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Angelo Avogaro, Gian Paolo Fadini, Giorgio Sesti, Enzo Bonora, Stefano Del Prato
Diabetic patients suffer from a high rate of cardiovascular events and such risk increases with HbA1c. However, lowering HbA1c does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. As the number of glucose-lowering medications increases, clinicians have to consider several open questions in the management of type 2 diabetes, one of which is the cardiovascular risk profile of each regimen. Recent placebo-controlled cardiovascular outcome trials (CVOTs) have responded to some of these questions, but careful interpretation is needed...
2016: Cardiovascular Diabetology
Kaixin Zhou, Sook Wah Yee, Eric L Seiser, Nienke van Leeuwen, Roger Tavendale, Amanda J Bennett, Christopher J Groves, Ruth L Coleman, Amber A van der Heijden, Joline W Beulens, Catherine E de Keyser, Linda Zaharenko, Daniel M Rotroff, Mattijs Out, Kathleen A Jablonski, Ling Chen, Martin Javorský, Jozef Židzik, Albert M Levin, L Keoki Williams, Tanja Dujic, Sabina Semiz, Michiaki Kubo, Huan-Chieh Chien, Shiro Maeda, John S Witte, Longyang Wu, Ivan Tkáč, Adriaan Kooy, Ron H N van Schaik, Coen D A Stehouwer, Lisa Logie, Calum Sutherland, Janis Klovins, Valdis Pirags, Albert Hofman, Bruno H Stricker, Alison A Motsinger-Reif, Michael J Wagner, Federico Innocenti, Leen M 't Hart, Rury R Holman, Mark I McCarthy, Monique M Hedderson, Colin N A Palmer, Jose C Florez, Kathleen M Giacomini, Ewan R Pearson
Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10(-14)) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry...
September 2016: Nature Genetics
Cris A Slentz, Lori A Bateman, Leslie H Willis, Esther O Granville, Lucy W Piner, Gregory P Samsa, Tracy L Setji, Michael J Muehlbauer, Kim M Huffman, Connie W Bales, William E Kraus
AIMS/HYPOTHESIS: Although the Diabetes Prevention Program (DPP) established lifestyle changes (diet, exercise and weight loss) as the 'gold standard' preventive therapy for diabetes, the relative contribution of exercise alone to the overall utility of the combined diet and exercise effect of DPP is unknown; furthermore, the optimal intensity of exercise for preventing progression to diabetes remains very controversial. To establish clinical efficacy, we undertook a study (2009 to 2013) to determine: how much of the effect on measures of glucose homeostasis of a 6 month programme modelled after the first 6 months of the DPP is due to exercise alone; whether moderate- or vigorous-intensity exercise is better for improving glucose homeostasis; and to what extent amount of exercise is a contributor to improving glucose control...
October 2016: Diabetologia
Camila Manrique, Javad Habibi, Annayya R Aroor, James R Sowers, Guanghong Jia, Melvin R Hayden, Mona Garro, Luis A Martinez-Lemus, Francisco I Ramirez-Perez, Thomas Klein, Gerald A Meininger, Vincent G DeMarco
BACKGROUND: Vascular stiffening, a risk factor for cardiovascular disease, is accelerated, particularly in women with obesity and type 2 diabetes. Preclinical evidence suggests that dipeptidylpeptidase-4 (DPP-4) inhibitors may have cardiovascular benefits independent of glycemic lowering effects. Recent studies show that consumption of a western diet (WD) high in fat and simple sugars induces aortic stiffening in female C57BL/6J mice in advance of increasing blood pressure. The aims of this study were to determine whether administration of the DPP-4 inhibitor, linagliptin (LGT), prevents the development of aortic and endothelial stiffness induced by a WD in female mice...
2016: Cardiovascular Diabetology
Gianluigi Savarese, Carmen D'Amore, Massimo Federici, Fabiana De Martino, Santo Dellegrottaglie, Caterina Marciano, Francesca Ferrazzano, Teresa Losco, Lars H Lund, Bruno Trimarco, Giuseppe M C Rosano, Pasquale Perrone-Filardi
BACKGROUND: Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis. METHODS: Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included...
October 1, 2016: International Journal of Cardiology
R C Bonadonna, C Borghi, A Consoli, M Volpe
AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Xueying Tan
Omarigliptin is a new once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the treatment of type 2 diabetes. It is indicated to have favorable effects on glycosylated hemoglobin (HbA1c), fasting and postmeal plasma glucose. It potently but reversibly inhibits DPP-4 enzyme, which prolongs the circulating half-life of glucagon-like peptide-1 that increases insulin secretion in a glucose-dependent manner. Benefiting from glucose-dependent insulin secretion, omarigliptin is associated with low risk of hypoglycemia...
