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Start Over Author "Avogaro, A" Publisher american diabetes association
344 results on '"Avogaro, A"'

2. Circulating Small Noncoding RNA Profiling as a Potential Biomarker of Atherosclerotic Plaque Composition in Type 1 Diabetes

Author

Giannella, Alessandra, primary, Castelblanco, Esmeralda, additional, Zambon, Carlo Federico, additional, Basso, Daniela, additional, Hernandez, Marta, additional, Ortega, Emilio, additional, Alonso, Nuria, additional, Mauricio, Didac, additional, Avogaro, Angelo, additional, Ceolotto, Giulio, additional, and Vigili de Kreutzenberg, Saula, additional

Published
2022
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3. Circulating small non-coding RNA profiling as potential biomarkers of atherosclerotic plaque composition in Type 1 diabetes

Author

Saula Vigili de Kreutzenberg, Giulio Ceolotto, Angelo Avogaro, Didac Mauricio, Nuria Alonso, Emilio Ortega, Marta Hernandez, Daniela Basso, Carlo Federico Zambon, Esmeralda Castelblanco, and Alessandra Giannella

Abstract

OBJECTIVE Cardiovascular disease (CVD) accounts for most deaths in patients with type 1 diabetes (T1D); however, the determinants of plaque composition are unknown. MicroRNAs (miRNAs) regulate gene expression, participate in the development of atherosclerosis and represent promising CVD biomarkers. This study analyzed the circulating miRNA expression profile in T1D with carotid either calcified (CCP) or fibrous (CFP) plaque. RESEARCH DESIGN AND METHODS Circulating small non-coding RNA were sequenced and quantified using NGS and bioinformatic analysis in an exploratory set of 26 T1D with CCP and in 25 with CFP. Then, in a validation set of 40 CCP, 40 CFP and 24 controls T1D, selected miRNAs expression was measured by digital droplet PCR. Putative gene targets enriched for pathways implicated in atherosclerosis/vascular calcification/diabetes were analyzed. Patient’s main clinical characteristics were also recorded. RESULTS miR-503-5p, let-7d-5p, miR-106b-3p, miR-93-5p were significantly up-regulated, while miR-10a-5p downregulated in CCP patients compared to CFP (all FC>±1.5, p CONCLUSIONS These findings characterize miRNAs and their signature in the regulatory network of carotid plaque phenotype, in T1D, providing new insights into plaque pathophysiology, and possibly novel biomarkers of plaque composition.

Published
2022

4. Inhibition of SGLT2 Rescues Bone Marrow Cell Traffic for Vascular Repair: Role of Glucose Control and Ketogenesis

Author

Roberta Cappellari, Antonio Rosato, Serena Tedesco, Marianna D’Anna, Angelo Avogaro, Gian Paolo Fadini, Gaia Zuccolotto, Francesco Ivan Amendolagine, Mattia Albiero, and Ludovica Migliozzi

Subjects
Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Bone Marrow Cells, Diabetes Mellitus, Experimental, Mice, chemistry.chemical_compound, Glucosides, Internal medicine, Diabetes mellitus, Ketogenesis, Human Umbilical Vein Endothelial Cells, Internal Medicine, medicine, Animals, Humans, Benzhydryl Compounds, Dapagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Hematopoietic Stem Cell Mobilization, business.industry, Insulin, Hematopoietic Stem Cells, medicine.disease, Haematopoiesis, medicine.anatomical_structure, Endocrinology, chemistry, Bone marrow, business, Homing (hematopoietic)
Abstract

The mechanisms by which sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in people with diabetes are incompletely understood. Recent studies show that SGLT2i may increase the levels of circulating cells with vascular regenerative capacity, at least in part by lowering glycemia. In this study, we used mice with streptozotocin-induced diabetes treated with the SGLT2i dapagliflozin at a dose that reduced glucose levels by 20%. Dapagliflozin improved the diabetes-associated defect of hematopoietic stem cell mobilization after stimulation with granulocyte colony-stimulating factor. Dapagliflozin rescued the traffic of bone marrow (BM)–derived cells to injured carotid arteries and improved endothelial healing in diabetic mice. Defective homing of CD49d+ granulocytes was causally linked with impaired endothelial repair and was reversed by dapagliflozin. The effects of dapagliflozin were mimicked by a similar extent of glucose reduction achieved with insulin therapy and by a ketone drink that artificially elevated β-hydroxybutyrate. Inhibition of endothelial repair by resident cells using the CXCR4 antagonist AMD3100 did not abolish the vascular effect of dapagliflozin, indirectly supporting that endothelial healing by dapagliflozin was mediated by recruitment of circulating cells. In summary, we show that dapagliflozin improved the traffic of BM-derived hematopoietic cells to the site of vascular injury, providing a hitherto unappreciated mechanism of vascular protection.

Published
2021

6. Circulating Small Noncoding RNA Profiling as a Potential Biomarker of Atherosclerotic Plaque Composition in Type 1 Diabetes.

Author

Giannella, Alessandra, Castelblanco, Esmeralda, Zambon, Carlo Federico, Basso, Daniela, Hernandez, Marta, Ortega, Emilio, Alonso, Nuria, Mauricio, Didac, Avogaro, Angelo, Ceolotto, Giulio, and Vigili de Kreutzenberg, Saula

Subjects
TYPE 1 diabetes, NON-coding RNA, GENE expression, ATHEROSCLEROTIC plaque, BIOMARKERS
Abstract

OBJECTIVE: Cardiovascular disease (CVD) accounts for most deaths in patients with type 1 diabetes (T1D); however, the determinants of plaque composition are unknown. miRNAs regulate gene expression, participate in the development of atherosclerosis, and represent promising CVD biomarkers. This study analyzed the circulating miRNA expression profile in T1D with either carotid calcified (CCP) or fibrous plaque (CFP). RESEARCH DESIGN AND METHODS: Circulating small noncoding RNAs were sequenced and quantified using next-generation sequencing and bioinformatic analysis in an exploratory set of 26 subjects with T1D with CCP and in 25 with CFP. Then, in a validation set of 40 subjects with CCP, 40 with CFP, and 24 control subjects with T1D, selected miRNA expression was measured by digital droplet PCR. Putative gene targets enriched for pathways implicated in atherosclerosis/vascular calcification/diabetes were analyzed. The patients' main clinical characteristics were also recorded. RESULTS: miR-503-5p, let-7d-5p, miR-106b-3p, and miR-93-5p were significantly upregulated, while miR-10a-5p was downregulated in patients with CCP compared with CFP (all fold change >±1.5; P < 0.05). All candidate miRNAs showed a significant correlation with LDL-cholesterol, direct for the upregulated and inverse for the downregulated miRNA, in CCP. Many target genes of upregulated miRNAs in CCP participate in osteogenic differentiation, apoptosis, inflammation, cholesterol metabolism, and extracellular matrix organization. CONCLUSIONS: These findings characterize miRNAs and their signature in the regulatory network of carotid plaque phenotype in T1D, providing new insights into plaque pathophysiology and possibly novel biomarkers of plaque composition. [ABSTRACT FROM AUTHOR]

Published
2023
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7. Pharmacologic PPAR-γ Activation Reprograms Bone Marrow Macrophages and Partially Rescues HSPC Mobilization in Human and Murine Diabetes

Author

Mattia Albiero, Roberta Cappellari, Stefano Ciciliot, Marianna D’Anna, Angelo Avogaro, Serena Tedesco, Gian Paolo Fadini, Valentina Scattolini, Andrea Cignarella, and Lisa Menegazzo

Subjects
Male, 0301 basic medicine, Src Homology 2 Domain-Containing, Transforming Protein 1, Stromal cell, Endocrinology, Diabetes and Metabolism, Bone Marrow Cells, 030209 endocrinology & metabolism, Oncostatin M, Diabetes Mellitus, Experimental, Mice, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Internal Medicine, medicine, Animals, Humans, Progenitor cell, Adipogenesis, Pioglitazone, biology, Chemistry, Macrophages, fungi, Cellular Reprogramming, Chemokine CXCL12, Hematopoietic Stem Cell Mobilization, Mice, Inbred C57BL, PPAR gamma, Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, Cancer research, biology.protein, Female, Bone marrow, medicine.drug
Abstract

Mobilization of hematopoietic stem/progenitor cells (HSPC) from the bone marrow (BM) is impaired in diabetes. Excess oncostatin M (OSM) produced by M1 macrophages in the diabetic BM signals through p66Shc to induce Cxcl12 in stromal cells and retain HSPC. BM adipocytes are another source of CXCL12 that blunts mobilization. We tested a strategy of pharmacologic macrophage reprogramming to rescue HSPC mobilization. In vitro, PPAR-γ activation with pioglitazone switched macrophages from M1 to M2, reduced Osm expression, and prevented transcellular induction of Cxcl12. In diabetic mice, pioglitazone treatment downregulated Osm, p66Shc, and Cxcl12 in the hematopoietic BM, restored the effects of granulocyte-colony stimulation factor (G-CSF), and partially rescued HSPC mobilization, but it increased BM adipocytes. Osm deletion recapitulated the effects of pioglitazone on adipogenesis, which was p66Shc independent, and double knockout of Osm and p66Shc completely rescued HSPC mobilization. In the absence of OSM, BM adipocytes produced less CXCL12, being arguably devoid of HSPC-retaining activity, whereas pioglitazone failed to downregulate Cxcl12 in BM adipocytes. In patients with diabetes on pioglitazone therapy, HSPC mobilization after G-CSF was partially rescued. In summary, pioglitazone reprogrammed BM macrophages and suppressed OSM signaling, but sustained Cxcl12 expression by BM adipocytes could limit full recovery of HSPC mobilization.

Published
2020

8. Reinterpreting Cardiorenal Protection of Renal Sodium–Glucose Cotransporter 2 Inhibitors via Cellular Life History Programming

Author

Angelo Avogaro, Stefano Del Prato, and Gian Paolo Fadini

Subjects
Hibernation, Anabolism, Endocrinology, Diabetes and Metabolism, Cell, 030209 endocrinology & metabolism, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Immune system, Diabetes mellitus, Internal Medicine, Animals, Humans, Medicine, 030212 general & internal medicine, Sodium-Glucose Transporter 2 Inhibitors, Advanced and Specialized Nursing, business.industry, Sodium, Fasting, Metabolism, Cellular Reprogramming, medicine.disease, Glucose, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Sodium/Glucose Cotransporter 2, Dormancy, business
Abstract

Cardiovascular outcome trials have provided evidence that sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is associated with remarkably favorable cardiovascular outcomes. Here, we offer a novel hypothesis that may encompass many of these hypothetical mechanisms, i.e., the ability of SGLT2i to modify the trajectory of cell response to a toxic environment through modifications of cellular life history programs, either the defense program or the dormancy program. The choice between these programs is mainly determined by the environment. Hyperglycemia can be considered a toxic determinant able to interfere with the basic programs of cell evolution. While the defense program is characterized by activation of the immune response and anabolic metabolism, the dormancy program is an energy-preserving state with high resistance to environmental stressors, and it has strong analogy with animal hibernation where fuel is stored, metabolic rate is suppressed, and insulin secretion is reduced. The metabolic changes that follow treatment with SGLT2i are reminiscent of the metabolic picture characteristic of the dormancy program. Therefore, we hypothesize that the beneficial cardioprotective effects of SGLT2i may be related to their ability to switch cell life programming from a defense to a dormancy state, thus lending additional benefit.

