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Diabetes, Obesity & Metabolism

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https://www.readbyqxmd.com/read/29227582/role-of-the-sodium-hydrogen-exchanger-in-mediating-the-renal-effects-of-drugs-commonly-used-in-the-treatment-of-type-2-diabetes
#1
REVIEW
Milton Packer
Diabetes is characterized by an increased activity of the sodium-hydrogen exchanger (NHE) in the glomerulus and renal tubules, which contributes importantly to the development of nephropathy. Despite the established role played by the exchanger in experimental studies, it has not been specifically targeted by those seeking to develop novel pharmacological treatments for diabetes. This review demonstrates that many existing drugs that are commonly prescribed to patients with diabetes act on the NHE1 and NHE3 isoforms in the kidney...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29227578/insulin-secretion-predicts-the-response-to-therapy-with-exenatide-plus-pioglitazone-but-not-to-basal-bolus-insulin-in-poorly-controlled-t2dm-patients-results-from-the-qatar-study
#2
Muhammad Abdul-Ghani, Osama Migahid, Ayman Megahed, Rajvir Singh, Dalia Kamal, Ralph A DeFronzo, Amin Jayyousi
The present study aims to identify predictors for response to combination therapy with pioglitazone plus exenatide versus basal/bolus insulin therapy in T2DM patients who are poorly controlled on maximum/near-maximum doses metformin plus a sulfonylurea. Participants in the Qatar study received a 75-gram OGTT with measurement of plasma glucose, insulin, and C-peptide concentration at baseline and then were randomized to receive treatment with pioglitazone plus exenatide or basal/bolus insulin therapy for one year...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29227575/effect-of-a-single-dose-of-the-dpp-4-inhibitor-sitagliptin-on-%C3%AE-cell-function-and-incretin-hormone-secretion-after-meal-ingestion-in-healthy-volunteers-and-drug-na%C3%A3-ve-well-controlled-type-2-diabetes-subjects
#3
Wathik Alsalim, Olga Göransson, Richard D Carr, Roberto Bizzotto, Andrea Tura, Giovanni Pacini, Andrea Mari, Bo Ahrén
To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on glucose-standardized insulin secretion and β-cell glucose sensitivity after meal ingestion, twelve healthy- and twelve drug naïve well-controlled type 2 diabetes subjects (T2D; mean HbA1c 43 mmol/mol, 6.2%) received sitagliptin (100mg) or placebo before a meal (525 kcal). β-cell function was measured as the insulin secretory rate at a standardized glucose concentration and the β-cell glucose sensitivity (the slope between glucose and insulin secretory rate)...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29227571/comparative-effectiveness-of-metformin-monotherapy-in-extended-release-and-immediate-release-formulations-for-the-treatment-of-type-2-diabetes-in-treatment-na%C3%A3-ve-chinese-patients-analysis-of-results-from-the-consent-trial
#4
Linong Ji, Jing Liu, Jing Yang, Yufeng Li, Li Liang, Dalong Zhu, Quanmin Li, Tianrong Ma, Haiyan Xu, Yanlan Yang, Jiaoe Zeng, Bo Feng, Shen Qu, Yiming Li, Lizhen Ma, Shanshan Lin, Jianping Wang, Wei Li, Weihong Song, Xiaoxing Li, Yong Luo, Shugang Xi, Mei Lin, Yu Liu, Zerong Liang
AIMS: Metformin treatment for type 2 diabetes (T2DM) can be limited by gastrointestinal (GI) adverse events (AEs), resulting in treatment discontinuation. We investigated whether once-daily metformin extended release (XR) is superior in terms of GI tolerability, with non-inferior efficacy, compared with thrice-daily metformin immediate release (IR) in treatment-naïve Chinese patients with T2DM. MATERIALS AND METHODS: This prospective, open-label, randomized, multicenter, phase IV interventional study enrolled Chinese T2DM patients to receive either metformin XR or metformin IR with a 2-week screening period, 16-week treatment period, and 2-week follow-up period without treatment...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29206339/reversibility-of-myocardial-metabolism-and-remodeling-in-morbidly-obese-patients-six-months-after-bariatric-surgery
#5
Jarna C Hannukainen, Riikka Lautamäki, Jussi Pärkkä, Marjatta Strandberg, Virva Saunavaara, Saija Hurme, Minna Soinio, Prince Dadson, Kirsi A Virtanen, Tove Grönroos, Sarita Forsback, Paulina Salminen, Patricia Iozzo, Pirjo Nuutila
