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2. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
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Wiviott S. D., Raz I., Bonaca M. P., Mosenzon O., Kato E. T., Cahn A., Silverman M. G., Zelniker T. A., Kuder J. F., Murphy S. A., Bhatt D. L., Leiter L. A., McGuire D. K., Wilding J. P. H., Ruff C. T., Nilsson G. I., Fredriksson M., Johansson P. A., Langkilde A. M., Sabatine M. S., Bansilal S., Furtado R., Fish M. P., Gabovitch D., Jevne A., Ahern S., Im K., Goodrich E. L., Lowe C., Fisher N., Gannon J., Trindade S., Towarowski A., Fox Y., Johnsson E., Ranft S., Faber B., Wallander M., Weiss A., Buskila A., Abola M. T. B., Ardissino D., Averkov O., Aylward P., Bode C., Bonnici F., Bonora E., Budaj A. J., Cernea S., Chiang C. E., Cooper M., Dalby A., Deerochanawong C., Dellborg M., Diaz R., Dimulescu D., Eliaschewitz F. G., Goudev A. R., Hadjadj S., Herrera M., Huo Y., Jermendy G., Ji L., Kadowaki T., Kiss R., Kooy A., Kumar K. M. P., Lewis B., Litwak L., Lopez-Sendon J., Ma R., Merlini P. A., Nauck M. A., Nguyen T. K., Nicolau J. C., Ostgren C. J., Ophuis T. O., Padilla F., Pais P., Park K. S., Parkhomenko A., Ray K., Rosenstock J., Ruda M., Satman I., Shestakova M., Smahelova A., Spinar J., Strojek K., Sy R., Tankova T., Theroux P., Tkac I., Van Gaal L., Wainstein J., Harrington R. A., Droller M. J., Lee K. L., Nesto R. W., Tuomilehto J., Hedlin H., Desai M., Sayfer I., Alexanian S., Awtry E., Bentley-Lewis R., Berger C. J., Croce K., Desai A., Garg R. K., Gelfand E., Gignac G., Goessling W., Ho C., Hochberg E., Lane A., Larrey D., Leeman D. E., Lewis J., Link M. S., McDonnell M. E., Norden A. D., Pande A., Rosenberg C., Rost N., Ruberg F., Schiff E., Silverman S., Singhal A., Wagner A., Wolpin B., Aizenberg D., Fernandez M., Sala J., Maffei L., Luquez C., Waitman J., Rista L., Nardone L., Sposetti G., Cantero M., Alvarisqueta A., Montana O., Cuadrado J., Cartasegna L., Baccaro C., Chertkoff A., Sanabria H., Vainstein N., Amerena J., Arya K., d'Emden M., Proietto J., Moses R., Colquhoun D., Stranks S., Lehman R., Hamilton A., Whelan A., Simpson R., Purnell P., Abhayaratna W., Hammett C., McKeirnan M., Sullivan D., Bach L., Hughes K., Mathieu C., Vercammen C., Scheen A., Duyck F., Cools F., De Wolf L., Verhaegen A., Nobels F., Missault L., Crenier L., Thoeng J., Wollaert B., Vandenbroucke M., Eliaschewitz F., Borges J. L. C., Turatti L., Lima F. G., dos Santos F., Kerr Saraiva J., Pereira M., Pereira A., Precoma D. B., Filho G. F. V., Reis G., Maia L. N., Bacheva T., Temelkova-Kurktschiev T., Maneva S., Stoyanovska B., Boshnyashka R., Stoykova Y., Georgiev D., Tagarev Z., Dimitrova E., Vitkina M., Yordanova L., Temelkova M., Vasileva S., Kuneva T., Zyumbyuleva M., Daskalova I., Genadieva V., Boyanov L., Farah G., Lazarova G., Georgieva M., Krasteva S., Slavcheva A., Yabroudi N., Veleva N., Zlateva A., Damyanova V., Elenkova A., Kotselova T., Genov K., Lyubenova L., Temelkova N., Harizanova B., Zaharieva S., Bajaj H., Goldenberg R., Aronson R., Twum-Barima D., Dumas R., Kouz S., Kaiser S. M., Ajala B., Cha J., Teitelbaum I., Chouinard G., Woo V., Dan Dattani I., Mazza G., Gaudet D., Poirier P., Conway J., Dion D., McKeough M., Manyari D., Harris S., St-Pierre B., Yale J. F., Landry D., Gupta M., Hramiak I., Lau D., DeGrace M., Gallo R., Montigny M., Dzongowski P., Liutkus J., Frechette A., Gosselin G., Sabbah E., Langlois M. F., Rabasa-Lhoret R., Bedard J., Hart R., Dowell A., Pandey A., O'Keefe D., Hill L., Weisnagel S. J., Muirhead N., Zimmermann R., Galiwango P., Tobe S., Priestman B., Zinman B., Ma J., Zhao X., Wang C., Zhang A., Dong Y., Dong X., Luo M., Guo J., Zheng Z., Li Y., Liang Y., Peng D., Maderic D., Spinarova L., Raclavska L., Ludka O., Rihacek I., Karasova J., Pelikanova M., Vlasakova H., Urbancova K., Zamrazil V., Hradec J., Vlasicova H., Racicka E., Okenka L., Naplava R., Skopecek J., Palova S., Krystl T., Pistek Z., Oznerova M., Andresova A., Sarbochova R., Taborska P., Petrova I., Stanek L., Reichert P., Lorenc Z., Szabo M., Petit C., Krempf M., Boye A., Dubois S., Clavel S., Gourdy P., Elbaz M., Jazayeri S., Gouet D., Verges B., Couffinhal T., Sendeski M., Klausmann G., Appel K., Pein M., Thieme R., Schumm-Draeger P., Jacob S., Toursarkissian N., Kleinecke-Pohl U., Tschope D., Ott P., Haak T., Nauck M., Derwahl K., Bugger H., Hui G., Tsang C., Zilahi Z., Puski L., Vangel S., Fulop T., Pall K., Hidvegi T., Revesz K., Koranyi L., Kajetan M., Kerenyi Z., Penzes J., Herczeg B., Laszloczky A., Turi T., Rapi J., Pentek Z., Gaal Z., Winkler G., Percs E., Czigany A., Harcsa E., Gurzo M., Tassaly J., Horthy R., Petro G., Farago K., Muller G., Varju I., Kirschner R., Kiss I., Bakai J., Kancz S., Marton Z., Kodur R., Yajnik C., Thomas N., Ayyar V., Iyengar P., Bashkin A., Daoud D., Itzhak B., Katz A., Tsur A., Nikolsky E., Atar S., Grossman A., Klainman E., Tsalihin D., Shotan A., Turgeman Y., Ferrario M., Merlini P., Piatti P., Zenari L., Trevisan R., Bosco B., Di Lorenzo L., Mannucci E., Avogaro A., Reimers B., Trimarco B., Silvestri O., Salvioni A., Nakagawa H., Sueyoshi A., Fukuda K., Yasumoto H., Matsubayashi S., Kawajiri K., Togashi Y., Senokuchi T., Ohta Y., Yamauchi T., Node K., Alcocer Gamba M., Herrera Marmolejo M., De los Rios Ibarra M., Gonzalez Galvez G., Garcia Cantu E., Leguizamo Dimas A., Luna Ceballos R., Medina Pech C., Stobschinski de Alba C., Gonzalez Gonzalez J., Padilla Padilla F., Fanghanel Salmon G., Robles Torres F., Lopez Rosas E., Pelayo 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T., Pawlowicz L., Sowinski D., Romanowski L., Rudzki H., Skorski M., Jasiel-Wojculewicz H., Stasiewski A., Budaj A., Kania G., Mirek-Bryniarska E., Wojnowski L., Korzeniak R., Oh T., Park K., Lee M., Lee K., Jang H., Kim S., Ku B., Cha B., Son H., Lee I., Park J., Yu S., Shon H., Rhee E., Cho J., Park T., Nam J., Pintilei E., Popescu A., Nafornita V., Gutu O., Dumitrescu A., Bala C., Caceaune E., Mindrescu N., Morosanu M., Bradescu