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https://www.readbyqxmd.com/read/29777569/improving-metabolic-stability-with-deuterium-the-discovery-of-hwl-066-a-potent-and-long-acting-free-fatty-acid-receptor-1-agonists
#1
Chunxia Liu, Zheng Li, Wei Shi, Huilan Li, Nasi Wang, Yuxuan Dai, Chen Liao, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancing of glucose-stimulated insulin secretion. The FFA1 agonist GW9508 has great potential for the treatment of type 2 diabetes mellitus, but it has been suffering from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify orally available analog without influence on the unique pharmacological mechanism of GW9508, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α-position of phenylpropionic acid affording compound 4 (HWL-066)...
May 18, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29777522/impact-of-insulin-degludec-in-hospitalized-patients-with-and-without-type-2-diabetes-requiring-parenteral-enteral-nutrition-an-observational-study
#2
Giuseppe Fatati, Agnese Di Donato, Ilenia Grandone, Pina Menicocci, Eva Mirri, Giuseppe Prosperini, Marco Scardapane, Maria Chiara Rossi, Mariangela Palazzi
INTRODUCTION: Hyperglycemia in inpatients is a major problem, especially when nutritional support is required. This study aims to assess the impact of treatment with insulin degludec (IDeg) on mean blood glucose (BG) and glycemic variability in noncritical hospitalized patients with and without type 2 diabetes (T2DM) receiving enteral and/or parenteral nutrition (EN, PN). METHODS: Mean BG and glycemic variability from admission up to 7 days of hospitalization were evaluated in consecutive cases with and without T2DM...
May 17, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29777519/combination-glucose-lowering-therapy-plans-in-t2dm-case-based-considerations
#3
REVIEW
Lawrence Blonde, Susana Dipp, Daniel Cadena
Type 2 diabetes mellitus (T2DM) is a complex disease, and while lifestyle interventions remain the cornerstone of therapy, most patients will also require pharmacotherapy. Current diabetes treatment guidelines and algorithms recommend an individualized approach to setting glycemic goals and selecting treatment. Although a single antihyperglycemic agent may be appropriate as the initial T2DM pharmacotherapy, the progressive nature of the disease due to declining pancreatic β-cell function will result in the vast majority of T2DM patients eventually requiring two or more antihyperglycemic agents...
May 18, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29773934/iglarlixi-a-new-once-daily-fixed-ratio-combination-of-basal-insulin-glargine-and-lixisenatide-for-the-management-of-type-2-diabetes
#4
Debbie Hinnen, Jodi Strong
Background: Patients with type 2 diabetes require treatment intensification to maintain glycemic control. Clinician reluctance, patient injection fears, hypoglycemia, weight gain, or other objections may lead to clinical inertia, whereby therapy is not intensified and patients live with uncontrolled hyperglycemia and increased risk for complications. Initiation of injectable therapy with a glucagon-like peptide (GLP)-1 receptor agonist and/or basal insulin is a recommended option for patients with type 2 diabetes inadequately controlled on one or more oral agents...
May 2018: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29770308/allo-and-auto-percutaneous-intra-portal-pancreatic-islet-transplantation-pipit-for-diabetes-cure-and-prevention-the-role-of-imaging-and-interventional-radiology
#5
REVIEW
Massimo Venturini, Claudio Sallemi, Paolo Marra, Anna Palmisano, Giulia Agostini, Carolina Lanza, Gianpaolo Balzano, Massimo Falconi, Antonio Secchi, Paolo Fiorina, Lorenzo Piemonti, Paola Maffi, Antonio Esposito, Francesco De Cobelli, Alessandro Del Maschio
Although the life expectancy of patients with type 1 diabetes mellitus (T1DM) has improved since the introduction of insulin therapy, the acute life-threatening and long-term complications from diabetes mellitus are significant causes of both mortality and morbidity. Percutaneous intra-portal pancreatic islet transplantation (PIPIT) is a minimally invasive, repeatable procedure which allows a β-cell replacement therapy through a liver islet engraftment, leading to insulin release and glycaemic control restoration in patients with diabetes...
