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Diabetes, Obesity & Metabolism

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https://www.readbyqxmd.com/read/27917591/the-pde4-inhibitor-roflumilast-reduces-weight-gain-by-increasing-energy-expenditure-and-leads-to-improved-glucose-metabolism
#1
Julia Möllmann, Florian Kahles, Corinna Lebherz, Ben Kappel, Christer Baeck, Frank Tacke, Christian Werner, Massimo Federici, Nikolaus Marx, Michael Lehrke
AIMS: The PDE4 inhibitor roflumilast is a clinically approved anti-inflammatory drug used for the treatment of chronic obstructive pulmonary disease. In addition, roflumilast was found to reduce body weight and improve glucose metabolism by a yet unknown mechanism. MATERIALS AND METHODS: Metabolic effects of roflumilast were investigated in C57BL/6J mice on high fat western-type diet treated with or without roflumilast for a period of 12 weeks. RESULTS: Roflumilast led to a marked reduction of body weight gain, which became apparent in the second week following treatment initiation and was attributable to a pronounced increase of energy expenditure...
December 5, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27898183/effect-of-exenatide-on-postprandial-glucose-fluxes-lipolysis-and-%C3%A3-cell-function-in-nondiabetic-morbidly-obese-patients
#2
Stefania Camastra, Brenno Astiarraga, Andrea Tura, Silvia Frascerra, Demetrio Ciociaro, Andrea Mari, Amalia Gastaldelli, Ele Ferrannini
AIMS: To investigate the effect of exenatide on glucose disposal, insulin secretion, ß-cell function, lipolysis, and hormone concentrations in non-diabetic, morbidly obese subjects under physiological conditions. MATERIALS AND METHODS: Patients were assigned to exenatide 10 µg twice daily (EXE, n = 15) or control (CT, n = 15) for 3 months. Patients received a meal test/tracer study (MTT) to measure endogenous glucose production (EGP), rate of oral glucose appearance (RaO), insulin secretion rate (ISR), ß-cell function, hepatic (HIR) and adipose tissue insulin resistance (AT-IR) and insulin sensitivity (IS)...
November 29, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27891769/exenatide-induces-an-increase-in-vasodilatory-and-a-decrease-in-vasoconstrictive-mediators
#3
Ajay Chaudhuri, Husam Ghanim, Antoine Makdissi, Kelly Green, Sanaa Abuaysheh, Manav Batra, Nitesh Kuhadiya, Paresh Dandona
In view of the known vasodilatory effects of GLP-1, and exenatide, we investigated the effects of exenatide on vasoactive factors. We analyzed blood samples and mononuclear cells (MNC) from a previous study collected after a single dose and following 12 weeks of exenatide or placebo treatment on a series of 24 patients with T2DM. Following exenatide, plasma concentrations of ANP, cGMP, cAMP increased significantly at 12 weeks. Plasma cGMP and adenylate cyclase expression in MNC increased significantly following single dose...
November 28, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27891757/a-randomized-double-blind-phase-iii-study-to-evaluate-efficacy-and-safety-of-once-daily-treatment-of-alogliptin-and-metformin-hydrochloride-in-japanese-patients-with-type-2-diabetes
#4
Kohei Kaku, Shuuji Sumino, Masafumi Katou, Yuya Nishiyama, Yoshinobu Kinugawa
This randomized, double-blind, phase III study evaluated the efficacy and safety of once-daily (q.d.) treatment of alogliptin (25 mg q.d.) alone or with metformin hydrochloride (500 mg q.d. or 250 mg twice daily [b.i.d.]) in Japanese patients with type 2 diabetes. The primary endpoint was change in haemoglobin A1c (HbA1c) from baseline to the end of treatment (week 24). The least-squares mean (LSM) change in HbA1c from baseline (standard error) to the end of treatment (week 24) was 0.16% (0.072) in alogliptin alone, -0...
November 28, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27888561/novel-hepato-preferential-basal-insulin-peglispro-bil-does-not-differentially-affect-insulin-sensitivity-compared-with-insulin-glargine-in-patients-with-type-1-and-type-2-diabetes
#5
Niels Porksen, Helle Linnebjerg, Parag Garhyan, Eric Chen Quin Lam, Mary Pat Knadler, Scott J Jacober, Ulrike Hoevelmann, Leona Plum-Moerschel, Elaine Watkins, Amalia Gastaldelli, Tim Heise
AIMS: Basal insulin peglispro (BIL) is a novel PEGylated basal insulin with a flat pharmacokinetic and glucodynamic profile and reduced peripheral effects, which results in a hepato-preferential action. In Phase 3 trials, patients with T1DM treated with BIL had lower prandial insulin requirements, yet improved prandial glucose control, relative to insulin glargine (GL). We hypothesized that this may be due to an enhanced sensitivity to prandial insulin with BIL resulting from lower chronic peripheral insulin action...