O., Munteanu M., Voitec M., Vlaiculescu M., Hancu N., Diaconu Sotropa M., Lupu S., Mateescu A., Carlan L., Marton R., Lupusoru D., Mot A., Coman A., Zaharie D., Rebrov A., Shutemova E., Bolieva L., Khalimov Y., Statsenko M., Galyavich A., Koziolova N., Shapovalova Y., Pavlysh E., Strongin L., Vertkin A., Vishneva E., Pavlova M., Khasanov N., Antsiferov M., Gavrisheva I., Sokolova N., Vorobyev S., Morugova T., Sinitsina I., Ezhov A., Kobalava Z., Belenkiy D., Supryadkina T., Kazakov Y., Oschepkova E., Dreval A., Novikova T., Vishnevsky A., Chizhov D., Akatova 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Wongvipaporn C., Kuanprasert S., Thongsri T., Srimahachota S., Boonyavarakul A., Suwanwalaikorn S., Tantiwong P., Sritara P., Sriwijitkamol A., Sanguanwong S., Chotinaiwattarakul C., Piyayotai D., Balci M., Orbay E., Saygili F., Oguz A., Altuntas Y., Comlekci A., Karpenko O., Tkach S., Vlasenko M., Fushtey I., Pertseva T., Reshotko D., Mostovoy Y., Vizir V., Kraiz I., Amosova K., Batushkin V., Tseluyko V., Koval O., Strang C., Bodalia B., Pieters R., Turner W., Asamoah-Owusu N., White C., Calvert J., McNally D., Jones N., McKaig G., Thompson J., Mohr S., Simpson H., Conn P., McCoye A., Rivero O., Yazdani S., Ince C., Zeitlin J., Wharton T., Platt G., Anderson R. J., Angueira-Serrano E., Lillestol M., Hanlon B., Soufer J., Garcia B., Iteld B., Venugopal C., Ahmed A., Duardo-Guerra Y., Jetty P., Miranda A., Wahlen J., Lederman S., Cohen K., Lake L., French W. J., Tahirkheli N., Baker S., Stoltz R., Wilson J., Nadar V., Brown J., Larrain G., Wiseman A., Ruoff G., Williams M., Tan A., Hartman I., Singh N., Graf R., Wakefield P., McNeill R., Byars W., Reyes Almodovar R., Jones S., Kantaros L., Hegedosh N., Graves M., Bernstein M., Falkowski S., Bialow M., Paraschos A., Dagher G., Arif A., Condit J., Chaykin L., Grunstra B., Earl J., Unks D., Srivastava S., Benson M., Huffman C., Miller G., Willis J., Bender K., Martin E., Blackmore R., Rohr K., Chilka S., Gadowski G., Fitz-Patrick D., Benjamin S., Morin D., Zias Dilena A., Acosta R., Claassen D., Miranda F., Raad G., Inzerello A., Porter J., Bhattacharya A., Gutmann J., Korpas D., Syed M., Zieve F., Raisinghani A., Alam S., Bartkowiak A., Boccalandro F., Talano J., Mercado A., Krichmar P., Oldfield C., Adams K., Gorman T., Lewis D., Shah R., Shockey G., Lefebvre G., Andrawis N., Tami L., Bittar N., Khan M. S., Rink L., Hendrix E., Wood J., Robinson J., Pavon H., Irfan M., Gonzalez E., Singal R., Shore K., Saba F., Bianco J., Erickson B., Gorson D., Puri S., Arauz-Pacheco C., Forman S., Akyea-Djamson A., Lieber I., Barker B., Desai P., Sotolongo C., Steinhoff J., Hill R., Radin M., Patel R., Lieberman S., Wenocur H., Dagogo-Jack S., Lupovitch S., Ison R., Bacharach J. M., Diogo J., Mazzella M., Greenwald J., Quadrel M., Mayer N., Datu J., McCartney M., Bruce T., Singal D., Turner J., Videau B., Fritz R., Fox D., Calatayud G., Sheldon W., Kereiakes D., Thomas J., Salacata A., McCullum K., Harris B., de Souza J., Rahman A., Blumenthal S., Narayan P., Bloch M., Augenbraun C., Bernstein R., Perlman R., Berman J., LaBryer L., Wynne A., Fish J., Zarich S., Gabra N., Popeil L., Hermany P., Barreto A., Pomposini D., Gonzalez-Campoy J. M., Langer M., Bayron C., Suneja R., Kamlet J., Wheeler K., Hurley S., Sharma S., Wefald F., Hershon K., O'Connor T., Pueblitz G., Laguerre J., Amin M., Alfonso T., Jaffrani N., Isserman S., Portnay E., Vlastaris A., Dy J., Hagan M., Noveck H., Kraft P., Andersen J., Foley B., Carr K., Gelormini J., Williams T., Landau C., Richwine R., Thakkar M., Karim A., Madhun Z., Francyk D., Lamantia J., Baker B., Zhang W., Lev V., Hasan M., Captain A., Herzog W., Friedman K., Lawson W., Desai V., Ow C., Simons R., Mandviwala M., Le T., Hack T., Zebrack J., Henderson D., DeJulia J., Mehta R., Reza S., Poonawala R., Awad A., Velasquez M., Mohiuddin S., Salazar Sharma M., Myrick G., Gottlieb D., Ovalle F., Alfieri A., Ahmed S., Bohula E., Donahoe S. M., Longshaw K., Eshaghian S., Lash J., Goldberg R. K., Fox B., Mostel E., Dobies D., Ward H., Burbano J., Puleo P., Lenhard M. J., Korn D., Thadani U., Bradley A., Kmetzo J., Heasley E., Raikhel M., Mahr N., Bittar G., Fuentes F., Raghu P., Diep T. T. B., Tran Q. K., Tran N., Nguyen D., Nguyen V., Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), VA Boston Healthcare System, Turbulence Research Laboratory [Goteborg], Chalmers University of Technology [Göteborg], Wiviott, S, Raz, I, Bonaca, M, Mosenzon, O, Kato, E, Cahn, A, Silverman, M, Zelniker, T, Kuder, J, Murphy, S, Bhatt, D, Leiter, L, Mcguire, D, Wilding, J, Ruff, C, Nilsson, G, Fredriksson, M, Johansson, P, Langkilde, A, Sabatine, M, Bansilal, S, Furtado, R, Fish, M, Gabovitch, D, Jevne, A, Ahern, S, Im, K, Goodrich, E, Lowe, C, Fisher, N, Gannon, J, Trindade, S, Towarowski, A, Fox, Y, Johnsson, E, Ranft, S, Faber, B, Wallander, M, Weiss, A, Buskila, A, Abola, M, Ardissino, D, Averkov, O, Aylward, P, Bode, C, Bonnici, F, Bonora, E, Budaj, A, Cernea, S, Chiang, C, Cooper, M, Dalby, A, Deerochanawong, C, Dellborg, M, Diaz, R, Dimulescu, D, Eliaschewitz, F, Goudev, A, Hadjadj, S, Herrera, M, Huo, Y, Jermendy, G, Ji, L, Kadowaki, T, Kiss, R, Kooy, A, Kumar, K, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Merlini, P, Nauck, M, Nguyen, T, Nicolau, J, Ostgren, C, Ophuis, T, Padilla, F, Pais, P, Park, K, Parkhomenko, A, Ray, K, Rosenstock, J, Ruda, M, Satman, I, Shestakova, M, Smahelova, A, Spinar, J, Strojek, K, Sy, R, Tankova, T, Theroux, P, Tkac, I, Van Gaal, L, Wainstein, J, Harrington, R, Droller, M, Lee, K, Nesto, R, Tuomilehto, J, Hedlin, H, Desai, M, Sayfer, I, Alexanian, S, Awtry, E, Bentley-Lewis, R, Berger, C, Croce, K, Desai, A, Garg, R, Gelfand, E, Gignac, G, Goessling, W, Ho, C, Hochberg, E, Lane, A, Larrey, D, Leeman, D, Lewis, J, Link, M, Mcdonnell, M, Norden, A, Pande, A, Rosenberg, C, Rost, N, Ruberg, F, Schiff, E, Silverman, S, Singhal, A, Wagner, A, Wolpin, B, Aizenberg, D, Fernandez, M, Sala, J, Maffei, L, Luquez, C, Waitman, J, Rista, L, Nardone, L, Sposetti, G, Cantero, M, Alvarisqueta, A, Montana, O, Cuadrado, J, Cartasegna, L, Baccaro, C, Chertkoff, A, Sanabria, H, Vainstein, N, Amerena, J, Arya, K, D'Emden, M, Proietto, J, Moses, R, Colquhoun, D, Stranks, S, Lehman, R, Hamilton, A, Whelan, A, Simpson, R, Purnell, P, Abhayaratna, W, Hammett, C, Mckeirnan, M, Sullivan, D, Bach, L, Hughes, K, Mathieu, C, Vercammen, C, Scheen, A, Duyck, F, Cools, F, De