Published
2020

9. Hyperglycemia, Reduced Hematopoietic Stem Cells, and Outcome of COVID-19

Author

Bonora, Benedetta Maria, primary, Fogar, Paola, additional, Zuin, Jenny, additional, Falaguasta, Daniele, additional, Cappellari, Roberta, additional, Cattelan, Annamaria, additional, Marinello, Serena, additional, Ferrari, Anna, additional, Avogaro, Angelo, additional, Plebani, Mario, additional, Basso, Daniela, additional, and Fadini, Gian Paolo, additional

Published
2022
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10. Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study

Author

Rossing, Peter, primary, Burgess, Ellen, additional, Agarwal, Rajiv, additional, Anker, Stefan D., additional, Filippatos, Gerasimos, additional, Pitt, Bertram, additional, Ruilope, Luis M., additional, Gillard, Pieter, additional, MacIsaac, Richard J., additional, Wainstein, Julio, additional, Joseph, Amer, additional, Brinker, Meike, additional, Roessig, Lothar, additional, Scott, Charlie, additional, Bakris, George L., additional, Vallejos, Augusto, additional, MacIsaac, Richard, additional, Schernthaner, Guntram, additional, Canziani, Maria Eugenia F., additional, Temelkova-Kurktschiev, Theodora, additional, Tobe, Sheldon, additional, González, Fernando, additional, Liu, Zhi-Hong, additional, Ángelo, Andrés, additional, Bonfanti, Cadena, additional, Francisco Jaramillo, Carlos, additional, Prazny, Martin, additional, Rossing, Peter, additional, Strand, Jorma, additional, Marre, Michel, additional, Schmieder, Roland, additional, Wanner, Christoph, additional, Sarafidis, Pantelis A., additional, Chan, Juliana, additional, Rosivall, László, additional, Eustace, Joseph, additional, Grossman, Ehud, additional, Yagil, Yoram, additional, Remuzzi, Giuseppe, additional, Koya, Daisuke, additional, Wada, Takashi, additional, Madero Rovalo, Magdalena, additional, Gansevoort, Ron, additional, Kooy, Adriaan, additional, Finnes, Trine, additional, De Leon, Froilan, additional, Gumprecht, Janusz, additional, Teixeira e Costa, Fernando, additional, Dreval, Alexander, additional, Vathsala, Anantharaman, additional, Amod, Aslam, additional, Gon Kim, Sin, additional, Wan Lee, Byung, additional, Pascual Santos, Julio, additional, Tengmark, Bengt-Olov, additional, Burnier, Michel, additional, Lee, Chien-Te, additional, Yamwong, Sukit, additional, Sari, Ramazan, additional, McCafferty, Kieran, additional, Mankovsky, Borys, additional, Adler, Sharon, additional, Fried, Linda, additional, Toto, Robert, additional, Williams, Mark, additional, Quang Khanh, Tran, additional, Aizenberg, Diego, additional, Bartolacci, Inés, additional, Besada, Diego, additional, Bittar, Julio, additional, Chahin, Mariano, additional, Elbert, Alicia, additional, Gelersztein, Elizabeth, additional, Liberman, Alberto, additional, Maffei, Laura, additional, Pérez Manghi, Federico, additional, Sanabria, Hugo, additional, Viñes, Gloria, additional, Wassermann, Alfredo, additional, Abhayaratna, Walter, additional, Acharya, Shamasunder, additional, Ekinci, Elif, additional, Lee, Darren, additional, Mann Mah, Peak, additional, Nelson, Craig, additional, Packham, David, additional, Pape, Alexia, additional, Roger, Simon, additional, Stephenson, Hugo, additional, Suranyi, Michael, additional, Wittert, Gary, additional, Vale, Elizabeth, additional, Clodi, Martin, additional, Ebenbichler, Christoph, additional, Fliesser-Görzer, Evelyn, additional, Hanusch, Ursula, additional, Krebs, Michael, additional, Lhotta, Karl, additional, Ludvik, Bernhard, additional, Mayer, Gert, additional, Neudorfer, Peter, additional, Paulweber, Bernhard, additional, Prager, Rudolf, additional, Preiß, Wolfgang, additional, Prischl, Friedrich, additional, Schernthaner, Gerit-Holger, additional, Sourij, Harald, additional, Wiesholzer, Martin, additional, Doubel, Peter, additional, Engelen, Wendy, additional, Hougardy, Jean-Michel, additional, Krzesinski, Jean-Marie, additional, Maes, Bart, additional, Speeckaert, Marijn, additional, Stas, Koen, additional, van Gaal, Luc, additional, Vanbelleghem, Hilde, additional, Antunes, Daniela, additional, Botelho, Roberto, additional, Brito, Claudia, additional, Canani, Luis, additional, Eugenia Canziani, Maria, additional, Cerqueira, Maria, additional, de Paula, Rogerio, additional, Eliaschewitz, Freddy, additional, Eduardo Figueiredo, Carlos, additional, Forti, Adriana, additional, Hissa, Miguel, additional, Leite Jr, Maurilo, additional, Lima, Emerson, additional, Noronha, Irene, additional, Paolino, Bruno, additional, Paschoalin, Nathalia, additional, Paschoalin, Raphael, additional, Pecoits Filho, Roberto, additional, Pereira, Marcio, additional, Portes, Evandro, additional, Precoma, Dalton, additional, Rea, Rosangela, additional, Riella, Miguel, additional, Eduardo Salles, Joao, additional, Vasconcellos, Eduardo, additional, Vencio, Sergio, additional, Apostolova, Emiliya, additional, Boshnyashka, Radostina, additional, Farah, Ghassan, additional, Georgiev, Dimitar, additional, Gushterova, Valentina, additional, Klyuchkova, Neli, additional, Lucheva, Mariya, additional, Manova, Petya, additional, Minkova, Dotska, additional, Nonchev, Boyan, additional, Pichmanova, Mariyana, additional, Prakova, Zhulieta, additional, Rangelov, Rangel, additional, Rashkov, Rosen, additional, Stanchev, Pavel, additional, Stoyanovska-Elencheva, Bilyana, additional, Tagarev, Zhivko, additional, Temelkova-Kurktschieva, Theodora, additional, Vasileva, Svetla, additional, Yoncheva-Mihaylova, Mariana, additional, Barre, Paul, additional, Carlson, Brian, additional, Conway, James, additional, Cournoyer, Serge, additional, Dumas, Richard, additional, Fikry, Sameh, additional, Goluch, Richard, additional, Hamet, Pavel, additional, Hart, Randolph, additional, Henein, Sam, additional, Liutkus, Joanne, additional, Madore, Francois, additional, Martinho, Valdemar, additional, Mazza, Giuseppe, additional, McFarlane, Philip, additional, O'Keefe, Dennis, additional, Peterson, Sean, additional, Schwartz, Daniel, additional, Shu, Daniel, additional, Steele, Andrew, additional, Tellier, Guy, additional, Tennankore, Karthik, additional, Tsoukas, George, additional, Tytus, Richard, additional, Vitou, Louise, additional, Walsh, Michael, additional, Weisnagel, Stanley, additional, Wilderman, Igor, additional, Yale, Jean-Francois, additional, Cobos, Jorge, additional, Godoy, Juan, additional, Lobos, Sergio, additional, Carlos Palma, Juan, additional, Carlos Prieto, Juan, additional, Reyes, Eliana, additional, Romero, Carmen, additional, Saavedra, Victor, additional, Vega, Mario, additional, Bu, Ruifang, additional, Cai, Hanqing, additional, Chen, Nan, additional, Chen, Qinkai, additional, Chen, Dejun, additional, Cheng, Jinluo, additional, Dong, Youping, additional, Dong, Junwu, additional, Guan, Tianjun, additional, Hao, Chuanming, additional, Huang, Wen, additional, Jiang, Fangfang, additional, Lei, Minxiang, additional, Li, Ling, additional, Li, Zhonghe, additional, Li, Xuemei, additional, Li, Jingmei, additional, Li, Yan, additional, Liang, Xinling, additional, Liang, Bo, additional, Liu, Fang, additional, Liu, Yinghong, additional, Liu, Yuantao, additional, Liu, Zhihong, additional, Long, Gang, additional, Lu, Guoyuan, additional, Lu, Weiping, additional, Lu, Yibing, additional, Luo, Ping, additional, Ma, Jianhua, additional, Mo, Zhaohui, additional, Niu, Jianying, additional, Peng, Ai, additional, Shen, Jiansong, additional, Shen, Feixia, additional, Shi, Bingyin, additional, Su, Qing, additional, Sun, Zhuxing, additional, Tang, Shuifu, additional, Tong, Nanwei, additional, Wang, Hao, additional, Wang, Xinjun, additional, Wang, Lihua, additional, Wang, Guixia, additional, Wang, Jianqin, additional, Wang, Yangang, additional, Wang, Li, additional, Wei, Jiali, additional, Wu, Tianfeng, additional, Wu, Chaoqing, additional, Xing, Changying, additional, Xiong, Fei, additional, Xu, Xudong, additional, Xu, Ning, additional, Yan, Tiekun, additional, Yang, Jinkui, additional, Yin, Aiping, additional, Zeng, Longyi, additional, Zhang, Hao, additional, Zhang, Yanlin, additional, Zhang, Ying, additional, Zhao, Wenjing, additional, Zhao, Zhiquan, additional, Zheng, Hongguang, additional, Zhong, Ling, additional, Zhu, Dalong, additional, Zhuang, Yongze, additional, Arango, Clara, additional, Barrera, Sandra, additional, Beltrán López, Nelly, additional, Benitez, Diego, additional, Blanco, Guillermo, additional, Cadena, Andrés, additional, Coronel, Julian, additional, Cure, Carlos, additional, Durán, Carlos, additional, González, Alexander, additional, Guzmán, Gustavo, additional, Hernández, Eric, additional, Ibarra, Jaime, additional, Jaramillo, Carlos, additional, Jaramillo, Nicolás, additional, Kattah, William, additional, Molina, Dora, additional, Sánchez, Gregorio, additional, Terront, Mónica, additional, Trujillo, Freddy, additional, Urina, Miguel, additional, Vargas, Ruben, additional, Villegas, Iván, additional, Yupanqui, Hernán, additional, Alferi, Dino, additional, Brada, Michal, additional, Brezina, Jiri, additional, Bucek, Petr, additional, Edelsberger, Tomas, additional, Gulakova, Drahomira, additional, Hasalova Zapletalova, Jitka, additional, Hola, Olga, additional, Hornova, Lucie, additional, Houdova, Jana, additional, Hrmova, Helena, additional, Karasek, David, additional, Kopecka, Sarka, additional, Kovar, Richard, additional, Krcova, Eva, additional, Kuchar, Jiri, additional, Kutejova, Vlasta, additional, Lubanda, Hana, additional, Matyasek, Ivo, additional, Mokrejsova, Magdalena, additional, Okenka, Libor, additional, Pumprla, Jiri, additional, Tomanek, Pavel, additional, Bech, Jesper, additional, Faber, Jens, additional, Gislason, Gunnar, additional, Hangaard, Jørgen, additional, Jaroslaw Pacyk, Grzegorz, additional, Juhl, Claus, additional, Krarup, Thure, additional, Lindhardt, Morten, additional, Madsbad, Sten, additional, Nielsen, Joan, additional, Pedersen-Bjergaard, Ulrik, additional, Poulsen, Per, additional, Rasmussen, Ole, additional, Schousboe, Karoline, additional, Honkasalo, Mikko, additional, Humaloja, Kari, additional, Kananen, Kristiina, additional, Kantola, Ilkka, additional, Koistinen, Arvo, additional, Korsoff, Pirkko, additional, Lahtela, Jorma, additional, Nieminen, Sakari, additional, Nieminen, Tuomo, additional, Sadeharju, Karita, additional, Sulosaari, Sakari, additional, Cariou, Bertrand, additional, Chantrel, François, additional, Clavel, Sylvaine, additional, Combe, Christian, additional, Fauvel, Jean-Pierre, additional, Gallouj, Karim, additional, Gouet, Didier, additional, Guerci, Bruno, additional, Guerrot, Dominique, additional, Hourmant, Maryvonne, additional, Klein, Alexandre, additional, Mariat, Christophe, additional, Mesbah, Rafik, additional, Le Meur, Yannick, additional, Monier, Arnaud, additional, Moranne, Olivier, additional, Serusclat, Pierre, additional, Vendrely, Benoit, additional, Verges, Bruno, additional, Zaoui, Philippe, additional, Axthelm, Christoph, additional, Bergmann, Andreas, additional, Birkenfeld, Andreas