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3. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

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Zhou Z., Jardine M. J., Li Q., Neuen B. L., Cannon C. P., De Zeeuw D., Edwards R., Levin A., Mahaffey K. W., Perkovic V., Neal B., Lindley R. I., Guerrero R. A. A., Aizenberg D., Albisu J. P., Alvarisqueta A., Bartolacci I., Berli M. A., Bordonava A., Calella P., Cantero M. C., Cartasegna L. R., Cercos E., Coloma G. C., Colombo H., Commendatore V., Cuadrado J., Cuneo C. A., Cusumano A. M., Douthat W. G., Dran R. D., Farias E., Fernandez M. F., Finkelstein H., Fragale G., Fretes J. O., Garcia N. H., Gastaldi A., Gelersztein E., Glenny J. A., Gonzalez J. P., Del Carmen Gonzalez Colaso P., Goycoa C., Greloni G. C., Guinsburg A., Hermida S., Juncos L. I., Klyver M. I., Kraft F., Krynski F., Lanchiotti P. V., De La Fuente R. A. L., Marchetta N., Mele P., Nicolai S., Novoa P. A., Orio S. I., Otreras F., Oviedo A., Raffaele P., Resk J. H., Rista L., Papini N. R., Sala J., Santos J. C., Schiavi L. B., Sessa H., Casabella T. S., Ulla M. R., Valdez M., Vallejos A., Villarino A., Visco V. E., Wassermann A., Zaidman C. J., Cheung N. W., Droste C., Fraser I., Johnson D., Mah P. M., Nicholls K., Packham D., Proietto J., Roberts A., Roger S., Tsang V., Raduan R. A., Da Costa F. A. A., Amodeo C., Turatti L. A. A., Bregman R., Sanches F. C. C., Canani L. H., Chacra A. R., Borges J. L. C., Vencio S. A. C., Da Silva Franco R. J., D'Avila D., De Souza Portes E., De Souza P., Deboni L. M., Filho F. F., Neto B. G., Gomes M., Kohara S. K., Keitel E., Saraiva J. F. K., Lisboa H. R. K., De Carvalho Contieri F. L., Milagres R., Junior R. M., De Brito C. M., Hissa M. N., Sabbag A. R. N., Noronha I., Panarotto D., Filho R. P., Pereira M. A., Saporito W., Scotton A. S., Schuch T., De Almeida R. S., Ramos C. S., Felicio J. S., Thome F., Hachmann J. C. T., Yamada S., Hayashida C. Y., Petry T. B. Z., Zanella M. T., Andreeva V., Angelova A., Dimitrov S., Genadieva V., Genova-Hristova G., Hristozov K., Kamenov Z., Koundurdjiev A., Lozanov L., Margaritov V., Nonchev B., Rangelov R., Shinkov A., Temelkova M., Velichkova E., Yakov A., Aggarwal N., Aronson R., Bajaj H., Cherney D., Chouinard G., Conway J., Cournoyer S., DaRoza G., De Serres S., Dube F., Goldenberg R., Gupta A., Gupta M., Henein S., Khandwala H., Leiter L., Madore F., Mc-Mahon A., Muirhead N., Pichette V., Rabasa-Lhoret R., Steele A., Tangri N., Torshizi A., Woo V., Zalunardo N., Montenegro M. A. F., Jorquera J. G. G., Farina M. M., Gajardo V. S., Vejar M., Chen N., Chen Q., Gan S., Kong Y., Li D., Li W., Li X., Lin H., Liu J., Lu W., Mao H., Ren Y., Song W., Sun J., Sun L., Tu P., Wang G., Yang J., Yin A., Yu X., Zhao M., Zheng H., Mendoza J. L. A., Arcos E., Avendano J., Ruiz J. E. A. D., Ortiz L. H. G., Gonzalez A., Triana E. H., Higuera J. D., Malaver N., De Salazar D. I. M., Rosero R., Lozano M. A. T., Cometa L. V., Valenzuela A., Alonso R. D. V., Villegas I., Yupanqui H., Bartaskova D., Barton P., Belobradkova J., Dohnalova L., Drasnar T., Ferkl R., Halciakova K., Klokocnikova V., Kovar R., Lastuvka J., Lukac M., Pesickova S., Peterka K., Pumprla J., Rychlik I., Saudek F., Tesar V., Valis M., Weiner P., Zemek S., Alamartine E., Borot S., Cariou B., Dussol B., Fauvel J. -P., Gourdy P., Klein A., Le Meur Y., Penfornis A., Roussel R., Saulnier P. -J., Thervet E., Zaoui P., Burst V., Faghih M., Faulmann G., Haller H., Jerwan-Keim R., Maxeiner S., Paschen B., Plassmann G., Rose L., Orellana R. A. G., Haase F. P., Diaz J. P. M., Roca L. A. R., Arenales J. A. S., Polo J. V. S., Juarez E. T., Csecsei