Wolf, L, Verhaegen, A, Nobels, F, Missault, L, Crenier, L, Thoeng, J, Wollaert, B, Vandenbroucke, M, Borges, J, Turatti, L, Lima, F, dos Santos, F, Kerr Saraiva, J, Pereira, M, Pereira, A, Precoma, D, Filho, G, Reis, G, Maia, L, Bacheva, T, Temelkova-Kurktschiev, T, Maneva, S, Stoyanovska, B, Boshnyashka, R, Stoykova, Y, Georgiev, D, Tagarev, Z, Dimitrova, E, Vitkina, M, Yordanova, L, Temelkova, M, Vasileva, S, Kuneva, T, Zyumbyuleva, M, Daskalova, I, Genadieva, V, Boyanov, L, Farah, G, Lazarova, G, Georgieva, M, Krasteva, S, Slavcheva, A, Yabroudi, N, Veleva, N, Zlateva, A, Damyanova, V, Elenkova, A, Kotselova, T, Genov, K, Lyubenova, L, Temelkova, N, Harizanova, B, Zaharieva, S, Bajaj, H, Goldenberg, R, Aronson, R, Twum-Barima, D, Dumas, R, Kouz, S, Kaiser, S, Ajala, B, Cha, J, Teitelbaum, I, Chouinard, G, Woo, V, Dan Dattani, I, Mazza, G, Gaudet, D, Poirier, P, Conway, J, Dion, D, Mckeough, M, Manyari, D, Harris, S, St-Pierre, B, Yale, J, Landry, D, Gupta, M, Hramiak, I, Lau, D, Degrace, M, Gallo, R, Montigny, M, Dzongowski, P, Liutkus, J, Frechette, A, Gosselin, G, Sabbah, E, Langlois, M, Rabasa-Lhoret, R, Bedard, J, Hart, R, Dowell, A, Pandey, A, O'Keefe, D, Hill, L, Weisnagel, S, Muirhead, N, Zimmermann, R, Galiwango, P, Tobe, S, Priestman, B, Zinman, B, Ma, J, Zhao, X, Wang, C, Zhang, A, Dong, Y, Dong, X, Luo, M, Guo, J, Zheng, Z, Li, Y, Liang, Y, Peng, D, Maderic, D, Spinarova, L, Raclavska, L, Ludka, O, Rihacek, I, Karasova, J, Pelikanova, M, Vlasakova, H, Urbancova, K, Zamrazil, V, Hradec, J, Vlasicova, H, Racicka, E, Okenka, L, Naplava, R, Skopecek, J, Palova, S, Krystl, T, Pistek, Z, Oznerova, M, Andresova, A, Sarbochova, R, Taborska, P, Petrova, I, Stanek, L, Reichert, P, Lorenc, Z, Szabo, M, Petit, C, Krempf, M, Boye, A, Dubois, S, Clavel, S, Gourdy, P, Elbaz, M, Jazayeri, S, Gouet, D, Verges, B, Couffinhal, T, Sendeski, M, Klausmann, G, Appel, K, Pein, M, Thieme, R, Schumm-Draeger, P, Jacob, S, Toursarkissian, N, Kleinecke-Pohl, U, Tschope, D, Ott, P, Haak, T, Derwahl, K, Bugger, H, Hui, G, Tsang, C, Zilahi, Z, Puski, L, Vangel, S, Fulop, T, Pall, K, Hidvegi, T, Revesz, K, Koranyi, L, Kajetan, M, Kerenyi, Z, Penzes, J, Herczeg, B, Laszloczky, A, Turi, T, Rapi, J, Pentek, Z, Gaal, Z, Winkler, G, Percs, E, Czigany, A, Harcsa, E, Gurzo, M, Tassaly, J, Horthy, R, Petro, G, Farago, K, Muller, G, Varju, I, Kirschner, R, Kiss, I, Bakai, J, Kancz, S, Marton, Z, Kodur, R, Yajnik, C, Thomas, N, Ayyar, V, Iyengar, P, Bashkin, A, Daoud, D, Itzhak, B, Katz, A, Tsur, A, Nikolsky, E, Atar, S, Grossman, A, Klainman, E, Tsalihin, D, Shotan, A, Turgeman, Y, Ferrario, M, Piatti, P, Zenari, L, Trevisan, R, Bosco, B, Di Lorenzo, L, Mannucci, E, Avogaro, A, Reimers, B, Trimarco, B, Silvestri, O, Salvioni, A, Nakagawa, H, Sueyoshi, A, Fukuda, K, Yasumoto, H, Matsubayashi, S, Kawajiri, K, Togashi, Y, Senokuchi, T, Ohta, Y, Yamauchi, T, Node, K, Alcocer Gamba, M, Herrera Marmolejo, M, De los Rios Ibarra, M, Gonzalez Galvez, G, Garcia Cantu, E, Leguizamo Dimas, A, Luna Ceballos, R, Medina Pech, C, Stobschinski de Alba, C, Gonzalez Gonzalez, J, Padilla Padilla, F, Fanghanel Salmon, G, Robles Torres, F, Lopez Rosas, E, Pelayo Orozco, E, Banda Elizondo, R, Escalona Caamano, A, Frenk Baron, P, Aguilar Salinas, C, Mustieles Rocha, C, Vidrio Velazquez, M, Rodriguez Briones, I, Saldate Alonso, M, Velasco Sanchez, R, Groenemeijer, B, Ronner, E, Kuijper, A, Strikwerda, S, Van Kempen, W, Gijsbers, S, Oude Ophuis, A, Swart, H, Hoogenberg, K, Hovens, M, van Hessen, M, Westerink, J, Kragten, J, Nierop, P, Bax, W, Hartong, S, Nieuwdorp, M, Gonkel, F, Al Windy, N, Troquay, R, Schaafsma, H, Lieverse, A, Knufman, N, Tirador, L, Guenon, M, Ferrolino, A, Atilano, A, Aportadera, M, Que, M, Denopol, M, Tolentino, M, Jimeno, C, Wee, J, Mirasol, R, Panelo, A, Roxas, D, Palmes, P, Silva, A, Salvador, D, Rosita, R, Maravilla, L, Rogelio, G, Pacheco, E, Tin Hay, L, Prado, J, Krzyzagorska, E, Witek, R, Miklaszewicz, B, Sudnik, W, Pomiecko, W, Bochenek, A, Fares, I, Wujkowski, M, Korol, M, Powierza, S, Goch, A, Miekus, P, Siegel, A, Skierkowska, J, Romanczuk, P, Cygler, J, Landa, K, Szyprowska, E, Stachlewski, P, Czerski, T, Pawlowicz, L, Sowinski, D, Romanowski, L, Rudzki, H, Skorski, M, Jasiel-Wojculewicz, H, Stasiewski, A, Kania, G, Mirek-Bryniarska, E, Wojnowski, L, Korzeniak, R, Oh, T, Lee, M, Jang, H, Kim, S, Ku, B, Cha, B, Son, H, Lee, I, Park, J, Yu, S, Shon, H, Rhee, E, Cho, J, Park, T, Nam, J, Pintilei, E, Popescu, A, Nafornita, V, Gutu, O, Dumitrescu, A, Bala, C, Caceaune, E, Mindrescu, N, Morosanu, M, Bradescu, O, Munteanu, M, Voitec, M, Vlaiculescu, M, Hancu, N, Diaconu Sotropa, M, Lupu, S, Mateescu, A, Carlan, L, Marton, R, Lupusoru, D, Mot, A, Coman, A, Zaharie, D, Rebrov, A, Shutemova, E, Bolieva, L, Khalimov, Y, Statsenko, M, Galyavich, A, Koziolova, N, Shapovalova, Y, Pavlysh, E, Strongin, L, Vertkin, A, Vishneva, E, Pavlova, M, Khasanov, N, Antsiferov, M, Gavrisheva, I, Sokolova, N, Vorobyev, S, Morugova, T, Sinitsina, I, Ezhov, A, Kobalava, Z, Belenkiy, D, Supryadkina, T, Kazakov, Y, Oschepkova, E, Dreval, A, Novikova, T, Vishnevsky, A, Chizhov, D, Akatova, E, Vorokhobina, N, Ivanov, I, Dudinskaya, E, Konstantinov, V, Kanderkova, D, Pavlik, L, Raslova, K, Paulovic, V, Babikova, J, Belesova, K, Merciakova, M, Truban, J, Vargova, A, Fabryova, L, Slovenska, M, Plasil, R, Tomasova, L, Kollarova, D, Spodniakova, D, Kosikova, M, Dzuponova, J, Kurcova, I, Skripova, D, Gabrisova, A, Kalinova, S, Ranjith, N, Burgess, L, Mitha, I, Conradie, M, Distiller, L, Pillai, P, Pillay, S, Horak, A, Nethononda, R, van den