April 2018: Gland Surgery
https://www.readbyqxmd.com/read/29766633/empagliflozin-as-adjunct-to-insulin-in-japanese-participants-with-type-1-diabetes-results-of-a-4-week-double-blind-randomized-placebo-controlled-phase-2-trial
#6
Akira Shimada, Toshiaki Hanafusa, Atsutaka Yasui, Ganghyuck Lee, Yusuke Taneda, Akiko Sarashina, Kosuke Shiki, Jyothis George, Nima Soleymanlou, Jan Marquard
AIMS: This phase 2, double-blind, randomized, placebo-controlled trial (4 sites in Japan) investigated the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of empagliflozin in Japanese participants with type 1 diabetes mellitus (T1DM) as adjunctive therapy to insulin. MATERIALS AND METHODS: Participants on multiple daily injections of insulin for ≥12 months with an HbA1c of 7.5%-10.0%, entered a 2-week, open-label, placebo run-in period followed by a 4-week, double-blind period where participants were randomized 1:1:1:1 to receive empagliflozin 2...
May 15, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29761615/efficacy-and-safety-of-mk-1293-insulin-glargine-compared-with-originator-insulin-glargine-lantus-in-type-2-diabetes-a-randomized-open-label-clinical-trial
#7
Priscilla A Hollander, Wendy L Carofano, Raymond L H Lam, Gregory T Golm, Roy Eldor, Michael F Crutchlow, Michael C Marcos, Marc S Rendell, Philip D Home, Baptist Gallwitz, Julio Rosenstock
AIMS: To compare the efficacy and safety of MK-1293 insulin glargine (Mk-Gla) and Lantus (Sa-Gla) in people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This Phase 3, randomized, active-controlled, open-label, 24-week clinical trial enrolled 531 participants with T2DM (HbA1c ≤11.0%) eligible for or currently taking basal insulin (≥10 U/day). Participants were randomized 1:1 to once-daily Mk-Gla (n=263) or Sa-Gla (n=263). Titration of insulin was guided by a fasting plasma glucose (FPG)-based dosing algorithm...
May 14, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29760944/characteristics-of-insulin-na%C3%A3-ve-people-with-type-2-diabetes-who-successfully-respond-to-insulin-glargine-u100-after-24-weeks-of-treatment-a-meta-analysis-of-individual-participant-data-from-3-randomized-clinical-trials
#8
M H Cummings, D Cao, I Hadjiyianni, L L Ilag, M H Tan
Background: To identify baseline/clinical characteristics associated with clinically meaningful responses to insulin glargine 100 U/mL (IGlar) in insulin-naive people with type 2 diabetes mellitus (T2DM). Methods: Individual participant data were pooled from 3 randomized trials to compare baseline characteristics and clinical outcomes associated with 24-week response to IGlar in combination with non-insulin antihyperglycemic agents in participants with T2DM. Responders were defined as achieving endpoint HbA1c target < 53 mmol/mol (< 7%) and/or ≥ 11 mmol/mol (≥ 1%) HbA1c reduction from baseline...
2018: Clinical Diabetes and Endocrinology
https://www.readbyqxmd.com/read/29756500/sirna-an-alternative-treatment-for-diabetes-and-associated-conditions
#9
Pravin Shende, Chirag Patel
Diabetes is a condition that is not completely treatable but life of a diabetic patient can be smoothed by preventing or delaying the associate conditions like diabetic retinopathy, nephropathy, impaired wound healing process etc. Apart from conventional methods to regulate diabetic condition, new techniques using siRNA have been emerged to prevent the associated conditions. This paper focuses on how siRNA used as a tool to silence the expression of genes which plays critical role in pathogenesis of these conditions...
