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https://www.readbyqxmd.com/read/28978545/disruption-of-glucagon-receptor-signaling-causes-hyperaminoacidemia-exposing-a-possible-liver-alpha-cell-axis
#1
Katrine D Galsgaard, Marie Winther-Sørensen, Cathrine Ørskov, Hannelouise Kissow, Steen S Poulsen, Hendrik Vilstrup, Cornelia Prehn, Jerzy Adamski, Sara L Jepsen, Bolette Hartmann, Jenna Hunt, Maureen J Charron, Jens Pedersen, Nicolai J Wewer Albrechtsen, Jens J Holst
Glucagon secreted from the pancreatic alpha-cells is essential for regulation of blood glucose levels. However, glucagon may play an equally important role in the regulation of amino acid metabolism by promoting ureagenesis. We hypothesized that disruption of glucagon receptor signaling would lead to an increased plasma concentration of amino acids, which in a feedback manner stimulates the secretion of glucagon, eventually associated with compensatory proliferation of the pancreatic alpha-cells. To address this, we performed plasma profiling of glucagon receptor knockout (Gcgr(-/-)) mice and wild-type (WT) littermates using liquid chromatography mass spectrometry (LC-MS)-based metabolomics, and tissue biopsies from the pancreas were analyzed for islet hormones and by histology...
October 3, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28933039/dose-dependent-effect-of-sitagliptin-on-carotid-atherosclerosis-in-patients-with-type-2-diabetes-mellitus-receiving-insulin-treatment-a-post-hoc-analysis
#2
Tomoya Mita, Naoto Katakami, Toshihiko Shiraiwa, Hidenori Yoshii, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce blood glucose in a dose-dependent manner, but the dose-dependent effect relationship between DPP-4 inhibitors and atherosclerosis has not been investigated. METHODS: Patients with type 2 diabetes mellitus (T2DM) treated with insulin were randomized to the sitagliptin (n = 137) or conventional treatment group (n = 137). In the sitagliptin group, each investigator was allowed to adjust the sitagliptin dose to avoid hypoglycemia...
September 20, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28923784/assessment-of-quality-of-life-on-4-year-growth-hormone-therapy-in-japanese-patients-with-adult-growth-hormone-deficiency-a-post-marketing-multicenter-observational-study
#3
Hitoshi Ishii, Akira Shimatsu, Hiromi Nishinaga, Osamu Murai, Kazuo Chihara
OBJECTIVE: Improvement of quality of life (QOL) by growth hormone (GH) therapy was not demonstrated in Japanese adult growth hormone deficiency (AGHD) patients by either the QOL Assessment of Growth Hormone Deficiency in Adults or the Questions on Life Satisfaction-Hypopituitarism, which are widely used to evaluate QOL in Western AGHD patients. We therefore evaluated QOL in Japanese AGHD patients receiving recombinant GH, Norditropin® (Novo Nordisk A/S, Denmark), using the newly developed Adult Hypopituitarism Questionnaire (AHQ)...
September 1, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28914987/diabetes-news
#4
Ann M Carracher, Payal H Marathe, Kelly L Close
More than 31,000 attendeesfrom around the world gathered in Barcelona, Spain for the 2017 European Society of Cardiology conference. In presentinga post-hoc analysis of the Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes(LEADER)(1) trial, Dr Neil Poulter (Imperial College London, UK) showedthat results are still positive, indicating cardioprotection, after adjusting for baseline history of stroke or myocardial infarction (MI), which had no mediating effect on the significant association between Novo Nordisk's (Copenhagen, Denmark) glucagon-like peptide-1 (GLP-1) agonist Victoza (liraglutide) and cardiovascular risk reduction...
September 15, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28905317/healthcare-resource-utilization-and-costs-associated-with-ketosis-events-in-pediatric-and-adult-patients-with-type-1-diabetes-mellitus-in-the-uk
#5
Nandu Thalange, Natalie Valerie Jane Aldhouse, Helen Kitchen, Daniel Howard, Deniz Tutkunkardas, Jonas Håkan-Bloch
INTRODUCTION: Ketosis is a metabolic state associated with insulin deficiency. Untreated, it develops into diabetic ketoacidosis, a significant contributor to mortality and morbidity in people with type 1 diabetes mellitus (T1DM). Little is understood about how patients utilize healthcare resources during ketosis events. This study aimed to identify and quantify healthcare resource utilization and provide estimates of associated costs of ketosis events in T1DM, treated unaided or with healthcare professional (HCP) assistance in the UK...
September 13, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28887314/novo-nordisk-pays-58-7m-to-settle-claims-of-mis-selling-liraglutide
#6
Owen Dyer
No abstract text is available yet for this article.