Berg, E, Nortje, H, Bayat, J, Corbett, C, Abelson, M, van Zyl, L, Pillay, T, Wing, J, Kapp, C, Hidalgo Urbano, R, Gonzalez Juanatey, J, Blanco Coronado, J, Bruguera Cortada, J, Ferreiro Gutierrez, J, Quesada Simon, M, Castro, A, Delgado Alvarez, E, Freixa, R, Boada, A, Larnefeldt, H, Mooe, T, Koskinen, P, Lagerback, P, Linderfalk, C, Liu, B, Berndtsson Blom, K, Tengmark, B, Lindholm, C, Oweling, M, Albertsson, P, Alvarsson, M, Fant, S, Berglund, O, Hsia, C, Fang, C, Ueng, K, Wang, K, Lai, W, Mamanasiri, S, Wongvipaporn, C, Kuanprasert, S, Thongsri, T, Srimahachota, S, Boonyavarakul, A, Suwanwalaikorn, S, Tantiwong, P, Sritara, P, Sriwijitkamol, A, Sanguanwong, S, Chotinaiwattarakul, C, Piyayotai, D, Balci, M, Orbay, E, Saygili, F, Oguz, A, Altuntas, Y, Comlekci, A, Karpenko, O, Tkach, S, Vlasenko, M, Fushtey, I, Pertseva, T, Reshotko, D, Mostovoy, Y, Vizir, V, Kraiz, I, Amosova, K, Batushkin, V, Tseluyko, V, Koval, O, Strang, C, Bodalia, B, Pieters, R, Turner, W, Asamoah-Owusu, N, White, C, Calvert, J, Mcnally, D, Jones, N, Mckaig, G, Thompson, J, Mohr, S, Simpson, H, Conn, P, Mccoye, A, Rivero, O, Yazdani, S, Ince, C, Zeitlin, J, Wharton, T, Platt, G, Anderson, R, Angueira-Serrano, E, Lillestol, M, Hanlon, B, Soufer, J, Garcia, B, Iteld, B, Venugopal, C, Ahmed, A, Duardo-Guerra, Y, Jetty, P, Miranda, A, Wahlen, J, Lederman, S, Cohen, K, Lake, L, French, W, Tahirkheli, N, Baker, S, Stoltz, R, Wilson, J, Nadar, V, Brown, J, Larrain, G, Wiseman, A, Ruoff, G, Williams, M, Tan, A, Hartman, I, Singh, N, Graf, R, Wakefield, P, Mcneill, R, Byars, W, Reyes Almodovar, R, Jones, S, Kantaros, L, Hegedosh, N, Graves, M, Bernstein, M, Falkowski, S, Bialow, M, Paraschos, A, Dagher, G, Arif, A, Condit, J, Chaykin, L, Grunstra, B, Earl, J, Unks, D, Srivastava, S, Benson, M, Huffman, C, Miller, G, Willis, J, Bender, K, Martin, E, Blackmore, R, Rohr, K, Chilka, S, Gadowski, G, Fitz-Patrick, D, Benjamin, S, Morin, D, Zias Dilena, A, Acosta, R, Claassen, D, Miranda, F, Raad, G, Inzerello, A, Porter, J, Bhattacharya, A, Gutmann, J, Korpas, D, Syed, M, Zieve, F, Raisinghani, A, Alam, S, Bartkowiak, A, Boccalandro, F, Talano, J, Mercado, A, Krichmar, P, Oldfield, C, Adams, K, Gorman, T, Lewis, D, Shah, R, Shockey, G, Lefebvre, G, Andrawis, N, Tami, L, Bittar, N, Khan, M, Rink, L, Hendrix, E, Wood, J, Robinson, J, Pavon, H, Irfan, M, Gonzalez, E, Singal, R, Shore, K, Saba, F, Bianco, J, Erickson, B, Gorson, D, Puri, S, Arauz-Pacheco, C, Forman, S, Akyea-Djamson, A, Lieber, I, Barker, B, Desai, P, Sotolongo, C, Steinhoff, J, Hill, R, Radin, M, Patel, R, Lieberman, S, Wenocur, H, Dagogo-Jack, S, Lupovitch, S, Ison, R, Bacharach, J, Diogo, J, Mazzella, M, Greenwald, J, Quadrel, M, Mayer, N, Datu, J, Mccartney, M, Bruce, T, Singal, D, Turner, J, Videau, B, Fritz, R, Fox, D, Calatayud, G, Sheldon, W, Kereiakes, D, Thomas, J, Salacata, A, Mccullum, K, Harris, B, de Souza, J, Rahman, A, Blumenthal, S, Narayan, P, Bloch, M, Augenbraun, C, Bernstein, R, Perlman, R, Berman, J, Labryer, L, Wynne, A, Fish, J, Zarich, S, Gabra, N, Popeil, L, Hermany, P, Barreto, A, Pomposini, D, Gonzalez-Campoy, J, Langer, M, Bayron, C, Suneja, R, Kamlet, J, Wheeler, K, Hurley, S, Sharma, S, Wefald, F, Hershon, K, O'Connor, T, Pueblitz, G, Laguerre, J, Amin, M, Alfonso, T, Jaffrani, N, Isserman, S, Portnay, E, Vlastaris, A, Dy, J, Hagan, M, Noveck, H, Kraft, P, Andersen, J, Foley, B, Carr, K, Gelormini, J, Williams, T, Landau, C, Richwine, R, Thakkar, M, Karim, A, Madhun, Z, Francyk, D, Lamantia, J, Baker, B, Zhang, W, Lev, V, Hasan, M, Captain, A, Herzog, W, Friedman, K, Lawson, W, Desai, V, Ow, C, Simons, R, Mandviwala, M, Le, T, Hack, T, Zebrack, J, Henderson, D, Dejulia, J, Mehta, R, Reza, S, Poonawala, R, Awad, A, Velasquez, M, Mohiuddin, S, Salazar Sharma, M, Myrick, G, Gottlieb, D, Ovalle, F, Alfieri, A, Ahmed, S, Bohula, E, Donahoe, S, Longshaw, K, Eshaghian, S, Lash, J, Goldberg, R, Fox, B, Mostel, E, Dobies, D, Ward, H, Burbano, J, Puleo, P, Lenhard, M, Korn, D, Thadani, U, Bradley, A, Kmetzo, J, Heasley, E, Raikhel, M, Mahr, N, Bittar, G, Fuentes, F, Raghu, P, Diep, T, Tran, Q, Tran, N, Nguyen, D, and Nguyen, V
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Male ,medicine.medical_specialty ,dapagliflozin, placebo ,[SDV]Life Sciences [q-bio] ,Renal function ,Type 2 diabetes ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,030204 cardiovascular system & hematology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glucosides ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Myocardial infarction ,Benzhydryl Compounds ,Dapagliflozin ,Sodium-Glucose Transporter 2 Inhibitors ,ComputingMilieux_MISCELLANEOUS ,Aged ,Heart Failure ,Canagliflozin ,business.industry ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,General Medicine ,Middle Aged ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,medicine.disease ,Hospitalization ,Diabetes Mellitus, Type 2 ,chemistry ,Cardiovascular Diseases ,Heart failure ,Cardiology ,Female ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Mace ,medicine.drug - Abstract
BACKGROUND The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to ≥60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], ≥1.3; P≥0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P = 0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P = 0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3%vs. 0.1%, P = 0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P≥0.001). CONCLUSIONS In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARETIMI 58 ClinicalTrials.gov number, NCT01730534
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- 2019
3. An Unsafe/Safe Typology in People with Type 2 Diabetes: Bridging Patients’ Expectations, Personality Traits, Medication Adherence, and Clinical Outcomes
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Reach G, Benarbia L, Benhamou PY, Delemer B, Dubois S, Gouet D, Guerci B, Jeandidier N, Lachgar K, Le Pape G, Leroy R, Masgnaux JH, Raclet P, Reznik Y, Riveline JP, Schaepelynck P, Vambergue A, and Vergès B