G., Csiky B., Danos P., Deak L., Dudas M., Harcsa E., Keltai K., Keresztesi S., Kiss K., Konyves L., Major L., Mileder M., Molnar M., Mucsi J., Oroszlan T., Ory I., Paragh G., Peterfai E., Petro G., Revesz K., Takacs R., Vangel S., Vasas S., Zsom M., Oomman A., Raju S. B., Dewan D., Fernando M. E., Gopalakrishnan N., Gracious N., Alva H., Jain D., Keshavamurthy C. B., Khullar D., Sahay M., Peringat J., Prasad N., Rao K. S., Reddy S., Melemadathil S., Sudhakar B., Vyasam R. C., Bonadonna R., Castellino P., Ceriello A., Chiovato L., De Cosmo S., De Nicola L., Derosa G., Carlo A. D., Cianni G. D., Frasca G., Fuiano G., Gambaro G., Garibotto G., Giorda C., Malberti F., Mandreoli M., Mannucci E., Orsi E., Piatti P., Santoro D., Sasso F. C., Serviddio G., Stella A., Trevisan R., Veronelli A. M., Zanoli L., Akiyama H., Aoki H., Asano A., Iitsuka T., Kajiyama S., Kashine S., Kawada T., Kodera T., Kono H., Koyama K., Kumeda Y., Miyauchi S., Mizuyama K., Niiya T., Oishi H., Ota S., Sakakibara T., Takai M., Tomonaga O., Tsujimoto M., Wada T., Wakasugi M., Wakida Y., Watanabe T., Yamada M., Yanagida K., Yanase T., Yumita W., Gaupsiene E., Kozloviene D., Navickas A., Urbanaviciene E., Ghani R. A., Kadir K. A., Ali N., Yusof M. D. C., Gan C. L., Ismail M., Kong W. Y., Lam S. W., Lee L. Y., Lim S. K., Loh C. L., Manocha A. B., Ng K. S., Ahmad N. N. F. N., Ratnasingam V., Shudim S. S. B., Vengadasalam P., Munoz L. D. A., Salazar M. A., Cruz J. B., Soto M. B., Ramos J. C., Wong A. C., Rotter J. R. C., Escalante T. D., Sosa F. E. E., Lozano F. F., Cervera L. F. F., Baron P. F., Ballesteros C. G., Rangel J. D. G., Jimenez L. E. H., Santana S. S. I., Flores F. J., Molina H. L., Ceballos R. I. L., Del Campo Blanco B. M., Franco G. M., Loza O. T. M., Rocha C. M., Vera G. O., Castellanos R. O., Calcaneo J. P., Rosano M. A. R., Pattzi H. R., Guzman J. R., Joerg I. E. R., Sanchez S. B. S., Mijangos J. H. S., Sanson P. S., Tamayo Y Orozco J. A., Chavez E. T., Cepeda A. V., Carrillo L. V., Mesa J. V., Escobedo R. Z., Baker J., Noonan P., Scott R., Walker R., Watson E., Williams M., Young S., Abejuela Z., Agra J., Aquitania G., Caringal C., Comia R. S., Santos L. D., Gomez O., Jimeno C., Santos F., Tan G., Tolentino M., Yao C., Yap Y. E., Ygpuara M. D. L., Bijata-Bronisz R., Hotlos L., Januszewicz A., Kaczmarek B., Kaminska A., Lazuka L., Madej A., Mazur S., Mlodawska-Choluj D., Nowicki M., Orlowska-Kowalik G., Popenda G., Rewerska B., Sowinski D., Angelescu L. M., Anghel V., Avram R. -I., Busegeanu M. -M., Cif A., Cosma D., Crisan C., Demian L. D., Ferariu I. E., Halmagyi I., Hancu N., Munteanu M., Negru D., Onaca A. G., Petrica L., Popa A. R., Ranetti A. -E., Serafinceanu C., Toarba C., Agafyina A., Barbarash O., Barysheva O., Chizhov D., Dobronravov V., Dreval A., Glinkina I., Grineva E., Khirmanov V., Kolmakova E., Koroleva T., Kvitkova L., Marasaev V., Mkrtumyan A., Morugova T., Nagibovich G., Nagibovich O., Nedogoda S., Osipova I., Raskina T., Samoylova Y., Sazonova O., Shamkhalova M., Shutemova E., Shwartz Y., Uriasyev O., Vorobyev S., Zateyshchikova A., Zateyshshikov D., Zykova T., Antic S., Djordjevic M., Kendereski A., Lalic K., Lalic N., Popovic-Radinovic V., Babikova J., Benusova O., Buganova I., Culak J., Dzupina A., Dzuponova J., Fulop P., Ilavska A., Martinka E., Ochodnicka Z., Pella D., Smatanova I., Ahmed F., Badat A., Breedt J., Distiller L., Govender V., Govender R., Joshi M., Jurgens J., Latiff G., Lombard L., Mookadam M., Ngcakani N., Nortje H., Oosthuizen H., Pillay-Ramaya L., Prozesky H., Reddy J., Rheeder P., Seeber M., Chae D. -W., Cho Y. M., Jeong I. -K., Kim S. G., Kim Y. H., Kwon H. -S., Kwon