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Diabetes, Obesity & Metabolism

Karen L Jones, Rachael S Rigda, Madeline Dm Buttfield, Seva Hatzinikolas, Hung T Pham, Chinmay S Marathe, Tongzhi Wu, Kylie Lange, Laurence G Trahair, Christopher K Rayner, Michael Horowitz
AIMS: To evaluate the effects of the prandial glucagon-like peptide-1 (GLP-1) receptor agonist (RA), lixisenatide, on gastric emptying (GE) and the blood pressure (BP), superior mesenteric artery (SMA) blood flow, and glycemic responses to a 75g oral glucose load in healthy and type 2 diabetes (T2DM) subjects. MATERIAL AND METHODS: Fifteen healthy subjects (9M, 6F; age: 67.2 ± 2.3yr) and 15 T2DM patients (9M, 6F; age: 61.9 ± 2.3yr) had measurements of GE, BP, SMA flow and plasma glucose for 180min after a radiolabeled 75g glucose drink on 2 separate days...
January 9, 2019: Diabetes, Obesity & Metabolism
Malcolm J Borg, Karen L Jones, Zilin Sun, Michael Horowitz, Christopher K Rayner, Tongzhi Wu
Metformin has been shown to modulate the cardiovascular response to intraduodenal glucose in patients with type 2 diabetes (T2DM), and may have the capacity to regulate postprandial blood pressure (BP), which is often inadequately compensated in T2DM resulting in postprandial hypotension. In the present study, we evaluated the acute effects of metformin on the BP and heart rate (HR) responses to oral glucose in patients with T2DM. 10 diet-controlled T2DM patients were evaluated on two occasions in a double-blind, randomized, crossover design...
January 7, 2019: Diabetes, Obesity & Metabolism
Silvina Gallo, Bernard Charbonnel, Allison Goldman, Harry Shi, Susan Huyck, Amanda Darekar, Brett Lauring, Steven G Terra
AIM: Phase III, randomized, double-blind study evaluating long-term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin. MATERIALS AND METHODS: 104-week double-blind study with a 26-week placebo-controlled period (Phase A) and a 78-week period (Phase B) where blinded glimepiride was added to non-rescued placebo participants with fasting fingerstick glucose ≥6.1 mmol/L. Results through Week 104 are reported...
January 7, 2019: Diabetes, Obesity & Metabolism
Anna Norhammar, Johan Bodegard, Thomas Nyström, Marcus Thuresson, David Nathanson, Jan W Eriksson
AIMS: To investigate cardiovascular (CV) safety and event rates for dapagliflozin versus other glucose lowering drugs (oGLD) in a real-world type 2 diabetes population after applying main inclusion criteria and outcomes from DECLARE-TIMI 58. METHODS: Patients with new initiation of dapagliflozin and/or oGLD were identified in Swedish nationwide health care registries during 2013-2016. Patients were included if satisfying the main DECLARE-TIMI 58 inclusion criteria; ≥40 years and established CV disease or risk factors (men ≥55 and women ≥60 years with hypertension or dyslipidaemia)...
January 4, 2019: Diabetes, Obesity & Metabolism
Sung Bum Park, Sun Young Lee, Won Hoon Jung, Junhee Lee, Hye Gwang Jeong, Jongki Hong, Dukjin Kang, Ki Young Kim
In the development of new drugs for metabolic diseases, there are many obstacles to overcome, including efficacy and toxicity problems in later stages of drug development. To overcome these problems and predict efficacy and toxicity in early stages, here we constructed a new model of insulin resistance in terms of communication between 3T3-L1 adipocytes and RAW264.7 macrophages by 3D culture and demonstrated that this 3D co-culture model had functional metabolic similarity to adipose tissue in diabetic mice...
January 4, 2019: Diabetes, Obesity & Metabolism
Dario Giugliano, Juris J Meier, Katherine Esposito
An excess heart failure (HF) risk persists in patients with type 2 diabetes (T2D) despite optimal control of an array of conventional risk factors, including hyperglycaemia. Twelve cardiovascular outcome trials (CVOTs) have been so far published, although none, with the exception of DECLARE with dapagliflozin, has included HF in the primary endpoint. The four trials with dipeptidyl-peptidase inhibitors (DPP-4i) (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin, and CARMELINA with linagliptin) failed to show any significant effect on HF risk in patients with T2D, with the notable exception of saxagliptin that was associated with a 27% increased risk...
January 4, 2019: Diabetes, Obesity & Metabolism
Wenjun Fan, Yang Song, Silvio E Inzucchi, Laurence Sperling, Christopher P Cannon, Suzanne V Arnold, Mikhail Kosiborod, Nathan D Wong
BACKGROUND AND OBJECTIVE: Patients with diabetes mellitus (DM) at composite atherosclerotic cardiovascular disease (ASCVD) risk factor (RF) targets have >50% lower ASCVD risks. Limited "real world" data exists on how often such targets are reached. We studied multiple RF target attainment for ASCVD prevention and its predictors in a contemporary DM registry. METHODS: In the US Diabetes Collaborative Registry we identified patients at target for HbA1c (<7...