AIMS/HYPOTHESIS: To study myocardial substrate uptake, structure and function before and after bariatric surgery to clarify the interaction between myocardial metabolism and cardiac remodeling in morbid obesity. METHODS: We studied 46 subjects (age 44±10 yrs, BMI 42±4 kg/m2), including 18 with type 2 diabetes before and six months after bariatric surgery and 25 healthy age-matched controls. Myocardial fasting free fatty acid uptake (MFAU) and insulin-stimulated glucose uptake (MGU) were measured using PET...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29206336/claims-based-studies-of-oral-glucose-lowering-medications-can-achieve-balance-in-critical-clinical-parameters-only-observed-in-electronic-health-records
#6
E Patorno, C Gopalakrishnan, J M Franklin, K G Brodovicz, E Masso-Gonzalez, D B Bartels, J Liu, S Schneeweiss
BACKGROUND: Healthcare claims databases can provide information on the effects of type 2 diabetes (T2DM) medications as used in routine care, but often do not contain data on important clinical characteristics, which may be captured in electronic health records (EHR). OBJECTIVES: To evaluate the extent to which balance in unmeasured patient characteristics was achieved in claims data, by comparing against more detailed information from linked EHR data. METHODS: Within a large US commercial insurance database and using a cohort design, we identified T2DM patients initiating linagliptin or a comparator agent within class (i...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29205856/use-and-effectiveness-of-a-fixed-ratio-combination-of-insulin-degludec-liraglutide-ideglira-in-a-real-world-population-with-type-2-diabetes-results-from-a-european-multicentre-retrospective-chart-review-study
#7
Hermione Price, Matthias Blüher, Rudolf Prager, Tra-Mi Phan, Brian Larsen Thorsted, Bernd Schultes
AIMS: EXTRA aimed to describe real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide. MATERIALS AND METHODS: This European, multicentre, retrospective chart review comprised adults (n=611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data available...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29205786/pharmacokinetics-and-tolerability-of-semaglutide-in-subjects-with-hepatic-impairment
#8
Lene Jensen, Viera Kupcova, Gerhard Arold, Jonas Pettersson, Julie B Hjerpsted
AIMS: To investigate whether the pharmacokinetic characteristics of semaglutide were altered in subjects with hepatic impairment, assessed using Child-Pugh criteria, versus those with normal hepatic function. METHODS: In this multicentre, open-label, parallel-group trial (sponsor Novo Nordisk, ClinicalTrials.gov ID NCT02210871), four groups of subjects with normal hepatic function (n = 19) or mild (n = 8), moderate (n = 10) or severe (n =7) hepatic impairment received a single, subcutaneous dose of 0...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29205774/comparison-of-glucose-lowering-agents-following-dual-therapy-failure-in-type-2-diabetes-systematic-review-and-network-meta-analysis-of-randomised-controlled-trials
#9
Francesco Zaccardi, Nafeesa N Dhalwani, Jolyon Dales, Hamid Mani, Kamlesh Khunti, Melanie J Davies, David R Webb
AIMS: To assess the evidence supporting the choice of third-line agents in adults with inadequately controlled type 2 diabetes. MATERIALS AND METHODS: We searched RCTs published between Jan 2000 and July 2017 reporting data on cardiometabolic outcomes and hypoglycaemia for glucose-lowering agents added to metformin-based dual treatments. Data were stratified by background therapy and RCT duration and synthesised, when possible, with network meta-analyses. RESULTS: 43 RCTs (16590 participants) were included, with metformin combined to sulphonylurea (SU) in 20 RCTs; thiazolidinedione (TZD) in 10; basal or rapid acting insulin in 6; DPP-4i in 3; GLP-1RA in 2; and SGLT-2i in 2...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29205760/plasma-pcsk9-and-cardiovascular-events-in-type-2-diabetes
#10
Petra El Khoury, Ronan Roussel, Frederic Fumeron, Yara Abou-Khalil, Gilberto Velho, Kamel Mohammedi, Marie-Paule Jacob, P Gabriel Steg, Louis Potier, Youmna Ghaleb, S El Bitar, S Ragot, Francesco Andreata, Giusepinna Caligiuri, Samy Hadjadj, Catherine Boileau, Michel Marre, Marianne Abifadel, Mathilde Varret, Boris Hansel
No abstract text is available yet for this article.
