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1. Glycated Albumin for Glycemic Control in T2DM Population: A Multi-Dimensional Evaluation

Author

Ferrario L, Schettini F, Avogaro A, Bellia C, Bertuzzi F, Bonetti G, Ceriello A, Ciaccio M, Corsi Romanelli M, Dozio E, Falqui L, Girelli A, Nicolucci A, Perseghin G, Plebani M, Valentini U, Zaninotto M, Castaldi S, and Foglia E

Subjects
glycated albumin, type 2 diabetes mellitus, t2dm, health technology assessment, economic evaluation, multidimensional approach, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Lucrezia Ferrario,1 Fabrizio Schettini,1 Angelo Avogaro,2 Chiara Bellia,3 Federico Bertuzzi,4 Graziella Bonetti,5 Antonio Ceriello,6 Marcello Ciaccio,3,7 Massimiliano Corsi Romanelli,8,9 Elena Dozio,9 Luca Falqui,10 Angela Girelli,11 Antonio Nicolucci,12 Gianluca Perseghin,13,14 Mario Plebani,15 Umberto Valentini,11 Martina Zaninotto,15 Silvana Castaldi,9,16 Emanuela Foglia1 1Centre for Health Economics, Social and Health Care Management, Università Carlo Cattaneo - LIUC, Castellanza, Italy; 2Department of Medicine, University-Hospital of Padova, Padova, Italy; 3Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy; 4Diabetology Unit, Grande Ospedale Metropolitano Niguarda Hospital, Milan, Italy; 5Department of Medicine Services, Valcamonica Hospital, Esine, Italy; 6Department of Cardiovascular and Metabolic Diseases, Multimedica Research Institute, Milan, Italy; 7Department of Laboratory Medicine, University-Hospital of Palermo, Palermo, Italy; 8Service of Laboratory Medicine 1-Clinical Pathology, Policlinico San Donato, Milan, Italy; 9Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy; 10Department of Medicine, Diabetes and Endocrinology, Multimedica Research Institute, Milan, Italy; 11Diabetes Care Unit, Spedali Civili Hospital, Brescia, Italy; 12Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy; 13Department of Medicine and Surgery, Università degli Studi di Milano Bicocca, Milan, Italy; 14Department of Medicine and Rehabilitation, Unit of Metabolic Medicine, Policlinico di Monza, Monza, Italy; 15Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy; 16Fondazione Ca’ Granda Ospedale Maggiore Policlinico Research Institute of Milano, Milano, ItalyCorrespondence: Lucrezia FerrarioCentre for Health Economics, Social and Health Care Management, Università Carlo Cattaneo – LIUC, Corso Matteotti 22, Castellanza, 21053, VA, ItalyTel +39 033 1572504Fax +39 033 1572513Email lferrario@liuc.itPurpose: To investigate the glycated albumin (GA) introduction implications, as an add-on strategy to traditional glycemic control (Hb1Ac and fasting plasma glucose – FPG) instruments, considering insulin-naïve individuals with type 2 diabetes mellitus (T2DM), treated with oral therapies.Methods: A Health Technology Assessment was conducted in Italy, as a multi-dimensional approach useful to validate any innovative technology. The HTA dimensions, derived from the EUnetHTA Core Model, were deployed by means of literature evidence, health economics tools and qualitative questionnaires, filled-in by 15 professionals.Results: Literature stated that the GA introduction could lead to a higher number of individuals achieving therapeutic success after 3 months of therapy (97.0% vs 71.6% without GA). From an economic point of view, considering a projection of 1,955,447 T2DM insulin-naïve individuals, potentially treated with oral therapy, GA introduction would imply fewer individuals requiring a therapy switch (− 89.44%), with a 1.06% in costs reduction, on annual basis, thus being also the preferable solution from a cost-effectiveness perspective (cost-effectiveness value: 237.74 vs 325.53). According to experts opinions, lower perceptions on GA emerged with regard to equity aspects (0.13 vs 0.72, p-value> 0.05), whereas it would improve both individuals (2.17 vs 1.33, p-value=0.000) and caregivers quality of life (1.50 vs 0.83, p-value=0.000). Even if in the short term, GA required additional investments in training courses (− 0.80 vs 0.10, p-value = 0.036), in the long run, GA could become the preferable technology (0.30 vs 0.01, p-value=0.018) from an organisational perspective.Conclusion: Adding GA to traditional glycaemic control instruments could improve the clinical pathway of individuals with T2DM, leading to economic and organisational advantages for both hospitals and National Healthcare Systems.Keywords: glycated albumin, type 2 diabetes mellitus, T2DM, Health Technology Assessment, economic evaluation, multidimensional approach

Published
2021

2. DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions

Author

De Nigris V, Prattichizzo F, Iijima H, and Ceriello A

Subjects
dpp-4 inhibitors, low grade inflammation, teneligliptin, macrophage polarization, endothelial inflammation, endothelial no, high glucose, antioxidant defense, Specialties of internal medicine, RC581-951
Abstract

Valeria De Nigris,1 Francesco Prattichizzo,2 Hiroaki Iijima,3 Antonio Ceriello2 1Institut d’Investigación Biomédiques August Pi i Sunyer, Barcelona, Spain; 2IRCCS MultiMedica, Milan, Italy; 3Medical Affairs Department, Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, JapanCorrespondence: Valeria De NigrisInsititut d’Investigacions Biomèdiques August Pi i Sunyer, C/Rosselló, 149-153, Barcelona, 08036, SpainTel +34932275400 Ext. 4562Fax +34932279240Email valeriadenigris@yahoo.itPurpose: We explored the anti-inflammatory role of the DPP-4 inhibitor teneligliptin, using sitagliptin as comparator, in different in vitro models of low-grade inflammation (LGI), evaluating the hyperglycemia-induced endothelial inflammation, the macrophage polarization, and the endothelium–macrophage interaction.Methods: The effects of DPP-4 and its inhibitors on macrophage polarization were evaluated in THP-1 cells by measuring mRNA expression of M1-M2 markers. HUVEC cells were used to analyze the effects of DPP-4 inhibitors on endothelial inflammation under normal and high glucose conditions. To evaluate the link between eNO and M1-M2 polarization, HUVECs were transfected with eNOS siRNA and co-cultured with THP-1 cells. The effects of DPP-4 inhibitors on macrophage polarization and eNO content were evaluated in a co-culture model of differentiated THP-1 cells + HUVECs under normal glucose (NG), high glucose (HG) and high metabolic memory (HM) conditions.Results: DPP-4 regulated M1/M2 macrophage polarization. Teneligliptin reduced M1 and enhanced M2 macrophage phenotype under DPP-4 stimulation, and attenuated hyperglycemia-induced endothelial inflammation. In THP-1 cells co-cultured with eNOS depleted HUVECs, M1 markers were enhanced, while M2 reduced, indicating an important role of eNO in polarization to M2 phenotype. In the co-culture model with HUVECs exposed to HG and HM, teneligliptin reduced M1 and enhanced M2 population, by increasing eNO levels. The anti-inflammatory effects of sitagliptin were not observed in these LGI models.Conclusion: Teneligliptin, but not sitagliptin, has anti-inflammatory effects in the various LGI models, by promoting a switch from M1 toward M2 phenotype and by decreasing hyperglycaemia-induced endothelial inflammation, suggesting that effects for LGI are different among DPP-4 inhibitors.Keywords: DPP-4 inhibitors, low-grade inflammation, teneligliptin, macrophage polarization, endothelial inflammation, endothelial NO, high glucose, antioxidant defense

Published
2021

6. CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes

Author

Schnell, Oliver, Barnard-Kelly, Katharine, Battelino, Tadej, Ceriello, Antonio, Larsson, Helena Elding, Fernández-Fernández, Beatriz, Forst, Thomas, Frias, Juan-Pablo, Gavin, III, James R., Giorgino, Francesco, Groop, Per-Henrik, Heerspink, Hiddo J. L., Herzig, Stephan, Hummel, Michael, Huntley, George, Ibrahim, Mahmoud, Itzhak, Baruch, Jacob, Stephan, Ji, Linong, Kosiborod, Mikhail, Lalic, Nebosja, Macieira, Sofia, Malik, Rayaz A., Mankovsky, Boris, Marx, Nikolaus, Mathieu, Chantal, Müller, Timo D., Ray, Kausik, Rodbard, Helena W., Rossing, Peter, Rydén, Lars, Schumm-Draeger, Petra-Maria, Schwarz, Peter, Škrha, Jan, Snoek, Frank, Tacke, Frank, Taylor, Bruce, Jeppesen, Britta Tendal, Tesfaye, Solomon, Topsever, Pinar, Vilsbøll, Tina, Yu, Xuefeng, and Standl, Eberhard

Published
2024
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7. GLP-1 receptor agonists-SGLT-2 inhibitors combination therapy and cardiovascular events after acute myocardial infarction: an observational study in patients with type 2 diabetes

Author

Marfella, Raffaele, Prattichizzo, Francesco, Sardu, Celestino, Rambaldi, Pier Francesco, Fumagalli, Carlo, Marfella, Ludovica Vittoria, La Grotta, Rosalba, Frigé, Chiara, Pellegrini, Valeria, D’Andrea, Davide, Cesaro, Arturo, Calabrò, Paolo, Pizzi, Carmine, Antonicelli, Roberto, Ceriello, Antonio, Mauro, Ciro, and Paolisso, Giuseppe

Published
2024
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8. Personalized therapy algorithms for type 2 diabetes: a phenotype-based approach