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type 2 diabetes ,adherence ,support programs ,typology ,personality traits ,clinical outcomes ,patients’ expectations ,Medicine (General) ,R5-920 - Abstract
Gérard Reach,1 Laurent Benarbia,2 Pierre-Yves Benhamou,3 Brigitte Delemer,4 Séverine Dubois,5 Didier Gouet,6 Bruno Guerci,7 Nathalie Jeandidier,8 Karim Lachgar,9 Gilles Le Pape,10 Rémy Leroy,11 Jean-Hugues Masgnaux,12 Philippe Raclet,13 Yves Reznik,14 Jean-Pierre Riveline,15,16 Pauline Schaepelynck,17 Anne Vambergue,18 Bruno Vergès19 1Health Education and Promotion Laboratory (LEPS EA 3412), Sorbonne Paris Nord University, Bobigny, France; 2Marketing Studio, Paris, France; 3Department of Endocrinology, Grenoble University Hospital; Grenoble Alpes University, INSERM U1055, LBFA, Grenoble, France; 4Service d’Endocrinologie – Diabète – Nutrition, CHU de Reims - Hôpital Robert Debré, and Université de Reims Champagne Ardenne, UFR Sciences Exactes Et Naturelles, Reims, France; 5Department of Diabetology and Endocrinology, CHU Angers, Angers, France; 6Department of Diabetology and Endocrinology, Saint Louis Hospital, La Rochelle, France; 7Department of Endocrinology, Diabetology and Nutrition, CHRU of Nancy, Brabois Hospital, and ILCV Lorraine University, Vandoeuvre-les-Nancy, France; 8Department of Endocrinology, Diabetes and Nutrition, Hôpitaux Universitaires de Strasbourg, and Université de Strasbourg, Strasbourg, France; 9Department of Diabetology and Endocrinology, Centre Hospitalier Simone Veil, Eaubonne, France; 10General Practice, Penmarc’h, France; 11Private Medical Practice, Endocrinology and Diabetology, Lille, France; 12M&M Conseil, Boulogne, France; 13Association Française des Diabétiques de Bourgogne Franche-Comté, Dijon, France; 14Department oEndocrinology and Diabetology, CHU Côte de Nacre, Caen, and University of Caen Basse-Normandie, Medical School, Caen, France; 15Department of Diabetology and Endocrinology, Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France; 16Unité INSERM U1138 Immunity and Metabolism in Diabetes, ImMeDiab Team, Centre de Recherches des Cordeliers, and Université de Paris, Paris, France; 17Department of Nutrition-Endocrinology-Metabolic Diseases, Pôle ENDO, APHM-Hôpital la Conception, Marseille, France; 18Department of Diabetology, Endocrinology, Metabolism and Nutrition, CHU Lille, and University Hospital European Genomic Institute for Diabetes, Lille, France; 19Department of Endocrinology-Diabetology,CHU Dijon, and University of Burgundy, INSERM LNC UMR1231, Dijon, FranceCorrespondence: Gérard Reach, Health Education and Promotion Laboratory (LEPS EA 3412), Sorbonne Paris Nord University, 74 Rue Marcel Cachin, Bobigny Cedex, 93017, France, Tel + 33 (0)6 60 84 53 25, Email gerardreach@icloud.comBackground: Support programs are provided to people with diabetes to help them manage their disease. However, adherence to and persistence in support programs are often low, making it difficult to demonstrate their effectiveness.Aim: To identify the determinants of patients’ perceived interest in diabetes support programs because it may be a powerful determinant of effective participation in such programs.Patients and Methods: An online study conducted in April 2021 in metropolitan France on 600 people with diabetes recruited from a consumer panel. A 64-item psychosocial questionnaire including a question asking to evaluate the helpfulness of a support program was used. Univariate, multivariate, and multiple correspondence analyses were performed.Results: The existence of a typology, known as Unsafe/Safe, was discovered, in which patients with type 2 diabetes respond in two distinct ways. Type U (unsafe) patients, who believe that a support program would be helpful, are more likely to be nonadherent to their treatment, have high hemoglobin A1c levels, have at least one diabetic complication, lack information regarding their disease and treatment, rate the burden of their disease and impairment of their quality of life as high, worry about their future, and are pessimistic. Type S (safe) patients have the opposite characteristics. Type U patients can be dichotomized into two broad classes: one in which they lack information regarding disease and treatment and the other in which alterations in the quality of life and burden of the disease predominate. Insulin-treated patients give more importance to the lack of information, whereas noninsulin-treated patients complain primarily about the burden of the disease and impairment of quality of life.Conclusion: This study describes this new U/S typology, proposes a simple method based on a nine-item questionnaire to identify type U patients by calculating a Program Helpfulness Score described herein, and clarifies the nature of the intervention to be provided to them. This novel approach could be applied to other chronic diseases.Keywords: type 2 diabetes, adherence, support programs, typology, personality traits, clinical outcomes, patients’ expectations
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- 2022
4. Physical activity and type 2 diabetes. Recommandations of the SFD (Francophone Diabetes Society) diabetes and physical activity working group.
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Duclos, M., Oppert, J.-M., Verges, B., Coliche, V., Gautier, J.-F., Guezennec, Y., Reach, G., and Strauch, G.
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Abstract: Although regular physical activity is an integral part of T2D management, few diabetic patients have a sufficient level of physical activity. However over the past decade or so, the beneficial effects of regular physical activity have been well demonstrated, both in T2D prevention (50% reduction in the incidence of T2D in subjects with high metabolic risk) as well as T2D management for the improvement of glycaemic control (mean 0.7% improvement of HbA