January 4, 2019: Diabetes, Obesity & Metabolism
Juan Pablo Frias, Zachary Zimmer, Raymond L H Lam, Guillermo Amorin Lic, Catherine Ntabadde, Carol Iredale, Edward A O'Neill, Samuel S Engel, Keith D Kaufman, Hideo Makimura, Michael F Crutchlow
AIMS: To characterize the glycemic efficacy and safety of initiation of the DPP-4 inhibitor sitagliptin during metformin dose escalation in participants with type 2 diabetes (T2D) not at HbA1c goal on a sub-maximal dose of metformin. MATERIALS AND METHODS: Study participants with HbA1c ≥7.5% and ≤11.0% while on 1000 mg/day metformin were randomized to sitagliptin 100 mg once daily or placebo. All were to up-titrate metformin to 2000 mg/day. A longitudinal data analysis model was used to test the primary hypothesis that sitagliptin is superior to placebo when initiated during up-titration of metformin in reducing HbA1c at Week 20...
January 4, 2019: Diabetes, Obesity & Metabolism
Gian Paolo Fadini, Benedetta Maria Bonora, Annunziata Lapolla, Bruno Fattor, Paola Silvia Morpurgo, Natalino Simioni, Angelo Avogaro
In this study, we retrospectively compared effectiveness of exenatide once weekly (ExeOW) versus liraglutide in non-insulin treated patients with type 2 diabetes followed under routine care. We also present a meta-analysis of similar observational studies available in the literature. In our multicentre retrospective study, patients initiating ExeOW (n=204) or liraglutide (n=410) had similar baseline clinical characteristics. Change in HbA1c at 6 months was superimposable in the two groups (-0.7±1.0%) and changes in body weight were also similar (ExeOW -2...
December 21, 2018: Diabetes, Obesity & Metabolism
Can Wang, Yao Xiao, Jue Wang, Ning Hou, Weiyi Cui, Xiaomin Hu, Fanxin Zeng, Ye Yuan, Dongwei Ma, Xueting Sun, Yan Zhang, Wen Zheng, Yuli Liu, Haibao Shang, Liangyi Chen, Rui-Ping Xiao, Xiuqin Zhang
AIMS: To investigate the progression of obesity-related type 2 diabetes mellitus (T2DM) in rhesus monkeys, especially dynamic changes in insulin and glucagon. MATERIALS AND METHODS: We followed a cohort of 52 rhesus monkeys for 7 years throughout the progression of obesity-related T2DM. Intravenous glucose tolerance tests were performed every 6 months to evaluate dynamic changes in glucose, insulin and glucagon levels. RESULTS: Obesity in rhesus monkeys increased the overall mortality and T2DM morbidity...
December 21, 2018: Diabetes, Obesity & Metabolism
Tim Heise, Grégory Meiffren, Bertrand Alluis, Cyril Seroussi, Aymeric Ranson, Jorge Arrubla, José Correia, Martin Gaudier, Olivier Soula, Rémi Soula, J Hans DeVries, Oliver Klein, Bruce Bode
We investigated the pharmacodynamics (PD) and pharmacokinetics (PK) of BioChaperone® insulin Lispro (BCLIS), faster insulin aspart (FIA) and insulin aspart (ASP) in patients with type 1 diabetes using an insulin pump. In this randomized, double-blind, three-way crossover glucose clamp study, 43 patients received a bolus dose of each insulin (0.15 U/kg) on top of a basal rate (0.01 U/kg/h), delivered via an insulin pump. With BCLIS, the AUC-GIR,0-60min (primary endpoint) was improved compared to ASP (Least Square Means Ratio 1...
December 18, 2018: Diabetes, Obesity & Metabolism
Manjiri Pawaskar, S Pinar Bilir, Stacey Kowal, Claudio Gonzalez, Swapnil Rajpathak, Glenn Davies
AIMS: Clinical benefits of dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) combination therapy have been demonstrated though clinical trials; however, understanding of economic benefits of these therapies in sequential pathways is limited. This study evaluated the long-term cost-effectiveness of an intensification strategy with SGLT2is (pathway 1) compared to neutral protamine Hagedorn (NPH) insulin (pathway 2) in United Kingdom (UK) type 2 diabetes (T2D) patients not at goal on metformin and sitagliptin...
December 18, 2018: Diabetes, Obesity & Metabolism
Wang Chen, Yue Zhou, Zili Kong, Xiang Wang, Wenshan Lv, Zhuang Geng, Yangang Wang
AIMS: We undertook a systematic review and meta-analysis to assess the efficacy and safety of Sodium-Glucose cotransporter 2 inhibitors (SGLT2is) on kidney outcomes in patients with type 2 diabetes mellitus (T2DM) with or without prevalent kidney disease. MATERIALS AND METHODS: PubMed, Web of science, Embase and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) to assess the efficacy and safety of SGLT2is treatment versus placebo in T2DM...