Author

Ceriello A, Gallo M, Candido R, De Micheli A, Esposito K, Gentile S, and Medea G

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Antonio Ceriello,1,2 Marco Gallo,3 Riccardo Candido,4 Alberto De Micheli,5 Katherine Esposito,6 Sandro Gentile,6 Gerardo Medea71Department of Endocrinology, Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi iSunyer, 2Centro de Investigacion Biomèdica en Red de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain; 3Oncological Endocrinology, AOU Città della Salute e della Scienza-Molinette, Turin, 4Diabetes Center, ASS 1 Triestina, Trieste, 5Ligurian Health Agency, Genoa, 6Department of Clinical and Experimental Medicine, Second University of Naples, Naples, 7Italian College of General Practitioners, Florence, ItalyAbstract: Type 2 diabetes is a progressive disease with a complex and multifactorial pathophysiology. Patients with type 2 diabetes show a variety of clinical features, including different "phenotypes" of hyperglycemia (eg, fasting/preprandial or postprandial). Thus, the best treatment choice is sometimes difficult to make, and treatment initiation or optimization is postponed. This situation may explain why, despite the existing complex therapeutic armamentarium and guidelines for the treatment of type 2 diabetes, a significant proportion of patients do not have good metabolic control and at risk of developing the late complications of diabetes. The Italian Association of Medical Diabetologists has developed an innovative personalized algorithm for the treatment of type 2 diabetes, which is available online. According to the main features shown by the patient, six algorithms are proposed, according to glycated hemoglobin (HbA1c, ≥9% or ≤9%), body mass index (≤30 kg/m2 or ≥30 kg/m2), occupational risk potentially related to hypoglycemia, chronic renal failure, and frail elderly status. Through self-monitoring of blood glucose, patients are phenotyped according to the occurrence of fasting/preprandial or postprandial hyperglycemia. In each of these six algorithms, the gradual choice of treatment is related to the identified phenotype. With one exception, these algorithms contain a stepwise approach for patients with type 2 diabetes who are metformin-intolerant. The glycemic targets (HbA1c, fasting/preprandial and postprandial glycemia) are also personalized. This accessible and easy to use algorithm may help physicians to choose a personalized treatment plan for each patient and to optimize it in a timely manner, thereby lessening clinical inertia.Keywords: type 2 diabetes, treatment guidelines, personalized treatment, Italian Association of Medical Diabetologists, Italian algorithm

Published
2014

9. BMI variability and cardiovascular outcomes within clinical trial and real-world environments in type 2 diabetes: an IMI2 SOPHIA study

Author

Robert J. Massey, Yu Chen, Marina Panova-Noeva, Michaela Mattheus, Moneeza K. Siddiqui, Nanette C. Schloot, Antonio Ceriello, Ewan R. Pearson, and Adem Y. Dawed

Subjects
BMI variability, Type 2 diabetes, 3P-MACE risk, Cardiovascular disease, HbA1c variability, Diabetes management, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability. Methods We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioresource (n = 6980) using Cox regression modelling. BMI variability was determined using average successive variability (ASV), with first major adverse cardiovascular event of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death (3P-MACE) as the primary outcome. Results After adjusting for cardiovascular risk factors, a + 1 SD increase in BMI variability was associated with increased 3P-MACE risk in Harmony Outcomes (HR 1.12, 95% CI 1.08–1.17, P

Published
2024
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10. GLP-1 reduces metalloproteinase-9 induced by both hyperglycemia and hypoglycemia in type 1 diabetes. The possible role of oxidative stress

Author

Ceriello A, La Sala L, De Nigris V, Pujadas G, Rondinelli M, and Genovese S

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Antonio Ceriello,1,2 Lucia La Sala,1 Valeria De Nigris,1 Gemma Pujadas,1 Maurizio Rondinelli,3 Stefano Genovese3 1Institut d’Investigación Biomédiques August Pi i Sunyer (IDIBAPS), 2Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Hospital Clinic, Barcelona, Spain; 3Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica, Sesto San Giovanni (MI), ItalyDear editorMMP-9 has been involved in favoring cardiovascular disease, and evidence suggests that oxidative stress favors its release. Previous studies demonstrated that during both acute hyperglycemia and hypoglycemia an oxidative stress is produced in type 1 diabetes. On the other hand, GLP-1 has shown an antioxidant power. In this study an acute hyperglycemia and hypoglycemia, with or without the simultaneous infusion of GLP-1, were produced. During both hyperglycemia and hypoglycemia, an acute increase of MMP-9 and 8-iso-PGF2α plasma levels was observed. GLP-1 significantly reduced this increase. This study suggests that metalloproteinase-9 is activated by acute hyperglycemia and hypoglycemia because they generate an oxidative stress and that GLP-1 counteracts this effect.

Published
2015

11. Our experience of liver Epithelioid Hemangioendothelioma: from a misdiagnosis to liver transplantation with long term follow-up

Author

Giuliani Antonio, Amato Bruno, Marsilia Giuseppina Marino, Tafuri Domenico, Ceriello Antonio, Santaniello Walter, Sodano Loredana, and Rocca Aldo

Subjects
Hepatichemangioendothelioma, liver transplantation, laparoscopic liver surgery, Medicine
Abstract

Malignant Hepatic Epithelioid hemangioendothelioma (HEHE) is an uncommon vascular tumor of intermediate malignant potential. HEHE is a rare tumor and it is difficult to diagnose for surgeons, hepatologists, radiologists and pathologists. So, misdiagnosis with a delay of the treatment is not uncommon. We describe a case of a young woman with a diagnosis of HEHE made 6 years after the first evidence of liver mass with a very long term follow-up after surgical treatment. She had two diagnoses of Hepatocellurar carcinoma (HCC) and a diagnosis of Cholangiocarcinoma after three different fine needle biopsies. After clinical observation, a new laparoscopic core biopsy was performed. In a first time approach, considering clinical and radiological patterns, a diagnosis of Budd-Chiari Syndrome was finally made. For that the patient underwent an orthotopicliver transplantation (OLTx). The surgical sample histological analysis allowed a definitive diagnosis of HEHE. At last, at follow up 7 years after three OLTx the patient is still alive and in good health with no evidence of recurrence.

Published
2015
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12. New-Onset Diabetes Mellitus in COVID-19: A Scoping Review

Author

Pantea Stoian, Anca, Bica, Ioana-Cristina, Salmen, Teodor, Al Mahmeed, Wael, Al-Rasadi, Khalid, Al-Alawi, Kamila, Banach, Maciej, Banerjee, Yajnavalka, Ceriello, Antonio, Cesur, Mustafa, Cosentino, Francesco, Firenze, Alberto, Galia, Massimo, Goh, Su-Yen, Janez, Andrej, Kalra, Sanjay, Kapoor, Nitin, Kempler, Peter, Lessan, Nader, Lotufo, Paulo, Mikhailidis, Dimitri P., Nibali, Luigi, Papanas, Nikolaos, Powell-Wiley, Tiffany, Rizvi, Ali A., Sahebkar, Amirhossein, Santos, Raul D., Toth, Peter P., Viswanathan, Vijay, and Rizzo, Manfredi

Published
2024
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13. CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes

Author

Oliver Schnell, Katharine Barnard-Kelly, Tadej Battelino, Antonio Ceriello, Helena Elding Larsson, Beatriz Fernández-Fernández, Thomas Forst, Juan-Pablo Frias, James R. Gavin, Francesco Giorgino, Per-Henrik Groop, Hiddo J. L. Heerspink, Stephan Herzig, Michael Hummel, George Huntley, Mahmoud Ibrahim, Baruch Itzhak, Stephan Jacob, Linong Ji, Mikhail Kosiborod, Nebosja Lalic, Sofia Macieira, Rayaz A. Malik, Boris Mankovsky, Nikolaus Marx, Chantal Mathieu, Timo D. Müller, Kausik Ray, Helena W. Rodbard, Peter Rossing, Lars Rydén, Petra-Maria Schumm-Draeger, Peter Schwarz, Jan Škrha, Frank Snoek, Frank Tacke, Bruce Taylor, Britta Tendal Jeppesen, Solomon Tesfaye, Pinar Topsever, Tina Vilsbøll, Xuefeng Yu, and Eberhard Standl

Subjects
Cardiovascular disease, Chronic kidney disease, CGM, Diabetes, Finerenone, GLP-1 RA, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5–6, 2024 ( http://www.cvot.org ).

Published
2024
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14. Correction to: New-Onset Diabetes Mellitus in COVID-19: A Scoping Review

Author

Pantea Stoian, Anca, Bica, Ioana-Cristina, Salmen, Teodor, Al Mahmeed, Wael, Al-Rasadi, Khalid, Al-Alawi, Kamila, Banach, Maciej, Banerjee, Yajnavalka, Ceriello, Antonio, Cesur, Mustafa, Cosentino, Francesco, Firenze, Alberto, Galia, Massimo, Goh, Su-Yen, Janez, Andrej, Kalra, Sanjay, Kapoor, Nitin, Kempler, Peter, Lessan, Nader, Lotufo, Paulo, Mikhailidis, Dimitri P., Nibali, Luigi, Papanas, Nikolaos, Powell-Wiley, Tiffany, Rizvi, Ali A., Sahebkar, Amirhossein, Santos, Raul D., Toth, Peter P., Viswanathan, Vijay, and Rizzo, Manfredi

Published
2024
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15. GLP-1 receptor agonists-SGLT-2 inhibitors combination therapy and cardiovascular events after acute myocardial infarction: an observational study in patients with type 2 diabetes

Author

Raffaele Marfella, Francesco Prattichizzo, Celestino Sardu, Pier Francesco Rambaldi, Carlo Fumagalli, Ludovica Vittoria Marfella, Rosalba La Grotta, Chiara Frigé, Valeria Pellegrini, Davide D’Andrea, Arturo Cesaro, Paolo Calabrò, Carmine Pizzi, Roberto Antonicelli, Antonio Ceriello, Ciro Mauro, and Giuseppe Paolisso

Subjects
SGLT-2 inhibitors, GLP-1 receptor agonists, MACE, Heart failure, Myocardial infarction, Glucose-lowering drugs, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Few studies explored the effect of the combination of glucose sodium-cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on the incidence of cardiovascular events in patients with type 2 diabetes (T2D) and acute myocardial infarction (AMI). Methods We recruited patients with T2D and AMI undergoing percutaneous coronary intervention, treated with either SGLT-2i or GLP-1RA for at least 3 months before hospitalization. Subjects with HbA1c 50% was higher in the SGLT-2i/GLP-1RA group compared with both SGLT-2i and GLP-1RA groups. Interpretation The combination of SGLT-2i and GLP-1RA is associated with a reduced incidence of cardiovascular events in patients with T2D and AMI compared with either drug used alone, with a significant effect also on peri-infarcted myocardial rescue in patients without a second event. Trial registraition ClinicalTrials.gov ID: NCT06017544.