May 14, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29756070/reducing-severe-hypoglycaemia-in-hospitalised-patients-with-diabetes-early-outcomes-of-standardised-reporting-and-management
#10
Katherine A Araque, Deepak K Kadayakkara, Nino Gigauri, Diane Sheehan, Sachin Majumdar, Gregory Buller, Clare A Flannery
Background: Severe hypoglycaemic events (HGEs) in hospitalised patients are associated with poor outcomes and prolonged hospitalization. Systematic, coordinated care is required for acute management and prevention of HGEs; however, studies evaluating quality control efforts are scarce. Objective: To investigate the effectiveness of system-based interventions to improve management response to HGEs. Methods: System-based interventions were designed and implemented following a root cause analysis of HGE in adult patients with diabetes from two general medical wards with the highest incidence of HGE...
2018: BMJ Open Quality
https://www.readbyqxmd.com/read/29755756/treatment-choice-medication-adherence-and-glycemic-efficacy-in-people-with-type-2-diabetes-a-uk-clinical-practice-database-study
#11
Jason Gordon, Phil McEwan, Iskandar Idris, Marc Evans, Jorge Puelles
Objective: Using primary care data obtained from the UK Clinical Practice Research Datalink, this retrospective cohort study examined the relationships between medication adherence and clinical outcomes in patients with type 2 diabetes. Research design and methods: Data were extracted for patients treated between 2008 and 2016, and stratified by oral antihyperglycemic agent (OHA) line of therapy (mono, dual or triple therapy). Patients were monitored for up to 365 days; associations between medication possession ratio (MPR) and outcomes at 1 year (glycated hemoglobin A1c (HbA1c), weight and hypoglycemia incidence) were assessed using linear regression modeling and descriptive analyses...
2018: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/29750969/tissue-distribution-and-biochemical-characteristics-of-receptors-for-sinus-gland-peptide-vii-as-a-crustacean-hyperglycemic-hormone-and-vitellogenesis-inhibiting-hormone-of-the-kuruma-prawn-marsupenaeus-japonicus
#12
Chiaki Nagai-Okatani, Shinji Nagata, Hiromichi Nagasawa
Crustacean hyperglycemic hormone (CHH) and vitellogenesis-inhibiting hormone (VIH) belong to the CHH family, a neuropeptide superfamily conserved in ecdysozoans. To date, no receptor for the CHH family peptides has been identified in crustaceans. Here, we used a CHH family isoform, Mj-sinus gland peptide (SGP) -VII, as a representative of CHH and VIH in order to determine its target tissues and obtain biochemical information regarding its receptor in the kuruma prawn Marsupenaeus japonicus (Crustacea, Decapoda)...
May 8, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29750952/glucostabilizer%C3%A2-software-guided-insulin-dosing-improves-intrapartum-glycemic-management-in-women-with-diabetes
#13
Cheryl Dinglas, Jolene Muscat, Tracy Adams, Virginia Peragallo-Dittko, Anthony Vintzileos, Hye J Heo
BACKGROUND: During labor, maintenance of maternal euglycemia is critical to decrease the risk of neonatal hypoglycemia and associated morbidities. When continuous intravenous insulin infusion is needed, standardized insulin dosing charts have been used for titration of insulin to maintain glucose in target range. GlucoStabilizer™ is a software-guided insulin dosing system that calculates the dose of intravenous insulin needed based on metabolic parameters, target glucose concentration, and an individual's response to insulin...
May 8, 2018: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29750770/genetic-characteristics-of-patients-with-congenital-hyperinsulinism
#14
Mary Ellen Vajravelu, Diva D De León
PURPOSE OF REVIEW: Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infants and children. Early and appropriate recognition and treatment of hypoglycemia is vital to minimize neurocognitive impairment. RECENT FINDINGS: There are at least 11 known monogenic forms of hyperinsulinism and several associated syndromes. Molecular diagnosis allows for prediction of the effectiveness of diazoxide and the likelihood of focal hyperinsulinism...
May 9, 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29750653/risk-of-hypoglycemia-in-youth-with-type-2-diabetes-on-insulin
#15
Madhia Shahid, Gabriel Q Shaibi, Hayley Baines, Pamela Garcia-Filion, Zoe Gonzalez-Garcia, Micah Olson
BACKGROUND: The objective of this study was to ascertain the risk of hypoglycemia among youth with type 2 diabetes (T2D) on insulin therapy. METHODS: Twenty-two youth with T2D on insulin therapy (M=12, F=10, age=14.4±4.0 years) were enrolled from a single pediatric endocrine practice. They were followed-up for 3 months with weekly phone calls and monthly in-person visits to review blood glucose logs and document any signs or symptoms of hypoglycemia (defined as finger stick glucose of ≤70 mg/dL)...