M. J., Lee B. -W., Lee J., Lee M. -K., Nam M. -S., Oh K. -H., Park C. -Y., Park S. -H., Yoon K. H., Garcia P. A., Mercadal L. A., Barrios C., Castro F. C., Guldris S. C., Lopez M. D., De Los Rios J. E., Fresnedo G. F., Serrano A. G., Garcia I., Martinez F. J. G., Gimeno J. E. J., Mendoza M. L., Marin T. M., Portillo C. M., Vila M. A. M., Torres M. M., Iglesias J. N., Perez J. P., Vera M. P., Perez J. M. P., Simon M. A. Q., Canonge R. S., Gonzalez A. S., Riera M. T., Madueno F. J. T., Plaza M. V., Chang C. -T., Chuang L. -M., Hsia T. -L., Hsieh C. -H., Hwang S. -J., Lin C. -C., Lu Y. -C., Sheu W. H. -H., Barna O., Bilyk S. D., Botsyurko V., Dudar I., Fushtey I., Godlevska O., Golovchenko O., Gyrina O., Kazmirchuk A., Kolesnyk M., Komisarenko I., Korzh O., Kravchun N., Legun O., Mankovskyy B., Martynyuk L., Mostovoy Y., Pashkovska N., Pererva L., Pertseva T., Samoylov O., Smirnov I., Svyshchenko Y., Tomashkevych H., Topchii I., Tryshchuk N., Tseluyko V., Vizir V., Vlasenko M., Zlova T., Zub L., Abusnana S., Railey M., Abouglila K., Ainsworth P., Ali Z., Arutchelvam V., Barnard M., Bellary S., Davies E., Davies M., Davies S., Dawson A., Kossi M. E., English P., Fraser D., Gnudi L., Gunstone A., Hall T., Hanif W., Jackson A., Johnson A., Joseph F., Krishnan S., Kumwenda M., MacDougall I., Nixon P., O'Hare J., Philip S., Ramtoola S., Saxena M., Sennik D., Simon G., Singh B., Stephens J., Strzelecka A., Symonds R., Turner W., Wahba M., Wakeling J., Wheeler D., Winocour P., Abdallah J., Abdullah R., Abramowitz M., Acosta I., Aiello J., Akright L., Akyea-Djamson A., Alappan R., Alicic R., Al-Karadsheh A., Allison D. C., Arauz-Pacheco C., Arfeen S., Arif A., Arvind M., Atray N., Awad A., Bakris G., Barnhill P., Barranco E., Barrera C., Beacom M., Behara V., Belo D., Bentley-Lewis R., Berenguer R., Bermudez L., Bernardo M., Biscoveanu M., Bowman-Stroud C., Brandon D., Brusco O., Busch R., Canaan Y., Chilito A., Christensen T., Christiano C., Christofides E., Chuateco C., Cohen K., Cohen R., Cohen-Stein D., Cook C., Coyne D., Daboul N., Darwish R., Daswani A., Deck K., Desouza C., Dev D., Dhillon M., Dua S., Eder F., Elosegui A. M., El-Shahawy M., Ervin J., Esquenazi A., Evans J., Fishbane S., Frias J., Galindo-Ramos E., Galphin C., Ghazi A., Gonzalez E., Gorson D., Gowda A., Greco B., Grubb S., Gulati R., Hammoud J., Handelsman S., Hartman I., Hershon K., Hiser D., Hon G., Jacob R., Jaime M., Jamal A., Kaupke C., Keightley G., Kern E., Khanna R., Khitan Z., Kim S., Kopyt N., Kovesdy C., Krishna G., Kropp J., Kumar A., Kumar J., Kumar N., Kusnir J., Lane W., Lawrence M., Lehrner L., Lentz J., Levinson D., Lewis D., Liss K., Maddux A., Maheshwari H., Mandayam S., Marar I., Mehta B., Middleton J., Mordujovich J., Moreda R., Moustafa M., Trenche S. M., Narayanan M., Narvarte J., Nassar T., Newman G., Nichol B., Nicol P., Nisnisan J., Nossuli A. K., Obialo C., Olelewe S., Oliver M., O'Shaughnessy A., Padron J., Pankhaniya R., Parker R., Patel D., Patel G., Patel N., Pavon H., Perez A., Perez C., Perlman A., Pettis K., Pharr W., Phillips A., Purighalla R., Quesada-Suarez L., Ranjan R., Rastogi S., Rendell M., Rich L., Robinson M., Rodriguez H., Rosas S., Saba F., Sankaram R., Sarin R., Schreiman R., Scott D., Sekkarie M., Sensenbrenner J., Shakeel M., Shanik M., Shaw S., Smith S., Solomon R., Sprague A., Spry L., Suchinda P., Sultan S., Surampudi P., Sussman S., Tan A., Terrelonge A., Thompson M., Trespalacios F., Trippe B., Trueba P., Twahirwa M., Updegrove J., Van Buren P., Vannorsdall M., Varghese F., Velasquez-Mieyer P., Ventrapragada S., Vukotic G., Wadud K., Warren M., Watson H., Watts R., Weiner