L., additional, Braun, Hermann, additional, Busch, Klaus, additional, Contzen, Christel, additional, Degenhardt, Stefan, additional, Derwahl, Karl, additional, Giebel, Thomas, additional, Hagenow, Andreas, additional, Haller, Hermann, additional, Hasslacher, Christoph, additional, Horacek, Thomas, additional, Jungmair, Wolfgang, additional, Kloos, Christof, additional, Koch, Thorsten, additional, Krüger, Thilo, additional, Mühlfeld, Anja, additional, Müller, Joachim, additional, Pfützner, Andreas, additional, Pistrosch, Frank, additional, Rose, Ludger, additional, Rump, Lars, additional, Schettler, Volker, additional, Schiefke, Ingolf, additional, Schlichthaar, Heike, additional, Schröppel, Bernd, additional, Schürholz, Thomas, additional, Sigal, Helena, additional, Stemler, Lutz, additional, Strack, Georg, additional, Täschner, Heidrun, additional, Toursarkissian, Nicole, additional, Tschöpe, Diethelm, additional, Ulmer, Achim, additional, van der Giet, Markus, additional, Winkelmann, Bernhard R., additional, Boletis, Ioannis, additional, Hatziagelaki, Erifili, additional, Ioannidis, Ioannis, additional, Kounadi, Theodora, additional, Makriniotou, Ioanna, additional, Papadopoulou, Dorothea, additional, Papagianni, Aikaterini, additional, Passadakis, Ploumis, additional, Stefanidis, Ioannis, additional, Pang Ip, Tai, additional, Lee, Paul, additional, Yan Andrea Luk, On, additional, Wang, Angela, additional, Yeung, Vincent, additional, Bajcsi, Dora, additional, Danos, Peter, additional, Harcsa, Eleonora, additional, Kazup, Szilvia, additional, Keltai, Katalin, additional, Kirschner, Robert, additional, Kiss, Julianna, additional, Kovacs, Laszlo, additional, Lamboy, Beata, additional, Literati-Nagy, Botond, additional, Mileder, Margit, additional, Nagy, Laszlo, additional, Noori, Ebrahim, additional, Nyirati, Gabor, additional, Petro, Gizella, additional, Schneider, Karoly, additional, Szocs, Albert, additional, Vasas, Szilard, additional, Wudi, Krisztina, additional, Zilahi, Zsolt, additional, Zsom, Marianna, additional, Eustace, Joe, additional, Holian, John, additional, Reddan, Donal, additional, O'Meara, Yvonne, additional, Abramof Ness, Rosane, additional, Adawi, Faiad, additional, Armaly, Zaher, additional, Atar, Shaul, additional, Ben Chetrit, Sydney, additional, Berar Yanay, Noa, additional, Chernin, Gil, additional, Darawsha, Mahmud, additional, Efrati, Shai, additional, Elias, Mazen, additional, Farber, Evgeny, additional, Glandt, Mariela, additional, Halabi, Majdi, additional, Khazim, Khaled, additional, Liberty, Idit, additional, Mosenzon, Ofri, additional, Nimer, Assy, additional, Schwartz, Doron, additional, Zukermann, Robert, additional, Ilieva Parvanova, Aneliya, additional, Avogaro, Angelo, additional, Giorgio Battaglia, Giovanni, additional, Tiziano Bevilacqua, Maurizio, additional, Bonora, Enzo, additional, Antonio Bossi, Carlo, additional, Calabrò, Paolo, additional, Luigi Cavalot, Franco, additional, Cimino, Roberto, additional, Gennaro Cozzolino, Mario, additional, David, Salvatore, additional, Emdin, Michele, additional, Fiaccadori, Enrico, additional, Fiorina, Paolo, additional, Bruno Giorda, Carlo, additional, Cristina Gregorini, Maria, additional, La Manna, Gaetano, additional, Carlo Maggi, Davide, additional, Manti, Roberta, additional, Meregalli, Giancarla, additional, Pani, Antonello, additional, Perico, Norberto, additional, Piatti, PierMarco, additional, Pisani, Antonio, additional, Ettore Pontiroli, Antonio, additional, Ponzani, Paola, additional, Santorelli, Gennaro, additional, Santoro, Domenico, additional, Scanziani, Renzo, additional, Teatini, Ugo, additional, Tonolo, Giancarlo, additional, Trevisan, Roberto, additional, Maria Veronelli, Anna, additional, Luciano Viviani, Giorgio, additional, Araki, Hideo, additional, Ebisui, Osamu, additional, Fujita, Naruhiro, additional, Furuya, Ryuichi, additional, Hamamoto, Yoshiyuki, additional, Hatazaki, Masahiro, additional, Hayashi, Terumasa, additional, Higashi, Takayuki, additional, Hirohata, Yoshihide, additional, Horinouchi, Shuji, additional, Inagaki, Masayuki, additional, Ishii, Masao, additional, Ishiko, Tamayo, additional, Jinnouchi, Hideaki, additional, Kanai, Hidetoshi, additional, Kanda, Daisuke, additional, Kanehara, Hideo, additional, Kashima, Masayuki, additional, Kato, Kiyoe, additional, Katsuki, Takeshi, additional, Kawamitsu, Katsunori, additional, Kawasaki, Satsuki, additional, Kikuchi, Fumi, additional, Kikuchi, Hidetoshi, additional, Kobayashi, Kunihisa, additional, Koide, Junko, additional, Kubota, Miyuki, additional, Kusano, Yoshiro, additional, Maeda, Hajime, additional, Matsubayashi, Sunao, additional, Matsumoto, Kazunari, additional, Matsuo, Yasuto, additional, Matsuoka, Naoki, additional, Miyaoka, Hiroaki, additional, Murao, Satoshi, additional, Nakayama, Mikihiro, additional, Nakazawa, Jun, additional, Nomiyama, Takashi, additional, Noritake, Masayuki, additional, Ogiwara, Takayuki, additional, Ohashi, Hiroshi, additional, Okamoto, Hideki, additional, Osonoi, Takeshi, additional, Sasaki, Nobuhiro, additional, Sekigami, Taiji, additional, Shibasaki, Taro, additional, Shibata, Hirotaka, additional, Shinoda, Junji, additional, Sobajima, Hiroshi, additional, Sugitatsu, Kazuya, additional, Sugiura, Toshiyuki, additional, Sugiyama, Toru, additional, Suzuki, Daisuke, additional, Suzuki, Hiroyuki, additional, Suzuki, Masaaki, additional, Takeda, Asami, additional, Tanaka, Asami, additional, Tanaka, Seiichi, additional, Tsunematsu, Izumi, additional, Ujihara, Makoto, additional, Yamada, Daishiro, additional, Yamada, Masayo, additional, Yamagata, Kazuo, additional, Yamakawa, Ken, additional, Yamakawa, Fumiko, additional, Yamasaki, Yoshimitsu, additional, Yambe, Yuko, additional, Yanagida, Taihei, additional, Yanai, Hidekatsu, additional, Yasuda, Tetsuyuki, additional, Kriauciuniene, Dovile, additional, Lasiene, Jurate, additional, Navickas, Antanas, additional, Radzeviciene, Lina, additional, Urbanaviciene, Egle, additional, Urbonas, Gediminas, additional, Velaviciene, Audrone, additional, Abd Ghani, Rohana, additional, Azizah Aziz, Nor, additional, Yuan Lee, Li, additional, Loong Loh, Chek, additional, Mohd Ali, Norhaliza, additional, Mohd Noor, Nurain, additional, Nur Fatnoon, Nik, additional, Ahmad, Nik, additional, Ratnasingam, Jeyakantha, additional, Hasnul Halimi Bin, Wan, additional, Hasan, Wan, additional, Mohd Izani, Wan, additional, Mohamed, Wan, additional, Avila Pardo, Sandro, additional, Bastidas Adrian, Miriam, additional, Chew Wong, Alfredo, additional, Escobedo de la Peña, Jorge, additional, Fanghänel Salmón, Guillermo, additional, González Gálvez, Guillermo, additional, Gutiérrez Ochoa, Ramiro, additional, Irizar Santana, Saúl, additional, Méndez Machado, Gustavo, additional, Nevarez Ruiz, Luis, additional, Ramos Ibarra, Denisse, additional, Ramos López, Gabriel, additional, Sauque Reyna, Leobardo, additional, Solache Ortiz, Gustavo, additional, Valdez Ortiz, Rafael, additional, Villagordoa Mesa, Juan, additional, Bakker, R.C., additional, Barendregt, J.N.M., additional, Boonstra, A.H., additional, Bos, Willem, additional, Brouwer, C.B., additional, van Buren, M., additional, Krekels, Marielle, additional, van Leendert, Ruud J.M., additional, Lieverse, Louis A.G., additional, Luik, P.T., additional, Lars Penne, E., additional, Smak Gregoor, Peter, additional, Vogt, Liffert, additional, Baker, John, additional, Crawford, Veronica, additional, Cutfield, Rick, additional, Dunn, Peter, additional, Krebs, Jeremy, additional, Nirmalaraj, Kingsley, additional, Scott, Russell, additional, Smuts, Nine, additional, Eriksen, Erik, additional, Høivik, Hans, additional, Karlsson, Thomas, additional, Scott Munk, Peter, additional, Radtke, Maria, additional, Risberg, Knut, additional, Rocke, Jan, additional, Solnør, Leidulv, additional, Stenehjem, Aud-Eldrid, additional, Tafjord, Anne-Beathe, additional, Pamugas, Glenda, additional, Panelo, Araceli, additional, Perez, Ronald, additional, Tanque, Maribel, additional, Tirador, Louie, additional, Villa, Michael, additional, Butrymowicz, Patrycja, additional, Ciechanowski, Kazimierz, additional, Cieslik, Grazyna, additional, Franek, Edward, additional, Hoffmann, Michal, additional, Krzykowska, Jolanta, additional, Kurnatowska, Ilona, additional, Landa, Katarzyna, additional, Madrzejewski, Adam, additional, Madziarska, Katarzyna, additional, Mazur, Stanislaw, additional, Napora, Piotr, additional, Nowicki, Michal, additional, Ocicka-Kozakiewicz, Anna, additional, Rewerska, Barbara, additional, Rusicka, Teresa, additional, Ruxer, Jan, additional, Skokowska, Ewa, additional, Stankiewicz, Andrzej, additional, Stompor, Tomasz, additional, Tiuryn-Petrulewicz, Agnieszka, additional, Wasilewska, Katarzyna, additional, Wierusz-Wysocka, Bogna, additional, Wnetrzak-Michalska, Renata, additional, Almeida, Edgar, additional, Ballesteros, Rosa, additional, Barreto, Carlos, additional, Beirao, Idalina, additional, Birne, Rita, additional, Esteves, Cesar, additional, Guia, Jose, additional, Heitor, Susana, additional, Marques, Olinda, additional, Melo, Pedro, additional, Nolasco, Fernando, additional, Pereira, Amalia, additional, Roque, Cristina, additional, Rosario, Francisco, additional, Silva, Gil, additional, Silva, Ana, additional, Vila Lobos, Ana, additional, Cortes-Maisonet, Gregorio, additional, Roman-Miranda, Amaury, additional, Albota, Adrian, additional, Bala, Cornelia, additional, Barbonta, Hortensia, additional, Caceaune, Elena, additional, Catrinoui, Doina, additional, Constantin, Ciprian, additional, Dumitrescu, Adriana, additional, Mindrescu, Nicoleta, additional, Mistode, Cristina, additional, Negrisanu, Gabriela, additional, Onaca, Adriana, additional, Paveliu, Silvia, additional, Pintilei, Ella, additional, Pop, Lavinia, additional, Popa, Amorin, additional, Popescu, Alexandrina, additional, Radulian, Gabriela, additional, Szilagyi, Iosif, additional, Turcu, Liana, additional, Vacaru, Georgeta, additional, Vlad, Adrian, additional, Antsiferov, Mikhail, additional, Arkhipov, Mikhail, additional, Babkin, Andrey, additional, Barbarash, Olga, additional, Baranov, Vitaliy, additional, Chernyavskaya, Elena, additional, Demko, Arkadiy, additional, Edin, Anton, additional, Ermakova, Polina, additional, Fadeev, Valentin, additional, Galyavich, Albert, additional, Gaysina, Leyla, additional, Gordeev, Ivan, additional, Ipatko, Irina, additional, Kalashnikova, Marina, additional, Khalimov, Yuriy, additional, Klimontov, Vadim, additional, Kobalava, Zhanna, additional, Kosmacheva, Elena, additional, Koziolova, Natalya, additional, Kvitkova Sergey