September 8, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28884311/improved-glycemic-control-achieved-by-switching-to-insulin-degludec-in-insulin-treated-patients-with-type-2-diabetes-in-a-real-world-setting-a-non-interventional-retrospective-cohort-study
#7
Cheli Melzer Cohen, Brian Larsen Thorsted, Michael Lyng Wolden, Gabriel Chodick, Avraham Karasik
INTRODUCTION: Retrospective cohort study evaluating the clinical effectiveness of insulin degludec (IDeg) in insulin-treated patients with type 2 diabetes switching from other insulins to IDeg in a real-world setting. METHODS: Data were drawn from the Maccabi Health Management Organization in Israel and included patients treated with IDeg between 1 September 2014 and 29 February 2016. Main inclusion criteria were age ≥18 years, diagnosis of type 2 diabetes, and treated with insulin for at least 1 year prior to IDeg initiation...
September 7, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28854582/incidence-prevalence-diagnostic-delay-morbidity-mortality-and-socioeconomic-status-in-males-with-46-xx-disorders-of-sex-development-a-nationwide-study
#8
A Berglund, T H Johannsen, K Stochholm, L Aksglaede, J Fedder, M H Viuff, K M Main, C H Gravholt
STUDY QUESTION: What is the epidemiology and trajectory of health and socioeconomic status in males with 46,XX disorders of sex development (DSD)? SUMMARY ANSWER: 46,XX DSD males had an increased overall morbidity compared to male background population controls, and the socioeconomic status was inferior on outcome parameters such as education and long-term income. WHAT IS KNOWN ALREADY: 46,XX DSD males are rare and estimates of prevalence and incidence are limited...
August 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28854085/liraglutide-and-renal-outcomes-in-type-2-diabetes
#9
RANDOMIZED CONTROLLED TRIAL
Johannes F E Mann, David D Ørsted, Kirstine Brown-Frandsen, Steven P Marso, Neil R Poulter, Søren Rasmussen, Karen Tornøe, Bernard Zinman, John B Buse
BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown...
August 31, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28838683/risk-of-atrial-fibrillation-in-people-with-type-1-diabetes-compared-with-matched-controls-from-the-general-population-a-prospective-case-control-study
#10
Sofia Dahlqvist, Annika Rosengren, Soffia Gudbjörnsdottir, Aldina Pivodic, Hans Wedel, Mikhail Kosiborod, Ann-Marie Svensson, Marcus Lind
BACKGROUND: Type 1 diabetes is associated with an increased risk of developing several cardiovascular complications. To our knowledge, the independent association between type 1 diabetes and atrial fibrillation has not been studied. METHODS: We did a prospective case-control study of individuals with type 1 diabetes in the Swedish National Diabetes Registry who were each matched with five controls for age, sex, and county of residence who were randomly selected from the Swedish Population Register...
August 21, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28780521/early-growth-hormone-treatment-start-in-childhood-growth-hormone-deficiency-improves-near-adult-height-analysis-from-nordinet%C3%A2-international-outcome-study
#11
MULTICENTER STUDY
Michel Polak, Jo Blair, Primoz Kotnik, Effie Pournara, Birgitte Tønnes Pedersen, Tilman R Rohrer
OBJECTIVE: To investigate the effect of age at growth hormone (GH) treatment start on near adult height (NAH) in children with isolated GH deficiency (GHD). DESIGN: NordiNet® International Outcome Study (IOS) (Nbib960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (somatropin) (Novo Nordisk A/S) in the real-life clinical setting. METHODS: Patients (n = 172) treated to NAH (height at ≥18 years, or height velocity <2 cm/year at ≥16 (boys) or ≥15 (girls) years) were grouped by age (years) at treatment start (early (girls, <8; boys, <9), intermediate (girls, 8-10; boys, 9-11) or late (girls, >10; boys, >11)) and GHD severity (<3 ng/mL or 3 to ≤10 ng/mL)...
November 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28741970/efficacy-and-safety-of-once-weekly-semaglutide-for-the-treatment-of-type-2-diabetes
#12
REVIEW
Xueying Tan, Xiaojing Cao, Minzhi Zhou, Ping Zou, Jingbo Hu
Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of Diabetes promote a patient-centered approach that takes into account a comprehensive consideration of pharmacological properties of drugs, including glucose-lowering action, effects on body weight, correction on multiple pathophysiologic defects, tolerability, and long-term safety...
September 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28704062/flextouch-an-insulin-pen-injector-with-a-low-activation-force-across-different-insulin-formulations-needle-technologies-and-temperature-conditions
#13
Niels Gudiksen, Thibaud Hofstätter, Birgitte B Rønn, Thomas Sparre
FlexTouch® (Novo Nordisk A/S, Bagsvaerd, Denmark) is a pen-injector with a torque spring mechanism requiring a low activation force. This laboratory-based study compared the activation force of FlexTouch during the injection of insulin with different needles and at temperature conditions within the range at which the device is recommended for use. Using a tensile tester, activation force was measured at maximum dose settings for insulin detemir (100 U/mL) and insulin degludec (100 and 200 U/mL) at standard (23°C ± 5°C), cool (5°C ± 3°C), and warm (30°C ± 2°C) conditions...
