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Diabetes, Obesity & Metabolism

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https://www.readbyqxmd.com/read/28345814/dapagliflozin-once-daily-plus-exenatide-once-weekly-in-obese-adults-without-diabetes-sustained-reductions-in-bodyweight-glycaemia-and-blood-pressure-over-1-year
#1
Per Lundkvist, Maria J Pereira, Petros Katsogiannos, C David Sjöström, Eva Johnsson, Jan W Eriksson
AIMS: Dapagliflozin and exenatide reduce bodyweight by differing mechanisms. Dual therapy with these agents reduces bodyweight, adipose tissue volume, glycaemia, and systolic blood pressure (SBP) over 24 weeks. Here, we examined these effects over 1 year in obese adults without diabetes. MATERIALS AND METHODS: Obese adults without diabetes (N = 50; aged 18-70 years; body mass index 30-45 kg/m(2) ) initially randomized to double-blind oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo entered an open-label extension from 24-52 weeks during which all participants received active treatment...
March 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28345792/adding-fast-acting-insulin-aspart-to-basal-insulin-significantly-improved-glycaemic-control-in-patients-with-type-2-diabetes-a-randomised-18-week-open-label-phase-3-trial-onset-3
#2
Helena W Rodbard, Devjit Tripathy, Maricela Vidrio Velázquez, Marek Demissie, Søren Can Tamer, Milivoj Piletič
AIM: To confirm glycaemic control superiority of mealtime fast-acting insulin aspart (faster aspart) in a basal-bolus (BB) regimen versus basal-only insulin. MATERIALS AND METHODS: In this open-label, randomised, 18-week trial (51 sites; 6 countries) adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c ] ±SD: 7.9 ± 0.7% [63.1 ± 7.5 mmol/mol) receiving basal insulin and oral antidiabetic drugs underwent 8-week optimisation of prior once-daily basal insulins followed by randomisation 1:1 to a BB regimen with faster aspart (n = 116) or continuation of once-daily basal insulin (n = 120), both with metformin...
March 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28345790/metabolic-responses-to-exogenous-ghrelin-in-obesity-and-early-after-roux-en-y-gastric-bypass-in-humans
#3
Robyn A Tamboli, Joseph Antoun, Reem M Sidani, B Austin Clements, Emily A Eckert, Pam Marks-Shulman, Bruce D Gaylinn, D Brandon Williams, Ronald H Clements, Vance L Albaugh, Naji N Abumrad
AIMS: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg(-1) min(-1) ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and two weeks after RYGB...
March 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28345762/short-term-effects-of-low-carbohydrate-diet-on-glycaemic-parameters-and-cardiovascular-risk-markers-in-patients-with-type-1-diabetes-a-randomised-open-label-cross-over-trial
#4
A Ranjan, S Schmidt, C Damm-Frydenberg, J Holst, S Madsbad, K Nørgaard
The objective was to compare effects of high carbohydrate diet (HCD) versus low carbohydrate diet (LCD) on glycaemic parameters and cardiovascular risk markers in patients with type 1 diabetes. Ten patients (4 women, insulin pump-treated, median±SD age: 48 ± 10 years, HbA1c: 53 ± 6 mmol/mol (7.0 ± 0.6%)) followed one week of isocaloric HCD (≥250 g/day) and one week of isocaloric LCD (≤50 g/day) in random order. After each week, we downloaded pump and sensor data and collected fasting blood and urine samples...
March 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28345162/reduction-of-postprandial-glucose-by-lixisenatide-versus-sitagliptin-in-japanese-patients-with-type-2-diabetes-on-background-insulin-glargine-a-randomised-phase-4-study
#5
Yuichiro Yamada, Masayuki Senda, Yusuke Naito, Masahiro Tamura, Daisuke Watanabe, Yujin Shuto, Yoshihisa Urita
AIM: To evaluate the pharmacodynamics of adjunctive lixisenatide once daily versus sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100. METHODS: This multicentre, open-label, phase 4 study (NCT02200991) randomly assigned 136 patients to either lixisenatide once-daily subcutaneous injection (10 µg initially increased weekly by 5 µg up to 20 µg) or once-daily oral sitagliptin (50 mg dose). The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration-time curve [AUC0:00-4:00h ]) from baseline to Day 29...
