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https://www.readbyqxmd.com/read/28101643/polymorphisms-in-genes-encoding-mir-155-and-mir-146a-are-associated-with-protection-to-type-1-diabetes-mellitus
#1
Taís S Assmann, Guilherme C K Duarte, Letícia A Brondani, Pedro H O de Freitas, Égina M Martins, Luís H Canani, Daisy Crispim
AIMS: Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation...
January 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28100340/-outcome-comparison-of-different-therapy-procedures-in-surgical-high-risk-elderly-patients-with-severe-aortic-stenosis
#2
Y Q Ye, Y T Wang, Z Li, M Y Wang, H Y Xu, W J Zhang, Q R Liu, G N Niu, Y J Wu
Objective: To compare the outcome of surgical high-risk elderly patients with severe aortic stenosis(SAS) treated by different therapy procedures, including transcatheter aortic valve implantation(TAVI), surgical aortic valve replacement(SAVR), and drug therapy. Methods: We retrospectively analyzed the clinical data of 242 surgical high-risk elderly (age ≥65 years old) SAS patients hospitalized in Fuwai Hospital between September 2012 and June 2015. According to the treatment method, patients were divided into TAVI group (81 cases), SAVR group (59 cases) and drug therapy group (102 cases)...
January 25, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28086882/differential-effects-of-glucagon-like-peptide-1-receptor-agonists-on-heart-rate
#3
REVIEW
Martin Lorenz, Francesca Lawson, David Owens, Denis Raccah, Christine Roy-Duval, Anne Lehmann, Riccardo Perfetti, Lawrence Blonde
While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms)...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27994747/discovery-and-optimization-of-a-novel-triazole-series-of-gpr142-agonists-for-the-treatment-of-type-2-diabetes
#4
Liangqin Guo, Dann L Parker, Yi Zang, Ramzi F Sweis, Weiguo Liu, Edward C Sherer, Nicole Buist, Jenna Terebetski, Terri Kelly, Randal Bugianesi, Birgit T Priest, Karen H Dingley, Xiaofang Li, Stan Mitelman, Gino Salituro, Maria E Trujillo, Michele Pachanski, Melissa Kirkland, Mary Ann Powles, George J Eiermann, Yue Feng, Jin Shang, Andrew D Howard, Feroze Ujjainwalla, Christopher J Sinz, John S Debenham, Scott D Edmondson, Ravi P Nargund, William K Hagmann, Derun Li
GPR142 has been identified as a potential glucose-stimulated insulin secretion (GSIS) target for the treatment of type 2 diabetes mellitus (T2DM). A class of triazole GPR142 agonists was discovered through a high throughput screen. The lead compound 4 suffered from poor metabolic stability and poor solubility. Lead optimization strategies to improve potency, efficacy, metabolic stability, and solubility are described. This optimization led to compound 20e, which showed significant reduction of glucose excursion in wild-type but not in GPR142 deficient mice in an oral glucose tolerance test (oGTT) study...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27958378/large-scale-pharmacogenomic-study-of-sulfonylureas-and-the-qt-jt-and-qrs-intervals-charge-pharmacogenomics-working-group
#5
J S Floyd, C M Sitlani, C L Avery, R Noordam, X Li, A V Smith, S M Gogarten, J Li, L Broer, D S Evans, S Trompet, J A Brody, J D Stewart, J D Eicher, A A Seyerle, J Roach, L A Lange, H J Lin, J A Kors, T B Harris, R Li-Gao, N Sattar, S R Cummings, K L Wiggins, M D Napier, T Stürmer, J C Bis, K F Kerr, A G Uitterlinden, K D Taylor, D J Stott, R de Mutsert, L J Launer, E L Busch, R Méndez-Giráldez, N Sotoodehnia, E Z Soliman, Y Li, Q Duan, F R Rosendaal, P E Slagboom, K C Wilhelmsen, A P Reiner, Y-DI Chen, S R Heckbert, R C Kaplan, K M Rice, J W Jukema, A D Johnson, Y Liu, D O Mook-Kanamori, V Gudnason, J G Wilson, J I Rotter, C C Laurie, B M Psaty, E A Whitsel, L A Cupples, B H Stricker
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27957699/metabolic-surgery-in-the-treatment-algorithm-for-type-2-diabetes-a-joint-statement-by-international-diabetes-organizations
#6
Francesco Rubino, David M Nathan, Robert H Eckel, Philip R Schauer, K George M M Alberti, Paul Z Zimmet, Stefano Del Prato, Linong Ji, Shaukat M Sadikot, William H Herman, Stephanie A Amiel, Lee M Kaplan, Gaspar Taroncher-Oldenburg, David E Cummings
BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II...