D., Welker J., Welsh J., Williams S., Zaniewski-Singh M., Zhou, Z., Jardine, M. J., Li, Q., Neuen, B. L., Cannon, C. P., De Zeeuw, D., Edwards, R., Levin, A., Mahaffey, K. W., Perkovic, V., Neal, B., Lindley, R. I., Guerrero, R. A. A., Aizenberg, D., Albisu, J. P., Alvarisqueta, A., Bartolacci, I., Berli, M. A., Bordonava, A., Calella, P., Cantero, M. C., Cartasegna, L. R., Cercos, E., Coloma, G. C., Colombo, H., Commendatore, V., Cuadrado, J., Cuneo, C. A., Cusumano, A. M., Douthat, W. G., Dran, R. D., Farias, E., Fernandez, M. F., Finkelstein, H., Fragale, G., Fretes, J. O., Garcia, N. H., Gastaldi, A., Gelersztein, E., Glenny, J. A., Gonzalez, J. P., Del Carmen Gonzalez Colaso, P., Goycoa, C., Greloni, G. C., Guinsburg, A., Hermida, S., Juncos, L. I., Klyver, M. I., Kraft, F., Krynski, F., Lanchiotti, P. V., De La Fuente, R. A. L., Marchetta, N., Mele, P., Nicolai, S., Novoa, P. A., Orio, S. I., Otreras, F., Oviedo, A., Raffaele, P., Resk, J. H., Rista, L., Papini, N. R., Sala, J., Santos, J. C., Schiavi, L. B., Sessa, H., Casabella, T. S., Ulla, M. R., Valdez, M., Vallejos, A., Villarino, A., Visco, V. E., Wassermann, A., Zaidman, C. J., Cheung, N. W., Droste, C., Fraser, I., Johnson, D., Mah, P. M., Nicholls, K., Packham, D., Proietto, J., Roberts, A., Roger, S., Tsang, V., Raduan, R. A., Da Costa, F. A. A., Amodeo, C., Turatti, L. A. A., Bregman, R., Sanches, F. C. C., Canani, L. H., Chacra, A. R., Borges, J. L. C., Vencio, S. A. C., Da Silva Franco, R. J., D'Avila, D., De Souza Portes, E., De Souza, P., Deboni, L. M., Filho, F. F., Neto, B. G., Gomes, M., Kohara, S. K., Keitel, E., Saraiva, J. F. K., Lisboa, H. R. K., De Carvalho Contieri, F. L., Milagres, R., Junior, R. M., De Brito, C. M., Hissa, M. N., Sabbag, A. R. N., Noronha, I., Panarotto, D., Filho, R. P., Pereira, M. A., Saporito, W., Scotton, A. S., Schuch, T., De Almeida, R. S., Ramos, C. S., Felicio, J. S., Thome, F., Hachmann, J. C. T., Yamada, S., Hayashida, C. Y., Petry, T. B. Z., Zanella, M. T., Andreeva, V., Angelova, A., Dimitrov, S., Genadieva, V., Genova-Hristova, G., Hristozov, K., Kamenov, Z., Koundurdjiev, A., Lozanov, L., Margaritov, V., Nonchev, B., Rangelov, R., Shinkov, A., Temelkova, M., Velichkova, E., Yakov, A., Aggarwal, N., Aronson, R., Bajaj, H., Cherney, D., Chouinard, G., Conway, J., Cournoyer, S., Daroza, G., De Serres, S., Dube, F., Goldenberg, R., Gupta, A., Gupta, M., Henein, S., Khandwala, H., Leiter, L., Madore, F., Mc-Mahon, A., Muirhead, N., Pichette, V., Rabasa-Lhoret, R., Steele, A., Tangri, N., Torshizi, A., Woo, V., Zalunardo, N., Montenegro, M. A. F., Jorquera, J. G. G., Farina, M. M., Gajardo, V. S., Vejar, M., Chen, N., Chen, Q., Gan, S., Kong, Y., Li, D., Li, W., Li, X., Lin, H., Liu, J., Lu, W., Mao, H., Ren, Y., Song, W., Sun, J., Sun, L., Tu, P., Wang, G., Yang, J., Yin, A., Yu, X., Zhao, M., Zheng, H., Mendoza, J. L. A., Arcos, E., Avendano, J., Ruiz, J. E. A. D., Ortiz, L. H. G., Gonzalez, A., Triana, E. H., Higuera, J. D., Malaver, N., De Salazar, D. I. M., Rosero, R., Lozano, M. A. T., Cometa, L. V., Valenzuela, A., Alonso, R. D. V., Villegas, I., Yupanqui, H., Bartaskova, D., Barton, P., Belobradkova, J., Dohnalova, L., Drasnar, T., Ferkl, R., Halciakova, K., Klokocnikova, V., Kovar, R., Lastuvka, J., Lukac, M., Pesickova, S., Peterka, K., Pumprla, J., Rychlik, I., Saudek, F., Tesar, V., Valis, M., Weiner, P., Zemek, S., Alamartine, E., Borot, S., Cariou, B., Dussol, B., Fauvel, J. -P., Gourdy, P., Klein, A., Le