March 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28338281/cardiovascular-safety-of-vildagliptin-in-patients-with-type-2-diabetes-a-european-multi-database-non-interventional-post-authorization-safety-study
#6
R Williams, F de Vries, W Kothny, C Serban, S Lopez-Leon, C Chu, R Schlienger
This non-interventional, multi-database, analytical cohort study assessed the cardiovascular (CV) safety of vildagliptin vs. other non-insulin antidiabetic drugs (NIADs) using real-world data from five European electronic healthcare databases. Patients with type 2 diabetes aged ≥18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) for the outcomes of interest (myocardial infarction [MI], acute coronary syndrome [ACS], stroke, congestive heart failure [CHF], individually and as a composite) were estimated using negative binomial regression...
March 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28332276/dual-ccr2-ccr5-antagonist-treatment-attenuates-adipose-inflammation-but-not-microvascular-complications-in-ob-ob-mice
#7
Phillipe D O'Brien, Lucy M Hinder, Sebastian D Parlee, John M Hayes, Carey Backus, Hongyu Zhang, Lijun Ma, Stacey A Sakowski, Frank C Brosius, Eva L Feldman
Diabetic peripheral neuropathy (DPN) and diabetic kidney disease (DKD) are common diabetic complications with limited treatment options. Experimental studies show that targeting inflammation using chemokine receptor (CCR) antagonists ameliorates DKD, presumably by reducing macrophage accumulation or activation. As inflammation is implicated in DPN development, we assessed whether CCR2 and CCR5 antagonism could also benefit DPN. Five-week-old ob/ob mice were fed a diet containing MK-0812, a dual CCR2-CCR5 receptor antagonist, for 8 weeks and DPN, DKD, and metabolic phenotyping were then performed to determine the effect of CCR inhibition...
March 23, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28321981/evaluation-of-the-modified-findrisc-diabetes-score-to-identify-individuals-at-high-risk-for-diabetes-among-middle-aged-white-and-black-aric-study-participants
#8
Manjusha Kulkarni, Randi E Foraker, Ann Marie McNeill, Cynthia Girman, Sherita Hill Golden, Wayne D Rosamond, Bruce Duncan, Maria Ines Schmidt, Jaakko Tuomilehto
OBJECTIVE: To evaluate a modified Finnish Diabetes Risk Score (FINDRISC) score for predicting the risk of incident diabetes among white and black middle-aged Atherosclerosis Risk in Communities (ARIC) study participants. Research Design and Methods We assessed 9,754 ARIC cohort participants who were free of diabetes at baseline. Logistic regression and receiver operator characteristic (ROC) curves were used to evaluate a modified FINDRISC score for predicting incident diabetes after 9 years of follow-up, overall and by race/gender group...
March 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28318105/metformin-as-add-on-to-intensive-insulin-therapy-in-type-1-diabetes-mellitus
#9
Frederik Staels, Carolien Moyson, Chantal Mathieu
We aimed to evaluate the effect of adjuvant metformin to intensive insulin therapy in patients with type 1 diabetes (T1DM). A 10 year retrospective study of 2 cohorts was performed. Cohort "MET" (n = 186) consisted of T1DM patients on adjuvant metformin for ≥ 6 months and cohort "CTR" (n = 62) consisted of T1DM patients who refused (n = 25) or adhered <6 months (n = 37) to metformin. HbA1c, BMI and daily insulin dose were registered yearly. A third cross-sectional group "REF" (n = 961) of T1DM patients not offered adjuvant metformin, was used as a reference for baseline comparison...