January 2017: Obesity Surgery
https://www.readbyqxmd.com/read/27933516/costs-of-diabetes-medication-among-male-former-elite-athletes-in-later-life
#7
M K Laine, R Kujala, J G Eriksson, H Kautiainen, S Sarna, U M Kujala
AIMS: Regular physical activity plays a major role, in both prevention and treatment of type 2 diabetes. Less is known whether vigorous physical activity during young adulthood is associated with costs of diabetes medication in later life. The aim of this study is to evaluate this question. METHODS: The study population consisted of 1314 former elite-class athletes and 860 matched controls. The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports...
December 8, 2016: Acta Diabetologica
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#8
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27917297/an-intrinsic-agonist-mechanism-for-activation-of-glucagon-like-peptide-1-receptor-by-its-extracellular-domain
#9
Yanting Yin, X Edward Zhou, Li Hou, Li-Hua Zhao, Bo Liu, Gaihong Wang, Yi Jiang, Karsten Melcher, H Eric Xu
The glucagon-like peptide-1 receptor is a class B G protein coupled receptor (GPCR) that plays key roles in glucose metabolism and is a major therapeutic target for diabetes. The classic two-domain model for class B GPCR activation proposes that the apo-state receptor is auto-inhibited by its extracellular domain, which physically interacts with the transmembrane domain. The binding of the C-terminus of the peptide hormone to the extracellular domain allows the N-terminus of the hormone to insert into the transmembrane domain to induce receptor activation...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#10
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27867889/liraglutide-effect-and-action-in-diabetes-in-lead-in-a-prospective-observational-study-assessing-safety-and-effectiveness-of-liraglutide-in-patients-with-type-2-diabetes-mellitus-treated-under-routine-clinical-practice-conditions-in-india
#11
Subhash Kumar Wangnoo, Surender Kumar, Arpandev Bhattacharyya, Sudhir Tripathi, Shahid Akhtar, Raman Shetty, Samit Ghosal
BACKGROUND: This 26-week, open-label observational study assessed the incidence and type of adverse events (AEs) associated with liraglutide use according to the standard clinical practice settings and the local label in India. MATERIALS AND METHODS: A total of 1416 adults with type 2 diabetes (T2D) treated with liraglutide in 125 sites across India were included in the study. Participants were newly diagnosed or already receiving antidiabetic medications. Safety and efficacy data were collected at baseline and at approximately weeks 13 and 26...
November 2016: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27866064/incretin-based-therapy-for-type-2-diabetes-a-real-class-effect
#12
Gianluigi Savarese, Lars H Lund, Giuseppe M C Rosano
No abstract text is available yet for this article.
January 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27843569/conceptual-model-for-early-health-technology-assessment-of-current-and-novel-heart-valve-interventions
#13
Simone A Huygens, Maureen P M H Rutten-van Mölken, Jos A Bekkers, Ad J J C Bogers, Carlijn V C Bouten, Steven A J Chamuleau, Peter P T de Jaegere, Arie Pieter Kappetein, Jolanda Kluin, Nicolas M D A van Mieghem, Michel I M Versteegh, Maarten Witsenburg, Johanna J M Takkenberg
OBJECTIVE: The future promises many technological advances in the field of heart valve interventions, like tissue-engineered heart valves (TEHV). Prior to introduction in clinical practice, it is essential to perform early health technology assessment. We aim to develop a conceptual model (CM) that can be used to investigate the performance and costs requirements for TEHV to become cost-effective. METHODS: After scoping the decision problem, a workgroup developed the draft CM based on clinical guidelines...
2016: Open Heart
https://www.readbyqxmd.com/read/27835062/class-i-restricted-t-cell-associated-molecule-is-a-marker-for-ifn-%C3%AE-producing-inkt-cells-in-healthy-subjects-and-patients-with-type-1-diabetes
#14
Nonantzin Beristain-Covarrubias, Elsy B Canche-Pool, Carlos Ramirez-Velazquez, Juan Carlos Barragan-Galvez, Rita A Gomez-Diaz, Vianney Ortiz-Navarrete
Class I-restricted T cell-associated molecule (CRTAM) is an activation marker expressed on the cell surface of activated invariant natural killer T (iNKT) cells, CD8(+) T cells, and a small subset of CD4(+) T cells. CRTAM has also been associated with a proinflammatory profile in murine CD4(+) T cells. However, CRTAM has not been thoroughly explored in human cells. This work focused on evaluating CRTAM expression in human iNKT lymphocytes after activation with α-galactosylceramide, its widely used specific glycolipid antigen...