Published
2024
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16. Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment

Author

Valeria Pellegrini, Rosalba La Grotta, Francesca Carreras, Angelica Giuliani, Jacopo Sabbatinelli, Fabiola Olivieri, Cesare Celeste Berra, Antonio Ceriello, and Francesco Prattichizzo

Subjects
inflammaging, obesity, senescence, metabolic memory, epigenetics, trained immunity, Cytology, QH573-671
Abstract

Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, and aging are all recognized triggers of LGI, promoting insulin resistance and sustaining the pathogenesis of T2D. Once developed, and even before frank appearance, people with T2D undergo a pathological metabolic remodeling, with an alteration of multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, and renal function. In turn, such variables foster a range of inflammatory pathways and mechanisms, e.g., immune cell stimulation, the accrual of senescent cells, long-lasting epigenetic changes, and trained immunity, which are held to chronically fuel LGI at the systemic and tissue levels. Targeting of CVD risk factors partially ameliorates LGI. However, some long-lasting inflammatory pathways are unaffected by common therapies, and LGI burden is still increased in many T2D patients, a phenomenon possibly underlying the residual inflammatory risk (i.e., having hs-CRP > 2 mg/dL despite optimal LDL cholesterol control). On the other hand, selected disease-modifying drugs, e.g., GLP-1RA, seem to also act on the pathogenesis of T2D, curbing the inflammatory trajectory of the disease and possibly preventing it if introduced early. In addition, selected trials demonstrated the potential of canonical anti-inflammatory therapies in reducing the rate of CVDs in patients with this condition or at high risk for it, many of whom had T2D. Since colchicine, an inhibitor of immune cell activation, is now approved for the prevention of CVDs, it might be worth exploring a possible therapeutic paradigm to identify subjects with T2D and an increased LGI burden to treat them with this drug. Upcoming studies will reveal whether disease-modifying drugs reverse early T2D by suppressing sources of LGI and whether colchicine has a broad benefit in people with this condition.

Published
2024
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18. Indirect effects of the COVID-19 pandemic on diagnosing, monitoring, and prescribing in people with diabetes and strategies for diabetes service recovery internationally

Author

Rutter, Martin K., Carr, Matthew J., Wright, Alison K., Kanumilli, Naresh, Milne, Nicola, Jones, Ewan, Elton, Peter, Ceriello, Antonio, Misra, Anoop, Del Prato, Stefano, Barron, Emma, Hambling, Clare, Sattar, Naveed, Khunti, Kamlesh, Valabhji, Jonathan, Feldman, Eva L., and Ashcroft, Darren M.

Published
2024
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20. Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop

Author

Ceriello, Antonio, Rodbard, Helena W., Battelino, Tadej, Brosius, Frank, Cosentino, Francesco, Green, Jennifer, Ji, Linong, Kellerer, Monika, Koob, Susan, Kosiborod, Mikhail, Lalic, Nebojsa, Marx, Nikolaus, Nedungadi, T. Prashant, Parkin, Christopher G., Rydén, Lars, Sheu, Wayne Huey-Herng, Standl, Eberhard, Vandvik, Per Olav, and Schnell, Oliver

Published
2023
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21. SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes

Author

Marfella, Raffaele, Sardu, Celestino, D’Onofrio, Nunzia, Fumagalli, Carlo, Scisciola, Lucia, Sasso, Ferdinando Carlo, Siniscalchi, Mario, Marfella, Ludovica Vittoria, D’Andrea, Davide, Minicucci, Fabio, Signoriello, Giuseppe, Cesaro, Arturo, Trotta, Maria Consiglia, Frigé, Chiara, Prattichizzo, Francesco, Balestrieri, Maria Luisa, Ceriello, Antonio, Calabrò, Paolo, Mauro, Ciro, del Viscovo, Luca, and Paolisso, Giuseppe

Published
2023
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22. CVOT Summit 2022 Report: new cardiovascular, kidney, and glycemic outcomes

Author

Schnell, Oliver, Battelino, Tadej, Bergenstal, Richard, Birkenfeld, Andreas L., Ceriello, Antonio, Cheng, Alice, Davies, Melanie, Edelman, Steve, Forst, Thomas, Giorgino, Francesco, Green, Jennifer, Groop, Per-Henrik, Hadjadj, Samy, J.L.Heerspink, Hiddo, Hompesch, Marcus, Izthak, Baruch, Ji, Linong, Kanumilli, Naresh, Mankovsky, Boris, Mathieu, Chantal, Miszon, Martin, Mustafa, Reem, Nauck, Michael, Pecoits-Filho, Roberto, Pettus, Jeremy, Ranta, Kari, Rodbard, Helena W., Rossing, Peter, Ryden, Lars, Schumm-Draeger, Petra-Maria, Solomon, Scott D., Škrha, Jan, Topsever, Pinar, Vilsbøll, Tina, Wilding, John, and Standl, Eberhard

Published
2023
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23. Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop

Author

Antonio Ceriello, Helena W. Rodbard, Tadej Battelino, Frank Brosius, Francesco Cosentino, Jennifer Green, Linong Ji, Monika Kellerer, Susan Koob, Mikhail Kosiborod, Nebojsa Lalic, Nikolaus Marx, T. Prashant Nedungadi, Christopher G. Parkin, Lars Rydén, Wayne Huey-Herng Sheu, Eberhard Standl, Per Olav Vandvik, Oliver Schnell, and for the Taskforce of the Guideline Workshop

Subjects
Network meta-analysis, Randomized controlled trial, Sodium glucose cotransporter 2 inhibitor, Glucose-dependent insulinotropic polypeptide, (GIP RA), Glucagon-like peptide-1 receptor agonist (GLP-1 RA), Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need.

Published
2023
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25. Testing and Visualization of Associations in Three-Way Contingency Tables: A Study of the Gender Gap in Patients with Type 1 Diabetes and Cardiovascular Complications

Author

Rosaria Lombardo, Eric J. Beh, Francesco Prattichizzo, Giuseppe Lucisano, Antonio Nicolucci, Björn Eliasson, Hanne Krage Carlsen, Rosalba La Grotta, Valeria Pellegrini, and Antonio Ceriello

Subjects
cardiovascular complication, Pearson’s three-way chi-squared statistic, partitioning, three-way correspondence analysis, Mathematics, QA1-939
Abstract

Using data from the Swedish National Diabetes Register, this study examines the gender disparity among patients with type 1 diabetes who have experienced a specific cardiovascular complication, while exploring the association between their weight variability, age group, and gender. Fourteen cardiovascular complications have been considered. This analysis is conducted using three-way correspondence analysis (CA), which allows for the partitioning and decomposition of Pearson’s three-way chi-squared statistic. The dataset comprises information organized in a data cube, detailing how weight variability among these patients correlates with a cardiovascular complication, age group, and gender. The three-way CA method presented in this paper allows one to assess the statistical significance of the association between these variables and to visualize this association, highlighting the gender gap among these patients. From this analysis, we find that the association between weight variability, age group, and gender varies among different types of cardiovascular complications.

Published
2024
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26. Postprandial Plasma Glucose between 4 and 7.9 h May Be a Potential Diagnostic Marker for Diabetes

Author

Yutang Wang, Yan Fang, Christopher L. Aberson, Fadi J. Charchar, and Antonio Ceriello

Subjects
postprandial, non-fasting, fasting, glucose, diabetes, Biology (General), QH301-705.5
Abstract

Postprandial glucose levels between 4 and 7.9 h (PPG4–7.9h) correlate with mortality from various diseases, including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. A receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. A simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Published
2024
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28. Pre-operative evaluation of spontaneous portosystemic shunts as a predictor of post-hepatectomy liver failure in patients undergoing liver resection for hepatocellular carcinoma

Author

Rompianesi, Gianluca, Han, Ho-Seong, Fusai, Giuseppe, Lopez-Ben, Santiago, Maestri, Marcello, Ercolani, Giorgio, Di Martino, Marcello, Diaz-Nieto, Rafael, Ielpo, Benedetto, Perez-Alonso, Alejandro, Morare, Nolitha, Casellas, Margarida, Gallotti, Anna, de la Hoz Rodriguez, Angela, Burdio, Fernando, Ravaioli, Federico, Venetucci, Pietro, Lo Bianco, Emanuela, Ceriello, Arianna, Montalti, Roberto, and Troisi, Roberto Ivan

Published
2024
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32. CVOT Summit 2022 Report: new cardiovascular, kidney, and glycemic outcomes

Author

Oliver Schnell, Tadej Battelino, Richard Bergenstal, Andreas L. Birkenfeld, Antonio Ceriello, Alice Cheng, Melanie Davies, Steve Edelman, Thomas Forst, Francesco Giorgino, Jennifer Green, Per-Henrik Groop, Samy Hadjadj, Hiddo J.L.Heerspink, Marcus Hompesch, Baruch Izthak, Linong Ji, Naresh Kanumilli, Boris Mankovsky, Chantal Mathieu, Martin Miszon, Reem Mustafa, Michael Nauck, Roberto Pecoits-Filho, Jeremy Pettus, Kari Ranta, Helena W. Rodbard, Peter Rossing, Lars Ryden, Petra-Maria Schumm-Draeger, Scott D. Solomon, Jan Škrha, Pinar Topsever, Tina Vilsbøll, John Wilding, and Eberhard Standl

Subjects
Cardiovascular disease, Chronic kidney disease, Diabetes, GIP/GLP-1 receptor agonist, Heart failure, Obesity, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10–12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year’s focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23–24, 2023 ( http://www.cvot.org ).