December 18, 2018: Diabetes, Obesity & Metabolism
Priyamvada Singh, Todd E Pesavento, Kenneth Washburn, Debbie Walsh, Shumei Meng
There is a limited published data regarding the approach to management of diabetes mellitus in Solid Organ Transplant (SOT). We performed a retrospective, chart-review of SOT-recipients (>18 years/old) with diabetes, and on dulaglutide. There was a sustained, statistically significant reduction in primary-endpoints of weight, Body mass index (BMI), and insulin requirement in 63 SOT-recipients at 6, 12, and 24 months respectively. A total of 59, 50, and 13 recipients were followed during 6, 12 and 24 months with the mean of paired difference for weight reduction 2...
December 18, 2018: Diabetes, Obesity & Metabolism
Kausik K Ray, David M Kendall, Zhenxiang Zhao, Xiaomei Peng, A Enrique Caballero, William H Polonsky, Beth L Nordstrom, Ludi Fan, Bradley H Curtis, Melanie J Davies
AIMS: To describe global patterns of insulin treatment and to assess impact of patient, provider, health system, and economic influences on treatment decisions for patients with insulin-treated type 2 diabetes (T2D). METHODS: This prospective cohort study of insulin-treated patients with T2D was conducted across 18 countries categorized as high, upper-middle, or lower-middle income regions. Information collected from patients included diabetes knowledge, experiences, and interactions with their healthcare provider...
December 18, 2018: Diabetes, Obesity & Metabolism
Ravi Retnakaran, Chang Ye, Caroline K Kramer
The current era of large-scale clinical trials in diabetes has generated thousands of biological samples from study participants that are being stored long-term under frozen conditions for the future measurement of analytes of interest. Insulin and C-peptide are two such analytes that can provide insight into underlying pathophysiologic processes (insulin sensitivity and beta-cell function). However, the validity of the inferences that may be drawn from such future measurements is contingent upon the stability of these analytes after long-term frozen storage...
December 18, 2018: Diabetes, Obesity & Metabolism
Joseph Tibaldi, Martin Hadley-Brown, Andreas Liebl, Steffen Haldrup, Viktor Sandberg, Michael Lyng Wolden, Helena W Rodbard
AIMS: To compare the real-world effectiveness of insulin degludec (degludec) and glargine 300 units/mL (glargine U300) in insulin-naïve adult patients with type 2 diabetes in routine US clinical practice. MATERIALS AND METHODS: CONFIRM is a non-interventional comparative effectiveness study following US patients across the continuum of care, through electronic medical records from multiple health systems and integrated delivery networks. Propensity-score matching controlled for confounding...
December 15, 2018: Diabetes, Obesity & Metabolism
Rebecca S Holmes, Elizabeth Crabtree, Marian S McDonagh
AIMS: To review evidence comparing benefits and harms of long-acting insulins in Type 1 and 2 diabetes. METHODS: MEDLINE and two Cochrane databases were searched through February 2018. Two authors selected studies meeting inclusion criteria and assessed their quality. Comparative studies of adult or pediatric patients with diabetes treated with insulin degludec, detemir, or glargine were included. Meta-analysis was used to combine results of similar studies, and the I2 statistic calculated to assess statistical heterogeneity...
December 15, 2018: Diabetes, Obesity & Metabolism
Peter Plomgaard, Jakob S Hansen, Bodil Ingerslev, Jens Otto Clemmesen, Niels H Secher, Gerrit van Hall, Andreas Fritsche, Cora Weigert, Rainer Lehmann, Hans-Ulrich Häring, Martin Heni
AIM: Pharmacologic administration of insulin as nasal spray in humans has demonstrated a modulation of endogenous glucose production via the brain when systemic insulin levels are high. Results are conflicting under fasting insulin concentrations. To evaluate effects of brain insulin on endogenous glucose production in fasting humans with focus on hepatic glucose release, we performed a randomized, placebo controlled, blinded, cross-over experiment. MATERIALS AND METHODS: On two separate days, 2 H2 -glucose was infused to nine healthy lean males and blood was sampled from the hepatic vein and a radial artery...
December 15, 2018: Diabetes, Obesity & Metabolism
Desiree Abdurrachim, Xing Qi Teo, Chern Chiuh Woo, Sing Yee Ong, Nurul Farhana Salleh, Janise Lalic, Ru San Tan, Philip Teck Hock Lee
AIMS: To investigate the effects of long-term low-carbohydrate low-protein ketogenic diet (KD) on cardiac metabolism and diabetic cardiomyopathy status in lean diabetic Goto-Kakizaki (GK) rats. MATERIALS AND METHODS: Diabetic GK rats were fed with KD for 62 weeks. Cardiac function and metabolism were assessed using magnetic resonance imaging and 13 C magnetic resonance spectroscopy (13 C-MRS), at rest and under dobutamine stress. 13 C-MRS was performed following injection of hyperpolarized [3-13 C]acetoacetate, [1-13 C]butyrate, or [1-13 C]pyruvate to assess ketone body, short-chain fatty acid, or glucose utilization, respectively...
December 11, 2018: Diabetes, Obesity & Metabolism
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