November 11, 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/27817160/novel-anti-glycemic-drugs-and-reduction-of-cardiovascular-risk-in-diabetes-expectations-realized-promises-unmet
#15
REVIEW
James H Flory, Jenny K Ukena, James S Floyd
PURPOSE OF REVIEW: The purpose is to review evidence on cardiovascular risks and benefits of new treatments for type 2 diabetes mellitus. RECENT FINDINGS: In response to guidance issued by the Food and Drug Administration, thousands of patients have been enrolled in large randomized trials evaluating the cardiovascular effects of the three newest diabetes drug classes: glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose cotransporter 2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors...
December 2016: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/27816544/low-health-literacy-flashcards-mobile-video-reinforcement-to-improve-medication-adherence-in-patients-on-oral-diabetes-heart-failure-and-hypertension-medications
#16
Denise L Yeung, Kristin S Alvarez, Marissa E Quinones, Christopher A Clark, George H Oliver, Carlos A Alvarez, Adeola O Jaiyeola
OBJECTIVE: To design and investigate a pharmacist-run intervention using low health literacy flashcards and a smartphone-activated quick response (QR) barcoded educational flashcard video to increase medication adherence and disease state understanding. DESIGN: Prospective, matched, quasi-experimental design. SETTING: County health system in Dallas, Texas. PARTICIPANTS: Sixty-eight primary care patients prescribed targeted heart failure, hypertension, and diabetes medications INTERVENTION: Low health literacy medication and disease specific flashcards, which were also available as QR-coded online videos, were designed for the intervention patients...
January 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/27776561/prenatal-exposure-to-very-severe-maternal-obesity-is-associated-with-adverse-neuropsychiatric-outcomes-in-children
#17
T H Mina, M Lahti, A J Drake, K Räikkönen, H Minnis, F C Denison, J E Norman, R M Reynolds
BACKGROUND: Prenatal maternal obesity has been linked to adverse childhood neuropsychiatric outcomes, including increased symptoms of attention deficit hyperactivity disorder (ADHD), internalizing and externalizing problems, affective disorders and neurodevelopmental problems but few studies have studied neuropsychiatric outcomes among offspring born to very severely obese women or assessed potential familial confounding by maternal psychological distress. METHOD: We evaluated neuropsychiatric symptoms in 112 children aged 3-5 years whose mothers had participated in a longitudinal study of obesity in pregnancy (50 very severe obesity, BMI ⩾40 kg/m2, obese class III and 62 lean, BMI 18...
January 2017: Psychological Medicine
https://www.readbyqxmd.com/read/27751668/low-fructosamine-and-mortality-a-long-term-follow-up-of-215-011-non-diabetic-subjects-in-the-swedish-amoris-study
#18
H Malmström, P E Wändell, M J Holzmann, J Ärnlöv, I Jungner, N Hammar, G Walldius, A C Carlsson
BACKGROUND AND AIMS: Both high and low fasting glucose has been associated with an increased mortality among individuals without diabetes. This J-shaped association has also been shown for HbA1c in relation to all-cause mortality. High fructosamine is associated with increased mortality. In this study we aim to evaluate if low fructosamine is also associated with increased mortality in non-diabetic subjects. METHODS AND RESULTS: We included 215,011 subjects from the AMORIS cohort undergoing occupational health screening or primary care in Stockholm, Sweden...
December 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27736893/detection-of-independent-associations-of-plasma-lipidomic-parameters-with-insulin-sensitivity-indices-using-data-mining-methodology
#19
Steffi Kopprasch, Srirangan Dheban, Kai Schuhmann, Aimin Xu, Klaus-Martin Schulte, Charmaine J Simeonovic, Peter E H Schwarz, Stefan R Bornstein, Andrej Shevchenko, Juergen Graessler
OBJECTIVE: Glucolipotoxicity is a major pathophysiological mechanism in the development of insulin resistance and type 2 diabetes mellitus (T2D). We aimed to detect subtle changes in the circulating lipid profile by shotgun lipidomics analyses and to associate them with four different insulin sensitivity indices. METHODS: The cross-sectional study comprised 90 men with a broad range of insulin sensitivity including normal glucose tolerance (NGT, n = 33), impaired glucose tolerance (IGT, n = 32) and newly detected T2D (n = 25)...
2016: PloS One
https://www.readbyqxmd.com/read/27717592/euglycemic-diabetic-ketoacidosis-with-elevated-acetone-in-a-patient-taking-a-sodium-glucose-cotransporter-2-sglt2-inhibitor
#20
Tory J Andrews, Robert D Cox, Christina Parker, James Kolb
BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days...
October 4, 2016: Journal of Emergency Medicine
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