July 2, 2016: Endocrine
M V Moskalev, A N Lukoyanov, E V Baranov, I L Fedushkin
The reaction of (dpp-bian)AlEt(Et2O) () (dpp-bian = 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) with 4,4'-dimethoxybenzophenone leads to the replacement of Et2O with the ketone resulting complex (dpp-bian)AlEt[O[double bond, length as m-dash]C(4-MeOC6H4)2] (). The reaction of compound with 2,6-di-tert-butyl-4-methylphenol (1 : 1) or Ph2NH (1 : 1) affords the addition products [dpp-bian(H)]AlEt[O(2,6-tBu2-4-MeC6H2)] () and [dpp-bian(H)]AlEt(NPh2) () correspondingly. Treatment of complex with 0...
June 15, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Oleg Baranov, Melanie Kahle, Carolyn F Deacon, Jens J Holst, Michael A Nauck
BACKGROUND: The present study was designed to directly compare clinical effects of vildagliptin and sitagliptin in patients with type 2 diabetes, with a special emphasis on incretin hormones and L-cell feedback inhibition induced by DPP-4 inhibition. PATIENTS/METHODS: 24 patients (12 diet/exercise, 12 on metformin) were treated, in randomized order, for 7-9 days , with either vildagliptin (50 mg b.i.d. = 100 mg/d), sitagliptin (100 mg q.d. in those on diet, 50 mg b...
June 14, 2016: Diabetes, Obesity & Metabolism
Nils Ekström, Ann-Marie Svensson, Mervete Miftaraj, Stefan Franzén, Björn Zethelius, Björn Eliasson, Soffia Gudbjörnsdottir
AIM: To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score...
October 2016: Diabetes, Obesity & Metabolism
A Baptista, I Teixeira, S Romano, Carneiro A Vaz, J Perelman
No abstract text is available yet for this article.
November 2014: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Hung-I Lu, Sheng-Ying Chung, Yi-Ling Chen, Tein-Hung Huang, Yen-Yi Zhen, Chu-Feng Liu, Meng-Wei Chang, Yung-Lung Chen, Jiunn-Jye Sheu, Sarah Chua, Hon-Kan Yip, Fan-Yen Lee
Inhibition of dipeptidyl peptidase-IV (DPP-4) enzyme activity has been revealed to protect myocardium from ischemia-reperfusion through enhancing the endogenous glucagon-like peptide-1 (GLP-1) level. However, whether exogenous supply of exendin-4, an analogue of GLP-1, would still offer benefit for protecting myocardial damage from trans-aortic constriction (TAC)-induced hypertrophic cardiomyopathy in preexistence of DPP-4 deficiency (DPP-4(D)) remained unclear. Male-adult (DPP-4(D)) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4(D) + TAC), group 3 [DPP-4(D) + TAC + exendin-4 10 µg/day], and group 4 [DPP-4(D) + TAC + exendin-4 10 µg + exendin-9-39 10 µg/day]...
2016: American Journal of Translational Research
Chien-Jung Chang, Ten-Fang Yang, Tin-I Lee, Yao-Chang Chen, Yu-Hsun Kao, Shih-Ann Chen, Yi-Jen Chen
BACKGROUND: The pulmonary veins (PVs) and atria are important foci during that period when atrial fibrillation (AF) is generated and maintained. It is well understood that hypertension and diabetes mellitus (DM) are important risk factors for AF. Dipeptidyl peptidase-IV (DPP-4) inhibitors are new agents in the fight against type 2 DM, though they have been found to have several cardiovascular effects. However, it is not clear whether DPP-4 may modulate the electrical and mechanical characteristics in hypertensive atrium or PVs...
January 2014: Acta Cardiol Sin
Song-Tao Tang, Huan Su, Qiu Zhang, Hai-Qin Tang, Chang-Jiang Wang, Qing Zhou, Wei Wei, Hua-Qing Zhu, Yuan Wang
Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors, including sitagliptin, exert favourable effects on the vascular endothelium. DPP-4 inhibitors suppress the degradation of glucagon-like peptide-1 (GLP‑1), which has been reported to enhance nitric oxide (NO) production. However, the effects of DPP-4 inhibitors on endothelin-1 (ET-1) expression in the aorta, as well as the underlying mechanisms responsible for these effects, have yet to be investigated in animal models of diabetes mellitus (DM)...
