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René Rodriguez-Gutierrez, Victor M Montori
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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
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
Adrian H Heald, Mark Livingston, Zuzanna Bien, Gabriela Y C Moreno, Ian Laing, Mike Stedman
BACKGROUND: In the financial year 2016/17 there were 52.0 million items prescribed for diabetes at a total net ingredient cost of £983.7 million - up from 28.9 million prescription items and £572.4 million in 2006/07. Anti-diabetes drugs (British National Formulary section 6.1.2) make up 45.1 per cent of the total £983.7 million net ingredient cost of drugs used in diabetes and account for 72.0 per cent of prescription items for all diabetes prescribing. METHODS: We examined the way that agents licensed to treat type 2 diabetes were used across GP practices in England in the year 2016/2017...
March 14, 2018: International Journal of Clinical Practice
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
A H Heald, A A Fryer, S G Anderson, M Livingston, M Lunt, M Davies, Gyc Moreno, R Gadsby, R J Young, M Stedman
AIMS: Despite increasing spend on new Type 2 diabetes mellitus (T2DM) therapies, the proportion of people with T2DM achieving target glycaemia outcomes is declining. Our aim was to determine, using published General Practice level data, how differences in T2DM prescribing patterns relate to glycaemic target achievement levels. METHODS: Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of class of medication in 2015/16 and changes to 2014/15 in medication to proportions achieving target glycaemic control (TGC; glycated haemoglobin A1c (HbA1c) ≤7...
March 8, 2018: Diabetes, Obesity & Metabolism
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
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
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
Tomohide Yamada, Nobuhiro Shojima, Hisashi Noma, Toshimasa Yamauchi, Takashi Kadowaki
New treatments for type 1 diabetes are an unmet need. We investigated the efficacy and safety of adding SGLT-2is to insulin for type 1 diabetes by meta-analysis of prospective randomized, placebo-controlled trials. Searching electronic databases up to October 2017 identified 1361 studies, among which 14 were investigated (N=4,591). Meta-analysis revealed that SGLT-2i therapy significantly reduced HbA1c by 0.4% (95% confidence interval [CI]: 0.35, 0.46; P<0.001; I2=0%), fasting plasma glucose by 1.14 mmol/l (0...
February 16, 2018: Diabetes, Obesity & Metabolism
Yan Cao, Xiaoli Chen, Ying Sun, Jialiang Shi, Xiaojuan Xu, Yong-Cheng Shi
Pyrodextrin shares some properties of resistant starch which is metabolically beneficial, and has potential applications as a functional food. In this study, we report that oral administration of pyrodextrin (50 mg/kg/d for 7 weeks) decreased the blood glucose (from 9.18±1.47 to 7.67±0.42 mmol/L), serum HbA1c, triglycerides, adipocyte size, and body weights (from 24.4±1.2 to 22.5±1.2 g) in high-fat diet-induced obese mice. The Western blotting analysis suggested that pyrodextrins decreased the intestinal SGLT-1 and GLUT-2 expression to ~70% and ~60% of the obese control to slow down glucose transportation from gut into blood, and improved the hepatic metabolism tentatively...
February 15, 2018: Journal of Agricultural and Food Chemistry
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
Cristina Otero-Rodiño, Ana Rocha, Rosa Álvarez-Otero, Rosa M Ceinos, Marcos A López-Patiño, Jesús M Míguez, José Miguel Cerdá-Reverter, José L Soengas
To assess the hypothesis of glucosensing systems present in fish telencephalon, we first demonstrated in rainbow trout by in situ hybridization the presence of glucokinase (GK). Then, we assessed the response of glucosensing markers in rainbow trout telencephalon 6h after ICV treatment with glucose or 2-deoxyglucose (inducing glucoprivation). We evaluated the response of parameters related to the mechanisms dependent on GK, liver X receptor (LXR), mitochondrial activity, sweet taste receptor, and sodium-glucose linked transporter 1 (SGLT-1)...
February 10, 2018: Journal of Neuroendocrinology
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
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