Meur, Y., Penfornis, A., Roussel, R., Saulnier, P. -J., Thervet, E., Zaoui, P., Burst, V., Faghih, M., Faulmann, G., Haller, H., Jerwan-Keim, R., Maxeiner, S., Paschen, B., Plassmann, G., Rose, L., Orellana, R. A. G., Haase, F. P., Diaz, J. P. M., Roca, L. A. R., Arenales, J. A. S., Polo, J. V. S., Juarez, E. T., Csecsei, G., Csiky, B., Danos, P., Deak, L., Dudas, M., Harcsa, E., Keltai, K., Keresztesi, S., Kiss, K., Konyves, L., Major, L., Mileder, M., Molnar, M., Mucsi, J., Oroszlan, T., Ory, I., Paragh, G., Peterfai, E., Petro, G., Revesz, K., Takacs, R., Vangel, S., Vasas, S., Zsom, M., Oomman, A., Raju, S. B., Dewan, D., Fernando, M. E., Gopalakrishnan, N., Gracious, N., Alva, H., Jain, D., Keshavamurthy, C. B., Khullar, D., Sahay, M., Peringat, J., Prasad, N., Rao, K. S., Reddy, S., Melemadathil, S., Sudhakar, B., Vyasam, R. C., Bonadonna, R., Castellino, P., Ceriello, A., Chiovato, L., De Cosmo, S., De Nicola, L., Derosa, G., Carlo, A. D., Cianni, G. D., Frasca, G., Fuiano, G., Gambaro, G., Garibotto, G., Giorda, C., Malberti, F., Mandreoli, M., Mannucci, E., Orsi, E., Piatti, P., Santoro, D., Sasso, F. C., Serviddio, G., Stella, A., Trevisan, R., Veronelli, A. M., Zanoli, L., Akiyama, H., Aoki, H., Asano, A., Iitsuka, T., Kajiyama, S., Kashine, S., Kawada, T., Kodera, T., Kono, H., Koyama, K., Kumeda, Y., Miyauchi, S., Mizuyama, K., Niiya, T., Oishi, H., Ota, S., Sakakibara, T., Takai, M., Tomonaga, O., Tsujimoto, M., Wada, T., Wakasugi, M., Wakida, Y., Watanabe, T., Yamada, M., Yanagida, K., Yanase, T., Yumita, W., Gaupsiene, E., Kozloviene, D., Navickas, A., Urbanaviciene, E., Ghani, R. A., Kadir, K. A., Ali, N., Yusof, M. D. C., Gan, C. L., Ismail, M., Kong, W. Y., Lam, S. W., Lee, L. Y., Lim, S. K., Loh, C. L., Manocha, A. B., Ng, K. S., Ahmad, N. N. F. N., Ratnasingam, V., Shudim, S. S. B., Vengadasalam, P., Munoz, L. D. A., Salazar, M. A., Cruz, J. B., Soto, M. B., Ramos, J. C., Wong, A. C., Rotter, J. R. C., Escalante, T. D., Sosa, F. E. E., Lozano, F. F., Cervera, L. F. F., Baron, P. F., Ballesteros, C. G., Rangel, J. D. G., Jimenez, L. E. H., Santana, S. S. I., Flores, F. J., Molina, H. L., Ceballos, R. I. L., Del Campo Blanco, B. M., Franco, G. M., Loza, O. T. M., Rocha, C. M., Vera, G. O., Castellanos, R. O., Calcaneo, J. P., Rosano, M. A. R., Pattzi, H. R., Guzman, J. R., Joerg, I. E. R., Sanchez, S. B. S., Mijangos, J. H. S., Sanson, P. S., Tamayo Y Orozco, J. A., Chavez, E. T., Cepeda, A. V., Carrillo, L. V., Mesa, J. V., Escobedo, R. Z., Baker, J., Noonan, P., Scott, R., Walker, R., Watson, E., Williams, M., Young, S., Abejuela, Z., Agra, J., Aquitania, G., Caringal, C., Comia, R. S., Santos, L. D., Gomez, O., Jimeno, C., Santos, F., Tan, G., Tolentino, M., Yao, C., Yap, Y. E., Ygpuara, M. D. L., Bijata-Bronisz, R., Hotlos, L., Januszewicz, A., Kaczmarek, B., Kaminska, A., Lazuka, L., Madej, A., Mazur, S., Mlodawska-Choluj, D., Nowicki, M., Orlowska-Kowalik, G., Popenda, G., Rewerska, B., Sowinski, D., Angelescu, L. M., Anghel, V., Avram, R. -I., Busegeanu, M. -M., Cif, A., Cosma, D., Crisan, C., Demian, L. D., Ferariu, I. E., Halmagyi, I., Hancu, N., Munteanu, M., Negru, D., Onaca, A. G., Petrica, L., Popa, A. R., Ranetti, A. -E., Serafinceanu, C., Toarba, C., Agafyina, A., Barbarash, O., Barysheva, O., Chizhov, D., Dobronravov, V., Dreval, A., Glinkina, I., Grineva, E., Khirmanov, V., Kolmakova, E., Koroleva, T., Kvitkova, L., Marasaev, V., Mkrtumyan, A., Morugova, T., Nagibovich, G., Nagibovich, O., Nedogoda, S., Osipova, I., Raskina, T., Samoylova, Y., Sazonova, O., Shamkhalova, M., Shutemova, E., Shwartz, Y., Uriasyev, O., Vorobyev, S., Zateyshchikova, A., Zateyshshikov, D., Zykova, T., Antic, S., Djordjevic, M., Kendereski, A., Lalic, K., Lalic, N., Popovic-Radinovic, V., Babikova, J., Benusova, O., Buganova, I., Culak, J., Dzupina, A., Dzuponova, J., Fulop, P., Ilavska, A., Martinka, E., Ochodnicka, Z., Pella, D., Smatanova, I., Ahmed, F., Badat, A., Breedt, J., Distiller, L., Govender, V., Govender, R., Joshi, M., Jurgens, J., Latiff, G., Lombard, L., Mookadam, M., Ngcakani, N., Nortje, H., Oosthuizen, H., Pillay-Ramaya, L., Prozesky, H., Reddy, J., Rheeder, P., Seeber, M., Chae, D. -W., Cho, Y. 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Subjects