1c ) and the reduction of T2D-related comorbidities (improvement in blood pressure values and lipid profile, decrease in insulin resistance). Physical activity has both acute effects (effects of one exercise session) and more prolonged effects of exercise when it is repeated on a regular basis (training effect). In addition, the physical activity recommendations have been extended to a wide range of physical activities (by combining both endurance and muscle strengthening exercises), thus varying the physical activity practiced according to the patient's available time, practice sites, preferences and interests. Following a pathophysiology review, the effects of physical activity will be discussed and presented in terms of evidence-based medicine. The recommendations will be defined and practical prescribing information will be suggested, while taking into account that clinicians are concerned with answering questions regarding how, where and with whom: how can patients be motivated to practice a physical activity over the long-term? And how can qualified exercise trainers and appropriate practice settings be found? [Copyright &y& Elsevier]- Published
- 2013
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5. Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a lower prevalence of steatosis in patients with type 2 diabetes.
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Petit, J.M., Guiu, B., Duvillard, L., Jooste, V., Brindisi, M.C., Athias, A., Bouillet, B., Habchi, M., Cottet, V., Gambert, P., Hillon, P., Cercueil, J.P., and Verges, B.
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Summary: Background & aims: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome and type 2 diabetes. Although dietary fat contributes substantially to the accumulation of liver fat, the role of individual fatty acids in this accumulation is unclear. Objective: In this study, we set out to determine whether liver fat content (LFC), was associated with red blood cell fatty acid (RBC-FA) composition in people with type 2 diabetes. Design, settings, and participants: One hundred and sixty-two type 2 diabetic patients were included in this study. LFC was measured using
1 H-MR Spectroscopy. RBC-FA composition was measured by gas chromatography. Results: One hundred and nine (67.2%) patients had steatosis. Patients with steatosis had a higher BMI (p =0.0005), and higher plasma triglyceride levels (p =0.009) than did patients without steatosis. We report a significant association between palmitic acid (16:0), palmitoleic acid (16:1n-7) concentrations and ratio of monounsaturated to saturated fatty acid (palmitoleic acid to palmitic acid) and higher liver fat content. Total polyunsaturated fatty acid (PUFA), homo-gamma-linolenic acid (20:3n-6), docosahexaenoic acid (22:6n-3), and arachidonic acid (20:4 n-6) were associated with lower LFC. Conclusions: Our data showed that an increased erythrocytes long-chain n-3 and n-6 fatty acids was associated with a lower prevalence of steatosis in patients with type 2 diabetes. These results suggest that n-3 and n-6 fatty acids supplementation could be a promising treatment for NAFLD in patients with type 2 diabetes. [Copyright &y& Elsevier]- Published
- 2012
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6. P1047 Stéatose des patients diabétiques de type 2 : description et facteurs de risque cliniques, biologiques et génétiques.
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Petit, J. Michel, Guiu, B., Masson, D., Duvillard, L., Brindisi, M. Claude, Bouillet, B., Crevisy, E., Beacco, M., Buffier, P., Cercueil, J. Pierre, and Verges, B.
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FATTY degeneration ,TYPE 2 diabetes ,OBESITY ,METABOLIC syndrome ,DIABETES ,ADIPOKINES - Abstract
Introduction: La stéatose non alcoolique est associée à l’obésité, au syndrome métabolique, au diabète, aux modifications de la sécrétion d’adipokines et à certains polymorphismes génétiques (adiponutrine, apoC3 et glucokinase regulatory protein (GCKR)). Le but de cette étude est d’évaluer les facteurs associés à la présence d’une stéatose d’une population de diabétiques de type 2 (DT2). Matériels et méthodes: 252 patients ont été inclus dans cette étude. Le contenu hépatique en graisse (CHG) a été mesuré par spectroscopie-RMN. Les polymorphismes rs738409 de l’adiponutrine et rs1260326 de GCKR et rs2854116 de l’apoC3, les taux d’adiponectine, RBP4, d’apeline et de leptine ont été évalués pour chaque sujet. Résultats: 149 (63,6 %) patients avait une stéatose (CHG>5,5 %). En analyse univariée les variables significativement associées à la présence d’une stéatose sont un âge plus jeune, une durée de diabète plus courte, un BMI plus élevé, des triglycérides élevés, un traitement par metformine, l’absence de statine, l’adiponectine abaissée, la leptine augmentée, l’allèle mineur de l’adiponutrine, et l’allèle mineur de GCKR. En analyse multivariée, seule la faible durée de diabète, les triglycérides, l’adiponectinémie basse, la prise de metformine et l’allèle mineur de l’adiponutrine restent significativement associées à la stéatose. Conclusion: Ces résultats suggèrent que chez les sujets DT2, indépendamment des facteurs connus que sont le polymorphisme rs738409 de l’adiponutrine, le taux d’adiponectine et les triglycérides, la stéatose est plus fréquente chez les patients ayant une faible durée de diabète. L’augmentation de la prévalence de la stéatose retrouvée chez les sujets traités par metformine peut être secondaire au profil particulier de ces patients obèses, insulinorésistants avec une fonction rénale conservée. Notre étude montre que les polymorphismes de GCKR et de l’apoC3 n’ont pas d’impact significatif sur la stéatose des patients diabétiques de type 2 et que les statines n’ont pas d’effet défavorable sur le CHG. [ABSTRACT FROM AUTHOR]
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- 2013
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7. O28 Diminution de la capacité des HDL de patients obèses, diabétiques de type 1 et diabétiques de type 2 à activer la NO synthase endothéliale.