Levashov, Lyudmila, additional, Libis, Roman, additional, Marasaev, Vyacheslav, additional, Malykh, Natalia, additional, Martynenko, Vladimir, additional, Malyutina, Sofya, additional, Merai, Imad, additional, Mkrtumyan, Ashot, additional, Nechaeva, Galina, additional, Petunina, Nina, additional, Palyutin, Shamil, additional, Pimenov, Leonid, additional, Rechkova, Elena, additional, Rodionova, Tatyana, additional, Rymar, Oksana, additional, Sardinov, Ruslan, additional, Semenova, Olga, additional, Sherenkov, Alexander, additional, Solovev, Oleg, additional, Smolyarchuk, Elena, additional, Strongin, Leonid, additional, Ukhanova, Olga, additional, Verlan, Nadezhda, additional, Vorokhobina, Natalya, additional, Yakhontov, Davyd, additional, Yakushin, Sergey, additional, Zakharova, Elena, additional, Zalevskaya, Alsu, additional, Zanozina, Olga, additional, Zhdanova, Elena, additional, Zhukova, Larisa, additional, Zykova, Tatyana, additional, Fang Sum, Chee, additional, Muhummad Suhail, Sufi, additional, San Tan, Ru, additional, Wong, Edmund, additional, Babikova, Jana, additional, Buganova, Ingrid, additional, Dzupina, Andrej, additional, Ochodnicka, Zuzana, additional, Sosovec, Dalibor, additional, Spodniakova, Denisa, additional, Ahmed, Fayzal, additional, Bhana, Sindeep, additional, Distiller, Larry, additional, Jansen van Rensburg, Dirkie, additional, Joshi, Mukesh, additional, Joshi, Shaifali, additional, Lakha, Deepak, additional, Mitha, Essack, additional, Podgorski, Gracjan, additional, Ranjith, Naresh, additional, Rayner, Brian, additional, Rheeder, Paul, additional, Sarvan, Mohamed, additional, Seeber, Mary, additional, Siebert, Heidi, additional, Tayob, Mohammed, additional, Trokis, Julien, additional, Urbach, Dorothea, additional, van Zyl, Louis, additional, Choi, Bum-Soon, additional, Gi Choi, Moon, additional, Chung, ChoonHee, additional, Hwang, YouCheol, additional, Kim, ChongHwa, additional, Kim, InJoo, additional, Kim, JaeHyeon, additional, Kim, SinGon, additional, Kim, SungGyun, additional, Hee Kim, Tae, additional, Lee, WooJe, additional, Lee, ByungWan, additional, Wook Lee, Kang, additional, Oh, Kook-Hwan, additional, Eun Oh, Ji, additional, Kyu Oh, Yun, additional, Oh, Dong-Jin, additional, Park, Junbeom, additional, Joon Shin, Seok, additional, Sung, Su-Ah, additional, Myung Yu, Jae, additional, Agraz, Irene, additional, Javier Ampudia, Francisco, additional, Bouarich, Hanane, additional, Calero, Francesca, additional, Castro, Cristina, additional, Cigarrán Guldris, Secundino, additional, Cruzado Garrit, Josep, additional, de Álvaro, Fernando, additional, Galcerán, Josep, additional, González Albarrán, Olga, additional, Hernández Jaras, Julio, additional, Ibernón, Meritxell, additional, Martínez Deben, Francisco, additional, Dolores Martínez Esteban, Ma, additional, María Pascual Izuel, José, additional, Martins, Judith, additional, Mediavilla, Juan, additional, Michán, Alfredo, additional, Poch, Esteban, additional, Polaina Rusillo, Manuel, additional, Sánchez Juan, Carlos, additional, Santamaría Olmo, Rafael, additional, Julián, José, additional, de la Morena, Segura, additional, Soto, Alfonso, additional, Troya, Maribel, additional, Bruchfeld, Annette, additional, Curiac, Dan, additional, Eliasson, Ken, additional, Frank, Malin, additional, Guron, Gregor, additional, Hellberg, Olof, additional, Hellgren, Margareta, additional, Larnefeldt, Hans, additional, Lindholm, Carl-Johan, additional, Löndahl, Magnus, additional, Rein-Hedin, Erik, additional, Soveri, Inga, additional, Spaak, Jonas, additional, Ackermann, Daniel, additional, Bilz, Stefan, additional, Forster, Christian, additional, Kalbermatter, Stefan, additional, Kistler, Andreas, additional, Pechére-Bertschi, Antoinette, additional, Schultes, Bernd, additional, Chang, Chiz-Tzung, additional, Hung, Cheng-Chieh, additional, Jiang, Ju-Ying, additional, Lin, Shuei-Liong, additional, Tarng, Der-Cherng, additional, Tu, Shih-Te, additional, Wu, Mai-Szu, additional, Wu, Ming-Ju, additional, Deerochanawong, Chaicharn, additional, Kitiyakara, Chagriya, additional, Ophascharoensuk, Vuddhidej, additional, Pongchaiyakul, Chatlert, additional, Satirapoj, Bancha, additional, Eren, Necmi, additional, Gul, Ibrahim, additional, Gulel, Okan, additional, Kocyigit, Ismail, additional, Kumbasar, Abdulbaki, additional, Sahin, Idris, additional, Sayin, Burak, additional, Tavli, Talat, additional, Ustundag, Sedat, additional, Yenicerioglu, Yavuz, additional, Bondarets, Iryna, additional, Botsyurko, Volodymyr, additional, Chernikova, Viktoriia, additional, Donets, Oleksandra, additional, Fushtey, Ivan, additional, Grachova, Mariia, additional, Isayeva, Anna, additional, Kogut, Dmytro, additional, Komisarenko, Julia, additional, Kravchun, Nonna, additional, Malyar, Kateryna, additional, Martynyuk, Liliya, additional, Maslyanko, Vitaliy, additional, Myshanych, Halyna, additional, Pererva, Larysa, additional, Pertseva, Nataliia, additional, Serhiyenko, Oleksandr, additional, Smirnov, Ivan, additional, Sokolova, Liubov, additional, Stryzhak, Vasyl, additional, Vlasenko, Maryna, additional, AbouSaleh, Ahmad, additional, Barratt, Jonathan, additional, Dang, Cuong, additional, Kahal, Hassan, additional, Kirk, Adam, additional, Kilvert, Anne, additional, Phi Kon, Sui, additional, Patel, Dipesh, additional, Rice, Sam, additional, Vijayaraman, Arutchelvam, additional, Wong, Yuk-ki, additional, Gibson, Martin, additional, Wahba, Mona, additional, Zaidi, Reza, additional, Acosta, Idalia, additional, Adams, Atoya, additional, Ajani, Dilawar, additional, Ali, Slamat, additional, Alicic, Radica, additional, Al-Karadsheh, Amer, additional, Alla, Sreedhara, additional, Allison, D., additional, Andrawis, Nabil, additional, Arif, Ahmed, additional, Awad, Ahmed, additional, Azizad, Masoud, additional, Bahrami, Michael, additional, Bansal, Shweta, additional, Barag, Steven, additional, Barakzoy, Ahmad, additional, Barney, Mark, additional, Barzilay, Joshua, additional, Bashir, Khalid, additional, Bautista, Jose, additional, Beddhu, Srinivasan, additional, Belo, Diogo, additional, Benjamin, Sabrina, additional, Berenji, Ramin, additional, Bhargava, Anuj, additional, Birriel, Jose, additional, Brietzke, Stephen, additional, Brosius, Frank, additional, Brusco, Osvaldo, additional, Burgner, Anna, additional, Busch, Robert, additional, Canadas, Rafael, additional, Caramori, Maria, additional, Cardona, Jose, additional, Case, Christopher, additional, Cruz, Humberto, additional, Dandillaya, Ramprasad, additional, Dawoud, Dalia, additional, Din, Zia, additional, Dixon, Bradley, additional, Doshi, Ankur, additional, Drakakis, James, additional, El Shahawy, Mahfouz, additional, El-Meanawy, Ashraf, additional, El-Shahawy, Mohammed, additional, Evans, John, additional, Fadda, George, additional, Farooq, Umar, additional, Fernando, Roland, additional, Fink, Raymond, additional, First, Brian, additional, Fitz-Patrick, David, additional, Flack, John, additional, Fluck, Patrick, additional, Fogelfeld, Leon, additional, Fonseca, Vivian, additional, Frias, Juan, additional, Galphin, Claude, additional, Garcia-Mayol, Luis, additional, Goldstein, Gary, additional, Gonzalez, Edgar, additional, Gonzalez-Abreu, Francisco, additional, Gore, Ashwini, additional, Grant, David, additional, Habwe, Violet, additional, Hamilton, Maxine, additional, Hammoud, Jamal, additional, Handelsman, Stuart, additional, Hartman, Israel, additional, Heigerick, Glenn, additional, Henry, Andrew, additional, Hernandez, German, additional, Hernandez-Cassis, Carlos, additional, Herrera, Carlos, additional, Hertel, Joachim, additional, Huang, Wenyu, additional, Iglesias, Rogelio, additional, Iranmanesh, Ali, additional, Jackson, Timothy, additional, Jain, Mahendra, additional, Jamerson, Kenneth, additional, Johnson, Karen, additional, Judd, Eric, additional, Kaplan, Joshua, additional, Kayali, Zeid, additional, Khan, Bobby, additional, Khan, Muhammad, additional, Kharait, Sourabh, additional, Sue Kirkman, M., additional, Kopyt, Nelson, additional, Kotzker, Wayne, additional, Kovesdy, Csaba, additional, Kreit, Camil, additional, Krishna, Arvind, additional, Kronfli, Saeed, additional, Lee, Keung, additional, LeJeune, Derek, additional, Lemus, Brenda, additional, Leon-Forero, Carlos, additional, Linfert, Douglas, additional, Lora, Henry, additional, Lurie, Alexander, additional, Maddukuri, Geetha, additional, Magno, Alexander, additional, Maletz, Louis, additional, Mandayam, Sreedhar, additional, Markell, Mariana, additional, Mayfield, Ronald, additional, Mbogua, Caroline, additional, McMullen, Dierdre, additional, Meisner, Carl, additional, Minton, Stephen, additional, Mocherla, Bharat, additional, Mohandas, Rajesh, additional, Montero, Manuel, additional, Moustafa, Moustafa, additional, Nadkarni, Salil, additional, Nakhle, Samer, additional, Navarro, Jesus, additional, Neyra, Nilda, additional, Nica, Romanita, additional, Nicol, Philip, additional, Norwood, Paul, additional, Numrungroad, Visal, additional, O'Donovan, Richard, additional, Odugbesan, A., additional, Paoli-Bruno, Jorge, additional, Parikh, Samir, additional, Patel, Rakesh, additional, Peixoto, Aldo, additional, Pergola, Pablo, additional, Perlman, Alan, additional, Pettis, Karlton, additional, Pisoni, Roberto, additional, Ponduchi, Mirela, additional, Posada, Jorge, additional, Prabhakar, Sharma, additional, Radhakrishnan, Jai, additional, Rahman, Mahboob, additional, Raina, Rupesh, additional, Rastogi, Anjay, additional, Reisin, Efrain, additional, Rendell, Marc, additional, Robertson, David, additional, Rocco, Michael, additional, Romeu, Hugo, additional, Rosas, Sylvia, additional, Rosenfeld, Jack, additional, Ross, Dennis, additional, Rothman, Jeffrey, additional, Rudolph, Lance, additional, Ruhullah, Yusuf, additional, Ruoff, Gary, additional, Ryu, Jeffrey, additional, Sahani, Mandeep, additional, Sam, Ramin, additional, Samuels, Garfield, additional, Sanchez, William, additional, Santos, Vladimir, additional, Satko, Scott, additional, Saxena, Sanjeev, additional, Scott, David, additional, Seco, Gilberto, additional, Seek, Melvin, additional, Serota, Harvey, additional, Shafi, Tariq, additional, Shahid, Nauman, additional, Shanik, Michael, additional, Sharma, Santosh, additional, Sinha, Arjun, additional, Smelser, James, additional, Smith, Mark, additional, Soe, Kyaw, additional, Solomon, Richard, additional, Soroka, Eugene, additional, Soufer, Joseph, additional, Spinowitz, Bruce, additional, Spry, Leslie, additional, Suarez, Rosa, additional, Subramanian, Bala, additional, Szerlip, Harold, additional, Tamirisa, Aparna, additional, Thomson, Stephen, additional, Tran, Tuan-Huy, additional, Treger, Richard, additional, Trullenque, Gretel, additional, Turk, Thomas, additional, Umpierrez, Guillermo, additional, Urbach, Daniel, additional, Valdes, Martin, additional, Valika, Shujauddin, additional, Vega, Damaris, additional, Weissman, Peter, additional, Whaley-Connell, Adam, additional, Winston, Jonathan, additional, Wise, Jonathan, additional, Wynne, Alan, additional, Zeig, Steven, additional, Chu, Phuong, additional, Van Hoang, Lam, additional, Khanh, Tran, additional, Thi Phi Nga, Nguyen, additional, Nguyen Son, Pham, additional, and Phuong Tran, Lan, additional

