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Susan L Samson, Alan J Garber
Incretin-based therapies are important addition to our armamentarium for the treatment of type 2 diabetes (T2DM). There are six Glucagon-like peptide-1 receptor agonists (GLP-1RAs) which have received regulatory approval for clinical use. The short-acting GLP-1RAs include exenatide twice daily, liraglutide once daily, and lixisenatide once daily. The approved long-acting GLP-1RAs are administered weekly and are exenatide, albiglutide, and dulaglutide. Although all of these therapies lower hemoglobin A1C (HbA1C), there also are unique features of GLP-1RAs that have been made manifest from clinical trial data with regard to weight-loss efficacy, fasting and post-prandial glucose control, cardiovascular safety and protection, and gastrointestinal and injection adverse effects...
December 2016: Current Diabetes Reports
Sung-Ho Kim, Jung-Hwa Yoo, Woo Je Lee, Cheol-Young Park
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agent for the treatment of type 2 diabetes mellitus. They increase endogenous levels of incretin hormones, which stimulate glucose-dependent insulin secretion, decrease glucagon secretion, and contribute to reducing postprandial hyperglycemia. Although DPP-4 inhibitors have similar benefits, they can be differentiated in terms of their chemical structure, pharmacology, efficacy and safety profiles, and clinical considerations. Gemigliptin (brand name: Zemiglo), developed by LG Life Sciences, is a potent, selective, competitive, and long acting DPP-4 inhibitor...
October 2016: Diabetes & Metabolism Journal
Juan Rosas-Guzmán, Juan Rosas-Saucedo, Alma R J Romero-García
Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin-America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications...
August 29, 2016: Reviews on Recent Clinical Trials
Alessandro Marcon, Alberto Vaona, Giulio Rigon, Marco Carazzolo, Franco Del Zotti, Sandro Girotto, Claudio Marafetti
OBIETTIVI: descrivere, nella ASL 21 di Legnago (VR), l'andamento di alcuni indicatori sanitari tra il 2009, anno precedente all'avvio di un progetto triennale per la gestione integrata dell'assistenza al paziente con diabete mellito di tipo 2, e il 2012, ultimo anno del progetto. DISEGNO: studio longitudinale trasversale ripetuto. SETTING E PARTECIPANTI: tutti i pazienti diabetici di tipo 2 della ASL 21, identificati nei database aziendali (in base a esenzioni per patologia, accessi al servizio diabetologico, consumo di farmaci antidiabetici e strisce per la determinazione della glicemia) e nelle cartelle cliniche dei medici di famiglia...
September 2016: Epidemiologia e Prevenzione
Monica L Castro-Acosta, Leanne Smith, Rosalind J Miller, Danielle I McCarthy, Jonathan A Farrimond, Wendy L Hall
Blackcurrants are rich in polyphenolic glycosides called anthocyanins, which may inhibit postprandial glycemia. The aim was to determine the dose-dependent effects of blackcurrant extract on postprandial glycemia. Men and postmenopausal women (14M, 9W, mean age 46 years, S.D.=14) were enrolled into a randomized, double-blind, crossover trial. Low sugar fruit drinks containing blackcurrant extract providing 150-mg (L-BE), 300-mg (M-BE) and 600-mg (H-BE) total anthocyanins or no blackcurrant extract (CON) were administered immediately before a high-carbohydrate meal...
September 14, 2016: Journal of Nutritional Biochemistry
Gunter Laux, Sarah Berger, Joachim Szecsenyi, Petra Kaufmann-Kolle, Rüdiger Leutgeb
BACKGROUND: The objective of this study was to analyze prescription decisions for family practice (FP) patients with Diabetes mellitus type 2 (DM2) using the case of the incretin mimetics Dipeptidyl peptidase-4 (DDP-4) inhibitors and Glucagon-like peptide-1 (GLP-1) agonists dependent on patients' health insurance status (statutory or private) in Germany. This study is important since the scientific debate is still open with regard to DPP-4-inhibitors and GLP-1-agonists, where some critics are raising questions on potential long-term risks for patients...