June 2016: International Journal of Molecular Medicine
Gwon Soo Jung, Jae Han Jeon, Mi Sun Choe, Sung Woo Kim, In Kyu Lee, Mi Kyung Kim, Keun Gyu Park
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the treatment of patients with type 2 diabetes and have proven protective effects on diabetic kidney disease (DKD). Whether DPP-4 inhibitors have renoprotective effects on insulin-deficient type 1 diabetes has not been comprehensively examined. The aim of this study was to determine whether gemigliptin, a new DPP-4 inhibitor, has renoprotective effects in streptozotocin (STZ)-induced type 1 diabetic mice. METHODS: Diabetes was induced by intraperitoneal administration of a single dose of STZ...
June 2016: Diabetes & Metabolism Journal
Oleg Tsuprykov, Ryotaro Ando, Christoph Reichetzeder, Karoline von Websky, Viktoriia Antonenko, Yuliya Sharkovska, Lyubov Chaykovska, Jan Rahnenführer, Ahmed A Hasan, Harald Tammen, Markus Alter, Thomas Klein, Seiji Ueda, Sho-Ichi Yamagishi, Seiya Okuda, Berthold Hocher
Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan. Interstitial fibrosis was significantly decreased by 48% with linagliptin but a non-significant 24% with telmisartan versus placebo...
May 2016: Kidney International
E Raschi, E Poluzzi, A Koci, I C Antonazzo, G Marchesini, F De Ponti
BACKGROUND AND AIMS: We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). METHODS: FAERS data reporting HF and DPP-4-Is use in the period from the fourth quarter of 2006 through 2013 were extracted, using the Standardized MedDRA Query "Cardiac failure". Disproportionality (case/non-case method) was implemented by calculating Reporting Odds Ratios (RORs) with 95% Confidence Interval (CI): (1) exploratory analysis on the entire FAERS (using rosiglitazone as positive control); (2) consolidated analyses by therapeutic area (within antidiabetics), correcting for event- and drug-related competition bias and adjusting for co-reported drugs as confounders...
May 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Lakshmi A Dave, Maria Hayes, Leticia Mora, Carlos A Montoya, Paul J Moughan, Shane M Rutherfurd
A recently proposed paradigm suggests that, like their dietary counterparts, digestion of gastrointestinal endogenous proteins (GEP) may also produce bioactive peptides. With an aim to test this hypothesis, in vitro digests of four GEP namely; trypsin (TRYP), lysozyme (LYS), mucin (MUC), serum albumin (SA) and a dietary protein chicken albumin (CA) were screened for their angiotensin-I converting (ACE-I), renin, platelet-activating factor-acetylhydrolase (PAF-AH) and dipeptidyl peptidase-IV inhibitory (DPP-IV) and antioxidant potential following simulated in vitro gastrointestinal digestion...
2016: International Journal of Molecular Sciences
Simon Veedfald, Marie Hansen, Louise Wulff Christensen, Sara Agnete Hjort Larsen, Karina Rahr Hjøllund, Astrid Plamboeck, Bolette Hartmann, Carolyn Fiona Deacon, Jens Juul Holst
What is the central question of this study? We investigated whether intestinal vagal afferents are necessary for the insulinotropic effect of glucagon-like peptide-1 (GLP-1) infused into a mesenteric artery or a peripheral vein before and after acute truncal vagotomy. What is the main finding and its importance? We found no effect of truncal vagotomy on the insulinotropic effect of exogenous GLP-1 and speculate that high circulating concentrations of GLP-1 after i.v. and i.a. infusion might have overshadowed any neural signalling component...
July 1, 2016: Experimental Physiology
E Patorno, B M Everett, A B Goldfine, R J Glynn, J Liu, C Gopalakrishnan, S C Kim
AIMS: To evaluate the comparative cardiovascular disease (CVD) safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in head-to-head comparisons with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in 'real-world' patients with type 2 diabetes mellitus (T2DM). METHODS: Within a large US commercial health plan database linked to laboratory test results, we identified three pairwise 1 : 1 propensity-score-matched cohorts of patients with T2DM aged ≥18 years treated with metformin who initiated a GLP-1 RA or a comparator, i...
August 2016: Diabetes, Obesity & Metabolism
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