October 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/28701318/%C3%A2-liraglutide-for-weight-management
#14
(no author information available yet)
Since 1950, 25 anti-obesity drugs have been withdrawn from use across the world, largely as a result of adverse effects.(1) For several years, orlistat has been the only drug licensed in the UK for weight management.(2) In January 2017, a new presentation of the glucagon-like peptide-1 (GLP-1) analogue liraglutide (▾Saxenda - Novo Nordisk) was launched in the UK as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults. Here, we review the evidence for its efficacy and safety and consider its place in managing people who are overweight or obese...
July 2017: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/28694034/insertion-and-deletion-derived-tumour-specific-neoantigens-and-the-immunogenic-phenotype-a-pan-cancer-analysis
#15
Samra Turajlic, Kevin Litchfield, Hang Xu, Rachel Rosenthal, Nicholas McGranahan, James L Reading, Yien Ning S Wong, Andrew Rowan, Nnennaya Kanu, Maise Al Bakir, Tim Chambers, Roberto Salgado, Peter Savas, Sherene Loi, Nicolai J Birkbak, Laurent Sansregret, Martin Gore, James Larkin, Sergio A Quezada, Charles Swanton
BACKGROUND: The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift nature of indel mutations, which create novel open reading frames and a large quantity of mutagenic peptides highly distinct from self, might contribute to the immunogenic phenotype. METHODS: We analysed whole-exome sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer Genome Atlas...
August 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28692108/safety-and-efficacy-of-a-glycopegylated-rfviii-turoctocog-alpha-pegol-n8-gp-in-paediatric-patients-with-severe-haemophilia-a
#16
Sandrine Meunier, Jayanthi Alamelu, Silke Ehrenforth, Hideji Hanabusa, Faraizah Abdul Karim, Kaan Kavakli, Melanie Khodaie, Janice Staber, Oleksandra Stasyshyn, Donald L Yee, Lina Rageliene
Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder™5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0-5 years [younger cohort]; >150 ED for patients aged 6-11 years [older cohort]) were included...
August 30, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28672139/management-of-surgical-third-lower-molar-extraction-and-postoperative-progress-in-patients-with-factor-vii-deficiency-a-clinical-protocol-and-focus-on-this-rare-pathologic-entity
#17
Pier Carmine Passarelli, Guido Pasquantonio, Antonio D'Addona
PURPOSE: The purpose of the present study was to analyze the management of surgical third molar extraction and postoperative progress in patients with a diagnosis of factor VII deficiency. Close collaboration between the oral-maxillofacial surgeon and hematologist will allow the team to categorize the risk and operate safely, thereby minimizing the incidence and severity of intraoperative and postoperative complications. MATERIALS AND METHODS: The present retrospective study included 7 patients with factor VII deficiency who had undergone third lower molar surgery...
October 2017: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28620113/cell-scientist-to-watch-mads-gyrd-hansen
#18
(no author information available yet)
Mads Gyrd-Hansen studied biochemistry at the University of Copenhagen and received his PhD in 2005 under the supervision of Marja Jäättelä at the Danish Cancer Society Research Centre. He then joined the laboratory of Pascal Meier at the Institute of Cancer Research in London to work on the inhibitor of apoptosis (IAP) proteins. Mads returned to Copenhagen in 2008 to the Biotech Research and Innovation Centre (BRIC) in a senior postdoctoral position with Morten Frödin, and subsequently started his own research group with a career-development fellowship from the Danish Research Councils as part of the laboratory of Niels Mailand at the Novo Nordisk Foundation Centre for Protein Research...
June 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28605603/efficacy-and-safety-of-degludec-versus-glargine-in-type-2-diabetes
#19
RANDOMIZED CONTROLLED TRIAL
Steven P Marso, Darren K McGuire, Bernard Zinman, Neil R Poulter, Scott S Emerson, Thomas R Pieber, Richard E Pratley, Poul-Martin Haahr, Martin Lange, Kirstine Brown-Frandsen, Alan Moses, Simon Skibsted, Kajsa Kvist, John B Buse
BACKGROUND: Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS: We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial...
August 24, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28599764/different-insulin-concentrations-in-resuspended-vs-unsuspended-nph-insulin-practical-aspects-of-subcutaneous-injection-in-patients-with-diabetes
#20
P Lucidi, F Porcellati, A Marinelli Andreoli, P Candeloro, P Cioli, G B Bolli, C G Fanelli
AIMS: This study measured the insulin concentration (Ins[C]) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R-; in the clear/cloudy phases of unsuspended NPH). METHODS: Measurements included Ins[C] in NPH(R+) and in the clear/cloudy phases of NPH(R-), and the time needed to resuspend NPH and time for NPH(R+) to separate again into clear/cloudy parts. RESULTS: In vials of NPH(R+) (assumed to be 100%), Ins[C] in the clear phase of NPH(R-) was<1%, but 230±41% and 234±54% in the cloudy phases of Novo Nordisk and Eli Lilly NPH, respectively...
June 6, 2017: Diabetes & Metabolism
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