October 19, 2016: BMC Family Practice
Takafumi Hara
FFA1 is a G protein-coupled receptor activated by medium- to long-chain fatty acids. FFA1 plays important roles in various physiological processes such as insulin secretion and energy metabolism. FFA1 expressed on pancreatic β-cells and intestine contributes to insulin and incretin secretion, respectively. These physiological functions of FFA1 are interesting as an attractive drug target for type II diabetes and metabolic disorders. A number of synthetic FFA1 ligands have been developed and they have contributed to our current understanding of the physiological and pathophysiological functions of FFA1 both in in vitro and in vivo studies...
October 19, 2016: Handbook of Experimental Pharmacology
G S M Paula, L L Souza, N O S Bressane, R Maravalhas, M Wilieman, T Bento-Bernardes, K R Silva, L S Mendonca, K J Oliveira, C C Pazos-Moura
Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48...
October 18, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Rae Woong Park
Big data indicates the large and ever-increasing volumes of data adhere to the following 4Vs: volume (ever-increasing amount), velocity (quickly generated), variety (many different types), veracity (from trustable sources). The last decade has seen huge advances in the amount of data we routinely generate and collect in pretty much everything we do, as well as our ability to use technology to analyze and understand it. The routine operation of modern health care systems also produces an abundance of electronically stored data on an ongoing basis as a byproduct of clinical practice...
September 2016: Journal of Hypertension
Peter Mertens
Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. The new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0...
September 2016: Journal of Hypertension
A P van Beek, M Emous, M Laville, J Tack
BACKGROUND: Dumping syndrome, a common complication of esophageal, gastric or bariatric surgery, includes early and late dumping symptoms. Early dumping occurs within 1 h after eating, when rapid emptying of food into the small intestine triggers rapid fluid shifts into the intestinal lumen and release of gastrointestinal hormones, resulting in gastrointestinal and vasomotor symptoms. Late dumping occurs 1-3 h after carbohydrate ingestion, caused by an incretin-driven hyperinsulinemic response resulting in hypoglycemia...
October 17, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Giulia Cantini, Alessandra Di Franco, Edoardo Mannucci, Michaela Luconi
Glucagon-like peptide 1(9-36) [GLP-1(9-36)] is generated by dipeptidyl peptidase-4 (DPP4) cleavage of the gut incretin hormone, GLP-1(7-36). Since GLP-1(9-36) has a very low affinity for the GLP-1 receptor (GLP-1R), it has so far been considered an inactive form of GLP-1. Here we show GLP-1(9-36) activity in human adipose stem cells (ASC) in vitro. GLP-1(9-36) inhibits human ASC proliferation, glucose uptake and adipogenesis, as well as induces cell apoptosis, to a similar extent as GLP-1(7-36) and liraglutide...
October 13, 2016: Molecular and Cellular Endocrinology
Chao-Ming Tseng, Wei-Chih Liao, Chi-Yang Chang, Ching-Tai Lee, Cheng-Hao Tseng, Yao-Chun Hsu, Jaw-Town Lin
BACKGROUND: Pancreatic safety remains a concern for diabetic patients using incretin-based medications. We aimed to determine if there was an association between incretin-based therapy and an increased risk for acute pancreatitis and pancreatic cancer in patients with type 2 diabetes mellitus (DM). METHODS: This retrospective population-based cohort study analyzed data from the Taiwan National Health Insurance Research Database. A total of 13 171 eligible type 2 DM patients who had received incretin-based treatment for a minimum of two months were matched 1:1 for age, gender, diabetes complications severity index, and inception date with DM patients who never used this pharmacotherapy...