November 26, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27883260/the-use-of-incretin-agents-and-risk-of-acute-and-chronic-pancreatitis-a-population-based-cohort-study
#6
Lotte M Knapen, Roy G P J de Jong, Johanna H M Driessen, Yolande C Keulemans, Nielka P van Erp, Marie L De Bruin, Hubert G M Leufkens, Sander Croes, Frank de Vries
BACKGROUND: Incretin-based therapies (Dipeptidyl Peptidase 4 inhibitors and Glucagon-Like Peptide-1 Receptor Agonists) are effective new agents for the treatment of Type 2 Diabetes Mellitus (T2DM). While incretin-based therapies have been associated with pancreatitis, evidence is conflicting for acute pancreatitis and lacks for chronic pancreatitis. OBJECTIVE: To determine the association between the use of incretin agents and the risk of any, acute and chronic pancreatitis...
November 24, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27868372/liraglutide-as-adjunct-to-insulin-treatment-in-type-1-diabetes-does-not-interfere-with-glycaemic-recovery-or-gastric-emptying-rate-during-hypoglycaemia-a-randomised-placebo-controlled-double-blind-parallel-group-study
#7
Christian Seerup Frandsen, Thomas Fremming Dejgaard, Henrik Ullits Andersen, Jens Juul Holst, Bolette Hartmann, Birger Thorsteinsson, Sten Madsbad
AIM: Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is a potential treatment as adjunct to insulin in type 1 diabetes (T1D). However, GLP-1RAs inhibit glucagon secretion and delay gastric emptying (GE) rate and may impair recovery from hypoglycaemia. We evaluated the effect of the GLP-1RA liraglutide on counterregulatory responses and GE rate during hypoglycaemia in persons with T1D. MATERIALS AND METHODS: In a 12-week, randomised, double-blinded, placebo-controlled study, 20 patients aged >18 years with T1D and HbA1c ≥8% (64 mmol/mol) were randomly assigned (1:1) to liraglutide 1...
November 21, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27868366/effects-of-gemigliptin-a-dipeptidyl-peptidase-4-inhibitor-on-lipid-metabolism-and-endotoxemia-after-a-high-fat-meal-in-patients-with-type-2-diabetes
#8
Chang Ho Ahn, Eun Ky Kim, Se Hee Min, Tae Jung Oh, Young Min Cho
We aimed to investigate the effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on postprandial lipoprotein levels and endotoxemia. This was a randomized, double-blind, placebo-controlled, crossover study. Ten patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral anti-diabetic medications and/or lifestyle modification were randomized to gemigliptin or placebo for four weeks. At the end of each treatment phase, the subjects underwent a high-fat meal tolerance test and needle aspiration of abdominal subcutaneous adipose tissue...
November 21, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27860160/effect-of-one-week-of-cpap-treatment-of-obstructive-sleep-apnoea-on-24-h-profiles-of-glucose-insulin-and-counter-regulatory-hormones-in-type-2-diabetes
#9
Babak Mokhlesi, Daniela Grimaldi, Guglielmo Beccuti, Eve Van Cauter
Studies examining the impact of CPAP treatment on glycaemic control have yielded conflicting results. We examined the 24-h profiles of glucose, insulin and counter-regulatory hormones in twelve subjects with type 2 diabetes and OSA before and after one week of effective in-laboratory CPAP therapy over an entire 8-h night. Blood samples were collected every 15-30 minutes for 24 hours under controlled conditions. The 24-h mean glucose decreased from 153.2 ± 33.0 to 139.7 ± 24.2 mg/dL with CPAP (-13...
November 17, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27860158/a-real-world-study-of-treatment-patterns-and-outcomes-in-us-managed-care-patients-with-type-2-diabetes-initiating-injectable-therapies
#10
W Wei, E Buysman, M Grabner, L Xie, L Brekke, X Ke, J W Chu, P A Levin
AIMS: Examine real-world outcomes in patients with type 2 diabetes mellitus (T2DM) initiating injectable therapy as part of the Initiation of New Injectable Treatment Introduced after Anti-diabetic Therapy with Oral-only Regimens (INITIATOR) study. MATERIALS AND METHODS: Linked insurance claims and medical record data were collected from two large US health insurers (1 April 2010 - 31 March 2012) of T2D adults initiating glargine (GLA) or liraglutide (LIRA). Baseline characteristics were examined and changes in 12-months' follow-up outcomes were described for both treatment groups: HbA1c, weight change, hypoglycaemia, persistence, healthcare utilisation and costs...
