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https://www.readbyqxmd.com/read/29770541/effect-of-short-term-treatment-with-sitagliptin-or-glibenclamide-on-daily-glucose-fluctuation-in-drug-na%C3%A3-ve-japanese-patients-with-type-2-diabetes-mellitus
#1
Ryo Suzuki, Jun-Ichi Eiki, Takashi Moritoyo, Kenichi Furihata, Akira Wakana, Yukari Ohta, Shigeru Tokita, Takashi Kadowaki
AIMS: To compare the effect of a dipeptidyl peptidase-4 inhibitor (DPP4-i) and a sulfonylurea (SU) on daily glucose fluctuation in drug-naïve Japanese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Fifty-three drug-naïve Japanese patients with T2DM (HbA1c of 7.0% to 9.0% and fasting plasma glucose of 6.1 mmol/L or higher) were randomly assigned to either sitagliptin 50 mg q.d. or glibenclamide 2.5 mg per day (given in divided doses) in a 1:1 ratio...
May 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29732725/time-trends-and-geographical-variation-in-prescribing-of-drugs-for-diabetes-in-england-1998-2017
#2
Helen J Curtis, John M Dennis, Beverley M Shields, Alex J Walker, Seb Bacon, Andrew T Hattersley, Angus G Jones, Ben Goldacre
AIMS: UK guidelines for type II diabetes leave the choice of glucose lowering therapies after metformin largely to prescribers. They vary greatly in cost, and comparative effectiveness data is lacking. We set out to measure the variation in prescribing of these second-line non-insulin diabetes drugs. MATERIALS AND METHODS: We evaluated time trends 1998-2016, using England's publicly available prescribing datasets, and stratified by the order prescribed to patients using the Clinical Practice Research Datalink (CPRD)...
May 7, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29727638/additive-effects-of-evogliptin-in-combination-with-pioglitazone-on-fasting-glucose-control-through-direct-and-indirect-hepatic-effects-in-diabetic-mice
#3
Tae-Hyoung Kim, Jeong-Ha Lee, Yu Na Chae, Il-Hoon Jung, Mi-Kyung Kim
Due to very limited preclinical reports, pharmacodynamic interactions between dipeptidyl peptidase 4 (DPP4) inhibitors and peroxisome proliferator-activated receptor γ (PPARγ) agonists are not conclusive yet. This study aimed to evaluate the pharmacological responses from adding evogliptin, a DPP4 inhibitor, to pioglitazone, a PPARγ agonist, in diabetic db/db mice after a 2-week treatment. This combination led to further decrease in both fasting and fed blood glucose levels compared to evogliptin alone (P < 0...
May 1, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29689192/hippo-signaling-plays-an-essential-role-in-cell-state-transitions-during-cardiac-fibroblast-development
#4
Yang Xiao, Matthew C Hill, Min Zhang, Thomas J Martin, Yuka Morikawa, Suya Wang, Alexander R Moise, Joshua D Wythe, James F Martin
During development, progenitors progress through transition states. The cardiac epicardium contains progenitors of essential non-cardiomyocytes. The Hippo pathway, a kinase cascade that inhibits the Yap transcriptional co-factor, controls organ size in developing hearts. Here, we investigated Hippo kinases Lats1 and Lats2 in epicardial diversification. Epicardial-specific deletion of Lats1/2 was embryonic lethal, and mutant embryos had defective coronary vasculature remodeling. Single-cell RNA sequencing revealed that Lats1/2 mutant cells failed to activate fibroblast differentiation but remained in an intermediate cell state with both epicardial and fibroblast characteristics...
April 23, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29580664/diabetes-mellitus-as-a-protective-factor-of-abdominal-aortic-aneurysm-possible-mechanisms
#5
Elisenda Climent, David Benaiges, Juan J Chillarón, Juana A Flores-Le Roux, Juan Pedro-Botet
Abdominal aortic aneurysm (AAA) shares several risk factors with atherosclerosis. Among these, diabetes mellitus (DM) could have a negative effect on the formation, growth and expansion of AAA. Several systematic reviews and meta-analyses reported up to 2016 have shown concordant results regarding the possible protective effect on AAA formation. However, the pathophysiological mechanisms of this supposed protective effect are still unknown. It appears that both hyperglycaemia and hyperinsulinemia, which are closely associated with DM, cause an increase in advanced glycation end-products, a decrease in fibrinolysis, and alterations in smooth muscle cells, leading to a decreased risk of aneurysm growth and expansion...
March 23, 2018: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/29562231/hepatocyte-secreted-dpp4-in-obesity-promotes-adipose-inflammation-and-insulin-resistance
#6
Devram S Ghorpade, Lale Ozcan, Ze Zheng, Sarah M Nicoloro, Yuefei Shen, Emily Chen, Matthias Blüher, Michael P Czech, Ira Tabas
Obesity-induced metabolic disease involves functional integration among several organs via circulating factors, but little is known about crosstalk between liver and visceral adipose tissue (VAT). In obesity, VAT becomes populated with inflammatory adipose tissue macrophages (ATMs). In obese humans, there is a close correlation between adipose tissue inflammation and insulin resistance, and in obese mice, blocking systemic or ATM inflammation improves insulin sensitivity. However, processes that promote pathological adipose tissue inflammation in obesity are incompletely understood...
