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https://www.readbyqxmd.com/read/29667232/the-pleiotropic-cardiovascular-effects-of-dipeptidyl-peptidase-4-inhibitors
#1
REVIEW
Angelo Avogaro, Gian Paolo Fadini
Patients with Type 2 Diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the Guidelines for the management of Type 2 Diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors (DPP-4-I), also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 GLP-1RA: this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. Beside incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y, and peptide YY...
April 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29658398/live-cell-imaging-reveals-the-dynamics-and-function-of-single-telomere-terra-molecules-in-cancer-cells
#2
Laura Avogaro, Emmanuelle Querido, Myriam Dalachi, Michael F Jantsch, Pascal Chartrand, Emilio Cusanelli
Telomeres cap the ends of eukaryotic chromosomes, protecting them from degradation and erroneous recombination events which may lead to genome instability. Telomeres are transcribed giving rise to telomeric repeat-containing RNAs, called TERRA. The TERRA long noncoding RNAs have been proposed to play important roles in telomere biology, including heterochromatin formation and telomere length homeostasis. While TERRA RNAs are predominantly nuclear and localize at telomeres, little is known about the dynamics and function of TERRA molecules expressed from individual telomeres...
April 16, 2018: RNA Biology
https://www.readbyqxmd.com/read/29549573/pharmacovigilance-evaluation-of-the-association-between-dpp-4-inhibitors-and-heart-failure-stimulated-reporting-and-moderation-by-drug-interactions
#3
Gian Paolo Fadini, Mayur Sarangdhar, Angelo Avogaro
INTRODUCTION: In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. METHODS: We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports...
March 16, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29546579/the-antidiabetic-drug-metformin-blunts-netosis-in-vitro-and-reduces-circulating-netosis-biomarkers-in-vivo
#4
Lisa Menegazzo, Valentina Scattolini, Roberta Cappellari, Benedetta Maria Bonora, Mattia Albiero, Mario Bortolozzi, Filippo Romanato, Giulio Ceolotto, Saula Vigili de Kreutzeberg, Angelo Avogaro, Gian Paolo Fadini
AIMS: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis. METHODS: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months. To control for the effect on glucose, we also measured NET components in the plasma of patients with type 2 diabetes before and after treatment with insulin or dapagliflozin...
March 15, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29517118/insulin-treatment-in-patients-with-diabetes-and-heart-failure-defendant-on-the-stand
#5
EDITORIAL
Angelo Avogaro, Gian Paolo Fadini
No abstract text is available yet for this article.
March 8, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29516612/use-and-effectiveness-of-dapagliflozin-in-routine-clinical-practice-an-italian-multicenter-retrospective-study
#6
Gian Paolo Fadini, Giancarlo Zatti, Ileana Baldi, Daniele Bottigliengo, Agostino Consoli, Andrea Giaccari, Giorgio Sesti, Angelo Avogaro
In randomized controlled trials (RCTs), SGLT-2 inhibitors (SGLT2i) showed glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) was a multicenter retrospective study designed to evaluate baseline characteristics of patients receiving dapagliflozin versus selected comparators (DPP-4 inhibitors, gliclazide, or GLP-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281,217 patients, the analysis included 17,285 initiating dapagliflozin or comparator glucose lowering medications (GLM), 6751 of whom had a follow-up examination...
March 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29466053/interplay-between-gut-microbiota-and-p66shc-affects-obesity-associated-insulin-resistance
#7
Stefano Ciciliot, Mattia Albiero, Stefano Campanaro, Nicol Poncina, Serena Tedesco, Valentina Scattolini, Francesca Dalla Costa, Andrea Cignarella, Monica Vettore, Iole Maria Di Gangi, Sara Bogialli, Angelo Avogaro, Gian Paolo Fadini
The 66 kDa isoform of the mammalian Shc gene promotes adipogenesis, and p66Shc-/- mice accumulate less body weight than wild-type (WT) mice. As the metabolic consequences of the leaner phenotype of p66Shc-/- mice is debated, we hypothesized that gut microbiota may be involved. We confirmed that p66Shc-/- mice gained less weight than WT mice when on a high-fat diet (HFD), but they were not protected from insulin resistance and glucose intolerance. p66Shc deletion significantly modified the composition of gut microbiota and their modification after an HFD...
