiro, Masami Shinohara, Fatchiyah Fatchiyah, Takeshi Ohta, Takahisa Yamada
Introduction: Impaired diabetic wound healing is an important issue in diabetic complications. The present study aims to evaluate the protective effect on glycemic control against impaired diabetic wound healing using a diabetic rat model. We investigated the wound healing process and effect on the impaired wound repair by glycemic control in the Spontaneously Diabetic Torii (SDT) fatty rat, which is a new animal model of obese type 2 diabetes and may be a good model for study impaired wound healing...
February 2018: Medical Archives
Konstantinos Avranas, Konstantinos Imprialos, Konstantinos Stavropoulos, Georgios Lales, Alexandos Manafis, Anastasia Skalkou, Lars Kihm
BACKGROUND: The treatment of diabetes remains over the decades challenging, even after the introduction of numerous novel drugs of different classes. Most patients with type 2 diabetes necessitate the combination of multiple agents and eventually use of insulin. The newest, and possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 inhibitors (SGLT-2i). This class has a unique mechanism inhibiting the glucose reabsorption in the proximal tubule of the kidney...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
Panteleimon Pantelidis, Andreas Kalliakmanis, Christos Mitas, Michail Sideris, Charalampos Grassos, Andreas Pittaras, Athanasios Manolis
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a new class of oral antidiabetic drugs. So far, there are three agents approved for use in Europe and in the USA, two in Japan and another four agents under testing. OBJECTIVE: The purpose of this study is to describe the mechanism of action and the favorable and adverse effects of SGLT-2 inhibitors. METHOD: A thorough review of literature indexed in PubMed, Scopus and Cochrane databases was conducted...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
Konstantinos Stavropoulos, Konstantinos Imprialos, Nikiforos Stavropoulos, Sofia Bouloukou, Georgios Kerpiniotis, Kyriakos Dimitriadis, Constantinos Tsioufis, Michael Doumas
BACKGROUND: Diabetic nephropathy is a crucial microvascular complication of diabetes mellitus that is associated with elevated cardiovascular risk. SGLT-2 inhibitors are a new class of hypoglycemic drugs that positively affect several risk factors of cardiorenal damage. OBJECTIVES: To review and critically discuss available data on the association of SGLT-2 inhibitors treatment with kidney function, progress of diabetic kidney disease, and renal related outcomes, as well to unveil potential mechanisms of action that mediate such effects...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
Konstantinos Imprialos, Konstantinos Stavropoulos, Nikiforos Stavropoulos, Dimitrios Patoulias, Konstantinos Petidis, Charalampos Grassos, Kyriakos Dimitriadis, Constantinos Tsioufis
BACKGROUND: Sodium-glucose co-transporters 2 inhibitors have emerged as a novel antidiabetic class of drugs offering significant ameliorating effects on a variety of cardiovascular risk factors, secondary to their mechanism of action, including blood pressure and body weight. OBJECTIVE: The purpose of this article is to discuss available data on the impact of SGLT-2 inhibitors on blood pressure and body weight compared with other available antidiabetic drugs and to present potential mechanisms mediating these effects...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
Dimitrios Patoulias, Alexandros Manafis, Christos Mitas, Konstantinos Avranas, Georgios Lales, Ioanna Zografou, Christos Sambanis, Asterios Karagiannis
BACKGROUND: SGLT-2 inhibitors are a novel class of antidiabetic drugs, recently approved for the treatment of patients with T2DM. Their cardioprotective and renoprotective action, along with their beneficial effects on metabolic parameters, make them an attractive therapeutic option. Since 2015, when the US FDA issued warning regarding the increased risk of euDKA in the setting of SGLT-2 inhibitors administration, a vivid discussion upon the direct connection between this novel class and the major metabolic complication of diabetes mellitus is still ongoing...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
Dimitrios Milonas, Konstantinos Tziomalos
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with substantially increased risk for cardiovascular events, including ischemic stroke. In turn, ischemic stroke represents a leading cause of mortality and long-term disability worldwide. The newest class of glucose-lowering agents is sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which act through inhibition of glucose reabsorption in the kidney, resulting in glucose excretion without stimulating insulin release. Accumulating data suggests that these agents improve multiple risk factors for ischemic stroke except their glucose-lowering effect...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
Maria J Peláez-Jaramillo, Allison A Cárdenas-Mojica, Paula V Gaete, Carlos O Mendivil
Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM...
February 6, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Abhiroop Chakravarty, Mohini Rastogi, Praveen Dhankhar, Kelly Bell
OBJECTIVE: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4 inhibitors (DPP-4i), all combined with metformin. METHODS: A short-term decision-analytic model with a 1-year time horizon was developed from a payer's perspective in the United States (US) setting...
January 29, 2018: Journal of Medical Economics
Liang Xu, Tsuguhito Ota
Obesity-associated low-grade inflammation underlies insulin resistance and associated metabolic comorbidities, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease. Excessive ectopic fat deposition in obesity causes disorders of energy homeostasis and low-grade chronic inflammation in metabolic tissues. In particular, obesity-induced recruitment and activation of adipose tissue macrophages play a key role in the pathogenesis of insulin resistance and T2D. Therefore, treatment options for energy metabolism and macrophage polarization in obese subjects are needed...
December 11, 2017: Adipocyte
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