November 17, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27862902/cardiovascular-events-and-all-cause-mortality-associated-with-sulfonylureas-compared-to-other-antihyperglycaemic-drugs-a-bayesian-meta-analysis-of-survival-data
#11
Steve Bain, Eric Druyts, Chakrapani Balijepalli, Carl A Baxter, Craig Currie, Romita Das, Richard Donnelly, Kamlesh Khunti, Haya Langerman, Paul Leigh, Gaye Siliman, Kristian Thorlund, Kabirraaj Toor, Jiten Vora, Edward J Mills
AIM: Our aim was to conduct a systematic review and meta-analysis to determine the risk of cardiovascular events and all-cause mortality associated with sulfonylureas versus other antihyperglycaemic drugs in patients with type 2 diabetes. MATERIALS AND METHODS: A systematic review of Medline, Embase, Cochrane, and clinicaltrials.gov was conducted comparing sulfonylurea to placebo or other antihyperglycaemic drugs in patients with type 2 diabetes. A cloglog model was employed in the Bayesian framework to obtain comparative hazard ratios between interventions...
November 14, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27862873/the-sustained-influence-of-metformin-therapy-on-circulating-glp-1-levels-in-individuals-with-and-without-type-2-diabetes
#12
David Preiss, Adem Dawed, Paul Welsh, Alison Heggie, Angus G Jones, Jacqueline Dekker, Robert Koivula, Tue H Hansen, Ms Caitlin Stewart, Rury R Holman, Paul W Franks, Mark Walker, Ewan R Pearson, Naveed Sattar
AIMS: Small, short studies suggest metformin influences the glucagon-like peptide (GLP)-1 axis in individuals with and without type 2 diabetes (T2DM). In the Carotid Atherosclerosis: Metformin for insulin ResistAnce (CAMERA) trial (NCT00723307) we investigated whether this effect is sustained and related to changes in glycaemia or weight. In the cross-sectional DIabetes REsearCh on patient straTification (DIRECT) study, we investigated basal and post-meal GLP-1 levels in diabetic patients...
November 13, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27862830/urinary-tract-and-genital-infections-in-patients-with-type-2-diabetes-treated-with-sodium-glucose-cotransporter-2-inhibitors-a-meta-analysis-of-randomized-controlled-trials
#13
Dandan Li, Tiansheng Wang, Su Shen, Zhenwei Fang, Yue Dong, Huilin Tang
AIMS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with increased risk of urinary tract infections (UTIs) and genital infections. However, differences among different doses were still controversial. Thus, we aimed to evaluate effects of different SGLT2 inhibitors on the risk of UTIs and genital infections in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We systematically searched PubMed, Embase, CENTRAL, and ClinicalTrials...
November 12, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27862801/long-term-mortality-following-acute-myocardial-infarction-among-those-with-and-without-diabetes-a-systematic-review-and-meta-analysis-of-studies-in-the-post-reperfusion-era
#14
Nitin N Gholap, Felix A Achana, Melanie J Davies, Kausik K Ray, Laura Gray, Kamlesh Khunti
AIMS: Considerable medical advances have seen an improved survival following an acute myocardial infarction (AMI), whether these benefits extend to those with diabetes remains less clear. This systematic review and meta-analysis aim to provide robust estimates of the association between diabetes and long-term mortality (≥one year) following AMI. MATERIAL AND METHODS: Medline, Embase and Web of Science databases were searched (January 1985 - July 2016) for terms related to long-term mortality, diabetes and AMI...
November 12, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27862814/gut-feelings-about-diabetes-and-glp-1-receptor-agonists-lessons-to-be-learnt-from-studies-in-functional-gastrointestinal-disorders
#15
EDITORIAL
Christopher K Rayner, Karen L Jones, Tongzhi Wu, Michael Horowitz
No abstract text is available yet for this article.