March 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28318098/decreased-insulin-stimulated-brown-adipose-tissue-glucose-uptake-after-short-term-exercise-training-in-healthy-middle-aged-men
#10
Piryanka Motiani, Kirsi A Virtanen, Kumail K Motiani, Joonas J Eskelinen, Roeland J Middelbeek, Laurie J Goodyear, Anna M Savolainen, Jukka Kemppainen, Jørgen Jensen, Mueez U Din, Virva Saunavaara, Riitta Parkkola, Eliisa Löyttyniemi, Juhani Knuuti, Pirjo Nuutila, Kari K Kalliokoski, Jarna C Hannukainen
AIMS: Little is known about the effects of exercise training on brown adipose tissue (BAT) metabolism in humans. We tested the hypothesis that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) improve BAT insulin sensitivity. MATERIALS AND METHODS: Healthy middle-aged men (n = 18, age 47 [CI: 49, 43] years, BMI 25.3 [CI: 24.1-26.3] kg · m(-2) , VO2peak 34.8[CI: 32.1, 37.4] ml · kg(-1)  · min(-1) ) were recruited and randomized into six HIIT or MICT sessions within two weeks...
March 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28304146/liraglutide-acutely-suppresses-glucagon-lipolysis-and-ketogenesis-in-type-1-diabetes
#11
Manisha Garg, Husam Ghanim, Nitesh D Kuhadiya, Kelly Green, Jeanne Hejna, Sanaa Abuaysheh, Barrett Torre, Manav Batra, Antoine Makdissi, Ajay Chaudhuri, Paresh Dandona
In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 (SGLT2) inhibitors in patients with type 1 diabetes (T1DM) and the relative absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty-six patients with inadequately controlled T1DM were randomly divided into two groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28304141/evidence-connecting-old-new-and-neglected-glucose-lowering-drugs-to-bile-acid-induced-glp-1-secretion-a-review
#12
REVIEW
Martin L Kårhus, Andreas Brønden, David P Sonne, Tina Vilsbøll, Fillip K Knop
Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut-derived incretin hormone glucagon-like peptide-1 (GLP-1), possibly via the transmembrane receptor Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor (FXR), in intestinal L cell...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28296055/efficacy-and-safety-of-saxagliptin-compared-with-acarbose-in-chinese-patients-with-type-2-diabetes-mellitus-uncontrolled-on-metformin-monotherapy-results-of-a-phase-iv-open-label-randomized-controlled-study-the-smart-study
#13
Jin Du, Li Liang, Hui Fang, Fengmei Xu, Wei Li, Liya Shen, Xueying Wang, Chun Xu, Fang Bian, Yiming Mu
AIM: To investigate the efficacy, safety and tolerability of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy. MATERIALS AND METHODS: SMART was a 24-week, multicentre, randomized, parallel-group, open-label Phase IV study conducted at 35 sites in China (24/09/2014-29/09/2015). The primary outcome was change from baseline in HbA1c at Week 24. Secondary efficacy outcomes assessed at Week 24 included the proportion of patients achieving HbA1c<7...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28295974/risk-factors-and-outcome-differences-in-hypoglycaemia-related-hospital-admissions-a-case-control-study-in-england
#14
Francesco Zaccardi, David R Webb, Melanie J Davies, Nafeesa N Dhalwani, Gemma Housley, Dominic Shaw, James W Hatton, Kamlesh Khunti
AIMS: To evaluate risk factors for hospital admissions for hypoglycaemia and compare length of hospitalisation, inpatient mortality, and hospital readmission between hypoglycaemia and non-hypoglycaemia-related admissions. MATERIALS AND METHODS: We used all admissions for hypoglycaemia in people with diabetes to English NHS hospital trusts between 2005 and 2014 (101,475 case admissions) and three random admissions per case in people with diabetes without hypoglycaemia (304,425 control admissions)...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28295962/improving-glycemic-control-in-type-2-diabetes-stimulate-insulin-secretion-or-provide-beta-cell-rest
#15
REVIEW
Daniël H van Raalte, C Bruce Verchere
Type 2 diabetes (T2D) is characterized by a gradual decline of pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycemia, chronic hyperglycemia itself is also detrimental for beta-cell function, likely by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28295959/the-albuminuria-lowering-response-to-dapagliflozin-is-variable-and-reproducible-between-individual-patients