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Duvillard, L., Monier, S., Perségol, L., Robin, I., Bouillet, B., Brindisi, M.-C., Petit, J.-M., and Verges, B.
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HIGH density lipoproteins ,ENDOTHELIAL cells ,NITRIC-oxide synthases ,OVERWEIGHT persons ,TYPE 2 diabetes ,CELLULAR signal transduction - Abstract
Introduction: HDL exercent leur effet anti-athérogène par des mécanismes multiples dont l’activation de la NO synthase endothéliale (eNOS), via des voies de signalisation impliquant Akt et la p38-MAP-kinase. Les HDL des patients non diabétiques avec une obésité androïde (Ob), diabétiques de type 1 (DT1) et diabétiques de type 2 (DT2), présentent des anomalies qualitatives avec notamment respectivement un enrichissement en triglycérides, une glycation et les 2 anomalies combinées, ce qui est susceptible d’altérer leur fonctionnalité. Patients et méthodes: Sur des cellules endothéliales humaines issues de cordons ombilicaux, incubées avec les HDL de 12 patients Ob, 16 DT1, 18 DT2, et 20 sujets contrôles. nous avons quantifié la synthèse de NO à partir de L [3H]arginine, ainsi que l’activation d’eNOS, Akt et p38 par phosphorylation respectivement de leur Ser1177, Ser473 et Tyr182 (quantification par cytométrie en flux). Résultats: L’augmentation de la synthèse de NO induite par les HDL, était inférieure pour les patients Ob, DT1 et DT2 comparés aux contrôles (+ 159±98 (p<0,01), 172±61 (p<0,01) et 129±47 (p<0,0001) vs 232±53 %, respectivement). La Ser1177-phospho-eNOS était diminuée avec les HDL des patients Ob, DT1 et DT2, comparées aux HDL des contrôles (+ 32±12 (p<0,01), 26±9 (p<0,001) et 19±14 (p<0,001) vs 46±17 %, respectivement). L’activité et la phosphorylation d’eNOS étaient supérieures avec les HDL des patients DT1 comparés aux DT2 (p<0,05). L’activation d’Akt et de la p38-MAP-kinase était également moindre avec les HDL des patients Ob, DT1 et DT2, comparées aux HDL des contrôles (augmentation de la Ser473-phospho-Akt = 35±16 (p<0,01), 24±17 (p<0,0001) et 26±28 (p<0,0001) vs 59±27 % respectivement, augmentation de la Tyr182-phospho-p38=87±32 % (p=0,06), 60±21 (p < 0,0001) et 73±26 (p<0,01) vs 110±47 %, respectivement). Conclusion: En conclusion, la capacité des HDL des patients Ob, DT1et DT2 à activer eNOS via Akt et p38-MAP-kinase est diminuée, ce qui est susceptible de contribuer à l’altération du pouvoir anti-athérogène de ces HDL. [ABSTRACT FROM AUTHOR]
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- 2013
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8. P219: Influence du polymorphisme rs738409 de l’adiponutrine (PNPLA3) sur le niveau de stéatose et de fibrose des patients diabétiques de type 2.
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Petit, J.M., Guiu, B., Masson, D., Sofia, R., Duvillard, L., Brindisi, M.C., Crevisy, E., Bouillet, B., Buffier, P., Robin, I., Gambert, P., Cercueil, J.P., Verges, B., and Hillon, P.
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GENETIC polymorphisms ,NITRILES ,FATTY degeneration ,FIBROSIS ,TYPE 2 diabetes ,OBESITY ,METABOLIC disorders - Abstract
Introduction: La stéatose hépatique non alcoolique est fréquemment associée à l’obésité, au syndrome métabolique et au diabète de type 2. Récemment, à partir d’études dans la population générale et chez les sujets atteint de stéatohépatite, un polymorphisme de l’adiponutrine à été retrouvé associé à la stéatose et la fibrose et cela indépendamment de l’insulino-résistance et de l’obésité. Le but de cette étude est d’évaluer l’influence de ce polymorphisme sur l’atteinte hépatique (stéatose et fibrose) d’une population de diabétiques de type 2. Matériels et méthodes: 234 patients diabétiques type 2 ont été inclus dans cette étude. Le contenu hépatique en graisse a été mesuré par spectroscopie RMN. La fibrose hépatique a été mesurée par le score non-invasif FIBROTEST-(Biopredictive) déterminé à partir de 5 paramètres biologiques (alpha2-macroglobuline, bilirubine, apoA1, GGT, haptoglobine). Le polymorphisme rs738409 de l’adiponutrine-PNPLA3 a été évalué pour chaque sujet. Résultats: 149 (63.6%) patients avait une stéatose (contenu hépatique en graisse > 5.5%). Le contenu hépatique en graisse est corrélé au BMI, aux taux de triglycérides, d’ASAT, et d’ALAT. Les porteurs de l’allèle mineur de l’adiponutrine ont un niveau de stéatose et de fibrose F2 plus élevé que les homozygotes majeurs (stéatose : 70.4% vs 57.1% ; p = 0.04 ; fibrose : 14.7% vs 7.5% ; p = 0.07). Chez le sous groupe des sujets au delà de la médiane d’âge (60 ans), le polymorphisme de l’adiponutrine est fortement associé à la fibrose F2 (mineur vs majeurs homozygotes : 25.7% vs 11.3% ; p = 0.02). En analyse multivariée dans la totalité de la population, les variables associées à la fibrose F2 sont : l’âge (p < 0.001), le sexe (p = 0.002), le BMI (p = 0.04) et l’allèle mineur de l’adiponutrine (p = 0.01). Conclusion: Ces résultats suggèrent que chez les sujets diabétiques de type 2, le polymorphisme rs738409 de l’adiponutrine est un déterminant important du niveau de stéatose et de fibrose hépatique. [Copyright &y& Elsevier]
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- 2011
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9. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial
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Paresh Dandona, Chantal Mathieu, Moshe Phillip, Lars Hansen, Steven C Griffen, Diethelm Tschöpe, Fredrik Thorén, John Xu, Anna Maria Langkilde, Joseph Proietto, Stephen Stranks, Roger Chen, David O'Neal, Alexia Pape, Mark Forbes, Claire Morbey, Anton Luger, Ursula Hanusch, Christoph Schnack, Evelyn Fliesser-Goerzer, Bertram Hoelzl, Christoph Ebenbichler, Rudolf Prager, Luc Van Gaal, Chris Vercammen, Andre Scheen, Francis Duyck, Frank Nobels, Johannes Ruige, Naresh Aggarwal, Vincent Woo, Bruno St-Pierre, Richard Dumas, Irene Hramiak, Thomas Elliott, Troels Krarup Hansen, Jan Erik Henriksen, Jeppe Gram, Aina Lihn, Jens Bruun, Juha Saltevo, Jyrki Taurio, Jorma Strand, Timo Valle, Sakari Nieminen, Kirsi Pietilainen, Bruno Guerci, Samy Hadjadj, Bertrand Cariou, Bruno Verges, Sophie Borot, Alfred Penfornis, Thomas Schaum, Diethelm Tschoepe, Cornelia Marck, Thomas Horacek, Ludger Rose, Gerhard Klausmann, Joerg Luedemann, Steffi Appelt, Ulrich Aigner, Rolf Goebel, Thomas Behnke, Anette-Gabriele Ziegler, Eva Peterfai, Zsuzsanna Kerenyi, Tamas Oroszlan, Gyula G. Kiss, Laszlo Konyves, Gyorgyi Piros, Ofri Mosenzon, Naim Shehadeh, Faiad Adawi, Julio Wainstein, Francesco Dotta, Piermarco Piatti, Stefano Genovese, Agostino Consoli, Paolo Di Bartolo, Edoardo Mannucci, Carla Giordano, Annunziata Lapolla, Carlos Aguilar, Alberto Esteban, Bazzoni Ruiz, Guillermo Mondragon Ramirez, Emilia Pelayo Orozco, Carlos Alejandro, Stobschinski de Alba, Carlos Medina Pech, Jose Garza Ruiz, Leobardo Sauque Reyna, Guillermo Llamas Esperon, Luis Alejandro Nevarez Ruiz, Maricela Vidrio Velazquez, Fernando Flores Lozano, Jose Gerardo Gonzalez Gonzalez, Pedro Alberto Garcia-Hernandez, Roberto Araujo-Silva, Efrain Villeda - Espinosa, Cristina Mistodie, Daniela Popescu, Ciprian Constantin, Alina Nicolau, Bogdan Popa, Romulus Timar, Cristian Serafinceanu, Ella Pintilei, Alfonso Soto, Margarita Gimenez, Juan Francisco Merino-Torres, Cristobal Morales, Pedro Mezquita, Johan Jendle, Bengt-Olov Tengmark, Jan Eriksson, Magnus Londahl, Bjorn Eliasson, Anthony Gunstone, Simon Heller, Ken Darzy, Peter Mansell, Melanie Davies, Rory Reed, Duncan Browne, Hamish Courtney, Wayne Turner, Mark Blagden, Rory McCrimmon, Richard Bergenstal, Wendy Lane, Kathryn Lucas, Alexander White, Shichun Bao, Judith White, Curtis Jantzi, Neda Rasouli, William Ervin, Lorena Lewy-Alterbaum, Yehuda Handelsman, Bresta Miranda-Palma, Alan Cleland, Raymond Fink, Helena Rodbard, Samer Nakhle, Craig Greenberg, Alan Schorr, Harold Bays, Debra Simmons, Eric Klein, Laurie Kane, Norman Fishman, Eli Ipp, Satish Garg, Anuj Bhargava, Michelle Zaniewski Singh, Julio Rosenstock, James Thrasher, Mark Warren, Laura Young, Vanita Aroda, Jeremy Pettus, David Liljenquist, Robert Busch, Jonathan Wise, David Kayne, William Biggs, Dandona P., Mathieu C., Phillip M., Hansen L., Griffen S.C., Tschope D., Thoren F., Xu J., Langkilde A.M., Proietto J., Stranks S., Chen R., O'Neal D., Pape A., Forbes M., Morbey C., Luger A., Hanusch U., Schnack C., Fliesser-Goerzer E., Hoelzl B., Ebenbichler C., Prager R., Van Gaal L., Vercammen C., Scheen A., Duyck F., Nobels F., Ruige J., Aggarwal N., Woo V., St-Pierre B., Dumas R., Hramiak I., Elliott T., Krarup Hansen T., Henriksen J.E., Gram J., Lihn A., Bruun J., Saltevo J., Taurio J., Strand J., Valle T., Nieminen S., Pietilainen K., Guerci B., Hadjadj S., Cariou B., Verges B., Borot S., Penfornis A., Schaum T., Tschoepe D., Marck C., Horacek T., Rose L., Klausmann G., Luedemann J., Appelt S., Aigner U., Goebel R., Behnke T., Ziegler A.-G., Peterfai E., Kerenyi Z., Oroszlan T., Kiss G.G., Konyves L., Piros G., Mosenzon O., Shehadeh N., Adawi F., Wainstein J., Dotta F., Piatti P., Genovese S., Consoli A., Di Bartolo P., Mannucci E., Giordano C., Lapolla A., Aguilar C., Esteban A., Ruiz B., Ramirez G.M., Pelayo Orozco E., Alejandro C., de Alba S., Medina Pech C., Garza Ruiz J., Sauque Reyna L., Llamas Esperon G., Nevarez Ruiz L.A., Vidrio Velazquez M., Flores Lozano F., Gonzalez Gonzalez J.G., Garcia-Hernandez P.A., Araujo-Silva R., Villeda - Espinosa E., Mistodie C., Popescu D., Constantin C., Nicolau A., Popa B., Timar R., Serafinceanu C., Pintilei E., Soto A., Gimenez M., Merino J., Morales C., Mezquita P., Jendle J., Tengmark B.-O., Eriksson J., Londahl M., Eliasson B., Gunstone A., Heller S., Darzy K., Mansell P., Davies M., Reed R., Browne D., Courtney H., Turner W., Blagden M., McCrimmon R., Bergenstal R., Lane W., Lucas K., White A., Bao S., White J., Jantzi C., Rasouli N., Ervin W., Lewy-Alterbaum L., Handelsman Y., Miranda-Palma B., Cleland A., Fink R., Rodbard H., Nakhle S., Greenberg C., Schorr A., Bays H., Simmons D., Klein E., Kane L., Fishman N., Ipp E., Garg S., Bhargava A., Singh M.Z., Rosenstock J., Thrasher J., Warren M., Young L., Aroda V., Pettus J., Liljenquist D., Busch R., Wise J., Kayne D., and Biggs W.
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Male ,Glycated Hemoglobin A ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Settore MED/13 - Endocrinologia ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,diabetes, dapaglifozin ,Glucosides ,Randomized controlled trial ,law ,Insulin ,03.02. Klinikai orvostan ,Dapagliflozin ,Middle Aged ,Diabetes and Metabolism ,Treatment Outcome ,Combination ,Drug Therapy, Combination ,Female ,Type 1 ,Adult ,medicine.medical_specialty ,Diabetic ketoacidosis ,030209 endocrinology & metabolism ,Placebo ,03 medical and health sciences ,Drug Therapy ,Diabetes management ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Benzhydryl Compounds ,Body Weight ,Diabetes Mellitus, Type 1 ,Hypoglycemia ,Glycated Hemoglobin ,Type 1 diabetes ,business.industry ,medicine.disease ,Surgery ,chemistry ,business - Abstract
Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1c after 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1c was 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1c compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42% [95% CI −0·56 to −0·28; p
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- 2017
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