Published
2022
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11. Diabetes causes bone marrow autonomic neuropathy and impairs stem cell mobilization via dysregulated p66Shc and Sirt1

Author

Albiero, Mattia, Poncina, Nicol, Tjwa, Marc, Ciciliot, Stefano, Menegazzo, Lisa, Ceolotto, Giulio, de Kreutzenberg, Saula Vigili, Moura, Rute, Giorgio, Marco, Pelicci, Piergiuseppe, Avogaro, Angelo, and Fadini, Gian Paolo

Subjects
Diabetes -- Research -- Analysis, Stem cells -- Research -- Analysis, Peripheral nerve diseases -- Research -- Analysis, Health
Abstract

Diabetes compromises the bone marrow (BM) microenvironment and reduces the number of circulating [CD34.sup.+] cells. Diabetic autonomic neuropathy (DAN) may impact the BM, because the sympathetic nervous system is prominently involved in BM stem cell trafficking. We hypothesize that neuropathy of the BM affects stem cell mobilization and vascular recovery after ischemia in patients with diabetes. We report that, in patients, cardiovascular DAN was associated with fewer circulating [CD34.sup.+] cells. Experimental diabetes (streptozotocin-induced and ob/ob mice) or chemical sympathectomy in mice resulted in BM autonomic neuropathy, impaired [Lin.sup.-][cKit.sup.+][Sca1.sup.+] (LKS) cell and endothelial progenitor cell (EPC; [CD34.sup.+][Flk1.sup.+]) mobilization, and vascular recovery after ischemia. DAN increased the expression of the 66-kDa protein from the src homology and collagen homology domain (p66Shc) and reduced the expression of sirtuin 1 (Sirt1) in mice and humans. p66Shc knockout (KO) in diabetic mice prevented DAN in the BM, and rescued defective LKS cell and EPC mobilization. Hematopoietic Sirt1 KO mimicked the diabetic mobilization defect, whereas hematopoietic Sirt1 overexpression in diabetes rescued defective mobilization and vascular repair. Through p66Shc and Sirt1, diabetes and sympathectomy elevated the expression of various adhesion molecules, including CD62L. CD62L KO partially rescued the defective stem/progenitor cell mobilization. In conclusion, autonomic neuropathy in the BM impairs stem cell mobilization in diabetes with dysregulation of the life-span regulators p66Shc and Sirt1. Diabetes 2014;63:1353-1365 | DOI: 10.2337/db13-0894, Diabetes reduces the availability of bone marrow (BM)-derived circulating angiocompetent [CD34.sup.+] cells, especially in the presence of chronic vascular complications (1,2). This is believed to represent a risk factor for [...]

Published
2014
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12. Day and night closed-loop control in adults with type 1 diabetes: a comparison of two closed-loop algorithms driving continuous subcutaneous insulin infusion versus patient self-management

Author

Luijf, Yoeri M., Devries, J. Hans, Zwinderman, Koos, Leelarathna, Lalantha, Nodale, Marianna, Caldwell, Karen, Kumareswaran, Kavita, Elleri, Daniela, Allen, Janet M., Wilinska, Malgorzata E., Evans, Mark L., Hovorka, Roman, Doll, Werner, Ellmerer, Martin, Mader, Julia K., Renard, Eric, Place, Jerome, Farret, Anne, Cobelli, Claudio, Del Favero, Simone, Man, Chiara Dalla, Avogaro, Angelo, Bruttomesso, Daniela, Filippi, Alessio, Scotton, Rachele, Magni, Lalo, Lanzola, Giordano, Palma, Federico Di, Soru, Paola, Toffanin, Chiara, De Nicolao, Giuseppe, Arnolds, Sabine, Benesch, Carsten, and Heinemann, Lutz

Subjects
DexCom Inc. -- Management, Diabetes therapy, Internet service providers, Type 1 diabetes -- Care and treatment, Insulin, Blood sugar, Adults, Glucose metabolism, Algorithms, Company business management, Algorithm, Internet service provider, Health, University of Cambridge -- Management, European Association for the Study of Diabetes -- Management
Abstract

OBJECTIVE--To compare two validated closed-loop (CL) algorithms versus patient self-control with CSII in terms of glycemic control. RESEARCH DESIGN AND METHODS--This study was a multicenter, randomized, three-way crossover, open-label trial [...]

Published
2013
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15. Pharmacologic PPAR-γ activation reprograms bone marrow macrophages and partially rescues HSPC mobilization in human and murine diabetes

Author

Gian Paolo Fadini, Mattia Albiero, Angelo Avogaro, Andrea Cignarella, Roberta Cappellari, Valentina Scattolini, Marianna D’Anna, Lisa Menegazzo, Stefano Ciciliot, Serena Tedesco, and Ada Admin

Abstract

Mobilization of hematopoietic stem/progenitor cells (HSPCs) from the bone marrow (BM) is impaired in diabetes. Excess oncostatin M (OSM) produced by M1 macrophages in the diabetic BM signals through p66Shc to induce Cxcl12 in stromal cells and retain HSPCs. BM adipocytes are another source of CXCL12 that blunts mobilization. We tested a strategy of pharmacologic macrophage reprogramming to rescue HSPC mobilization. In vitro, PPAR-γ activation with pioglitazone switched macrophages from M1 to M2, reduced Osm expression, and prevented transcellular induction of Cxcl12. In diabetic mice, pioglitazone treatment downregulated Osm, p66Shc and Cxcl12 in the hematopoietic BM, restored the effects of granulocyte-colony stimulation factor (G-CSF), and partially rescued HSPC mobilization, but it increased BM adipocytes. Osm deletion recapitulated the effects of pioglitazone on adipogenesis, which was p66Shc-independent, and double knockout of Osm and p66Shc completely rescued HSPC mobilization. In the absence of OSM, BM adipocytes produced less CXCL12, being arguably devoid of HSPC-retaining activity, whereas pioglitazone failed to downregulate Cxcl12 in BM adipocytes. In diabetic patients under pioglitazone therapy, HSPC mobilization after G-CSF was partially rescued. In summary, pioglitazone reprogrammed BM macrophages and suppressed OSM signaling, but sustained Cxcl12 expression by BM adipocytes could limit full recovery of HSPC mobilization.

Published
2020

16. Feasibility of outpatient fully integrated closed-loop control first studies of wearable artificial pancreas

Author

Kovatchev, Boris P., Renard, Eric, Cobelli, Claudio, Zisser, Howard C., Keith-Hynes, Patrick, Anderson, Stacey M., Brown, Sue A., Chernavvsky, Daniel R., Breton, Marc D., Farret, Anne, Pelletier, Marie-Josee, Place, Jerome, Bruttomesso, Daniela, Del Favero, Simone, Visentin, Roberto, Filippi, Alessio, Scotton, Rachele, Avogaro, Angelo, and Doyle, III, Francis J. Doyle

Subjects
Dextrose, Type 1 diabetes -- Research, Smart phones, Glucose, Glucose metabolism, Smart phone, Health, University of Virginia
Abstract

OBJECTIVE--To evaluate the feasibility of a wearable artificial pancreas system, the Diabetes Assistant (DiAs), which uses a smart phone as a closed-loop control platform. RESEARCH DESIGN AND METHODS--Twenty patients with [...]

Published
2013
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17. Diabetes impairs stem cell and proangiogenic cell mobilization in humans

Author

Fadini, Gian Paolo, Albiero, Mattia, De Kreutzenberg, Saula Vigili, Boscaro, Elisa, Cappellari, Bsc Roberta, Marescotti, Mariacristina, Poncina, Ncol, Agostini, Carlo, and Avogaro, Angelo

Subjects
Diabetes -- Complications and side effects -- Prognosis -- Research, Stem cells -- Physiological aspects -- Research, Cardiovascular diseases -- Risk factors -- Development and progression -- Research, Health
Abstract

OBJECTIVE--Diabetes mellitus (DM) increases cardiovascular risk, at least in part, through shortage of vascular regenerative cells derived from the bone marrow (BM). In experimental models, DM causes morphological and functional [...]

Published
2013
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18. Real-time improvement of continuous glucose monitoring accuracy: the smart sensor concept

Author

Facchinetti, Andrea, Sparacino, Giovanni, Guerra, Stefania, Luijf, Yoeri M., Devries, J. Hans, Mader, Julia K., Ellmerer, Martin, Benesch, Carsten, Heinemann, Lutz, Bruttomesso, Daniela, Avogaro, Angelo, and Cobelli, Claudio

Subjects
Glucose monitors -- Usage, Type 2 diabetes -- Diagnosis -- Care and treatment, Health
Abstract

OBJECTIVE--Reliability of continuous glucose monitoring (CGM) sensors is key in several applications. In this work we demonstrate that real-time algorithms can render CGM sensors smarter by reducing their uncertainty and [...]