November 9, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27860132/occurrence-of-nausea-vomiting-and-diarrhoea-reported-as-adverse-events-in-clinical-trials-studying-glucagon-like-peptide-1-receptor-agonists-a-systematic-analysis-of-published-clinical-trials
#16
Karolin Bettge, Melanie Kahle, Mirna S Abd El Aziz, Juris J Meier, Michael A Nauck
AIM: GLP-1 receptor agonists (RAs) may cause nausea, vomiting or diarrhoea. The purpose was to assess the risk of adverse events (AEs) with GLP-1 RAs and their relation to dose, background medication and duration of action. MATERIAL AND METHODS: The PubMed database was searched and 32 clinical trials with GLP-1 RAs (phase 3) were selected. We performed a systematic analysis and compared the proportion of patients reporting nausea, vomiting or diarrhoea, for different doses and glucose-lowering background medications, and relative to a reference compound within the subclasses of short- (exenatide b...
November 9, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27807924/effect-modification-in-the-relation-between-hba1c-and-cardiovascular-disease-and-mortality-in-patients-with-type-2-diabetes
#17
Sanne N van Munster, Yolanda van der Graaf, Harold W de Valk, Frank L J Visseren, Jan Westerink
AIMS: Strict glycemic control has been shown to reduce cardiovascular events in patients with type 2 diabetes, but may also be associated with increased mortality in certain subgroups. Identifying patients who would benefit from strict glycemic control is therefore paramount. This study aimed to identify patients with T2D that may benefit from lower or higher HbA1c targets, based on readily available patient characteristics. MATERIALS AND METHODS: T2D patients were included from the SMART (Second Manifestations of ARTerial disease) cohort...
November 2, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27804190/glycemic-control-impacts-the-relationship-between-plasma-pcsk9-and-ldl-cholesterol-in-type-1-diabetes
#18
Stéphanie Laugier-Robiolle, Bruno Vergès, Maëlle Le Bras, Elise Gand, Benjamin Bouillet, Pierre-Jean Saulnier, Cédric Le May, Matthieu Pichelin, Richard Maréchaud, Jean-Michel Petit, Samy Hadjadj, Bertrand Cariou
Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of LDL cholesterol (LDL-C) metabolism. However, little is known about the regulation of PCSK9 in patients with type 1 diabetes (T1D). Here, we aimed to determine the relationship between circulating PCSK9 and metabolic parameters in T1D. Plasma PCSK9 levels were measured in 195 T1D (mean age: 38.8 years; mean diabetes duration: 17.2 years; mean HbA1c: 8.3%) who were free of any lipid-lowering agent. Plasma PCSK9 was positively correlated with LDL-C (p = 0...
November 2, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27800649/effects-of-dpp-4-inhibitor-linagliptin-and-glp-1-receptor-agonist-liraglutide-on-physiological-response-to-hypoglycemia-in-japanese-subjects-with-type-2-diabetes-a-randomized-open-label-2-arm-parallel-comparative-exploratory-trial
#19
Daisuke Yabe, Takashi Eto, Masanari Shiramoto, Shin Irie, Kenta Murotani, Yusuke Seino, Hitoshi Kuwata, Takeshi Kurose, Susumu Seino, Bo Ahren, Yutaka Seino
Dipeptidyl peptidase-4 (DPP-4) inhibitors reduces the risk of hypoglycemia, possibly through augmentation of glucose-dependent insulinotropic polypeptide (GIP) action but not that of glucagon-like peptide-1 (GLP-1) on glucagon secretion. To examine this model in Japanese individuals with type 2 diabetes (T2D), the effects of the DPP-4 inhibitor linagliptin on glucagon and other counterregulatory hormone responses to hypoglycemia were evaluated and compared with those of the GLP-1 receptor agonist liraglutide in a multi-center, randomized, open-label, 2 arm parallel comparative, exploratory trial...
November 1, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27800648/treatment-with-a-novel-agent-combining-docosahexaenoate-and-metformin-increases-protectin-dx-and-il-6-production-in-skeletal-muscle-and-reduces-insulin-resistance-in-obese-diabetic-db-db-mice
#20
Patricia L Mitchell, Renato Nachbar, Dominic Lachance, Philippe St-Pierre, Jocelyn Trottier, Olivier Barbier, André Marette
AIMS: To compare the therapeutic potential of TP-113, a unique molecular entity linking DHA with metformin, for alleviating insulin resistance in obese diabetic mice through the PDX/IL-6 pathway. MATERIAL AND METHODS: We utilized the generically obese diabetic db/db mouse model for all experiments. Initial studies investigated both a dose and time course response. These results were then utilized to design a long term (5wk) treatment protocol. Mice were gavaged twice a day with one of three treatments: 200 mg/kg BW TP113, and equivqlent dose of metformin alone (70 mg/kg BW) or water...
November 1, 2016: Diabetes, Obesity & Metabolism
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