medicine.medical_specialty, Original Contributions, atrial fibrillation, canagliflozin, glomerular filtration rate, hemorrhagic stroke, ischemic stroke, Renal function, Disease, Brain Ischemia, Clinical and Population Sciences, Meta-Analysis as Topic, Internal medicine, CREDENCE Trial Investigators, Atrial Fibrillation, medicine, Diabetes Mellitus, Humans, Diabetic Nephropathies, Canagliflozin, Stroke, 1102 Cardiorespiratory Medicine and Haematology, Sodium-Glucose Transporter 2 Inhibitors, Advanced and Specialized Nursing, Neurology & Neurosurgery, business.industry, Atrial fibrillation, 1103 Clinical Sciences, medicine.disease, Diabetes Mellitus, Type 2, Meta-analysis, Cardiology, Albuminuria, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, 1109 Neurosciences, Kidney disease, medicine.drug
Abstract

Supplemental Digital Content is available in the text., Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (

Published
2021

5. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Author

Natarajan, P. (Pradeep), Pampana, A. (Akhil), Graham, S. E. (Sarah E.), Ruotsalainen, S. E. (Sanni E.), Perry, J. A. (James A.), de Vries, P. S. (Paul S.), Broome, J. G. (Jai G.), Pirruccello, J. P. (James P.), Honigbere, M. C. (Michael C.), Aragam, K. (Krishna), Wolford, B. (Brooke), Brody, J. A. (Jennifer A.), Antonacci-Fulton, L. (Lucinda), Arden, M. (Moscati), Aslibekyan, S. (Stella), Assimes, T. L. (Themistocles L.), Ballantyne, C. M. (Christie M.), Bielak, L. F. (Lawrence F.), Bisl, J. C. (Joshua C.), Cade, B. E. (Brian E.), Do, R. (Ron), Doddapaneni, H. (Harsha), Emery, L. S. (Leslie S.), Hung, Y.-J. (Yi-Jen), Irvin, M. R. (Marguerite R.), Khan, A. T. (Alyna T.), Lange, L. (Leslie), Lee, J. (Jiwon), Lemaitre, R. N. (Rozenn N.), Martin, L. W. (Lisa W.), Metcalf, G. (Ginger), Montasser, M. E. (May E.), Moon, J.-Y. (Jee-Young), Muzny, D. (Donna), Connell, J. R. (Jeffrey R. O.), Palmer, N. D. (Nicholette D.), Peralta, J. M. (Juan M.), Peyser, P. A. (Patricia A.), Stilp, A. M. (Adrienne M.), Tsai, M. (Michael), Wang, F. F. (Fei Fei), Weeks, D. E. (Daniel E.), Yanek, L. R. (Lisa R.), Wilson, J. G. (James G.), Abecasis, G. (Goncalo), Arnett, D. K. (Donna K.), Becker, L. C. (Lewis C.), Blangercy, J. (John), Boerwinkle, E. (Eric), Bowden, D. W. (Donald W.), Chang, Y.-C. (Yi-Cheng), Chen, Y. I. (Yii-Der, I), Choi, W. J. (Won Jung), Correa, A. (Adolfo), Curran, J. E. (Joanne E.), Daly, M. J. (Mark J.), DutcherE, S. K. (Susan K.), Ellinor, P. T. (Patrick T.), Fornage, M. (Myriam), Freedman, B. I. (Barry, I), Gabriel, S. (Stacey), Germer, S. (Soren), Gibbs, R. A. (Richard A.), He, J. (Jiang), Hveem, K. (Kristian), Jarvik, G. P. (Gail P.), Kaplan, R. C. (Robert C.), Kardia, S. L. (Sharon L. R.), Kennyn, E. (Eimear), Kim, R. W. (Ryan W.), Kooperberg, C. (Charles), Laurie, C. C. (Cathy C.), Lee, S. (Seonwook), Lloyd-Jones, D. M. (Don M.), Loos, R. J. (Ruth J. F.), Lubitz, S. A. (Steven A.), Mathias, R. A. (Rasika A.), Martinez, K. A. (Karine A. Viaud), McGarvey, S. T. (Stephen T.), Mitche, B. D. (Braxton D.), Nickerson, D. A. (Deborah A.), North, K. E. (Kari E.), Palotie, A. (Aarno), Park, C. J. (Cheol Joo), Psat, B. M. (Bruce M. Y.), Rao, D. C. (D. C.), Redline, S. (Susan), Reiner, A. P. (Alexander P.), Seo, D. (Daekwan), Seo, J.