Published
2023
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33. Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring

Author

Lehnert Hendrik, Hanson Mark, Vatish Manu, Cagampang Felino R, Bruce Kimberley D, Didelot Xavier, Zhang Fang, Zhang Junlong, Ceriello Antonio, and Byrne Christopher D

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background miRNAs play important roles in the regulation of gene functions. Maternal dietary modifications during pregnancy and gestation have long-term effects on the offspring, but it is not known whether a maternal high fat (HF) diet during pregnancy and lactation alters expression of key miRNAs in the offspring. Results We studied the effects of maternal HF diet on the adult offspring by feeding mice with either a HF or a chow diet prior to conception, during pregnancy and lactation, and all offspring were weaned onto the same chow diet until adulthood. Maternal HF fed offspring had markedly increased hepatic mRNA levels of peroxisome proliferator activated receptor-alpha (ppar-alpha) and carnitine palmitoyl transferase-1a (cpt-1a) as well as insulin like growth factor-2 (Igf2). A HF diet induced up-regulation of ppar-alpha and cpt-1a expression in the wild type but not in Igf2 knock out mice. Furthermore, hepatic expression of let-7c was also reduced in maternal HF fed offspring. Among 579 miRNAs measured with microarray, ~23 miRNA levels were reduced by ~1.5-4.9-fold. Reduced expression of miR-709 (a highly expressed miRNA), miR-122, miR-192, miR-194, miR-26a, let-7a, let7b and let-7c, miR-494 and miR-483* (reduced by ~4.9 fold) was validated by qPCR. We found that methyl-CpG binding protein 2 was the common predicted target for miR-709, miR-let7s, miR-122, miR-194 and miR-26a using our own purpose-built computer program. Conclusion Maternal HF feeding during pregnancy and lactation induced co-ordinated and long-lasting changes in expression of Igf2, fat metabolic genes and several important miRNAs in the offspring.

Published
2009
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34. A global research priority agenda to advance public health responses to fatty liver disease

Author

Lazarus, Jeffrey V., Mark, Henry E., Allen, Alina M., Arab, Juan Pablo, Carrieri, Patrizia, Noureddin, Mazen, Alazawi, William, Alkhouri, Naim, Alqahtani, Saleh A., Arrese, Marco, Bataller, Ramon, Berg, Thomas, Brennan, Paul N., Burra, Patrizia, Castro-Narro, Graciela E., Cortez-Pinto, Helena, Cusi, Kenneth, Dedes, Nikos, Duseja, Ajay, Francque, Sven M., Hagström, Hannes, Huang, Terry T-K., Wajcman, Dana Ivancovsky, Kautz, Achim, Kopka, Christopher J., Krag, Aleksander, Miller, Veronica, Newsome, Philip N., Rinella, Mary E., Romero, Diana, Sarin, Shiv Kumar, Silva, Marcelo, Spearman, C. Wendy, Tsochatzis, Emmanuel A., Valenti, Luca, Villota-Rivas, Marcela, Zelber-Sagi, Shira, Schattenberg, Jörn M., Wong, Vincent Wai-Sun, Younossi, Zobair M., Aberg, Fredrik, Adams, Leon, Al-Naamani, Khalid, Albadawy, Reda M., Alexa, Zinaida, Allison, Michael, Alnaser, Faisal A., Alswat, Khalid, Alvares-da-Silva, Mario Reis, Alvaro, Domenico, Alves-Bezerra, Michele, Andrade, Raul J., Anstee, Quentin M., Awuku, Yaw Asante, Baatarkhuu, Oidov, Baffy, Gyorgy, Bakieva, Shokhista, Bansal, Meena B., Barouki, Robert, Batterham, Rachel L., Behling, Cynthia, Belfort-DeAguiar, Renata, Berzigotti, Annalisa, Betel, Michael, Bianco, Cristiana, Bosi, Emanuele, Boursier, Jerome, Brunt, Elizabeth M., Bugianesi, Elisabetta, Byrne, Christopher J., Cabrera Cabrejos, Maria Cecilia, Caldwell, Stephen, Carr, Rotonya, Castellanos Fernández, Marlen Ivón, Castera, Laurent, Castillo-López, Maria Gabriela, Caussy, Cyrielle, Cerda-Reyes, Eira, Ceriello, Antonio, Chan, Wah- Kheong, Chang, Yoosoo, Charatcharoenwitthaya, Phunchai, Chavez-Tapia, Norberto, Chung, Raymond T., Colombo, Massimo, Coppell, Kirsten, Cotrim, Helma P., Craxi, Antonio, Crespo, Javier, Dassanayake, Anuradha, Davidson, Nicholas O., De Knegt, Robert, de Ledinghen, Victor, Demir, Münevver, Desalegn, Hailemichael, Diago, Moises, Dillon, John F., Dimmig, Bruce, Dirac, M. Ashworth, Dirchwolf, Melisa, Dufour, Jean-François, Dvorak, Karel, Ekstedt, Mattias, El-Kassas, Mohamed, Elsanousi, Osama M., Elsharkawy, Ahmed M., Elwakil, Reda, Eskridge, Wayne, Eslam, Mohammed, Esmat, Gamal, Fan, Jian- Gao, Ferraz, Maria Lucia, Flisiak, Robert, Fortin, Davide, Fouad, Yasser, Freidman, Scott L., Fuchs, Michael, Gadano, Adrian, Gastaldelli, Amalia, Geerts, Anja, Geier, Andreas, George, Jacob, Gerber, Lynn H., Ghazinyan, Hasmik, Gheorghe, Liana, Kile, Denise Giangola, Girala, Marcos, Boon Bee, George Goh, Goossens, Nicolas, Graupera, Isabel, Grønbæk, Henning, Hamid, Saeed, Hebditch, Vanessa, Henry, Zachary, Hickman, Ingrid J., Hobbs, L. Ansley, Hocking, Samantha L., Hofmann, Wolf Peter, Idilman, Ramazan, Iruzubieta, Paula, Isaacs, Scott, Isakov, Vasily A., Ismail, Mona H., Jamal, Mohammad H., Jarvis, Helen, Jepsen, Peter, Jornayvaz, François, Sudhamshu, K.C., Kakizaki, Satoru, Karpen, Saul, Kawaguchi, Takumi, Keating, Shelley E., Khader, Yousef, Kim, Seung Up, Kim, Won, Kleiner, David E., Koek, Ger, Joseph Komas, Narcisse Patrice, Kondili, Loreta A., Koot, Bart G., Korenjak, Marko, Kotsiliti, Eleni, Koulla, Yiannoula, Kugelmas, Carina, Kugelmas, Marcelo, Labidi, Asma, Lange, Naomi F., Lavine, Joel E., Lazo, Mariana, Leite, Nathalie, Lin, Han-Chieh, Lkhagvaa, Undram, Long, Michelle T., Lopez-Jaramillo, Patricio, Lozano, Adelina, Macedo, Maria Paula, Malekzadeh, Reza, Marchesini, Giulio, Marciano, Sebastian, Martinez, Kim, Martínez Vázquez, Sophia E., Mateva, Lyudmila, Mato, José M., Nlombi, Charles Mbendi, McCary, Alexis Gorden, McIntyre, Jeff, McKee, Martin, Mendive, Juan M., Mikolasevic, Ivana, Miller, Pamela S., Milovanovic, Tamara, Milton, Terri, Moreno-Alcantar, Rosalba, Morgan, Timothy R., Motala, Ayesha, Muris, Jean, Musso, Carla, Nava-González, Edna J., Negro, Francesco, Nersesov, Alexander V., Neuschwander-Tetri, Brent A., Nikolova, Dafina, Norris, Suzanne, Novak, Katja, Ocama, Ponsiano, Ong, Janus P., Ong-Go, Arlinking, Onyekwere, Charles, Padilla, Martin, Pais, Raluca, Pan, Calvin, Panduro, Arturo, Panigrahi, Manas K., Papatheodoridis, Georgios, Paruk, Imran, Patel, Keyur, Gonçalves, Carlos Penha, Figueroa, Marlene Pérez, Pérez-Escobar, Juanita, Pericàs, Juan M., Perseghin, Gianluca, Pessoa, Mário Guimarães, Petta, Salvatore, Marques Souza de Oliveira, Claudia Pinto, Prabhakaran, Dorairaj, Pyrsopoulous, Nikolaos, Rabiee, Atoosa, Ramji, Alnoor, Ratziu, Vlad, Ravendhran, Natarajan, Ray, Katrina, Roden, Michael, Romeo, Stefano, Romero-Gómez, Manuel, Rotman, Yaron, Rouabhia, Samir, Rowe, Ian A., Sadirova, Shakhlo, Alkhatry, Maryam Salem, Salupere, Riina, Satapathy, Sanjaya K., Schwimmer, Jeffrey B., Sebastiani, Giada, Seim, Lynn, Seki, Yosuke, Serme, Abdel Karim, Shapiro, David, Sharvadze, Lali, Shaw, Jonathan E., Shawa, Isaac Thom, Shenoy, Thrivikrama, Shibolet, Oren, Shimakawa, Yusuke, Shubrook, Jay H., Singh, Shivaram Prasad, Sinkala, Edford, Skladany, Lubomir, Skrypnyk, Igor, Song, Myeong Jun, Sookoian, Silvia, Sridharan, Kannan, Stefan, Norbert, Stine, Jonathan G., Stratakis, Nikolaos, Sheriff, Dhastagir Sultan, Sundaram, Shikha S., Svegliati-Baroni, Gianluca, Swain, Mark G., Tacke, Frank, Taheri, Shahrad, Tan, Soek-Siam, Tapper, Elliot B., Targher, Giovanni, Tcaciuc, Eugen, Thiele, Maja, Tiniakos, Dina, Tolmane, Ieva, Torre, Aldo, Torres, Esther A., Treeprasertsuk, Sombat, Trenell, Michael, Turcan, Svetlana, Turcanu, Adela, Valantinas, Jonas, van Kleef, Laurens A., Velarde Ruiz Velasco, Jose Antonio, Vesterhus, Mette, Vilar-Gomez, Eduardo, Waked, Imam, Wattacheril, Julia, Wedemeyer, Heiner, Wilkins, Fonda, Willemse, José, Wong, Robert J., Yilmaz, Yusuf, Yki-Järvinen, Hannele, Yu, Ming-Lung, Yumuk, Volkan, Zeybel, Müjdat, Zheng, Kenneth I., Zheng, Ming-Hua, and Huang, Terry T.-K.

