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Carol H Wysham, Dominic Pilon, Mike Ingham, Marie-Hélène Lafeuille, Bruno Emond, Rhiannon Kamstra, Michael Pfeifer, Patrick Lefebvre
OBJECTIVE: To compare achievement of quality goals (HbA1c, weight loss/body mass index[BMI], systolic blood pressure[SBP]), including maintaining HbA1c, between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300mg (CANA) or a GLP-1 in an actual practice setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 were identified from the IQVIATM Real-World Data Electronic Medical Records - US database (2012Q2-2016Q1). To account for differences in baseline characteristics, inverse probability of treatment weighting was used...
March 20, 2018: Current Medical Research and Opinion
Dandan Zhao, Shaoqian Zhao, Xiao Wang, Mingbo Su, Wen Liu, Qinyun Ma, Jie Hong, Weiqiong Gu, Jingya Li, Ruixin Liu, Guang Ning, Jiqiu Wang, Yifei Zhang
The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, DPP4 mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects...
2018: Frontiers in Endocrinology
Harumi Takahashi, Shihomi Hidaka, Chihiro Seki, Norihide Yokoi, Susumu Seino
The dynamics of insulin secretion stimulated by repaglinide, a glinide, and the combinatorial effects of repaglinide and incretin were investigated. At 4.4mM glucose, repaglinide induced insulin secretion with a gradually increasing first phase, showing different dynamics from that induced by glimepiride, a sulfonylurea. In the presence of glucagon-like peptide-1 (GLP-1), insulin secretion by repaglinide was augmented significantly but to lesser extent and showed different dynamics from that by glimepiride...
March 16, 2018: European Journal of Pharmacology
Gianluca Iacobellis
No abstract text is available yet for this article.
March 15, 2018: Endocrinology
Keiichi Torimoto, Yosuke Okada, Yoshiya Tanaka
Vascular endothelial function is important for maintaining the homeostasis of the living body. Especially, nitric oxide (NO) produced in vascular endothelial cells regulates blood vessel tone and has an antiatherosclerotic effect. Type 2 diabetes is a typical disease that causes impaired vascular endothelial function, resulting in various vascular complications and damage to organs. Cardiovascular disease associated with type 2 diabetes is a chronic inflammatory disease that starts with endothelial dysfunction (ED), and vascular ED is important as an initial change in arteriosclerotic lesions...
2018: Journal of UOEH
Akira Kurozumi, Yosuke Okada, Kei Sugai, Keiichi Torimoto, Yoshiya Tanaka
Our purpose was to determine the effects of teneligliptin and sitagliptin, two dipeptidyl peptidase 4 inhibitors (DPP4-Is) with different half-lives, on glycemic variability and glucagon-like peptide-1 (GLP-1) levels in Japanese patients with type 2 diabetes mellitus (T2DM). The study subjects were 14 drug-naïve patients with T2DM who were allocated to either a 20 mg/day teneligliptin group (n = 7) or a 50 mg/day sitagliptin group (n = 7) for 7 days, then switched to the other treatment for another 7 days...
2018: Journal of UOEH
Yue Cao, Christian Hölscher, Meng-Ming Hu, Ting Wang, Fang Zhao, Yu Bai, Jun Zhang, Mei-Na Wu, Jin-Shun Qi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there is no cure. The early primary symptom of AD is the decline of memory ability, which gradually develops into complete dementia. Type 2 diabetes mellitus (T2DM) is an important risk factor of AD; and mimetics of the incretin hormone GLP-1 developed to treat diabetes are being tested as a novel therapeutic strategy for AD. In the present study, we reported for the first time the neuroprotective effects of a novel GLP-1/GIP dual agonist DA5-CH that activates the incretin hormone GLP-1 and GIP receptors in the APP/PS1 transgenic AD mouse model...
March 15, 2018: European Journal of Pharmacology
André J Scheen
No abstract text is available yet for this article.
January 6, 2018: Diabetes & Metabolism
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
March 9, 2018: Epilepsy Research
Luisella Bocchio Chiavetto, Roberta Zanardini, Sarah Tosato, Mariacarla Ventriglia, Clarissa Ferrari, Chiara Bonetto, Antonio Lasalvia, Franco Giubilini, Angelo Fioritti, Francesca Pileggi, Michela Pratelli, Michele Pavanati, Angela Favaro, Giovanni De Girolamo, Giovanni Battista Frisoni, Mirella Ruggeri, Massimo Gennarelli
The molecular underpinnings associated to first episode psychosis (FEP) remains to be elucidated, but compelling evidence supported an association of FEP with blood alterations in biomarkers related to immune system, growth factors and metabolism regulators. Many of these studies have not been already confirmed in larger samples or have not considered the FEP diagnostic subgroups. In order to identify biochemical signatures of FEP, the serum levels of the growth factors BDNF and VEGF, the immune regulators IL-1RA, IL-6, IL-10 and IL-17, RANTES/CCL5, MIP-1b/CCL4, IL-8 and the metabolic regulators C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin and visfatin were analysed in 260 subjects collected in the GET UP project...