#16
Sergei I Petrykiv, Gozewijn D Laverman, Dick de Zeeuw, Hiddo J L Heerspink
AIMS: Albuminuria reduction is essential for renal and cardiovascular protection. We characterized the efficacy of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, on albuminuria. Secondly, we assessed whether the albuminuria lowering effect varies between patients, and whether this variability in response is reproducible. MATERIAL AND METHODS: A double-blind, randomized, placebo controlled crossover trial was conducted. Patients with type 2 diabetes and albumin:creatinine ratio >100 mg/g on a stable dose of an Angiotensin Converting Enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) were enrolled...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28295934/insulin-degludec-lower-day-to-day-and-within-day-variability-in-pharmacodynamic-response-compared-to-insulin-glargine-u300-in-type-1-diabetes
#17
Tim Heise, Marianne Nørskov, Leszek Nosek, Kadriye Kaplan, Susanne Famulla, Hanne L Haahr
AIM: To compare day-to-day and within-day variability in glucose-lowering effect between insulin degludec (IDeg) and insulin glargine 300 U/mL (IGlar-U300) in type 1 diabetes. MATERIALS AND METHODS: In this double-blind, crossover study, patients were randomly assigned to 0.4 U/kg of IDeg or IGlar-U300 once-daily for two treatment periods lasting 12 days each. Pharmacodynamic parameters were assessed at steady state from glucose infusion rate profiles of three 24h euglycaemic glucose clamps (Days 6, 9 and 12) during each treatment period...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28295931/salsalate-improves-glycemia-in-overweight-persons-with-diabetes-risk-factors-of-stable-statin-treated-cardiovascular-disease-a-30-month-randomized-placebo-controlled-trial
#18
Ninad Salastekar, Tanvi Desai, Thomas Hauser, Ernst J Schaefer, Kristen Fowler, Stacey Joseph, Steven Shoelson, Allison B Goldfine
Obesity related sub-acute chronic inflammation contributes to type 2 diabetes and atherosclerosis (1,2) . Multiple studies target inflammation to reduce dysglycemia and/or coronary heart disease (CHD) using diverse anti-inflammatory approaches. Several show salsalate, a pro-drug of salicylate, improves glycemia in type 2 diabetes, obesity, or impaired glucose tolerance. Durability of glycemic efficacy and safety of salsalate remains less well understood.
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28294499/a-placebo-controlled-randomised-trial-of-the-addition-of-once-weekly-glp-1-receptor-agonist-dulaglutide-to-titrated-daily-insulin-glargine-in-patients-with-type-2-diabetes-award-9
#19
Paolo Pozzilli, Paul Norwood, Esteban Jodar, Melanie J Davies, Tibor Ivanyi, Honghua Jiang, Brad Woodward, Zvonko Milicevic
AIMS: Compare the addition of weekly dulaglutide versus the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimal HbA1c . METHODS: Patients (N = 300) from this Phase 3, double-blind, parallel-arm, placebo-controlled study were randomised to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± SD baseline dose: 39 ± 22 U), with or without metformin (≥1,500 mg/day)...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28296194/association-between-diabetes-mellitus-and-incidence-and-case-fatality-after-stroke-due-to-intracerebral-haemorrhage-a-retrospective-population-based-cohort-study
#20
Marion Boulanger, Rustam Al-Shahi Salman, Jan Kerssens, Sarah H Wild
We investigated the associations between types of diabetes and ICH incidence and case-fatality after ICH, in a retrospective cohort study of people aged 40-89 years in Scotland 2004-2013 using linkage of population-based records of diagnosed diabetes, hospital discharges and deaths. We calculated ICH incidence and 30-day case-fatality after hospital admission for ICH and their relative risks (RR) and 95% confidence intervals (95%CI) for people with type 1 or type 2 diabetes compared to people without diabetes adjusting for age, sex and socio-economic status (SES)...
March 9, 2017: Diabetes, Obesity & Metabolism
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