Published
2023
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35. A long-term 'memory' of HIF induction in response to chronic mild decreased oxygen after oxygen normalization

Author

Green Dixy E, Ceriello Antonio, Shenoy Satyendra S, Thorpe Jessica E, Kamat Chandrashekhar D, Warnke Linda A, and Ihnat Michael A

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Endothelial dysfunction (ED) is functionally characterized by decreased vasorelaxation, increased thrombosis, increased inflammation, and altered angiogenic potential, has been intimately associated with the progression and severity of cardiovascular disease. Patients with compromised cardiac function oftentimes have a state of chronic mild decreased oxygen at the level of the vasculature and organs, which has been shown to exacerbate ED. Hypoxia inducible factor (HIF) is a transcription factor complex shown to be the master regulator of the cellular response to decreased oxygen levels and many HIF target genes have been shown to be associated with ED. Methods Human endothelial and aortic smooth muscle cells were exposed either to A) normoxia (21% O2) for three weeks, or to B) mild decreased oxygen (15% O2) for three weeks to mimic blood oxygen levels in patients with heart failure, or to C) mild decreased oxygen for two weeks followed by one week of normoxia ("memory" treatment). Levels of HIF signaling genes (HIF-1α, HIF-2α, VEGF, BNIP3, GLUT-1, PAI-1 and iNOS) were measured both at the protein and mRNA levels. Results It was found that chronic exposure to mild decreased oxygen resulted in significantly increased HIF signaling. There was also a "memory" of HIF-1α and HIF target gene induction when oxygen levels were normalized for one week, and this "memory" could be interrupted by adding a small molecule HIF inhibitor to the last week of normalized oxygen. Finally, levels of ubiquitylated HIF-1α were reduced in response to chronic mild decreased oxygen and were not full restored after oxygen normalization. Conclusion These data suggest that HIF signaling may be contributing to the pathogenesis of endothelial dysfunction and that normalization of oxygen levels may not be enough to reduce vascular stress.

Published
2007
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38. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Author