March 29, 2018: Nature
https://www.readbyqxmd.com/read/29556215/clinical-and-physiological-characterization-of-elevated-plasma-glucagon-like-peptide-1-levels-hyperglipemia-in-a-dipeptidyl-peptidase-iv-mutation-carrier
#7
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
https://www.readbyqxmd.com/read/29553070/comparison-of-the-effects-of-teneligliptin-and-sitagliptin-two-dipeptidyl-peptidase-4-inhibitors-with-different-half-lives-on-glucose-fluctuation-and-glucagon-like-peptide-1-in-type-2-diabetes-mellitus
#8
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
https://www.readbyqxmd.com/read/29547706/clinical-implications-of-current-cardiovascular-outcome-trials-with-sodium-glucose-cotransporter-2-sglt2-inhibitors
#9
REVIEW
Soo Lim, Robert H Eckel, Kwang Kon Koh
The final goal in the management of patients with type 2 diabetes (T2D) is reduction in cardiovascular (CV) complications and total mortality. Various factors including hyperglycemia contribute to these complications and mortality directly and indirectly. In recent years, large-scale CV outcome trials with new antidiabetic medications, such as dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) receptor agonists, and sodium glucose cotransporter-2 (SGLT2) inhibitors, have been completed...
May 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29535389/combination-of-sodium-glucose-cotransporter-2-inhibitor-and-dipeptidyl-peptidase-4-inhibitor-in-type-2-diabetes-a-systematic-review-with-meta-analysis
#10
Se Hee Min, Jeong-Hwa Yoon, Sun Joon Moon, Seokyung Hahn, Young Min Cho
Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline...
March 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29531541/sitagliptin-accelerates-endothelial-regeneration-after-vascular-injury-independent-from-glp1-receptor-signaling
#11
Friederike Remm, Nicolle Kränkel, Daniela Lener, Daniel J Drucker, Sieghart Sopper, Christoph Brenner
Introduction: DPP4 inhibitors (gliptins) are commonly used antidiabetic drugs for the treatment of type 2 diabetes. Gliptins also act in a glucose-independent manner and show vasoregenerative effects. We have shown that gliptins can remarkably accelerate vascular healing after vascular injury. However, the underlying mechanisms remain unclear. Here, we examined potential signaling pathways linking gliptins to enhanced endothelial regeneration. Methods and Results: We used wild-type and GLP1 receptor knockout ( Glp1r -/- ) mice to investigate the underlying mechanisms of gliptin-induced reendothelialization...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29520964/type-2-diabetes-mellitus-and-heart-failure-a-position-statement-from-the-heart-failure-association-of-the-european-society-of-cardiology
#12
REVIEW
Petar M Seferović, Mark C Petrie, Gerasimos S Filippatos, Stefan D Anker, Giuseppe Rosano, Johann Bauersachs, Walter J Paulus, Michel Komajda, Francesco Cosentino, Rudolf A de Boer, Dimitrios Farmakis, Wolfram Doehner, Ekaterini Lambrinou, Yuri Lopatin, Massimo F Piepoli, Michael J Theodorakis, Henrik Wiggers, John Lekakis, Alexandre Mebazaa, Mamas A Mamas, Carsten Tschöpe, Arno W Hoes, Jelena P Seferović, Jennifer Logue, Theresa McDonagh, Jillian P Riley, Ivan Milinković, Marija Polovina, Dirk J van Veldhuisen, Mitja Lainscak, Aldo P Maggioni, Frank Ruschitzka, John J V McMurray
The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice...
May 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29508169/combined-sglt2-and-dpp4-inhibition-reduces-the-activation-of-the-nlrp3-asc-inflammasome-and-attenuates-the-development-of-diabetic-nephropathy-in-mice-with-type-2-diabetes
#13
Yochai Birnbaum, Mandeep Bajaj, Hsiu-Chiung Yang, Yumei Ye
BACGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors (DPP4I) are used to treat type 2 diabetes (T2DM). DPP4 inhibitors (DPP4) attenuate Nlrp3 inflammasome activation in the kidney. SGLT2 inhibition reduces inflammation and attenuates the progression of diabetic nephropathy (DN). The effects of dapagliflozin (Dapa) on the activation of the Nlrp3 inflammasome and the combined effect of SGLT2 and DPP4 on T2DM-induced inflammasome activation and progression of DN have not been previously studied...
