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https://www.readbyqxmd.com/read/28346775/hyperinsulinism-causing-mutations-cause-multiple-molecular-defects-in-sur1-nbd1
#1
Claudia Paola Alvarez, Marijana Stagljar, D Ranjith Muhandiram, Voula Kanelis
The sulfonylurea receptor 1 (SUR1) protein forms the regulatory subunit in ATP sensitive K+ (KATP) channels in the pancreas. SUR proteins are members of the ATP-binding cassette (ABC) superfamily of proteins. Binding and hydrolysis of MgATP at the SUR nucleotide binding domains (NBDs) lead to channel opening. Pancreatic KATP channels play an important role in insulin secretion. SUR1 mutations that result in increased channel opening ultimately inhibit insulin secretion and lead to neonatal diabetes. In contrast, SUR1 mutations that disrupt trafficking and/or decrease gating of KATP channels cause congenital hyperinsulinism, where over secretion of insulin occurs even in the presence of low glucose...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28345313/acute-hyperglycemia-associated-with-anti-cancer-medication
#2
REVIEW
Yul Hwangbo, Eun Kyung Lee
Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output...
March 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28344112/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-insulin-glargine-as-add-on-to-metformin-with-or-without-sulfonylureas-in-insulin-naive-patients-with-type-2-diabetes-sustain-4-a-randomised-open-label-parallel-group-multicentre-multinational
#3
Vanita R Aroda, Stephen C Bain, Bertrand Cariou, Milivoj Piletič, Ludger Rose, Mads Axelsen, Everton Rowe, J Hans DeVries
BACKGROUND: Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). METHODS: We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries...
March 23, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28342563/type-2-diabetes-mellitus-treatment-patterns-across-europe-a-population-based-multi-database-study
#4
Jetty A Overbeek, Edith M Heintjes, Daniel Prieto-Alhambra, Patrick Blin, Régis Lassalle, Gillian C Hall, Francesco Lapi, Elisa Bianchini, Niklas Hammar, Irene D Bezemer, Ron M C Herings
PURPOSE: The aim of this study was to determine the similarities and differences of type 2 diabetes mellitus (T2DM) treatment patterns in daily practice in 5 European countries and whether these reflect differences in guidelines. METHODS: Prescriptions for drugs used in diabetes treatment during a 5-year study period were obtained from electronic databases. Patients initiating T2DM treatment during the study period were included. An SAS analysis tool was developed to create episodes of use of drug classes, which resulted in treatment patterns...
March 22, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28340990/identification-of-sulfonylurea-biodegradation-pathways-enabled-by-a-novel-nicosulfuron-transforming-strain-pseudomonas-fluorescens-sg-1-toxicity-assessment-and-effect-of-formulation
#5
Louis Carles, Muriel Joly, Frédérique Bonnemoy, Martin Leremboure, Isabelle Batisson, Pascale Besse-Hoggan
Nicosulfuron is a selective herbicide belonging to the sulfonylurea family, commonly used on maize culture. A bacterial strain SG-1 was isolated from an agricultural soil previously treated with nicosulfuron. This strain was identified as Pseudomonas fluorescens and is able to quantitatively dissipate 77.5% of nicosulfuron (1mM) at 28°C in the presence of glucose within the first day of incubation. Four metabolites were identified among which ASDM (2-(aminosulfonyl)-N,N-dimethyl-3-pyridinecarboxamide) and ADMP (2-amino-4,6-dimethoxypyrimidine) in substantial proportions, corresponding to the hydrolytic sulfonylurea cleavage...
February 15, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28338946/instrumental-variable-methods-for-continuous-outcomes-that-accommodate-nonignorable-missing-baseline-values
#6
Ashkan Ertefaie, James H Flory, Sean Hennessy, Dylan S Small
Instrumental variable (IV) methods provide unbiased treatment effect estimation in the presence of unmeasured confounders under certain assumptions. To provide valid estimates of treatment effect, treatment effect confounders that are associated with the IV (IV-confounders) must be included in the analysis, and not including observations with missing values may lead to bias. Missing covariate data are particularly problematic when the probability that a value is missing is related to the value itself, which is known as nonignorable missingness...