Published
2013
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19. Fully integrated artificial pancreas in type 1 diabetes modular closed-loop glucose control maintains near normoglycemia

Author

Breton, Marc, Farret, Anne, Bruttomesso, Daniela, Anderson, Stacey, Magni, Lalo, Patek, Stephen, Man, Chiara Dalla, Place, Jerome, Demartini, Susan, Del Favero, Simone, Toffanin, Chiara, Hughes-Karvetski, Colleen, Dassau, Eyal, Zisser, Howard, Doyle, III, Francis J., De Nicolao, Giuseppe, Avogaro, Angelo, Cobelli, Claudio, Renard, Eric, and Kovatchev, Boris

Subjects
Artificial organs -- Research -- Methods -- Usage, Type 1 diabetes -- Research -- Control -- Care and treatment, Health
Abstract

Integrated closed-loop control (CLC), combining continuous glucose monitoring (CGM) with insulin pump (continuous subcutaneous insulin infusion [CSII]), known as artificial pancreas, can help optimize glycemic control in diabetes. We present a fundamental modular concept for CLC design, illustrated by clinical studies involving 11 adolescents and 27 adults at the Universities of Virginia, Padova, and Montpellier. We tested two modular CLC constructs: standard control to range (sCTR), designed to augment pump plus CGM by preventing extreme glucose excursions; and enhanced control to range (eCTR), designed to truly optimize control within near normoglycemia of 3.9-10 mmol/L. The CLC system was fully integrated using automated data transfer CGM → algorithm → CSII. All studies used randomized crossover design comparing CSII versus CLC during identical 22-h hospitalizations including meals, overnight rest, and 30-min exercise, sCTR increased significantly the time in near normoglycemia from 61 to 74%, simultaneously reducing hypoglycemia 2.7-fold. eCTR improved mean blood glucose from 7.73 to 6.68 mmol/L without increasing hypoglycemia, achieved 97% in near normoglycemia and 77% in tight glycemic control, and reduced variability overnight. In conclusion, sCTR mad eCTR represent sequential steps toward automated CLC, preventing extremes (sCTR) and further optimizing control (eCTR). This approach inspires compelling new concepts: modular assembly, sequential deployment, testing, mad clinical acceptance of custom-built CLC systems tailored to individual patient needs. Diabetes 61:2230-2237, 2012, The maintenance of close-to-normal blood glucose (BG) levels slows the onset and progression of long-term microvascular complications in patients with type 1 diabetes (1); therefore, the ultimate therapeutic goal of [...]

Published
2012
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22. Pharmacologic PPAR-γ Activation Reprograms Bone Marrow Macrophages and Partially Rescues HSPC Mobilization in Human and Murine Diabetes

Author

Tedesco, Serena, primary, Ciciliot, Stefano, additional, Menegazzo, Lisa, additional, D’Anna, Marianna, additional, Scattolini, Valentina, additional, Cappellari, Roberta, additional, Cignarella, Andrea, additional, Avogaro, Angelo, additional, Albiero, Mattia, additional, and Fadini, Gian Paolo, additional

Published
2020
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24. Endothelial dysfunction in diabetes: the role of reparatory mechanisms

Author

Avogaro, Angelo, Albiero, Mattia, Menegazzo, Lisa, de Kreutzenberg, Saula, and Fadini, Gian Paolo

Subjects
Dextrose -- Physiological aspects, Carbohydrate metabolism -- Physiological aspects, Endothelium -- Physiological aspects, Prediabetic state -- Development and progression -- Physiological aspects, Glucose -- Physiological aspects, Cardiovascular diseases -- Development and progression -- Physiological aspects, Type 2 diabetes -- Development and progression -- Physiological aspects, Hyperglycemia -- Development and progression -- Physiological aspects, Health
Abstract

Type 2 diabetes is characterized by a two- to fourfold increased risk of cardiovascular disease. This is generally attributed to the adverse effects of hyperglycemia and oxidative stress on vascular [...]

Published
2011
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25. The redox enzyme p66Shc contributes to diabetes and ischemia-induced delay in cutaneous wound healing

Author

Fadini, Gian Paolo, Albiero, Mattia, Menegazzo, Lisa, Boscaro, Elisa, Pagnin, Elisa, Iori, Elisabetta, Cosma, Chiara, Lapolla, Annunziata, Pengo, Vittorio, Stendardo, Massimo, Agostini, Carlo, Pelicci, Pier Giuseppe, Giorgio, Marco, and Avogaro, Angelo

Subjects
Diabetes -- Care and treatment, Diabetic ulcers -- Care and treatment, Quality of life, Health
Abstract

OBJECTIVE--The redox enzyme p66Shc produces hydrogen peroxide and triggers proapoptotic signals. Genetic deletion of p66Shc prolongs life span and protects against oxidative stress. In the present study, we evaluated the role of p66Shc in an animal model of diabetic wound healing. RESEARCH DESIGN AND METHODS--Skin wounds were created in wild-type (WT) and [p66Shc.sup.-/-] control and streptozotocin-induced diabetic mice with or without hind limb ischemia. Wounds were assessed for collagen content, thickness and vascularity of granulation tissue, apoptosis, reepithelialization, and expression of c-myc and β-catenin. Response to hind limb ischemia was also evaluated. RESULTS--Diabetes delayed wound healing in WT mice with reduced granulation tissue thickness and vascularity, increased apoptosis, epithelial expression of c-myc, and nuclear localization of β-catenin. These nonhealing features were worsened by hind limb ischemia. Diabetes induced p66Shc expression and activation; wound healing was significantly faster in [p66Shc.sup.-/-] than in WT diabetic mice, with or without hind limb ischemia, at 1 and 3 months of diabetes duration and in both SV129 and C57BL/6 genetic backgrounds. Deletion of p66Shc reversed nonhealing features, with increased collagen content and granulation tissue thickness, and reduced apoptosis and expression of c-myc and β-catenin. p66Shc deletion improved response to hind limb ischemia in diabetic mice in terms of tissue damage, capillary density, and perfusion. Migration of [p66Shc.sup.-/-] dermal fibroblasts in vitro was significantly faster than WT fibroblasts under both high glucose and hypoxia. CONCLUSIONS---p66Shc is involved in the delayed woundhealing process in the setting of diabetes and ischemia. Thus, p66Shc may represent a potential therapeutic target against this disabling diabetes complication. Diabetes 59:2306-2314, 2010, Impaired cutaneous wound healing is a major source of morbidity and mortality in the diabetic population (1,2). It is estimated that foot ulcers affect about 15% of diabetic patients with [...]

Published
2010
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26. Nitric oxide synthesis is reduced in subjects with type 2 diabetes and nephropathy

Author

Tessari, Paolo, Cecchet, Diego, Cosma, Alessandra, Vettore, Monica, Coracina, Anna, Millioni, Renato, Iori, Elisabetta, Puricelli, Lucia, Avogaro, Angelo, and Vedovato, Monica

Subjects
Insulin resistance -- Research -- Physiological aspects -- Care and treatment, Nitric oxide -- Physiological aspects -- Health aspects -- Research, Type 2 diabetes -- Care and treatment -- Research, Diabetic nephropathies -- Physiological aspects -- Research -- Care and treatment, Health
Abstract

OBJECTIVE--Nitric oxide (NO) is a key metabolic and vascular regulator. Its production is stimulated by insulin. A reduced urinary excretion of NO products (NOx) is frequently found in type 2 diabetes, particularly in association with nephropathy. However, whether the decreased NOx excretion in type 2 diabetes is caused by a defective NOx production from arginine in response to hyperinsulinemia has never been studied. RESEARCH DESIGN AND METHODS--We measured NOx fractional (FSR) and absolute (ASR) synthesis rates in type 2 diabetic patients with diabetic nephropathy and in control subjects, after L-[[sup.15][N.sub.2]-guanidino]-arginine infusion, and use of precursor-product relationships. The study was conducted both before and after an euglycemic hyperinsulinemic (~1,000-1,200 pmol/l) clamp. RESULTS--In type 2 diabetes, NOx FSR was reduced both under basal (19.3 ± 3.9% per day, vs. 22.9 ± 4.5% per day in control subjects) and hyperinsulinemic states (24.0 ± 5.6% per day, vs. 37.9 ± 6.4% per day in control subjects; P < 0.03 by ANOVA). Similarly, in type 2 diabetes, NOx ASR was lower than in control subjects under both conditions (basal, 0.32 ± 0.06 vs. 0.89 ± 0.34 tool per day; hyperinsulinemia, 0.35 ± 0.07 vs. 1.15 ± 0.38 mol per day; P = 0.01 by ANOVA). In type 2 diabetes, the ability of insulin to stimulate both the FSR (4.7 ± 3.2% per day) and the ASR (0.03 ± 2 0.04 mol per day) of NOx was several-fold lower than that in control subjects (15.0 [+ or -] 2.9% per day and 0.25 ± 0.07 mol per day, P < 0.03 and P < 0.02, respectively). Also the fraction of arginine flux converted to NOx (basal, 0.22 ± 0.05% vs. 0.65 ± 0.25%; hyperinsulinemia, 0.32 ± 0.06% vs. 1.03 ± 0.33%) was sharply reduced in the patients (P < 0.01 by ANOVA). CONCLUSIONS--In type 2 diabetic patients with nephropathy, intravascular NOx synthesis from arginine is decreased under both basal and hyperinsulinemic states. This defect extends the concept of insulin resistance to NO metabolism. Diabetes 59: 2152-2159, 2010, Nitric oxide (NO) is a key regulatory molecule with extensive metabolic, vascular, and cellular effects (1-6). The regulation of NO metabolism is particularly important in type 2 diabetes, because activation [...]

Published
2010
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27. Time course and mechanisms of circulating progenitor cell reduction in the natural history of type 2 diabetes

Author

Fadini, Gian Paolo, Boscaro, Elisa, de Kreutzenberg, Saula, Agostini, Carlo, Seeger, Florian, Dimmeler, Stefanie, Zeiher, Andreas, Tiengo, Antonio, and Avogaro, Angelo

Subjects
Cholesterol -- Physiological aspects, Dextrose -- Physiological aspects, Cell research -- Physiological aspects, Carbohydrate metabolism -- Physiological aspects, Diabetes -- Research, Glucose -- Physiological aspects, Glucose metabolism -- Physiological aspects, Cardiovascular diseases -- Physiological aspects, Type 2 diabetes -- Physiological aspects, Health
Abstract

OBJECTIVE--Reduction of bone marrow-derived circulating progenitor cells has been proposed as a novel mechanism of cardiovascular disease in type 2 diabetes. The present study was designed to describe the extent [...]

Published
2010
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28. Downregulation of the longevity-associated protein Sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms

Author

de Kreutzenberg, Saula Vigili, Ceolotto, Giulio, Papparella, Italia, Bortoluzzi, Alessia, Semplicini, Andrea, Man, Chiara Dalla, Cobelli, Claudio, Fadini, Gian Paolo, and Avogaro, Angelo

Subjects
Metabolic syndrome X -- Complications and side effects -- Research, Monocytes -- Physiological aspects -- Genetic aspects -- Research, Cellular proteins -- Health aspects -- Genetic aspects -- Research, Atherosclerosis -- Risk factors -- Research, Health
Abstract

OBJECTIVE--Sirtuins (SIRTs) are [NAD.sup.+]-dependent deacetylases that regulate metabolism and life span. We used peripheral blood mononuclear cells (PBMCs) to determine ex vivo whether insulin resistance/metabolic syndrome influences SIRTs. We also assessed the potential mechanisms linking metabolic alterations to SIRTs in human monocytes (THP-1) in vitro. RESEARCH DESIGN AND METHODS--SIRT1-SIRT7 gene and protein expression was determined in PBMCs of 54 subjects (41 with normal glucose tolerance and 13 with metabolic syndrome). Insulin sensitivity was assessed by the minimal model analysis. Subclinical atherosclerosis was assessed by carotid intima-media thickness (IMT). In THP-1 cells exposed to high glucose or fatty acids in vitro, we explored SIRT1 expression, p53 acetylation, Jun N[H.sub.2]-terminal kinase (JNK) activation, [NAD.sup.+] levels, and nicotinamide phosphoribosyltransferase (NAMPT) expression. The effects of SIRT1 induction by resveratrol and of SIRT1 gene silencing were also assessed. RESULTS--In vivo, insulin resistance and metabolic syndrome were associated with low PBMC SIRT1 gene and protein expression. SIRT1 gene expression was negatively correlated with carotid IMT. In THP-1 cells, high glucose and palmitate reduced SIRT1 and NAMPT expression and reduced the levels of intracellular [NAD.sup.+] through oxidative stress. No effect was observed in cells exposed to linoleate or insulin. High glucose and palmitate increased p53 acetylation and JNK phosphorylation; these effects were abolished in siRNA SIRTl-treated cells. Glucose-and palmitate-mediated effects on NAMPT and SIRT1 were prevented by resveratrol in vitro. CONCLUSIONS--Insulin resistance and subclinical atherosclerosis are associated with SIRT1 downregulation in monocytes. Glucotoxicity and lypotoxicity play a relevant role in quenching SIRT1 expression., Metabolic syndrome is increasingly prevalent in the general population. Excess caloric intake and nutrient availability are the obvious culprits that lead to obesity and insulin resistance. In turn, metabolic syndrome [...]