May 11, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29745917/which-factors-may-affect-the-quality-of-life-in-patients-with-type-1-diabetes-mellitus-using-the-medtronic-veo-continuous-subcutaneous-insulin-infusion-pump
#16
P Thomakos, G Panagopoulos, O Kepaptsoglou, C Zoupas, A Mitrakou
Continuous Subcutaneous Insulin Infusion (CSII) is considered an effective therapeutic approach to the treatment of patients with Type 1 Diabetes Mellitus (T1DM). Literature offers limited information regarding the quality of life (QoL) in patients using CSII. The aim of the study was to investigate the impact of diabetes related factors on the QoL of patients with T1DM on CSII treatment, in a Greek urban population. A cross-sectional study was conducted on 80 patients with T1DM using CSII. [(Mean±SD) age: 35...
April 2018: Georgian Medical News
https://www.readbyqxmd.com/read/29743868/insulin-resistance-as-a-therapeutic-target-in-the-treatment-of-alzheimer-s-disease-a-state-of-the-art-review
#17
REVIEW
Christian Benedict, Claudia A Grillo
Research in animals and humans has shown that type 2 diabetes and its prodromal state, insulin resistance, promote major pathological hallmarks of Alzheimer's disease (AD), such as the formation of amyloid plaques and neurofibrillary tangles (NFT). Worrisomely, dysregulated amyloid beta (Aβ) metabolism has also been shown to promote central nervous system insulin resistance; although the role of tau metabolism remains controversial. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted insulin signaling...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29739729/congenital-hyperinsulinism-and-evolution-to-sulfonylurea-responsive-diabetes-later-in-life-due-to-a-novel-homozygous-p-l171f-abcc8-mutation
#18
Emregül Işık, Huseyin Demirbilek, Jayne A L Houghton, Sian Ellard, Sarah E Flanagan, Khalid Hussain
BACKGROUND: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children. Recessive inactivating mutations in the ABCC8 and KCNJ11 genes account for approximately 50 % of all CHI cases. Hyperinsulinaemic hypoglycaemia (HH) in infancy and diabetes in later life have been reported in subjects with HNF1A , HNF4A and ABCC8 mutations. CASE REPORT: Herein, we present a child who was diagnosed with CHI at birth, then developed diabetes mellitus at the age of 9 years due to a novel homozygous missense, p...
March 29, 2018: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29731652/adjunctive-therapy-for-glucose-control-in-patients-with-type-1-diabetes
#19
REVIEW
Kira Harris, Cassie Boland, Lisa Meade, Dawn Battise
Type 1 diabetes mellitus (T1DM) is characterized by relative or absolute insulin deficiency. Despite treatment with insulin therapy, glycemic goals are not always met, and insulin therapy is sometimes limited by adverse effects, including hypoglycemia and weight gain. Several adjunctive therapies have been evaluated in combination with insulin in patients with T1DM to improve glycemic control while minimizing adverse effects. Pramlintide, an amylin analog, can improve glycemic control, primarily through lowering postprandial blood glucose levels...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/29730391/pharmacotherapy-for-hyperglycemia-in-pregnancy-the-new-insulins
#20
REVIEW
Yoel Toledano, Eran Hadar, Moshe Hod
Hyperglycemia in pregnancy may lead to adverse maternal, fetal and neonatal outcomes. Tight glycemic control is prudent in order to reduce pregnancy complications. For many years, the gold standard pharmacological therapy during pregnancy was human insulin. Recently, insulin analogues were also introduced to clinical use in pregnancy. This brief review aims to summarize the information on the efficacy and safety of insulin analogue therapy during gestation. The strengths and pitfalls of insulin analogue administration during gestation, compared with human insulin, are presented...
May 3, 2018: Diabetes Research and Clinical Practice
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