February 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29449951/glucagon-like-peptide-1-receptor-agonists-are-not-associated-with-retinal-adverse-events-in-the-fda-adverse-event-reporting-system
#8
Gian Paolo Fadini, Mayur Sarangdhar, Angelo Avogaro
Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used for the treatment of type 2 diabetes. In large trials, the GLP-1RAs liraglutide and semaglutide improved cardiovascular outcomes, but semaglutide was associated with an increased risk of retinopathy progression. We herein evaluated the association between GLP-1RA and retinal adverse events (AE) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Research design and methods: We mined the FAERS between 2004q1 and 2017q1 (for a total of 9 217 555 AE reports) to analyze disproportionality and evaluate the association between GLP-1RAs and AEs involving the retina...
2018: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/29438401/systemic-and-vascular-inflammation-in-an-in-vitro-model-of-central-obesity
#9
Arti Ahluwalia, Alessandra Misto, Federico Vozzi, Chiara Magliaro, Giorgio Mattei, Maria Cristina Marescotti, Angelo Avogaro, Elisabetta Iori
Metabolic disorders due to over-nutrition are a major global health problem, often associated with obesity and related morbidities. Obesity is peculiar to humans, as it is associated with lifestyle and diet, and so difficult to reproduce in animal models. Here we describe a model of human central adiposity based on a 3-tissue system consisting of a series of interconnected fluidic modules. Given the causal link between obesity and systemic inflammation, we focused primarily on pro-inflammatory markers, examining the similarities and differences between the 3-tissue model and evidence from human studies in the literature...
2018: PloS One
https://www.readbyqxmd.com/read/29394900/how-to-interpret-the-role-of-sdf-1%C3%AE-on-diabetic-complications-during-therapy-with-dpp-4-inhibitors
#10
EDITORIAL
Gian Paolo Fadini, Angelo Avogaro
No abstract text is available yet for this article.
February 2, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29377537/counterpoint-to-the-hypothesis-that-sglt2-inhibitors-protects-the-heart-by-antagonizing-leptin
#11
Angelo Avogaro, Gian Paolo Fadini
Galileo Galilei, who was Professor at the University of Padova, taught us one of the foundations of modern science: experimental evidence always supersedes theoretical evidence. As fascinating as a hypothesis can be, it should be backed by solid experimental data and should be verifiable or rebuttable experimentally.
January 27, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29343271/p66shc-gene-expression-in-peripheral-blood-mononuclear-cells-and-progression-of-diabetic-complications
#12
Gian Paolo Fadini, Mattia Albiero, Benedetta Maria Bonora, Nicol Poncina, Saula Vigili de Kreutzenberg, Angelo Avogaro
BACKGROUND: The risk of diabetic complications is modified by genetic and epigenetic factors. p66Shc drives the hyperglycaemic cell damage and its deletion prevents experimental diabetic complications. We herein tested whether p66Shc expression in peripheral blood mononuclear cells (PBMCs) predicts adverse outcomes in people with diabetes. METHODS: In a cohort of 100 patients with diabetes (16 type 1 and 84 type 2), we quantified baseline p66Shc expression in PBMCs by quantitative PCR...
January 17, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29320602/when-metformin-is-not-enough-pros-and-cons-of-sglt2-and-dpp-4-inhibitors-as-a-second-line-therapy
#13
REVIEW
Angelo Avogaro, Elías Delgado, Ildiko Lingvay
The newer oral therapies for type 2 diabetes mellitus, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors, have advantages over older agents. Dipeptidyl peptidase-4 inhibitors are weight neutral and have few adverse effects. Sodium glucose cotransporter 2 inhibitors have additional benefits: weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. Sodium glucose cotransporter 2 inhibitors have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis...
January 10, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29300991/effects-of-hypoglycemia-on-circulating-stem-and-progenitor-cells-in-diabetic-patients
#14
Gian Paolo Fadini, Federico Boscari, Roberta Cappellari, Silvia Galasso, Mauro Rigato, Benedetta Maria Bonora, Marianna D'Anna, Daniela Bruttomesso, Angelo Avogaro
Context: Iatrogenic hypoglycemia is the most common acute diabetic complication, and it significantly increases morbidity. In people with diabetes, reduction in the levels of circulating stem and progenitor cells predicts adverse outcomes. Objective: To evaluate whether hypoglycemia in diabetes affects circulating stem cells and endothelial progenitor cells (EPCs). Design: We performed an experimental hypoglycemia study (Study 1) and a case-control study (Study 2)...