March 16, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28335557/ros-production-and-erk-activity-are-involved-in-the-effects-of-d-%C3%AE-hydroxybutyrate-and-metformin-in-a-glucose-deficient-condition
#7
Santosh Lamichhane, Tonking Bastola, Ramesh Pariyar, Eun-Sol Lee, Ho-Sub Lee, Dae Ho Lee, Jungwon Seo
Hypoglycemia, a complication of insulin or sulfonylurea therapy in diabetic patients, leads to brain damage. Furthermore, glucose replenishment following hypoglycemic coma induces neuronal cell death. In this study, we investigated the molecular mechanism underlying glucose deficiency-induced cytotoxicity and the protective effect of d-β-hydroxybutyrate (D-BHB) using SH-SY5Y cells. The cytotoxic mechanism of metformin under glucose deficiency was also examined. Cell viability under 1 mM glucose (glucose deficiency) was significantly decreased which was accompanied by increased production of reactive oxygen species (ROS) and decreased phosphorylation of extracellular signal-regulated kinase (ERK) and glycogen synthase 3 (GSK3β)...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334673/presence-of-the-%C3%AE-triketone-herbicide-tefuryltrione-in-drinking-water-sources-and-its-degradation-product-in-drinking-waters
#8
Motoyuki Kamata, Mari Asami, Yoshihiko Matsui
Triketone herbicides are becoming popular because of their herbicidal activity against sulfonylurea-resistant weeds. Among these herbicides, tefuryltrione (TFT) is the first registered herbicide for rice farming, and recently its distribution has grown dramatically. In this study, we developed analytical methods for TFT and its degradation product 2-chloro-4-methylsulfonyl-3-[(tetrahydrofuran-2-yl-methoxy) methyl] benzoic acid (CMTBA). TFT was found frequently in surface waters in rice production areas at concentrations as high as 1...
March 20, 2017: Chemosphere
https://www.readbyqxmd.com/read/28332144/efficacy-and-safety-of-ideglira-in-participants-with-type-2-diabetes-in-india-uncontrolled-on-oral-antidiabetic-drugs-and-basal-insulin-data-from-the-dual-clinical-trial-program
#9
Kamlesh Khunti, Viswanathan Mohan, Sunil M Jain, Trine Welløv Boesgaard, Kamilla Begtrup, Bipin Sethi
INTRODUCTION: The efficacy and safety of insulin degludec/liraglutide (IDegLira) has been evaluated in the Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) phase 3 clinical trial program. In this post hoc analysis, we compared the efficacy and safety of IDegLira in the Indian subpopulation with the results from the global trial population of DUAL trials. The analysis includes participants uncontrolled on oral antidiabetic drugs (OADs) in DUAL I and DUAL IV and participants uncontrolled on basal insulin and OADs in DUAL II...
March 22, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28331986/renal-function-preservation-with-pioglitazone-or-with-basal-insulin-as-an-add-on-therapy-for-patients-with-type-2-diabetes-mellitus
#10
Yu-Hung Chang, Der-Wei Hwu, Dao-Ming Chang, Ling-Wang An, Chang-Hsun Hsieh, Yau-Jiunn Lee
AIMS: Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. METHODS: Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included...