October 7, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
M Chondronikola, L L S Harris, S Klein
Type 2 diabetes (T2D) is a major worldwide public health concern. Despite a large armamentarium of T2D medications, a large proportion of patients fail to achieve recommended treatment goals for glycemic control. Weight loss has profound beneficial effects on the metabolic abnormalities involved in the pathogenesis of T2D. Accordingly, bariatric surgery, which is the most effective available weight loss therapy, is also the most effective therapy for treating patients with T2D. Surgical procedures that bypass the upper gastrointestinal (UGI) tract are particularly effective in achieving partial and even complete remission of T2D, suggesting that UGI bypass has weight loss-independent effects on glycemic control...
October 14, 2016: Journal of Internal Medicine
Tongzhi Wu, Christopher K Rayner, Michael Horowitz
The GI tract is central to the regulation of postprandial glycemia, with the rate of gastric emptying and the secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, being key determinants. Gastric emptying exhibits a large interindividual variation; the latter not only accounts for differences in postprandial glycemia but also determines postprandial incretin profiles. Accordingly, the rate of gastric emptying may affect the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors...
October 13, 2016: Biomarkers in Medicine
Hiroshi Nomoto, Hideaki Miyoshi, Tomoo Furumoto, Koji Oba, Hiroyuki Tsutsui, Atsushi Inoue, Tatsuya Atsumi, Naoki Manda, Yoshio Kurihara, Shin Aoki
OBJECTIVES: The DPP-4 inhibitors are incretin-related drugs that improve hyperglycemia in a glucose-dependent manner and have been reported to exert favorable effects on atherosclerosis. However, it has not been fully elucidated whether DPP-4 inhibitors are able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of sitagliptin, a DPP-4 inhibitor, on endothelial function and glycemic metabolism compared with that of the sulfonylurea glimepiride...
2016: PloS One
Michael A Nauck, Melanie Kahle, Oleg Baranov, Carolyn F Deacon, Jens J Holst
AIMS/HYPOTHESIS: GLP-1 receptor agonists and DPP-4 inhibitors both stimulate GLP-1 receptors. Our objective was to determine, whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal. METHODS: 16 subjects with type 2 diabetes treated with metformin and liraglutide (1.2 mg/d for ≥ 2 weeks) were randomized (sealed envelopes), within a cross-over design, to be studied on two occasions, after an overnight fast, with (a) sitagliptin (100 mg p...
October 6, 2016: Diabetes, Obesity & Metabolism
Andrea Egger, Marius E Kraenzlin, Christian Meier
Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk...
October 5, 2016: Current Osteoporosis Reports
Renald Delanoue, Eleonora Meschi, Neha Agrawal, Alessandra Mauri, Yonit Tsatskis, Helen McNeill, Pierre Léopold
Animals adapt their growth rate and body size to available nutrients by a general modulation of insulin-insulin-like growth factor signaling. In Drosophila, dietary amino acids promote the release in the hemolymph of brain insulin-like peptides (Dilps), which in turn activate systemic organ growth. Dilp secretion by insulin-producing cells involves a relay through unknown cytokines produced by fat cells. Here, we identify Methuselah (Mth) as a secretin-incretin receptor subfamily member required in the insulin-producing cells for proper nutrient coupling...
September 30, 2016: Science
Jayasankar Kosaraju, R M Damian Holsinger, Lixia Guo, Kin Yip Tam
Glucagon-like peptide-1 (GLP-1) is an incretin hormone shown to be active in the treatment of type-2 diabetes (T2D) and has also been shown as efficacious in Alzheimer's disease (AD). Dipeptidyl peptidase-4 (DPP-4), an enzyme that is expressed in numerous cells, rapidly inactivates endogenous GLP-1. Therefore, DPP-4 inhibition is employed as a therapeutic avenue to increase GLP-1 levels in the management of T2D. The effectiveness of DPP-4 inhibitors in the treatment of AD has been reported in various animal models of AD...
October 3, 2016: Molecular Neurobiology
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