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29205751/lh-21-and-abn-cbd-improve-%C3%AE-cell-function-in-isolated-human-and-mouse-islets-through-gpr55-dependent-and-independent-signalling
#11
Inmaculada Ruz-Maldonado, Attilio Pingitore, Bo Liu, Patricio Atanes, Guo Cai Huang, David Baker, Francisco José Alonso, Francisco Javier Bermúdez-Silva, Shanta J Persaud
AIMS: CB1 and GPR55 are GPCRs expressed by islet β-cells. Pharmacological compounds have been used to investigate their function, but off-target effects of ligands have been reported. This study examined the effects of Abn-CBD (GPR55 agonist) and LH-21 (CB1 antagonist) on human and mouse islet function, and islets from GPR55-/- mice were used to determine signalling via GPR55. MATERIALS AND METHODS: Islets isolated from human organ donors and mice were incubated in the absence or presence of Abn-CBD or LH-21 and insulin secretion, [Ca2+ ]i, cAMP, apoptosis, β-cell proliferation and CREB and AKT phosphorylation were examined by standard techniques...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29205734/clinical-correlates-of-hypoglycaemia-over-4-years-in-people-with-type-2-diabetes-starting-insulin-an-analysis-from-the-credit-study
#12
Philip Home, Francoise Calvi-Gries, Lawrence Blonde, Valerie Pilorget, Joseph Berlingieri, Nick Freemantle
AIM: To identify factors associated with documented symptomatic and severe hypoglycaemia over 4 years in people with type 2 diabetes starting insulin therapy. MATERIALS AND METHODS: CREDIT, a prospective international observational study, collected data over 4 years on people starting any insulin in 314 centers; 2729 and 2271 people had hypoglycaemia data during the last 6 months of years 1 and 4. Multivariable logistic regression was used to select characteristics associated with documented symptomatic hypoglycaemia, and the model tested against severe hypoglycaemia...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29194917/treatment-of-clozapine-associated-obesity-and-diabetes-with-exenatide-codex-in-adults-with-schizophrenia-a-randomised-controlled-trial
#13
Dan Siskind, Anthony W Russell, Clare Gamble, Karl Winckel, Karla Mayfield, Sam Hollingworth, Ingrid Hickman, Victor Siskind, Steve Kisely
Clozapine causes obesity and type-2 diabetes (T2DM). Glucagon-like-peptide-1 (GLP-1) agonists (e.g. exenatide) can counter clozapine-associated GLP-1 dysregulation in animals, and may be beneficial in people on clozapine. This randomised, controlled, open-label, pilot trial evaluated weekly exenatide for weight loss among clozapine-treated obese adults with schizophrenia, with or without T2DM. Twenty-eight outpatients were randomised to once-weekly extended-release sub-cutaneous exenatide or usual care for 24 weeks...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29193572/incretin-based-therapies-and-risk-of-pancreatic-cancer-in-patients-with-type-2-diabetes-a-meta-analysis-of-randomised-controlled-trials
#14
Haining Wang, Ye Liu, Qing Tian, Jin Yang, Ran Lu, Siyan Zhan, Jari Haukka, Tianpei Hong
AIMS: Conflicting evidence exists regarding the potential risk of pancreatic cancer with use of incretin drugs in patients with type 2 diabetes (T2DM). We performed a meta-analysis of randomised controlled trials (RCTs), including six recently published large-scale cardiovascular outcome trials (CVOTs), to evaluate the risk of pancreatic cancer with incretin-based therapies in patients with T2DM. MATERIALS AND METHODS: The PubMed, Embase, Cochrane Central Register and ClininalTrials...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29193561/effectiveness-and-tolerability-of-therapy-with-exenatide-once-weekly-versus-basal-insulin-among-injectable-na%C3%A3-ve-elderly-or-renal-impaired-patients-with-type-2-diabetes-in-the-united-states
#15
Anita M Loughlin, Qing Qiao, Anthony Philip Nunes, Peter Öhman, Stephen Ezzy, Laura Yochum, C Robin Clifford, Robert Gately, David D Dore, John Seeger
AIM: To evaluate the effectiveness and tolerability of exenatide once-weekly (EQW) compared to basal insulin (BI) among injectable-naïve T2DM patients who are elderly or have renal impairment (RI). METHODS AND MATERIALS: Initiators of EQW and BI with T2DM were identified from 2012-2015 within a United States electronic health record database and matched by propensity score. Matched EQW and BI initiators aged 65+ years or who have RI were compared. Weight, HbA1c, eGFR, blood pressure, and lipids were obtained at baseline and quarterly (Q1-Q4) or semi-annually for one year following drug initiation...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29193555/overtreatment-of-older-patients-with-type-2-diabetes-mellitus-in-primary-care