March 22, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28331351/long-term-management-of-type-2-diabetes-with-glucagon-like-peptide-1-receptor-agonists
#11
REVIEW
Hamish Courtney, Rahul Nayar, Chinnadorai Rajeswaran, Ravi Jandhyala
Continuously reducing excess blood glucose is a primary goal for the management of type 2 diabetes (T2D). Most patients with T2D require glucose-lowering medications to achieve and maintain adequate glycemic control; however, treatment failure may occur, limiting treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an emerging therapeutic class that can be prescribed for patients instead of basal insulin after the failure of oral therapies. Recent studies have focused on the durability and tolerability of long-term GLP-1RA therapy...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28331198/remote-control-of-glucose-homeostasis-in-vivo-using-photopharmacology
#12
Zenobia B Mehta, Natalie R Johnston, Marie-Sophie Nguyen-Tu, Johannes Broichhagen, Peter Schultz, Dean P Larner, Isabelle Leclerc, Dirk Trauner, Guy A Rutter, David J Hodson
Photopharmacology describes the use of light to precisely deliver drug activity in space and time. Such approaches promise to improve drug specificity by reducing off-target effects. As a proof-of-concept, we have subjected the fourth generation photoswitchable sulfonylurea JB253 to comprehensive toxicology assessment, including mutagenicity and maximum/repeated tolerated dose studies, as well as in vivo testing in rodents. Here, we show that JB253 is well-tolerated with minimal mutagenicity and can be used to optically-control glucose homeostasis in anesthetized mice following delivery of blue light to the pancreas...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330386/the-effects-of-dual-therapy-intensification-with-insulin-or-dipeptidylpeptidase-4-inhibitor-on-cardiovascular-events-and-all-cause-mortality-in-patients-with-type-2-diabetes-a-retrospective-cohort-study
#13
Mamza Jil, Mehta Rajnikant, Donnelly Richard, Idris Iskandar
PURPOSE: To compare time to a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke or all-cause mortality in patients with type 2 diabetes mellitus who had their treatment intensified with a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy (metformin plus sulfonylurea) failure. METHODS: A retrospective cohort study was conducted on 5238 patients newly treated with either a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy failure (2007-2014)...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28325799/a-proposal-for-an-out-of-range-glycemic-population-health-safety-measure-for-older-adults-with-diabetes
#14
Leonard Pogach, Chin-Lin Tseng, Orysya Soroka, Miriam Maney, David Aron
OBJECTIVE: To evaluate patient-level glycemic control and facility variation of a proposed out-of-range (OOR) measure (overtreatment [OT] [HbA1c <7% (53 mmol/mol)] or undertreatment [UT] [>9% (75 mmol/mol)]) compared with the standard measure (SM) (HbA1c <8% [64 mmol/mol]) in high-risk older adults. RESEARCH DESIGN AND METHODS: Veterans Health Administration patients ≥65 years of age in 2012 who were taking antihyperglycemic agents in 2013 were identified...
April 2017: Diabetes Care
https://www.readbyqxmd.com/read/28324038/efficacy-of-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-t2dm-patients-with-very-high-hba1c
#15
Muhammad Abdul-Ghani, Osama Mujahid, Ayman Mujahid, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
Aim: To examine the efficacy and safety of combination therapy with exenatide plus pioglitazone versus basal-bolus insulin in poorly controlled type 2 diabetic patients with very high HbA1c (HbA1c>10%) on metformin plus sulfonylurea and long duration of disease. Research Design and Methods: 101 participants in Qatar Study with very poor glycemic control (HbA1c > 10%) and long duration of diabetes (10.9 years) on maximum/near-maximum doses of sulfonylurea plus metformin were randomized to receive: (i) pioglitazone plus weekly exenatide (Combination Therapy), or (ii) basal plus prandial insulin (Insulin Therapy) to maintain HbA1c <7...
February 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28319006/high-rates-of-severe-hypoglycemia-among-african-american-patients-with-diabetes-the-surveillance-prevention-and-management-of-diabetes-mellitus-supreme-dm-network
#16
Andrew J Karter, Kasia J Lipska, Patrick J O'Connor, Jennifer Y Liu, Howard H Moffet, Emily B Schroeder, Jean M Lawrence, Gregory A Nichols, Katherine M Newton, Ram D Pathak, Jay Desai, Beth Waitzfelder, Melissa G Butler, Abraham Thomas, John F Steiner
AIMS: Seven-year surveillance study (2005-2011) to evaluate race/ethnic differences in the trends in rates of severe hypoglycemia (SH) in a population of insured, at-risk adults with diabetes. METHODS: SH events were identified via any primary or principal diagnosis from emergency department or inpatient encounters among African American, Asian, Latino and White adult diabetes patients treated with insulin or secretagogues (Sulfonylureas or Meglitinides), receiving care from integrated healthcare delivery systems across the United States...