Perkovic, Vlado, Mahaffey, Kenneth W., Agarwal, Rajiv, Bakris, George, Brenner, Barry M., Cannon, Christopher P., Charytan, David M., de Zeeuw, Dick, Greene, Tom, Jardine, Meg J., Heerspink, Hiddo J.L., Levin, Adeera, Meininger, Gary, Neal, Bruce, Pollock, Carol, Wheeler, David C., Zhang, Hong, Zinman, Bernard, Jardine, Meg, Li, Nicole, Kolesnyk, Inna, Aizenberg, Diego, Pecoits-Filho, Roberto, Cherney, David, Obrador, Gregorio, Chertow, Glenn, Chang, Tara, Hawley, Carmel, Ji, Linong, Wada, Takashi, Jha, Vivekanand, Lim, Soo Kun, Lim-Abrahan, Mary Anne, Santos, Florence, Chae, Dong-Wan, Hwang, Shang-Jyh, Vazelov, Evgueniy, Rychlík, Ivan, Hadjadj, Samy, Krane, Vera, Rosivall, László, De Nicola, Luca, Dreval, Alexander, Nowicki, Michał, Schiller, Adalbert, Distiller, Larry, Górriz, Jose L., Kolesnyk, Mykola, David, Wheeler, C., Guerrero, Rodolfo Andres Ahuad, Albisu, Juan Pablo, Alvarisqueta, Andres, Bartolacci, Ines, Berli, Mario Alberto, Bordonava, Anselmo, Calella, Pedro, Cantero, Maria Cecilia, Cartasegna, Luis Rodolfo, Cercos, Esteban, Coloma, Gabriela Cecilia, Colombo, Hugo, Commendatore, Victor, Cuadrado, Jesus, Cuneo, Carlos Alberto, Cusumano, Ana Maria, Douthat, Walter Guillermo, Dran, Ricardo Dario, Farias, Eduardo, Fernandez, Maria Florencia, Finkelstein, Hernan, Fragale, Guillermo, Fretes, Jose Osvaldo, Garcia, Nestor Horacio, Gastaldi, Anibal, Gelersztein, Elizabeth, Glenny, Jorge Archibaldo, Gonzalez, Joaquin Pablo, Colaso, Patricia del Carmen Gonzalez, Goycoa, Claudia, Greloni, Gustavo Cristian, Guinsburg, Adrian, Hermida, Sonia, Juncos, Luis Isaias, Klyver, Maria Isabel, Kraft, Florencia, Krynski, Fernando, Lanchiotti, Paulina Virginia, Leon de la Fuente, Ricardo Alfonso, Marchetta, Nora, Mele, Pablo, Nicolai, Silvia, Novoa, Pablo Antonio, Orio, Silvia Ines, Otreras, Fabian, Oviedo, Alejandra, Raffaele, Pablo, Resk, Jorge Hector, Rista, Lucas, Papini, Nelson Rodriguez, Sala, Jorgelina, Santos, Juan Carlos, Schiavi, Lilia Beatriz, Sessa, Horacio, Casabella, Tomas Smith, Ulla, Maria Rosa, Valdez, Maria, Vallejos, Augusto, Villarino, Adriana, Visco, Virginia Esther, Wassermann, Alfredo, Zaidman, Cesar Javier, Cheung, Ngai Wah, Droste, Carolyn, Fraser, Ian, Johnson, David, Mah, Peak Mann, Nicholls, Kathy, Packham, David, Proietto, Joseph, Roberts, Anthony, Roger, Simon, Tsang, Venessa, Raduan, Roberto Abrão, Costa, Fernando Augusto Alves da, Amodeo, Celso, Turatti, Luiz Alberto Andreotti, Bregman, Rachel, Sanches, Fernanda Cristina Camelo, Canani, Luis Henrique, Chacra, Antônio Roberto, Borges, João Lindolfo Cunha, Vêncio, Sérgio Alberto Cunha, Franco, Roberto Jorge da Silva, d’Avila, Domingos, Portes, Evandro de Souza, de Souza, Pedro, Deboni, Luciane Mônica, Fraige Filho, Fadlo, Neto, Bruno Geloneze, Gomes, Marcus, Kohara, Suely Keiko, Keitel, Elizete, Saraiva, Jose Francisco Kerr, Lisboa, Hugo Roberto Kurtz, Contieri, Fabiana Loss de Carvalho, Milagres, Rosângela, Junior, Renan Montenegro, de Brito, Claudia Moreira, Hissa, Miguel Nasser, Sabbag, Ângela Regina Nazario, Noronha, Irene, Panarotto, Daniel, Filho, Roberto Pecoits, Pereira, Márcio Antônio, Saporito, Wladmir, Scotton, Antonio Scafuto, Schuch, Tiago, de Almeida, Roberto Simões, Ramos, Cássio Slompo, Felício, João Soares, Thomé, Fernando, Hachmann, Jean Carlo Tibes, Yamada, Sérgio, Hayashida, Cesar Yoiti, Petry, Tarissa Beatrice Zanata, Zanella, Maria Teresa, Andreeva, Viktoria, Angelova, Angelina, Dimitrov, Stefan, Genadieva, Veselka, Genova-Hristova, Gabriela, Hristozov, Kiril, Kamenov, Zdravko, Koundurdjiev, Atanas, Lozanov, Lachezar, Margaritov, Viktor, Nonchev, Boyan, Rangelov, Rangel, Shinkov, Alexander, Temelkova, Margarita, Velichkova, Ekaterina, Yakov, Andrian, Aggarwal, Naresh, Aronson, Ronnie, Bajaj, Harpreet, Chouinard, Guy, Conway, James, Cournoyer, Serge, DaRoza, Gerald, De Serres, Sacha, Dubé, François, Goldenberg, Ronald, Gupta, Anil, Gupta, Milan, Henein, Sam, Khandwala, Hasnain, Leiter, Lawrence, Madore, François, McMahon, Alan, Muirhead, Norman, Pichette, Vincent, Rabasa-Lhoret, Remi, Steele, Andrew, Tangri, Navdeep, Torshizi, Ali, Woo, Vincent, Zalunardo, Nadia, Montenegro, María Alicia Fernández, Gonzalo Godoy Jorquera, Juan, Fariña, Marcelo Medina, Gajardo, Victor Saavedra, Vejar, Margarita, Chen, Nan, Chen, Qinkai, Gan, Shenglian, Kong, Yaozhong, Li, Detian, Li, Wenge, Li, Xuemei, Lin, Hongli, Liu, Jian, Lu, Weiping, Mao, Hong, Ren, Yan, Song, Weihong, Sun, Jiao, Sun, Lin, Tu, Ping, Wang, Guixia, Yang, Jinkui, Yin, Aiping, Yu, Xueqing, Zhao, Minghui, Zheng, Hongguang, Mendoza, Jose Luis Accini, Arcos, Edgar, Avendano, Jorge, Diaz Ruiz, Jorge Ernesto Andres, Ortiz, Luis Hernando Garcia, Gonzalez, Alexander, Triana, Eric Hernandez, Higuera, Juan Diego, Malaver, Natalia, de Salazar, Dora Inés Molina, Rosero, Ricardo, Alexandra Terront Lozano, Monica, Cometa, Luis Valderrama, Valenzuela, Alex, Vargas Alonso, Ruben Dario, Villegas, Ivan, Yupanqui, Hernan, Bartaskova, Dagmar, Barton, Petr, Belobradkova, Jana, Dohnalova, Lenka, Drasnar, Tomas, Ferkl, Richard, Halciakova, Katarina, Klokocnikova, Vera, Kovar, Richard, Lastuvka, Jiri, Lukac, Martin, Pesickova, Satu, Peterka, Karel, Pumprla, Jiri, Rychlik, Ivan, Saudek, Frantisek, Tesar, Vladimir, Valis, Martin, Weiner, Pavel, Zemek, Stanislav, Alamartine, Eric, Borot, Sophie, Cariou, Bertrand, Dussol, Bertrand, Fauvel, Jean-Pierre, Gourdy, Pierre, Klein, Alexandre, Le Meur, Yannick, Penfornis, Alfred, Roussel, Ronan, Saulnier, Pierre-Jean, Thervet, Eric, Zaoui, Philippe, Burst, Volker, Faghih, Markus, Faulmann, Grit, Haller, Hermann, Jerwan-Keim, Reinhold, Maxeiner, Stephan, Paschen, Björn, Plassmann, Georg, Rose, Ludger, Gonzalez Orellana, Ronaldo Arturo, Haase, Franklin Paul, Moreira Diaz, Juan Pablo, Ramirez Roca, Luis Alberto, Sánchez Arenales, Jose Antonio, Sanchez Polo, José Vicente, Juarez, Erick Turcios, Csecsei, Gyongyi, Csiky, Botond, Danos, Peter, Deak, Laszlo, Dudas, Mihaly, Harcsa, Eleonora, Keltai, Katalin, Keresztesi, Sandor, Kiss, Krisztian, Konyves, Laszlo, Major, Lajos, Mileder, Margit, Molnar, Marta, Mucsi, Janos, Oroszlan, Tamas, Ory, Ivan, Paragh, Gyorgy, Peterfai, Eva, Petro, Gizella, Revesz, Katalin, Takacs, Robert, Vangel, Sandor, Vasas, Szilard, Zsom, Marianna, Abraham, Oomman, Bhushan, Raju Sree, Deepak, Dewan, Edwin, Fernando M., Gopalakrishnan, Natarajan, Gracious, Noble, Hansraj, Alva, Jain, Dinesh, Keshavamurthy, C.B., Khullar, Dinesh, Manisha, Sahay, Peringat, Jayameena, Prasad, Narayan, Satyanarayana, Rao K., Sreedhar, Reddy, Sreelatha, Melemadathil, Sudhakar, Bhimavarapu, Chandra Vyasam, Ramesh, Bonadonna, Riccardo, Castellino, Pietro, Ceriello, Antonio, Chiovato, Luca, De Cosmo, Salvatore, Derosa, Giuseppe, Di Carlo, Alberto, Di Cianni, Graziano, Frascà, Giovanni, Fuiano, Giorgio, Gambaro, Giovanni, Garibotto, Giacomo, Giorda, Carlo, Malberti, Fabio, Mandreoli, Marcora, Mannucci, Edoardo, Orsi, Emanuela, Piatti, Piermarco, Santoro, Domenico, Sasso, Ferdinando Carlo, Serviddio, Gaetano, Stella, Andrea, Trevisan, Roberto, Veronelli, Anna Maria, Zanoli, Luca, Akiyama, Hitoshi, Aoki, Hiromi, Asano, Akimichi, Iitsuka, Tadashi, Kajiyama, Shizuo, Kashine, Susumu, Kawada, Toshio, Kodera, Takamoto, Kono, Hiroshi, Koyama, Kazunori, Kumeda, Yasuro, Miyauchi, Shozo, Mizuyama, Kazuyuki, Niiya, Tetsuji, Oishi, Hiroko, Ota, Satoshi, Sakakibara, Terue, Takai, Masahiko, Tomonaga, Osamu, Tsujimoto, Mitsuru, Wakasugi, Masakiyo, Wakida, Yasushi, Watanabe, Takayuki, Yamada, Masayo, Yanagida, Kazuhiro, Yanase, Toshihiko, Yumita, Wataru, Gaupsiene, Egle, Kozloviene, Dalia, Navickas, Antanas, Urbanaviciene, Egle, Abdul Ghani, Rohana, Kadir, Khalid Abdul, Ali, Norsiah, Che Yusof, Mohd Daud, Gan, Chye Lee, Ismail, Mastura, Kong, Wei Yen, Lam, Swee Win, Lee, Li Yuan, Loh, Chek Loong, Manocha, Anita Bhajan, Ng, Kee Sing, Ahmad, Nik Nur Fatnoon Nik, Ratnasingam, Vanassa, Shudim, Saiful Shahrizal Bin, Vengadasalam, Paranthaman, Abraira Munoz, Luis David, Salazar, Melchor Alpizar, Cruz, Juan Baas, Soto, Mario Burgos, Ramos, Jose Chevaile, Wong, Alfredo Chew, Correa Rotter, Jose Ricardo, Escalante, Tonatiu Diaz, Enriquez Sosa, Favio Edmundo, Lozano, Fernando Flores, Flota Cervera, Luis Fernando, Baron, Paul Frenk, Ballesteros, Cecilia Garcia, Gomez Rangel, Jose David, Herrera Jimenez, Luis Enrique, Irizar Santana, Sergio Saul, Flores, Fernando Jimenez, Molina, Hugo Laviada, Luna Ceballos, Rosa Isela, del Campo Blanco, Belia Martin, Franco, Guadalupe Morales, Moreno Loza, Oscar Tarsicio, Rocha, Cynthia Mustieles, Vera, Gregorio Obrador, Castellanos, Ricardo Orozco, Calcaneo, Juan Peralta, Reyes Rosano, Miguel Angel, Pattzi, Hiromi Rodriguez, Guzman, Juan Rosas, Rucker Joerg, Isabel Erika, Saavedra Sanchez, Sandra Berenice, Sanchez Mijangos, Jose Hector, Sanson, Pablo Serrano, Tamayo y Orozco, Juan Alfredo, Chavez, Eloisa Tellez, Cepeda, Alejandro Valdes, Carrillo, Luis Venegas, Mesa, Juan Villagordoa, Escobedo, Rolando Zamarripa, Baker, John, Noonan, Paul, Scott, Russell, Walker, Robert, Watson, Edward, Williams, Michael, Young, Simon, Abejuela, Zaynab, Agra, Jeimeen, Aquitania, Grace, Caringal, Clodoaido, Comia, Rhea Severina, Santos, Lalaine Delos, Gomez, Olivert, Jimeno, Cecilia, Tan, Gerry, Tolentino, Marsha, Yao, Christy, Yap, Yvette Ethel, Lallaine Ygpuara, Ma. Dovie, Bijata-Bronisz, Renata, Hotlos, Lucyna, Januszewicz, Andrzej, Kaczmarek, Barbara, Kaminska, Anna, Lazuka, Lech, Madej, Andrzej, Mazur, Stanislaw, Mlodawska-Choluj, Dorota, Nowicki, Michal, Orlowska-Kowalik, Grazyna, Popenda, Grazyna, Rewerska, Barbara, Sowinski, Dariusz, Angelescu, Liliana Monica, Anghel, Veronica, Avram, Rodica-Ioana, Busegeanu, Mihaela-Magdalena, Cif, Adriana, Cosma, Dana, Crisan, Carmen, Demian, Luiza Despina, Ferariu, Ioana Emilia, Halmagyi, Ildiko, Hancu, Nicolae, Munteanu, Mircea, Negru, Doru, Onaca, Adriana Gabriela, Petrica, Ligia, Popa, Amorin Remus, Ranetti, Aurelian-Emil, Serafinceanu, Cristian, Toarba, Cristina, Agafyina, Alina, Barbarash, Olga, Barysheva, Olga, Chizhov, Daniil, Dobronravov, Vladimir, Glinkina, Irina, Grineva, Elena, Khirmanov, Vladimir, Kolmakova, Elena, Koroleva, Tatiana, Kvitkova, Liudmila, Marasaev, Viacheslav, Mkrtumyan, Ashot, Morugova, Tatiana, Nagibovich, Galina, Nagibovich, Oleg, Nedogoda, Sergei, Osipova, Irina, Raskina, Tatiana, Samoylova, Yulia, Sazonova, Olga, Shamkhalova, Minara, Shutemova, Elena, Shwartz, Yuriy, Uriasyev, Oleg, Vorobyev, Sergey, Zateyshchikova, Anna, Zateyshshikov, Dmitry, Zykova, Tatyana, Antic, Slobodan, Djordjevic, Miodrag, Kendereski, Aleksandra, Lalic, Katarina, Lalic, Nebojsa, Popovic-Radinovic, Vesna, Babikova, Jana, Benusova, Olga, Buganova, Ingrid, Culak, Jan, Dzupina, Andrej, Dzuponova, Jana, Fulop, Peter, Ilavska, Adriana, Martinka, Emil, Ochodnicka, Zuzana, Pella, Daniel, Smatanova, Iveta, Ahmed, Fayzal, Badat, Aysha, Breedt, Johannes, Distiller, Lawrence, Govender, Vimladhevi, Govender, Ravendran, Joshi, Mukesh, Jurgens, Jaco, Latiff, Gulam, Lombard, Landman, Mookadam, Mohamed, Ngcakani, Nomangesi, Nortje, Hendrik, Oosthuizen, Helena, Pillay-Ramaya, Larisha, Prozesky, Hans, Reddy, Jeevren, Rheeder, Paul, Seeber, Mary, Cho, Young Min, Jeong, In-Kyung, Kim, Sin Gon, Kim, Yeong Hoon, Kwon, Hyuk-Sang, Kwon, Min Jeong, Lee, Byung-Wan, Lee, JungEun, Lee, Moon-Kyu, Nam, Moon-Suk, Oh, Kook-Hwan, Park, Cheol- Young, Park, Sun-Hee, Yoon, Kun Ho, Garcia, Pere Alvarez, Mercadal, Luis Asmarats, Barrios, Clara, Castro, Fernando Cereto, Guldris, Secundino Cigarran, Lopez, Marta Dominguez, Egido de los Rios, Jesus, Fresnedo, Gema Fernandez, Serrano, Antonio Galan, Garcia, Isabel, Gonzalez Martinez, Francisco Javier, Jodar Gimeno, Jose Esteban, Mendoza, Manuel Lopez, Marin, Tamara Malek, Portillo, Cristobal Morales, Munar Vila, Maria Antonia, Torres, Manuel Muñoz, Iglesias, Javier Nieto, Perez, Jonay Pantoja, Vera, Merce Perez, Portoles Perez, Jose M., Quesada Simón, María Angustias, Canonge, Rafael Simo, Gonzalez, Alfonso Soto, Riera, Manel Terns, Tinahones Madueno, Francisco Jose, Plaza, Mercedes Velo, Chang, Chwen-Tzuei, Chuang, Lee-Ming, Hsia, Te-Lin, Hsieh, Chang-Hsun, Lin, Chih-Ching, Lu, Yung- Chuan, Sheu, Wayne H-H, Barna, Olga, Bilyk, Svitlana D., Botsyurko, Volodymyr, Dudar, Iryna, Fushtey, Ivan, Godlevska, Olga, Golovchenko, Oleksandr, Gyrina, Olga, Kazmirchuk, Anatoliy, Komisarenko, Iuliia, Korzh, Oleksii, Kravchun, Nonna, Legun, Oleg, Mankovskyy, Borys, Martynyuk, Liliya, Mostovoy, Yuriy, Pashkovska, Nataliia, Pererva, Larysa, Pertseva, Tetyana, Samoylov, Oleksandr, Smirnov, Ivan, Svyshchenko, Yevgeniya, Tomashkevych, Halyna, Topchii, Ivan, Tryshchuk, Nadiya, Tseluyko, Vira, Vizir, Vadym, Vlasenko, Maryna, Zlova, Tetiana, Zub, Liliia, Abusnana, Salah, Railey, Mohamed, Abouglila, Kamal, Ainsworth, Paul, Ali, Zishan, Arutchelvam, Vijayaraman, Barnard, Maria, Bellary, Srikanth, Davies, Emyr, Davies, Mark, Davies, Simon, Dawson, Alison, El Kossi, Mohsen, English, Patrick, Fraser, Donald, Gnudi, Luigi, Gunstone, Anthony, Hall, Timothy, Hanif, Wasim, Jackson, Alan, Johnson, Andrew, Joseph, Franklin, Krishnan, Singhan, Kumwenda, Mick, MacDougall, Iain, Nixon, Paul, O'Hare, Joseph, Philip, Sam, Ramtoola, Shenaz, Saxena, Manish, Sennik, Davesh, Simon, Godwin, Singh, Baldev, Stephens, Jeffrey, Strzelecka, Anna, Symonds, Rehan, Turner, Wayne, Wahba, Mona, Wakeling, John, Wheeler, David, Winocour, Peter, Abdallah, Joseph, Abdullah, Raied, Abramowitz, Matthew, Acosta, Idalia, Aiello, Joseph, Akright, Laura, Akyea-Djamson, Ayim, Alappan, Rajendran, Alicic, Radica, Al-Karadsheh, Amer, Allison, Dale Crawford, Arauz-Pacheco, Carlos, Arfeen, Shahabul, Arif, Ahmed, Arvind, Moogali, Atray, Naveen, Awad, Ahmed, Barnhill, Peggy, Barranco, Elizabeth, Barrera, Carlos, Beacom, Matthew, Behara, Venkata, Belo, Diogo, Bentley-Lewis, Rhonda, Berenguer, Ramon, Bermudez, Lidia, Bernardo, Marializa, Biscoveanu, Mihaela, Bowman-Stroud, Cynthia, Brandon, Donald, Brusco, Osvaldo, Busch, Robert, Canaan, Yamil, Chilito, Alicia, Christensen, Tom, Christiano, Cynthia, Christofides, Elena, Chuateco, Caroucel, Cohen, Kenneth, Cohen, Robert, Cohen-Stein, Debbie, Cook, Charles, Coyne, Daniel, Daboul, Nizar, Darwish, Riad, Daswani, Adarsh, Deck, Kenneth, Desouza, Cyrus, Dev, Devasmita, Dhillon, Monika, Dua, Sohan, Eder, Frank, Elosegui, Ana Maria, El-Shahawy, Mohamed, Ervin, John, Esquenazi, Alberto, Evans, John, Fishbane, Steven, Frias, Juan, Galindo-Ramos, Eugenia, Galphin, Claude, Ghazi, Adline, Gonzalez, Enrique, Gorson, David, Gowda, Anupama, Greco, Barbara, Grubb, Stephen, Gulati, Rakesh, Hammoud, Jamal, Handelsman, Stuart, Hartman, Israel, Hershon, Kenneth, Hiser, Daniel, Hon, George, Jacob, Radu, Jaime, Maria, Jamal, Aamir, Kaupke, Charles, Keightley, Gerald, Kern, Elizabeth, Khanna, Rakhi, Khitan, Zeid, Kim, Sun, Kopyt, Nelson, Kovesdy, Csaba, Krishna, Gopal, Kropp, Jeffrey (Jay), Kumar, Amrendra, Kumar, Jayant, Kumar, Neil, Kusnir, Jorge, Lane, Wendy, Lawrence, Mary, Lehrner, Lawrence, Lentz, John, Levinson, Dennis, Lewis, Derek, Liss, Kenneth, Maddux, Andreas, Maheshwari, Hiralal, Mandayam, Sreedhar, Marar, Isam, Mehta, Bhasker, Middleton, John, Mordujovich, Jorge, Moreda, Ramon, Moustafa, Moustafa, Trenche, Samuel Mujica, Narayanan, Mohanram, Narvarte, Javier, Nassar, Tareq, Newman, George, Nichol, Brian, Nicol, Philip, Nisnisan, Josier, Nossuli, A. Kaldun, Obialo, Chamberlain, Olelewe, Sarah, Oliver, Michael, O'Shaughnessy, Andrew, Padron, John, Pankhaniya, Rohit, Parker, Reginald, Patel, Devesh, Patel, Gnyandev, Patel, Nina, Pavon, Humberto, Perez, Armando, Perez, Carlos, Perlman, Alan, Pettis, Karlton, Pharr, Walter, Phillips, Andrea, Purighalla, Raman, Quesada-Suarez, Luis, Ranjan, Rajiv, Rastogi, Sanjeev, Reddy, Jakkidi, Rendell, Marc, Rich, Lisa, Robinson, Michael, Rodriguez, Hector, Rosas, Sylvia, Saba, Fadi, Sankaram, Rallabhandi, Sarin, Ravi, Schreiman, Robert, Scott, David, Sekkarie, Mohamed, Sensenbrenner, John, Shakeel, Muhammad, Shanik, Michael, Shaw, Sylvia, Smith, Stephen, Solomon, Richard, Sprague, Amy, Spry, Leslie, Suchinda, Pusadee, Sultan, Senan, Surampudi, Prasanth, Sussman, Sherry, Tan, Anjanette, Terrelonge, Antonio, Thompson, Michael, Trespalacios, Fernando, Trippe, Bruce, Trueba, Pilar, Twahirwa, Marcel, Updegrove, John, Van Buren, Peter, Vannorsdall, Mark, Varghese, Freemu, Velasquez-Mieyer, Pedro, Ventrapragada, Sailaja, Vukotic, Goga, Wadud, Khurram, Warren, Mark, Watson, Henry, Watts, Ronald, Weiner, Daniel, Welker, James, Welsh, Jean, Williams, Shelley, Zaniewski-Singh, Michelle, Yi, Tae Won, Smyth, Brendan, Di Tanna, Gian Luca, Arnott, Clare, Cardoza, Kathryn, and Kang, Amy