Published
2010
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29. Recurrence of cardiovascular events in patients with type 2 diabetes: epidemiology and risk factors

Author

Giorda, Carlo B., Avogaro, Angelo, Maggini, Marina, Lombardo, Flavia, Mannucci, Edoardo, Turco, Salvatore, Alegiani, Stefania Spila, Raschetti, Roberto, Velussi, Mario, and Ferrannini, Ele

Subjects
Cholesterol, Diabetes -- Research, Antilipemic agents -- Complications and side effects, Cardiovascular diseases -- Risk factors -- Complications and side effects, Epidemiology, Cardiac patients, Type 2 diabetes -- Risk factors -- Complications and side effects, Health, Complications and side effects, Risk factors
Abstract

OBJECTIVE--The purpose of this study was to assess incidence of and risk factors for recurrent cardiovascular disease (CVD) in type 2 diabetes. RESEARCH DESIGN AND METHODS--We estimated the incidence of [...]

Published
2008

30. A functional variant of the adipocyte glycerol channel aquaporin 7 gene is associated with obesity and related metabolic abnormalities

Author

Prudente, Sabrina, Flex, Elisabetta, Morini, Eleonora, Turchi, Federica, Capponi, Daria, De Cosmo, Salvatore, Tassi, Vittorio, Guida, Valentina, Avogaro, Angelo, Folli, Franco, Maiani, Francesca, Frittitta, Lucia, Dallapiccola, Bruno, and Trischitta, . Vincenzo

Subjects
Obesity -- Risk factors -- Genetic aspects -- Research, Adipose tissues -- Genetic aspects -- Research, Health, Research, Genetic aspects, Risk factors
Abstract

Aquaporin 7 (AQP7), the gateway protein controlling glycerol release, has recently emerged as a modulator of adipocyte metabolism. AQP7 knockout mice develop obesity and hyperglycemia. The contribution of AQP7 to these abnormalities in humans is unknown. We examined whether common single nucleotide polymorphisms (SNPs) in the AQP7 gene modulate the risk of obesity and related abnormalities. Among several SNPs we identified, A-953G in the AQP7 promoter was associated with type 2 diabetes in 977 (530 female/447 male) Caucasians: odds ratio for XG (i.e., AG+GG) versus AA individuals was 1.36 (95% CI 1.01-1.84), P = 0.04. This finding was entirely due to the association among females (1.8 [1.2-2.6], P = 0.004), which was no longer significant when adjusted for BMI. In fact, BMI was higher in XG than in AA females (30.8 ± 6.6 vs. 28.9 ± 5.2, P = 0.002). This association was confirmed in independent case-control study (n = 299 female subjects) for morbid obesity (1.66 [1.01-2.74], P = 0.04). Luciferase and mobility shift assays showed that, compared with -953A, the -953G promoter had reduced transcriptional activity (P = 0.001) and impaired ability to bind CCAAT/ enhancer binding protein (C/EBP)β transcription factor (P = 0.01). Finally, AQP7 expression in adipose tissue decreased from AA to AG to GG individuals (P = 0.036). These data strongly suggest that AQP7 downregulation is pathogenic for obesity and/or type 2 diabetes., Obesity and related abnormalities, including type 2 diabetes and dyslipidemia, are becoming epidemic, thus representing major health care problems (1). Although these abnormalities have a clear genetic component, the involved [...]

Published
2007

31. Significance of endothelial progenitor cells in subjects with diabetes

Author

Fadini, Gian Paolo, Sartore, Saverio, Agostini, Carlo, and Avogaro, Angelo

Subjects
Glycocalyx -- Research -- Health aspects, Diabetes -- Research -- Health aspects -- Causes of, Health, Research, Health aspects, Causes of
Abstract

Diabetes complications represent a huge burden for patients and health services. The fight against each single complication has led to significant improvements in diabetes care, especially for microvascular complications, yet [...]

Published
2007

32. Incidence of coronary heart disease in type 2 diabetic men and women: impact of microvascular complications, treatment, and geographic location

Author

Avogaro, Angelo, Giorda, Carlo, Maggini, Marina, Mannucci, Edoardo, Raschetti, Roberto, Lombardo, Flavia, Spila-Alegiani, Stefania, Turco, Salvatore, Velussi, Mario, and Ferrannini, Ele

Subjects
Coronary heart disease -- Risk factors -- Care and treatment -- Research -- Complications and side effects, Type 2 diabetes -- Research -- Risk factors -- Complications and side effects -- Care and treatment, Health, Care and treatment, Complications and side effects, Research, Risk factors
Abstract

OBJECTIVE--Cardiovascular disease (CVD) is the main cause of morbidity/mortality in diabetes. We set forth to determine incidence and identify predictors (including microvascular complications and treatment) of first coronary heart disease [...]

Published
2007

33. Effects of different insulin regimes on postprandial myocardial perfusion defects in type 2 diabetic patients

Author

Scognamiglio, Roldano, Negut, Christian, de Kreutzenberg, Saula Vigili, Tiengo, Antonio, and Avogaro, Angelo

Subjects
Regular Insulin (Medication) -- Dosage and administration, Cardiovascular diseases -- Drug therapy, Type 2 diabetes -- Drug therapy, Health, Drug therapy, Dosage and administration
Abstract

OBJECTIVE--Postprandial glycemia is an independent risk factor for cardiovascular disease that is more powerful than fasting glycemia and determines myocardial perfusion defects in type 2 diabetes. We examined the efficacy [...]

Published
2006

34. Metformin prevents glucose-induced protein kinase c-β2 activation in human umbilical vein endothelial cells through an antioxidant mechanism

Author

Gallo, Alessandra, Ceolotto, Giulio, Pinton, Paolo, Iori, Elisabetta, Murphy, Ellen, Rutter, Guy A., Rizzuto, Rosario, Semplicini, Andrea, and Avogaro, Angelo

Subjects
Diabetes -- Drug therapy -- Research, Metformin -- Dosage and administration -- Evaluation -- Research, Protein kinases -- Evaluation -- Research, Health, Drug therapy, Evaluation, Research, Dosage and administration
Abstract

Hyperglycemia determines the vascular complications of diabetes through different mechanisms: one of these is excessive activation of the isoform β2 of protein kinase C (PKC-β2). Metformin, a widely used antidiabetic agent, is associated with decreased cardiovascular mortality in obese type 2 diabetic patients. Therefore, we assessed the role of metformin in glucose-induced activation of PKC-β2 and determined the mechanism of its effect in human umbilical venous endothelial cells grown to either normo- (5 mmol/l) or hyperglycemia (10 mmol/l) and moderately and acutely exposed to 25 mmol/l glucose. We studied PKC-β2 activation by developing adenovirally expressed chimeras encoding fusion protein between green fluorescent protein (GFP) and conventional 132 isoform (PKC-β2-GFP). Glucose (25 mmol/l) induced the translocation of PKC-β2-GFP from the cytosol to the membrane in cells grown to hyperglycemia but not in those grown in normal glucose medium. Metformin (20 µmol/l)prevented hyperglycemia-induced PKC-β2-GFP translocation. We also assessed oxidative stress under the same conditions with a 4-((9-acridine-carbonyl)amino)-2,2,6,6- tetramethylpiperidin-oxyl, free radical (TEMPO-9-AC) fluorescent probe. We observed significantly increased radical oxygen species production in cells grown in hyperglycemia medium, and this effect was abolished by metformin. We show that in endothelial cells, metformin inhibits hyperglycemia-induced PKC-β2 translocation because of a direct antioxidant effect. Our data substantiate the findings of previous large intervention studies on the beneficial effect of this drug in type 2 diabetic patients., Substantial clinical and experimental evidence suggests that diabetes causes endothelial dysfunction (1): this condition includes decreased endothelium-dependent vasorelaxation, increased leukocyte-endothelial cell adhesion, and increased vascular permeability (2-4). One of the [...]

Published
2005

35. Acute alcohol consumption improves insulin action without affecting insulin secretion in type 2 diabetic subjects

Author

Avogaro, Angelo, Watanabe, Richard M., Dall'Arche, Alessandra, De Kreutzenberg, Saula Vigili, Tiengo, Antonio, and Pacini, Giovanni

Subjects
Diabetes -- Causes of -- Research -- Risk factors, Insulin -- Health aspects -- Research, Alcohols -- Risk factors -- Research -- Health aspects, Type 2 diabetes -- Research -- Risk factors, Health, Research, Risk factors, Health aspects, Causes of
Abstract

OBJECTIVE--Long-term exposure to alcohol is associated with an improvement in insulin sensitivity. At this time, however, there is no definitive proof that alcohol per se has an effect on the [...]

Published
2004

36. Insulin generates free radicals by an NAD(P)H, phosphatidylinositol 3'-kinase--dependent mechanism in human skin fibroblasts ex vivo

Author

Ceolotto, Giulio, Bevilacqua, Michela, Papparella, Italia, Baritono, Elisabetta, Franco, Lorenzo, Corvaja, Carlo, Mazzoni, Martina, Semplicini, Andrea, and Avogaro, Angelo

Subjects
Free radicals (Chemistry) -- Research -- Health aspects, Diabetes -- Research -- Risk factors, Insulin -- Health aspects -- Research, Blood circulation disorders -- Risk factors -- Research, Phosphatidylinositol -- Health aspects -- Research, Health, Research, Risk factors, Health aspects
Abstract

Oxidative stress may be involved in the development of vascular complications associated with diabetes; however, the molecular mechanism responsible for increased production of free radicals in diabetes remains uncertain. Therefore, we examined whether acute hyperinsulinemia increases the production of free radicals and whether this condition affects proliferative extracellular signal-regulated kinase (ERK-1 and -2) signaling in human fibroblasts in vitro. Insulin treatment significantly increased intracellular superoxide anion ([O.sub.2.sup.-]) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Furthermore, insulin-induced [O.sub.2.sup.-] production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Inhibition of the phosphatidylinositol 3'-kinase (PI 3'-kinase) pathway with LY294002 blocked insulin-stimulated [O.sub.2.sup.-] production, suggesting a direct involvement of PI 3'-kinase in the activation of NAD(P)H oxidase. The insulin-induced free radical production led to membranous translocation of p47phox and markedly enhanced ERK-1 and -2 activation in human fibroblasts. In conclusion, these findings provided direct evidence that elevated insulin levels generate [O.sub.2.sup.-] by an NAD(P)H-dependent mechanism that involves the activation of PI 3'-kinase and stimulates ERK-1--and ERK-2--dependent pathways. This effect of insulin may contribute to the pathogenesis and progression of cardiovascular disease in the insulin resistance syndrome., Macrovascular disease is the major cause of morbidity and mortality in patients with type 1 and type 2 diabetes (1,2). Despite several clinical and epidemiological studies, the molecular pathways for [...]