-S. (Jeong-Sun), Smith, A. V. (Albert, V), Tracy, R. P. (Russell P.), Kathiresan, S. (Sekar), Cupples, L. A. (L. Adrienne), Rotten, J. I. (Jerome, I), Morrison, A. C. (Alanna C.), Rich, S. S. (Stephen S.), Ripatti, S. (Samuli), Wilier, C. (Cristen), Peloso, G. M. (Gina M.), Vasan, R. S. (Ramachandran S.), Abe, N. (Namiko), Albert, C. (Christine), Almasy, L. (Laura), Alonso, A. (Alvaro), Ament, S. (Seth), Anderson, P. (Peter), Applebaum-Bowden, D. (Deborah), Arking, D. (Dan), Ashley-Koch, A. (Allison), Auer, P. (Paul), Avramopoulos, D. (Dimitrios), Barnard, J. (John), Barnes, K. (Kathleen), Barr, R. G. (R. Graham), Barron-Casella, E. (Emily), Beaty, T. (Terri), Becker, D. (Diane), Beer, R. (Rebecca), Begum, F. (Ferdouse), Beitelshees, A. (Amber), Benjamin, E. (Emelia), Bezerra, M. (Marcos), Bielak, L. (Larry), Blackwel, T. (Thomas), Bowler, R. (Russell), Broecke, U. (Ulrich), Bunting, K. (Karen), Burchard, E. (Esteban), Buth, E. (Erin), Cardwel, J. (Jonathan), Carty, C. (Cara), Casaburi, R. (Richard), Casella, J. (James), Chaffin, M. (Mark), Chang, C. (Christy), Chasman, D. (Daniel), Chavan, S. (Sameer), Chen, B.-J. (Bo-Juen), Chen, W.-M. (Wei-Min), Chol, M. (Michael), Choi, S. H. (Seung Hoan), Chuang, L.-M. (Lee-Ming), Chung, M. (Mina), Conomos, M. P. (Matthew P.), Cornell, E. (Elaine), Crapo, J. (James), Curtis, J. (Jeffrey), Custer, B. (Brian), Damcott, C. (Coleen), Darbar, D. (Dawood), Das, S. (Sayantan), David, S. (Sean), Davis, C. (Colleen), Daya, M. (Michelle), de Andrade, M. (Mariza), DeBaunuo, M. (Michael), Duan, Q. (Qing), Devine, R. D. (Ranjan Deka Dawn DeMeo Scott), Duggirala, Q. R. (Qing Ravi), Durda, J. P. (Jon Peter), Dutcher, S. (Susan), Eaton, C. (Charles), Ekunwe, L. (Lynette), Farber, C. (Charles), Farnaml, L. (Leanna), Fingerlin, T. (Tasha), Flickinger, M. (Matthew), Franceschini, N. (Nora), Fu, M. (Mao), Fullerton, S. M. (Stephanie M.), Fulton, L. (Lucinda), Gan, W. (Weiniu), Gao, Y. (Yan), Gass, M. (Margery), Ge, B. (Bruce), Geng, X. P. (Xiaoqi Priscilla), Gignoux, C. (Chris), Gladwin, M. (Mark), Glahn, D. (David), Gogarten, S. (Stephanie), Gong, D.-W. (Da-Wei), Goring, H. (Harald), Gu, C. C. (C. Charles), Guan, Y. (Yue), Guo, X. (Xiuqing), Haessler, J. (Jeff), Hall, M. (Michael), Harris, D. (Daniel), Hawle, N. Y. (Nicola Y.), Heavner, B. (Ben), Heckbert, S. (Susan), Hernandez, R. (Ryan), Herrington, D. (David), Hersh, C. (Craig), Hidalgo, B. (Bertha), Hixson, J. (James), Hokanson, J. (John), Hong, E. (Elliott), Hoth, K. (Karin), Hsiung, C. A. (Chao Agnes), Huston, H. (Haley), Hwu, C. M. (Chii Min), Jackson, R. (Rebecca), Jain, D. (Deepti), Jaquish, C. (Cashell), Jhun, M. A. (Min A.), Johnsen, J. (Jill), Johnson, A. (Andrew), Johnson, C. (Craig), Johnston, R. (Rich), Jones, K. (Kimberly), Kang, H. M. (Hyun Min), Kaufman, L. (Laura), Kell, S. Y. (Shannon Y.), Kessler, M. (Michael), Kinney, G. (Greg), Konkle, B. (Barbara), Kramer, H. (Holly), Krauter, S. (Stephanie), Lange, C. (Christoph), Lange, E. (Ethan), Laurie, C. (Cecelia), LeBoff, M. (Meryl), Lee, S. S. (Seunggeun Shawn), Lee, W.-J. (Wen-Jane), LeFaive, J. (Jonathon), Levine, D. (David), Levy, D. (Dan), Lewis, J. (Joshua), Li, Y. (Yun), Lin, H. (Honghuang), Lin, K. H. (Keng Han), Lin, X. (Xihong), Liu, S. (Simin), Liu, Y. (Yongmei), Lunetta, K. (Kathryn), Luo, J. (James), Mahaney, M. (Michael), Make, B. (Barry), Manichaikul, A. (Ani), Mansonl, J. (JoAnn), Margolin, L. (Lauren), Mathai, S. (Susan), McArdle, P. (Patrick), Mcdonald, M.