Published
2023
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40. SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes

Author

Raffaele Marfella, Celestino Sardu, Nunzia D’Onofrio, Carlo Fumagalli, Lucia Scisciola, Ferdinando Carlo Sasso, Mario Siniscalchi, Ludovica Vittoria Marfella, Davide D’Andrea, Fabio Minicucci, Giuseppe Signoriello, Arturo Cesaro, Maria Consiglia Trotta, Chiara Frigé, Francesco Prattichizzo, Maria Luisa Balestrieri, Antonio Ceriello, Paolo Calabrò, Ciro Mauro, Luca del Viscovo, and Giuseppe Paolisso

Subjects
Restenosis, Type 2 diabetes, SGLT-2 inhibitors, Major adverse cardiovascular events, Glycemic control, Medicine
Abstract

Abstract Background No study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Methods We recruited 377 patients with T2DM and AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 T2DM were treated with SGLT2 inhibitors before PCI. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiac death, re-infarction, and heart failure related to ISR. In patients without ISR, minimal lumen area and minimal lumen diameter were assessed by coronary CT-angiography at 1-year follow-up. Results Glycemic control was similar in SGLT2i-treated patients and never SGLT2i-users. The incidence of ISR-related MACE was higher in never SGLT2i-users compared with SGLT2i-treated patients, an effect independent of glycemic status (HR = 0.418, 95% CI = 0.241–0.725, P = 0.002) and observed also in the subgroup of patients with HbA1c < 7% (HR = 0.393, 95% CI = 0.157–0.984, P = 0.027). In patients without the event, the stent patency was greater in SGLT2i-treated patients compared with never SGLT2i-users at 1-year follow-up. Conclusions SGLT2i treatment in T2DM is associated with a reduced incidence of ISR-related events, independently of glycemic control.