March 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29277378/assessment-of-hypoglycaemia-during-basal-insulin-therapy-temporal-distribution-and-risk-of-events-using-a-predefined-or-an-expanded-definition-of-nocturnal-events
#15
M C Riddle, G B Bolli, A Avogaro, M Gimenez Álvarez, A Merino-Trigo, E Boëlle-Le Corfec, P D Home
AIM: To describe in type 2 diabetes the 24-hour distribution of hypoglycaemia and compare the frequency of nocturnal events based on a predefined nocturnal window or an expanded interval, using illustrative data for two insulin glargine formulations. METHODS: Temporal distribution of hypoglycaemic events was assessed descriptively and by profile using participant-level data from three randomized trials comparing insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100)...
December 11, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29258716/freestyle-libre-and-dexcom-g4-platinum-sensors-accuracy-comparisons-during-two-weeks-of-home-use-and-use-during-experimentally-induced-glucose-excursions
#16
F Boscari, S Galasso, A Facchinetti, M C Marescotti, V Vallone, A M L Amato, A Avogaro, D Bruttomesso
BACKGROUND AND AIMS: This study compared the accuracy of the FreeStyle Libre (Abbott, Alameda, CA) and Dexcom G4 Platinum (DG4P, Dexcom, San Diego, CA) CGM sensors. METHODS AND RESULTS: Twenty-two adults with type 1 diabetes wore the two sensors simultaneously for 2 weeks. Libre was used according to manufacturer-specified lifetime (MSL); DG4P was used 7 days beyond MSL. At a clinical research center (CRC), subjects were randomized to receive the same breakfast with standard insulin bolus (standard) or a delayed and increased (delayed & increased) bolus to induce large glucose swings during weeks 1 and 2; venous glucose was checked every 5-15 min for 6 h...
February 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29251397/keeping-the-right-track-in-the-treatment-of-patients-with-type-2-diabetes
#17
EDITORIAL
Angelo Avogaro
No abstract text is available yet for this article.
January 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29134608/factors-that-may-account-for-cardiovascular-risk-reduction-with-a-dipeptidyl-peptidase-4-inhibitor-vildagliptin-in-young-patients-with-type-2-diabetes-mellitus
#18
Marc Evans, Plamen Kozlovski, Päivi M Paldánius, James E Foley, Vaishali Bhosekar, Carmen Serban, Angelo Avogaro
INTRODUCTION: In a meta-analysis, we observed a significant 37% relative risk reduction in prospectively adjudicated major adverse cardiac events [MACEs, comprising of non-fatal myocardial infarction, non-fatal stroke, cardiovascular (CV) death] with vildagliptin vs. comparators in younger (< 65 years) patients with type 2 diabetes mellitus (T2DM), while the risk was similar in older patients (≥ 65 years). We carried out an exploratory analysis to identify the patient characteristics and on-treatment effects that may have contributed to the different outcomes in the two age groups...
November 13, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29053207/dpp-4-inhibitors-moderate-the-risk-of-genitourinary-tract-infections-associated-with-sglt2-inhibitors
#19
Gian Paolo Fadini, Benedetta Maria Bonora, Mayur Sarangdhar, Mauro Rigato, Angelo Avogaro
Genito-urinary tract infections (GUTI) are the most common adverse event (AE) during therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i). We evaluated whether dipeptidyl peptidase 4 inhibitors (DPP4i) moderate the risk of GUTI during therapy with SGLT2i, using two approaches. First, we screened the literature for randomized controlled trials (RCTs) directly comparing the frequency of GUTI in patients receiving a DPP4i/SGLT2i combination therapy versus those receiving a SGLT2i only. In the 5 trials we retrieved, the pooled RR for genital tract infections (GTI) in patients on a DPP4i/SGLT2i combination therapy versus those on SGLT2i alone was 0...
October 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29017104/shift-of-monocyte-subsets-along-their-continuum-predicts-cardiovascular-outcomes
#20
Roberta Cappellari, Marianna D'Anna, Benedetta Maria Bonora, Mauro Rigato, Andrea Cignarella, Angelo Avogaro, Gian Paolo Fadini
BACKGROUND AND AIMS: Distribution of monocyte subsets has been shown to predict cardiovascular outcomes. However, monocytes form a continuum and categorization into discrete subsets may be an oversimplification. We herein aimed at establishing whether distribution of monocytes based on CD14 and CD16 fluorescence intensity provides incremental and complementary information on cardiovascular outcomes beyond enumeration of traditional subsets. METHODS: A cohort of 227 patients at high cardiovascular risk was characterized at baseline and followed for a median of 4 years...
November 2017: Atherosclerosis
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