March 13, 2018: Brain, Behavior, and Immunity
Geoffrey P Roberts, Richard G Kay, James Howard, Richard H Hardwick, Frank Reimann, Fiona M Gribble
BACKGROUND: Altered enteroendocrine hormone responses are widely believed to underlie the beneficial effects of bariatric surgery in type 2 diabetes. While elevated postprandial glucagon-like peptide-1 (GLP-1) is considered one of the mediators, increased postprandial glucagon levels have recently been implicated. OBJECTIVES: We investigated hormonal responses in lean patients after prophylactic total gastrectomy (PTG), as a model of Roux-en-Y gastric bypass without the confounding effects of obesity or massive weight loss...
February 3, 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
Line Engelbrechtsen, Yuvaraj Mahendran, Anna Jonsson, Anette Prior Gjesing, Peter E Weeke, Marit E Jørgensen, Kristine Færch, Daniel R Witte, Jens J Holst, Torben Jørgensen, Niels Grarup, Oluf Pedersen, Henrik Vestergaard, Signe Torekov, Jørgen K Kanters, Torben Hansen
BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfunctional Kv11.1 voltage-gated potassium channel. Based on these findings in patients with rare variants in hERG, we hypothesized that common variants in hERG may also lead to alterations in glucose homeostasis...
March 16, 2018: BMC Genetics
Rika Fukumori, Yoji Masuda, Ayaka Takeuchi, Rina Yanai, Khurchabiling Atchalalt, Borjigin Sarentonglaga, Kazuko Ogata, Mio Yamaguchi, Asuka Hara, Akane Sato, Toshihisa Sugino, Yoshikazu Nagao
The aim of this study was to investigate how intra-duodenal infusions of fatty acids (FA) affect appetite-related gut peptides such as glucagon-like peptide-1 (GLP-1) and ghrelin in sheep. We hypothesized that these peptides can be highly reactive to unsaturated long-chain FA, because they are well known to decrease DMI. Four ewes were fitted with a duodenal cannula and a jugular vein catheter for a 6-h duodenal infusion of the nine FA (C8:0, C10:0, C12:0, C14:0, C16:0, C18:0, C18:1, C18:2, C18:3) and water (control)...
March 14, 2018: Journal of Animal Science
Carol H Wysham, Dominic Pilon, Mike Ingham, Marie-Hélène Lafeuille, Bruno Emond, Rhiannon Kamstra, Michael Pfeifer, Patrick Lefebvre
OBJECTIVE: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012-April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics...
March 2018: Endocrine Practice
Martin M Grajower
Hypoglycemia is the major side effect of insulin therapy. The elderly are especially vulnerable to episodes of hypoglycemia, and with greater risks of complications such as falls. Two new long-acting basal insulins, glargine-300 (Gla-300) and degludec, are associated with lower incidences of hypoglycemia than previously available basal insulins. One of them, Gla-300, was studied in the elderly and has a lower incidence of hypoglycemia in patients over 65 years old. These new data should be incorporated into decision making when treating the elderly patient with insulin, whether they have type 1 or 2 diabetes...
March 2018: Endocrine Practice
Cyndya A Shibao, Jorge E Celedonio, Robyn Tamboli, Reem Sidani, Latisha Love-Gregory, Terri Pietka, Yanhua Xiong, Yan Wei, Naji N Abumrad, Nada A Abumrad, Charles Robb Flynn
Context: Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism but whether it has similar actions in humans is unknown. We examined impact of a coding single-nucleotide polymorphism in CD36 on post-prandial hormone and bile acid (BA) responses. Objective: To examine if the minor allele (G) of coding CD36 variant rs3211938 (G/T) which reduces CD36 level by approximately 50% influences hormonal responses to a high-fat meal (HFM)...
March 12, 2018: Journal of Clinical Endocrinology and Metabolism
Sudha S Shankar, R Ravi Shankar, Lori A Mixson, Deborah L Miller, Barnali Pramanik, Amy K O'Dowd, Donna M Williams, Clay B Frederick, Chan R Beals, S Aubrey Stoch, Helmut O Steinberg, David E Kelley
Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, increased energy expenditure, and weight loss in obese humans via activation of GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis remain ill-defined. To address this gap, we evaluated the effects of an intravenous (IV) infusion of native OXM on insulin secretory rates (ISR) and glycemic excursion in a graded glucose infusion (GGI) procedure in two separate randomized, placebo-controlled, single dose crossover trials in 12 overweight and obese subjects without diabetes, and in 12 obese subjects with Type 2 diabetes (T2DM) respectively, using the GLP-1 analog, liraglutide as a comparator in the T2DM...
March 15, 2018: Diabetes
Xuan Du, Wen Lu, Zijun Lu, Xinyu Shao, Chunhong Hu, Bimin Shi
Background: To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods: 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups...
2018: Journal of Diabetes Research
Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
Yu Sasaki, Yasuhiko Abe, Hiroaki Takeda, Shoichi Nishise, Takao Yaoita, Makoto Yagi, Kazuhiro Sakuta, Naoko Mizumoto, Masakuni Shoji, Yusuke Onozato, Sumio Kawata, Yoshiyuki Ueno
BACKGROUND/AIMS: Obesity and insulin resistance are associated with an increased risk of colorectal adenoma (CRA). Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis through its amplification of insulin secretion in response to oral nutrients; however, its role in human CRA remains unknown. We investigated oral glucose-mediated GLP-1 secretion in patients with adenoma. METHODS: We performed a case-control study of 15 nondiabetic patients with pathologically diagnosed CRA and 10 age-matched healthy controls without adenoma...
March 14, 2018: Digestion
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