#16
E Hart Huberta, E Rutten Guy, N Bontje Kyra, C Vos Rimke
There are indications of overtreatment in older type 2 diabetes patients in both the US and Europe. We assessed the level of personalized diabetes treatment for older patients in primary care, focusing on overtreatment. Based on Dutch guidelines individuals ≥ 70 years were classified into three HbA1c treatment target groups: 7% (53 mmol/mol), 7.5% (58 mmol/mol) and 8% (64 mmol/mol). In our cohort of 1.002 patients (n=319 ≥ 70 yrs), the 165 patients with target above 7% had more micro- and macrovascular complications, used more often ≥ 5 medicines and were more often frail compared to those with an HbA1c target ≤ 7%...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29193543/initiation-of-dapagliflozin-and-treatment-emergent-fractures
#17
Konstantinos A Toulis, John P Bilezikian, G Neil Thomas, Wasim Hanif, Kalliopi Kotsa, Rasiah Thayakaran, Deepiksana Keerthy, Abd Tahrani, Krishnarajah Nirantharakumar
An increase in the fracture risk was reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced by all members of the sodium-glucose co-transporter 2 inhibitors (SGLT2i) class. It is unclear whether initiation of dapagliflozin is followed by an increase in the risk of fracture. Therefore, we performed a population-based, open cohort study was performed (January 2013-January 2016) using The Health Improvement Network (THIN). 22,618 patients with T2DM (4,548 exposed to dapagliflozin and 18,070 under standard antidiabetic treatment, matched for age and sex) with no history of fractures at baseline...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29178635/the-effect-of-non-surgical-weight-management-on-weight-and-glycaemic-control-in-people-with-type-2-diabetes-a-comparison-of-interventional-and-non-interventional-outcomes-at-three-years
#18
Shani Botha, Lorna Forde, Sheila MacNaughton, Ross Shearer, Robert Lindsay, Naveed Sattar, David Morrison, Paul Welsh, Jennifer Logue
BACKGROUND: Lifestyle weight management interventions are recommended in clinical guidelines for patients with type 2 diabetes and obesity, but lack evidence regarding their long term effectiveness. MATERIALS AND METHODS: Electronic health records were used to follow 23,208 patients with type 2 diabetes and obesity in Glasgow, Scotland, for up to 3 years between 2005 and 2014. Patients were stratified by referral to and attendance at a lifestyle weight management intervention, and by attainment of a target weight loss of ≥5kg over 7-9 sessions ("successful completers")...
November 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29178536/effects-of-an-energy-restricted-low-carbohydrate-high-unsaturated-fat-low-saturated-fat-diet-versus-a-high-carbohydrate-low-fat-diet-in-type-2-diabetes-a-2-year-randomized-clinical-trial
#19
Jeannie Tay, Campbell H Thompson, Natalie D Luscombe-Marsh, Thomas P Wycherley, Manny Noakes, Jonathan D Buckley, Gary A Wittert, William S Yancy, Grant D Brinkworth
AIM: To examine whether a low-carbohydrate, high unsaturated/low saturated fat diet (LC) improves glycemic control and cardiovascular disease (CVD) risk factors in overweight and obese patients with type 2 diabetes (T2D). METHODS: 115 adults with T2D (mean[SD]; BMI:34.6[4.3]kg/m2 , age:58[7]yrs, HbA1c:7.3[1.1]%) were randomized to one of two planned energy-matched, hypocaloric diets combined with aerobic/resistance exercise (1hr,3d/wk) for 2 years:(1) LC:14% energy as carbohydrate, 28% protein, 58% fat [<10% saturated fat]) or (2) low fat, high-carbohydrate, low glycemic index diet (HC):53% CHO, 17% protein, 30% fat [<10% saturated fat])...
November 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29178519/semaglutide-reduction-in-hba1c-and-the-risk-of-diabetic-retinopathy
#20
Tina Vilsbøll, Stephen C Bain, Lawrence A Leiter, Ildiko Lingvay, David Matthews, Rafael Simó, Ida Carøe Helmark, Nelun Wijayasinghe, Michael Larsen
AIMS: To evaluate diabetic retinopathy data from across the SUSTAIN clinical trial programme. MATERIALS AND METHODS: The SUSTAIN clinical trial programme evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6 - a 2-year, preapproval cardiovascular outcomes trial - semaglutide was associated with a significant increase in the risk of diabetic retinopathy complications (DRC) versus placebo...
November 27, 2017: Diabetes, Obesity & Metabolism
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