Published
2023
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43. The Dual Pandemics of COVID-19 and Obesity: Bidirectional Impact

Author

Kapoor, Nitin, Kalra, Sanjay, Al Mahmeed, Wael, Al-Rasadi, Khalid, Al-Alawi, Kamila, Banach, Maciej, Banerjee, Yajnavalka, Ceriello, Antonio, Cesur, Mustafa, Cosentino, Francesco, Firenze, Alberto, Galia, Massimo, Goh, Su-Yen, Janez, Andrej, Kempler, Peter, Lessan, Nader, Lotufo, Paulo, Papanas, Nikolaos, Rizvi, Ali A., Sahebkar, Amirhossein, Santos, Raul D., Stoian, Anca Pantea, Toth, Peter P., Viswanathan, Vijay, and Rizzo, Manfredi

Published
2022
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44. Evidence of an anti-inflammatory effect of PCSK9 inhibitors within the human atherosclerotic plaque

Author

Marfella, Raffaele, Prattichizzo, Francesco, Sardu, Celestino, Paolisso, Pasquale, D'Onofrio, Nunzia, Scisciola, Lucia, La Grotta, Rosalba, Frigé, Chiara, Ferraraccio, Franca, Panarese, Iacopo, Fanelli, Mara, Modugno, Piero, Calafiore, Antonio Maria, Melchionna, Mario, Sasso, Ferdinando Carlo, Furbatto, Fulvio, D'Andrea, Davide, Siniscalchi, Mario, Mauro, Ciro, Cesaro, Arturo, Calabrò, Paolo, Santulli, Gaetano, Balestrieri, Maria Luisa, Barbato, Emanuele, Ceriello, Antonio, and Paolisso, Giuseppe

Published
2023
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45. Continuous glucose monitoring and metrics for clinical trials: an international consensus statement

Author

Battelino, Tadej, Alexander, Charles M, Amiel, Stephanie A, Arreaza-Rubin, Guillermo, Beck, Roy W, Bergenstal, Richard M, Buckingham, Bruce A, Carroll, James, Ceriello, Antonio, Chow, Elaine, Choudhary, Pratik, Close, Kelly, Danne, Thomas, Dutta, Sanjoy, Gabbay, Robert, Garg, Satish, Heverly, Julie, Hirsch, Irl B, Kader, Tina, Kenney, Julia, Kovatchev, Boris, Laffel, Lori, Maahs, David, Mathieu, Chantal, Mauricio, Dídac, Nimri, Revital, Nishimura, Rimei, Scharf, Mauro, Del Prato, Stefano, Renard, Eric, Rosenstock, Julio, Saboo, Banshi, Ueki, Kohjiro, Umpierrez, Guillermo E, Weinzimer, Stuart A, and Phillip, Moshe

Published
2023
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46. The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetesResearch in context

Author

Antonio Ceriello, Giuseppe Lucisano, Francesco Prattichizzo, Rosalba La Grotta, Chiara Frigé, Salvatore De Cosmo, Paolo Di Bartolo, Graziano Di Cianni, Paola Fioretto, Carlo Bruno Giorda, Roberto Pontremoli, Giuseppina Russo, Francesca Viazzi, and Antonio Nicolucci

Subjects
AMD Annals initiative, Type 2 diabetes, Metabolic memory, Legacy effect, Cardiovascular diseases, Sodium-glucose cotransporter 2 inhibitors, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: A delay in reaching HbA1c targets in patients with newly-diagnosed type 2 diabetes (T2D) is associated with an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether an early introduction of glucose-lowering drugs with proven benefit on CVD can attenuate this phenomenon is unknown. Methods: Using data derived from a large Italian clinical registry, i.e. the AMD Annals, we identified 251,339 subjects with newly-diagnosed T2D and without CVD at baseline. Through Cox regressions adjusted for multiple risk factors, we examined the association between having a mean HbA1c between 7.1 and 8% or >8%, compared with ≤7%, for various periods of early exposure (0–1, 0–2, 0–3 years) and the development of later (mean subsequent follow-up 4.6 ± 2.9 years) CVD, evaluated as a composite of myocardial infarction, stroke, coronary or peripheral revascularization, and coronary or peripheral bypass. We performed this analysis in the overall cohort and then splitting the population in two groups of patients: those that introduced sodium-glucose transport protein 2 inhibitors (SGLT-2i) during the exposure phase and those not treated with these drugs. Findings: Considering the whole cohort, subjects with both a mean HbA1c between 7.1 and 8% and >8%, compared with patients attaining a mean HbA1c ≤ 7%, showed an increased risk of developing the outcome in all the three early exposure periods assessed, with the highest risk observed in patients with mean HbA1c > 8% in the 3 years exposure period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063–1.365). The introduction of SGLT-2i during the exposure periods of 0–1 and 0–2 years eliminated the association between poor glycemic control and the outcome (p for interaction 0.006 and 0.003, respectively, vs. patients with the same degree of glycemic control but not treated with these drugs). Interpretation: Among patients with newly diagnosed T2D and free of CVD at baseline, a poor glycemic control in the first three years after diagnosis is associated with an increased subsequent risk of CVD. This association is no longer evident when SGLT-2i are introduced in the first two years, suggesting that these drugs attenuate the phenomenon of legacy effect. An early treatment with these drugs might thus promote a long-lasting benefit in patients not attaining proper glycemic control after T2D diagnosis. Funding: This work was supported, in part, by the Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica.

Published
2023
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47. MiR-27b attenuates mitochondrial oxidative stress and inflammation in endothelial cells

Author

Nunzia D'Onofrio, Francesco Prattichizzo, Elisa Martino, Camilla Anastasio, Luigi Mele, Rosalba La Grotta, Celestino Sardu, Antonio Ceriello, Raffaele Marfella, Giuseppe Paolisso, and Maria Luisa Balestrieri

Subjects
Endothelial dysfunction, Mitochondria, hsa-miR-27b-3p, Inflammation, Apoptosis, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

MiR-27b is highly expressed in endothelial cells (EC) but its function in this context is poorly characterized. This study aims to investigate the effect of miR-27b on inflammatory pathways, cell cycle, apoptosis, and mitochondrial oxidative imbalances in immortalized human aortic endothelial cells (teloHAEC), human umbilical vein endothelial cells (HUVEC), and human coronary artery endothelial cells (HCAEC) exposed to TNF-α. Treatment with TNF-α downregulates the expression of miR-27b in all EC lines, promotes the activation of inflammatory pathways, induces mitochondrial alteration and reactive oxygen species accumulation, fostering the induction of intrinsic apoptosis. Moreover, miR-27b mimic counteracts the TNF-α-related cytotoxicity and inflammation, as well as cell cycle arrest and caspase-3-dependent apoptosis, restoring mitochondria redox state, function, and membrane polarization. Mechanistically, hsa-miR-27b-3p targets the 3′untranslated regions of FOXO1 mRNA to downregulate its expression, blunting the activation of the Akt/FOXO1 pathway. Here, we show that miR-27b is involved in the regulation of a broad range of functionally intertwined phenomena in EC, suggesting its key role in mitigating mithochondrial oxidative stress and inflammation, most likely through targeting of FOXO1. Overall, results reveal for the first time that miR-27b could represent a possible target for future therapies aimed at improving endothelial health.

Published
2023
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48. Takotsubo Syndrome during Pertuzumab and Trastuzumab Therapy for HER2-Positive Metastatic Breast Cancer

Author

Azzurra Irelli, Laura Ceriello, Leonardo Valerio Patruno, Alessandra Tessitore, Edoardo Alesse, Katia Cannita, and Donatello Fabiani

Subjects
pertuzumab, trastuzumab, fulvestrant, denosumab, cardiac toxicity, Takotsubo syndrome, Biology (General), QH301-705.5
Abstract

Pertuzumab and trastuzumab have been shown to improve the outcomes of patients with metastatic breast cancer, with a rate of left ventricular dysfunction of approximately 6%. We report the case of a postmenopausal woman who presented with Takotsubo syndrome during maintenance therapy with pertuzumab and trastuzumab, in association with fulvestrant (an anti-estrogen) and denosumab. After normalization of cardiac function, therapy with pertuzumab and trastuzumab was resumed in the absence of new cardiac toxicity. We report the first clinical case of Takotsubo syndrome during double anti-HER2 blockade in association with an antiestrogen. Furthermore, we show how anti-HER2 therapy can be safely resumed after the detection of Takotsubo syndrome.

Published
2024
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49. Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health

Author

Lo Presti, Elena, Nuzzo, Domenico, Al Mahmeed, Wael, Al-Rasadi, Khalid, Al-Alawi, Kamila, Banach, Maciej, Banerjee, Yajnavalka, Ceriello, Antonio, Cesur, Mustafa, Cosentino, Francesco, Firenze, Alberto, Galia, Massimo, Goh, Su-Yen, Janez, Andrej, Kalra, Sanjay, Kapoor, Nitin, Kempler, Peter, Lessan, Nader, Lotufo, Paulo, Papanas, Nikolaos, Rizvi, Ali A., Sahebkar, Amirhossein, Santos, Raul D., Stoian, Anca P., Toth, Peter P., Viswanathan, Vijay, and Rizzo, Manfredi

Published
2022
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50. Downstaging Strategies Prior to Liver Transplantation

Author

Vennarecci, Giovanni, primary, Ferraro, Daniele, additional, Pisaniello, Donatella, additional, Falaschi, Federica, additional, Terrone, Alfonso, additional, Maniscalco, Marilisa, additional, Ceriello, Antonio, additional, Esposito, Ciro, additional, and Di Martino, Marcello, additional

Published
2022
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