February 21, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28318091/insulin-responsive-glucagon-delivery-for-prevention-of-hypoglycemia
#17
Jicheng Yu, Yuqi Zhang, Wujin Sun, Anna R Kahkoska, Jinqiang Wang, John B Buse, Zhen Gu
Hypoglycemia, the state of abnormally low blood glucose level, is an acute complication of insulin and sulfonylurea therapy in diabetes management. Frequent insulin dosing and boluses during daily diabetes care leads to an increased risk of dangerously low glucose levels, which can cause behavioral and cognitive disturbance, seizure, coma, and even death. This study reports an insulin-responsive glucagon delivery method based on a microneedle (MN)-array patch for the prevention of hypoglycemia. The controlled release of glucagon is achieved in response to elevated insulin concentration by taking advantage of the specific interaction between insulin aptamer and target insulin...
March 20, 2017: Small
https://www.readbyqxmd.com/read/28314484/impact-of-health-policy-and-practice-on-finding-the-best-fit-for-patients-with-type-2-diabetes-after-metformin-failure-croatian-pilot-study
#18
Maja Cigrovski Berković, Davorka Herman Mahečić, Marina Gradišer, Ines Bilić-Ćurčić
AIM: We assessed the impact of clinical practice and health policy on the choice and efficacy of different second-line therapies for the treatment of type 2 diabetes (T2DM) after failure of metformin. METHODS: This retrospective database analysis included 200 patients with a follow-up period of 6 months. The primary end-point was achievement of HbA1c <7% and fasting (FBG) and postprandial glucose levels (PPG) <7.2mmol/L and <10mmol/L, respectively after three and six months of different add-on treatments...
March 14, 2017: Primary Care Diabetes
https://www.readbyqxmd.com/read/28314393/simple-cost-effective-and-sensitive-liquid-chromatography-diode-array-detector-method-for-simultaneous-determination-of-eight-sulfonylurea-herbicides-in-soya-milk-samples
#19
Tomasz Rejczak, Tomasz Tuzimski
In this study authors propose a simple, cost-effective and sensitive liquid chromatography diode array detector (HPLC-DAD) method for the simultaneous determination of eight sulfonylurea herbicides (oxasulfuron, metsulfuron-methyl, triasulfuron, rimsulfuron, chlorsulfuron, mesosulfuron-methyl, amidosulfuron and bensulfuron-methyl) in soya milk samples. QuEChERS-based extraction procedure presents good performance for all of the analytes with recoveries in the range of 61-108% and relative standard deviations (RSD%) less than 15%...
November 18, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28303143/copy-number-variation-in-acetolactate-synthase-genes-of-thifensulfuron-methyl-resistant-alopecurus-aequalis-shortawn-foxtail-accessions-in-japan
#20
Satoshi Iwakami, Yoshiko Shimono, Yohei Manabe, Masaki Endo, Hiroyuki Shibaike, Akira Uchino, Tohru Tominaga
Severe infestations of Alopecurus aequalis (shortawn foxtail), a noxious weed in wheat and barley cropping systems in Japan, can occur even after application of thifensulfuron-methyl, a sulfonylurea (SU) herbicide. In the present study, nine accessions of A. aequalis growing in a single wheat field were tested for sensitivity to thifensulfuron-methyl. Seven of the nine accessions survived application of standard field rates of thifensulfuron-methyl, indicating that severe infestations likely result from herbicide resistance...
2017: Frontiers in Plant Science
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