Published
2004

37. L-arginine-nitric oxide kinetics in normal and type 2 diabetic subjects: a stable-labelled [sup.15]N arginine approach. (Pathophysiology)

Author

Avogaro, Angelo, Toffolo, Gianna, Kiwanuka, Edward, de Kreutzenberg, Saula Vigili, Tessari, Paolo, and Cobelli, Claudio

Subjects
Arginine -- Physiological aspects, Nitric oxide -- Physiological aspects, Type 2 diabetes -- Complications and side effects -- Development and progression, Atherosclerosis -- Development and progression -- Complications and side effects, Health, Physiological aspects, Complications and side effects, Development and progression
Abstract

Defective endothelium is a key event in the development of atherosclerosis in diabetes: alteration of the L-arginine-nitric oxide (NO) pathway has been suggested. We propose a modeling approach of the L-arginine-NO pathway in vivo in both control and type 2 diabetic subjects based on the intravenous bolus injection of L-[[sup.15]N]arginine and subsequent noncompartmental and compartmental model analysis of L-[[sup.15]N] arginine in plasma and [[sup.15]N]nitrate in the urine. No differences in arginine kinetics were observed between normal subjects and diabetic patients. [[sup.15]N]nitrates were detectable up to 48 h from the L-[sup.15]ℕarginine administration; no differences were found in the tracer-to-tracee ratio in each urine collection. However, the NO synthesis in plasma from arginine was lower (P = 0.05 for the noncompartmental and 0.1208 for the compartmental analysis, by Mann-Whitney test) in diabetic patients than in control subjects when expressed both in absolute terms (50% decrease) and as percentage of NO turnover (30% decrease). This new modeling approach of L-arginine-NO pathway provides a detailed picture of arginine kinetics and nitrate metabolism. From our data, it appears that noncomplicated type 2 diabetic patients have a decreased conversion of arginine to NO., Endothelial dysfunction is a possible culprit of the accelerated atherosclerosis in diabetic patients. Several different mechanisms negatively act on endothelial function (1). The assessment of endothelial function in humans can [...]

Published
2003

38. Effects of treatment with sulfonylurea drugs or insulin on ischemia-induced myocardial dysfunction in type 2 diabetes

Author

Scognamiglio, Roldano, Avogaro, Angelo, de Kreutzenberg, Saula Vigili, Negut, Christian, Palisi, Monica, Bagolin, Eros, and Tiengo, Antonio

Subjects
Heart diseases -- Physiological aspects, Hypoglycemic sulfonylureas -- Evaluation -- Physiological aspects, Insulin -- Evaluation, Sulfonylurea compounds -- Evaluation -- Physiological aspects, Type 2 diabetes -- Physiological aspects, Health, Evaluation, Physiological aspects
Abstract

In patients with diabetes and coronary artery disease, the potential negative role of sulfonylurea drugs is under intensive investigation. We assessed the effects of treatment with glibenclamide or insulin on [...]

Published
2002

39. Diabetes-Associated Myelopoiesis Drives Stem Cell Mobilopathy Through an OSM-p66Shc Signaling Pathway

Author

Albiero, Mattia, primary, Ciciliot, Stefano, additional, Tedesco, Serena, additional, Menegazzo, Lisa, additional, D’Anna, Marianna, additional, Scattolini, Valentina, additional, Cappellari, Roberta, additional, Zuccolotto, Gaia, additional, Rosato, Antonio, additional, Cignarella, Andrea, additional, Giorgio, Marco, additional, Avogaro, Angelo, additional, and Fadini, Gian Paolo, additional

Published
2019
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41. Epinephrine exerts opposite effects on peripheral glucose disposal and glucose-stimulated insulin secretion: a stable label intravenous glucose tolerance test minimal model study

Author

Avogaro, Angelo, Toffolo, Gianna, Valerio, Anna, and Cobelli, Claudio

Subjects
Insulin -- Measurement -- Physiological aspects, Glucose metabolism -- Physiological aspects -- Measurement, Epinephrine -- Physiological aspects -- Measurement, Health, Physiological aspects, Measurement
Abstract

Epinephrine (EPI) plays a pivotal role in regulating glucose metabolism both in splanchnic and peripheral tissues. Nevertheless, previous studies did not clarify the mechanisms by which EPI affect both glucose [...]

Published
1996

42. The hemodynamic abnormalities in short-term insulin deficiency: the role of prostaglandin inhibition

Author

Avogaro, Angelo, Crepaldi, Cristina, Piarulli, Francesco, Milan, Daniele, Valerio, Anna, Pavan, Paola, Sacerdoti, David, Calabro, Alessio, Macdonald, Ian, Crepaldi, Gaetano, Scognamiglio, Roldano, and Tiengo, Antonio

Subjects
Ketoacidosis -- Physiological aspects, Diabetic acidosis -- Physiological aspects, Prostaglandins -- Physiological aspects, Hemodynamics -- Abnormalities -- Physiological aspects, Health, Physiological aspects, Abnormalities
Abstract

It has been suggested that the hemodynamic derangements present in diabetic ketoacidogis are the results not only of profound volume depletion but also of the effects of increased production of [...]

Published
1996

43. The Toll of Lockdown Against COVID-19 on Diabetes Outpatient Care: Analysis From an Outbreak Area in Northeast Italy.

Author

Bonora, Benedetta Maria, Morieri, Mario Luca, Avogaro, Angelo, and Fadini, Gian Paolo

Subjects
COVID-19, STAY-at-home orders, OUTPATIENT medical care, MEDICAL care, DIABETES
Abstract

The article offers information on spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from China, Italy became the second most affected country. Topics include the most residents with symptomatic coronavirus disease 2019 (COVID-19) were admitted to the Padua Hospital, and estimating equation to compare clinical characteristics of patients seen during lockdown with characteristics of those attending the clinic in the same period of 2018–2019.

Published
2021
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44. Postprandial glucose: marker or risk factor?

Author

Avogaro, Angelo

Subjects
Vascular endothelium -- Physiological aspects -- Research, Blood sugar -- Physiological aspects -- Research, Hyperglycemia -- Research, Health
Abstract

Postprandial glucose (PPG) has a noxious effect on the vascular endothelium, which is mainly mediated by oxidative stress. This condition leads to endothelial activation and dysfunction, two prerequisites for the [...]

Published
2011
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45. Alcohol intake impairs glucose counterregulation during acute insulin-induced hypoglycemia in IDDM patients: evidence for a critical role of free fatty acids

Author

Avogaro, Angelo, Beltramello, Piero, Gnudi, Luigi, Maran, Alberto, Valerio, Anna, Miola, Marina, Marin, Narciso, Crepaldi, Cristina, Confortin, Loris, Costa, Franco, MacDonald, Ian, and Tiengo, Antonio

Subjects
Drinking of alcoholic beverages -- Physiological aspects, Glucose metabolism -- Physiological aspects, Hypoglycemia -- Causes of -- Physiological aspects, Health, Physiological aspects, Causes of
Abstract

Evidence for a Critical Role of Free Fatty Acids In this study, we assessed the effects of alcohol intake on glucose counterregulation in response to acute insulin-induced hypoglycemia in IDDM [...]

Published
1993

46. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1α

Author

Fadini, Gian Paolo, Boscaro, Elisa, Albiero, Mattia, Menegazzo, Lisa, Frison, Vera, de Kreutzenberg, Saula, Agostini, Carlo, Tiengo, Antonio, and Avogaro, Angelo

Subjects
Endothelial growth factors -- Physiological aspects, Sitagliptin -- Dosage and administration -- Physiological aspects, Proteases -- Physiological aspects, Endothelium -- Properties -- Physiological aspects, Type 2 diabetes -- Physiological aspects
Abstract

OBJECTIVE--Vasculoprotective endothelial progenitor cells (EPCs) are regulated by stromal-derived factor-1α (SDF-1α and are reduced in type 2 diabetes. Because SDF-1α is a substrate of dipeptidyl-peptidase-4 (DPP-4), we investigated whether the [...]

Published
2010
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47. Ketone body metabolism in NIDDM: effect of sulfonylurea treatment

Author

Avogaro, Angelo, Valerio, Anna, Gnudi, Luigi, Maran, Alberto, Zolli, Mario, Duner, Elena, Riccio, Antonio, Del Prato, Stefano, Tiengo, Antonio, and Nosadini, Romano

Subjects
Hypoglycemic sulfonylureas -- Health aspects -- Physiological aspects, Ketones -- Physiological aspects -- Health aspects, Sulfonylurea compounds -- Health aspects -- Physiological aspects, Type 2 diabetes -- Care and treatment, Health, Care and treatment, Physiological aspects, Health aspects
Abstract

We assessed the metabolism of the two KBs, AcAc and 3-BOH; the relationships between ketogenesis and FFA inflow rate; and the effect of chronic sulfonylurea treatment in mild NIDDM patients [...]

Published
1992

48. The Effects of Dipeptidyl Peptidase-4 Inhibition on Microvascular Diabetes Complications

Author

Gian Paolo Fadini and Angelo Avogaro

Subjects
medicine.medical_specialty, Dipeptidyl Peptidase 4, Endocrinology, Diabetes and Metabolism, Kidney, Bioinformatics, Nephropathy, Glucagon-Like Peptide 1, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Albuminuria, Humans, Dipeptidyl peptidase-4, Advanced and Specialized Nursing, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Microangiopathy, medicine.disease, Endocrinology, Blood pressure, Metabolic control analysis, Endothelium, Vascular, medicine.symptom, business, Diabetic Angiopathies, Retinopathy
Abstract

We performed a review of the literature to determine whether the dipeptidyl peptidase-4 inhibitors (DPP4-I) may have the capability to directly and positively influence diabetic microvascular complications. The literature was scanned to identify experimental and clinical evidence that DPP4-I can ameliorate diabetic microangiopathy. We retrieved articles published between 1 January 1980 and 1 March 2014 in English-language peer-reviewed journals using the following terms: (“diabetes” OR “diabetic”) AND (“retinopathy” OR “retinal” OR “nephropathy” OR “renal” OR “albuminuria” OR “microalbuminuria” OR “neuropathy” OR “ulcer” OR “wound” OR “bone marrow”); (“dipeptidyl peptidase-4” OR “dipeptidyl peptidase-IV” OR “DPP-4” OR “DPP-IV”); and (“inhibition” OR “inhibitor”). Experimentally, DPP4-I appears to improve inflammation, endothelial function, blood pressure, lipid metabolism, and bone marrow function. Several experimental studies report direct potential beneficial effects of DPP4-I on all microvascular diabetes-related complications. These drugs have the ability to act either directly or indirectly via improved glucose control, GLP-1 bioavailability, and modifying nonincretin substrates. Although preliminary clinical data support that DPP4-I therapy can protect from microangiopathy, insufficient evidence is available to conclude that this class of drugs directly prevents or decreases microangiopathy in humans independently from improved glucose control. Experimental findings and preliminary clinical data suggest that DPP4-I, in addition to improving metabolic control, have the potential to interfere with the onset and progression of diabetic microangiopathy. Further evidence is needed to confirm these effects in patients with diabetes.

Published
2014

49. Maternal insulin therapy increases fetal endothelial progenitor cells during diabetic pregnancy

Author

Fadini, Gian Paolo, Baesso, Ilenia, Agostini, Carlo, Cuccato, Emily, Nardelli, Giovanni Battista, Lapolla, Annunziata, and Avogaro, Angelo

Subjects
Diabetes therapy -- Physiological aspects -- Health aspects, Diabetes in pregnancy -- Development and progression -- Diagnosis -- Complications and side effects, Bone marrow -- Physiological aspects -- Health aspects, Insulin -- Physiological aspects -- Complications and side effects, Pregnant women -- Health aspects -- Physiological aspects, Atherosclerosis -- Development and progression -- Diagnosis -- Complications and side effects, Health, Diagnosis, Physiological aspects, Complications and side effects, Development and progression, Health aspects
Abstract

Endothelial progenitor cells (EPCs) are bone marrow--derived cells involved in endothelial homeostasis and angiogenesis. Reduction and dysfunction of EPCs have been associated with the development of atherosclerosis and diabetic complications [...]

Published
2008

50. Endothelial progenitor cells and the diabetic paradox

Author

Fadini, Gian Paolo, Sartore, Saverio, Baesso, Ilenia, Lenzi, Maddalena, Agostini, Carlo, Tiengo, Antonio, and Avogaro, Angelo

Subjects
Endothelial growth factors -- Research -- Health aspects, Diabetic retinopathy -- Health aspects -- Research, Peripheral vascular diseases -- Health aspects -- Research, Diabetics -- Health aspects -- Research, Health, Research, Health aspects
Abstract

An unexplained paradox puzzles diabetologists: diabetic patients must face both poor vessel growth in ischemic heart and limbs and increased angiogenesis in retinal complications (1,2). Endothelial progenitor cells (EPCs) are [...]

Published
2006

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