March 5, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29481642/lncrna-ois1-regulates-dpp4-activation-to-modulate-senescence-induced-by-ras
#14
Li Li, Pieter C van Breugel, Fabricio Loayza-Puch, Alejandro Pineiro Ugalde, Gozde Korkmaz, Naama Messika-Gold, Ruiqi Han, Rui Lopes, Eric P Barbera, Hans Teunissen, Elzo de Wit, Ricardo J Soares, Boye S Nielsen, Kim Holmstrøm, Dannys J Martínez-Herrera, Maite Huarte, Annita Louloupi, Jarno Drost, Ran Elkon, Reuven Agami
Oncogene-induced senescence (OIS), provoked in response to oncogenic activation, is considered an important tumor suppressor mechanism. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt without a protein-coding capacity. Functional studies showed that deregulated lncRNA expression promote tumorigenesis and metastasis and that lncRNAs may exhibit tumor-suppressive and oncogenic function. Here, we first identified lncRNAs that were differentially expressed between senescent and non-senescent human fibroblast cells...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29472575/glial-cell-type-specific-changes-in-spinal-dipeptidyl-peptidase-4-expression-and-effects-of-its-inhibitors-in-inflammatory-and-neuropatic-pain
#15
Kornél Király, Márk Kozsurek, Erika Lukácsi, Benjamin Barta, Alán Alpár, Tamás Balázsa, Csaba Fekete, Judit Szabon, Zsuzsanna Helyes, Kata Bölcskei, Valéria Tékus, Zsuzsanna E Tóth, Károly Pap, Gábor Gerber, Zita Puskár
Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29461566/nya-glukoss%C3%A3-nkande-l%C3%A3-kemedel-%C3%A3-r-kardiovaskul%C3%A3-rt-s%C3%A3-kra-enstaka-diabetesl%C3%A3-kemedel-har-%C3%A3-ven-visats-skydda-mot-kardiovaskul%C3%A3-ra-och-renala-komplikationer
#16
Eva Toft, Mikael Rydén
Do novel therapies in type 2 diabetes have protective effects on cardiovascular and renal complications? A number of new antidiabetic drug classes have been introduced on the market in the last decade. Regulatory authorities have required that their safety in type 2 diabetes populations with high cardiovascular risk must be assessed. Consequently, a large number of outcome studies have been initiated, several of which have been published in recent years. Overall, this has so far shown that long-acting insulin analogues, DPP4-inhibitors, GLP1-receptor agonists and SGLT2-inhibitors are safe...
February 20, 2018: Läkartidningen
https://www.readbyqxmd.com/read/29450684/application-and-impact-of-run-in-studies
#17
Michael Fralick, Jerry Avorn, Jessica M Franklin, Abdurrahman Abdurrob, Aaron S Kesselheim
BACKGROUND: A run-in phase is often employed prior to randomization in a clinical trial to exclude non-adherent patients, placebo responders, active drug non-responders, or patients who do not tolerate the active drug. This may impact the generalizability of trial results. OBJECTIVE: To determine if clinical outcomes differed between randomized controlled trials with run-in phases compared with randomized controlled trials of the same medication without run-in phases...
May 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29449690/diabetes-clinical-markers-of-glycaemic-response-to-dpp4-inhibitor-therapy
#18
Ivone Leong
No abstract text is available yet for this article.
April 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29449146/efficacy-and-safety-of-combination-therapy-with-sglt2-and-dpp4-inhibitors-in-the-treatment-of-type-2-diabetes-a-systematic-review-and-meta-analysis
#19
Y K Cho, Y M Kang, S E Lee, J Lee, J-Y Park, W J Lee, Y-J Kim, C H Jung
BACKGROUND: This review evaluated the efficacy and safety of a combination therapy comprising a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) in type 2 diabetes. METHODS: A literature search through to May 2017 was carried out of PubMed, Embase and the Cochrane Central Register of Controlled Trials. Studies were eligible if they were randomized controlled trials (RCTs) comparing SGLT2i plus DPP4i (SGLT2i/DPP4i) against DPP4i±placebo or SGLT2i±placebo and published in English...
February 3, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29426867/crystal-structures-of-a-bacterial-dipeptidyl-peptidase-iv-reveal-a-novel-substrate-recognition-mechanism-distinct-from-that-of-mammalian-orthologues
#20
Saori Roppongi, Yoshiyuki Suzuki, Chika Tateoka, Mayu Fujimoto, Saori Morisawa, Ippei Iizuka, Akihiro Nakamura, Nobuyuki Honma, Yosuke Shida, Wataru Ogasawara, Nobutada Tanaka, Yasumitsu Sakamoto, Takamasa Nonaka
Dipeptidyl peptidase IV (DPP IV, DPP4, or DAP IV) preferentially cleaves substrate peptides with Pro or Ala at the P1 position. The substrate recognition mechanism has been fully elucidated for mammalian DPP IV by crystal structure analyses but not for bacterial orthologues. Here, we report the crystal structures of a bacterial DPP IV (PmDAP IV) in its free form and in complexes with two kinds of dipeptides as well as with a non-peptidyl inhibitor at 1.90 to 2.47 Å resolution. Acyl-enzyme intermediates were observed for the dipeptide complexes of PmDAP IV, whereas tetrahedral intermediates were reported for the oligopeptide complexes of mammalian DPP IVs...
February 9, 2018: Scientific Reports
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