-L. (Merry-Lynn), McFarland, S. (Sean), McHugh, C. (Caitlin), Mei, H. (Hao), Meyers, D. A. (Deborah A.), Mikulla, J. (Julie), Min, N. (Nancy), Minear, M. (Mollie), Minster, R. L. (Ryan L.), Musani, S. (Solomon), Mwasongwe, S. (Stanford), Mychaleckyj, J. C. (Josyf C.), Nadkarni, G. (Girish), Naik, R. (Rakhi), Naseri, T. (Take), Nekhai, S. (Sergei), Nelson, S. C. (Sarah C.), Nickerson, D. (Deborah), Connell, J. O. (Jeff O.), Connor, T. O. (Tim O.), Ochs-Balcom, H. (Heather), Pankow, J. (James), Papanicolaou, G. (George), Parkerl, M. (Margaret), Parsa, A. (Afshin), Penchey, S. (Sara), Perez, M. (Marco), Peters, U. (Ulrike), Phillips, L. S. (Lawrence S.), Phillips, S. (Sam), Pollin, T. (Toni), Post, W. (Wendy), Becker, J. P. (Julia Powers), Boorgula, M. P. (Meher Preethi), Preuss, M. (Michael), Prokopenko, D. (Dmitry), Qasba, P. (Pankaj), Qiao, D. (Dandi), Rafaels, N. (Nicholas), Raffield, L. (Laura), Rasmussen-Torvik, L. (Laura), Ratan, A. (Aakrosh), Reed, R. (Robert), Reganl, E. (Elizabeth), Reupena, M. S. (Muagututi Sefuiva), Rice, K. (Ken), Roden, D. (Dan), Roselli, C. (Carolina), Ruczinski, I. (Ingo), Russel, P. (Pamela), Ruuska, S. (Sarah), Ryan, K. (Kathleen), Sabino, E. C. (Ester Cerdeira), Sakornsakolpatl, P. (Phuwanat), Salzberg, S. (Steven), Sandow, K. (Kevin), Sankaran, V. G. (Vijay G.), Scheller, C. (Christopher), Schmidt, E. (Ellen), Schwander, K. (Karen), Schwartz, D. (David), Sciurba, F. (Frank), Seidman, C. (Christine), Seidman, J. (Jonathan), Sheehan, V. (Vivien), Shetty, A. (Amol), Shetty, A. (Aniket), Sheu, W. H. (Wayne Hui-Heng), Shoemaker, M. B. (M. Benjamin), Silver, B. (Brian), Silvermanl, E. (Edwin), Smith, J. (Jennifer), Smith, J. (Josh), Smith, N. (Nicholas), Smith, T. (Tanja), Smoller, S. (Sylvia), Snively, B. (Beverly), Soferlm, T. (Tamar), Streeten, E. (Elizabeth), Su, J. L. (Jessica Lasky), Sung, Y. J. (Yun Ju), Sylvia, J. (Jody), Sztalryd, C. (Carole), Taliun, D. (Daniel), Tang, H. (Hua), Taub, M. (Margaret), Taylor, K. D. (Kent D.), Taylor, S. (Simeon), Telen, M. (Marilyn), Thornton, T. A. (Timothy A.), Tinker, L. (Lesley), Tirschwel, D. (David), Tiwari, H. (Hemant), Vaidya, D. (Dhananjay), VandeHaar, P. (Peter), Vrieze, S. (Scott), Walker, T. (Tarik), Wallace, R. (Robert), Waits, A. (Avram), Wan, E. (Emily), Wang, H. (Heming), Watson, K. (Karol), Weir, B. (Bruce), Weiss, S. (Scott), Weng, L.-C. (Lu-Chen), Williams, K. (Kayleen), Williams, L. K. (L. Keoki), Wilson, C. (Carla), Wong, Q. (Quenna), Xu, H. (Huichun), Yang, I. (Ivana), Yang, R. (Rongze), Zaghlou, N. (Norann), Zekavat, M. (Maryam), Zhang, Y. (Yingze), Zhao, S. X. (Snow Xueyan), Zhao, W. (Wei), Zni, D. (Degui), Zhou, X. (Xiang), Zhu, X. (Xiaofeng), Zody, M. (Michael), Zoellner, S. (Sebastian), Daly, M. (Mark), Jacob, H. (Howard), Matakidou, A. (Athena), Runz, H. (Heiko), John, S. (Sally), Plenge, R. (Robert), McCarthy, M. (Mark), Hunkapiller, J. (Julie), Ehm, M. (Meg), Waterworth, D. (Dawn), Fox, C. (Caroline), Malarstig, A. (Anders), Klinger, K. (Kathy), Call, K. (Kathy), Mkel, T. (Tomi), Kaprio, J. (Jaakko), Virolainen, P. (Petri), Pulkki, K. (Kari), Kilpi, T. (Terhi), Perola, M. (Markus), Partanen, J. (Jukka), Pitkranta, A. (Anne), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Savinainen, K. (Kimmo), Kosma, V.-M. (Veli-Matti), Kujala, U. (Urho), Tuovila, O. (Outi), Hendolin, M. (Minna), Pakkanen, R. (Raimo), Waring, J. (Jeff), Riley-Gillis, B. (Bridget), Liu, J. (Jimmy), Biswas, S. (Shameek), Diogo, D. (Dorothee), Marshall, C. (Catherine), Hu, X. (Xinli), Gossel, M. (Matthias), Schleutker, J. (Johanna), Arvas, M. (Mikko), Hinttala, R. (Reetta), Kettunen, J. (Johannes), Laaksonen, R. (Reijo), Mannermaa, A. (Arto), Paloneva, J. (Juha), Soininen, H. (Hilkka), Julkunen, V. (Valtteri), Remes, A. (Anne), Klviinen, R. (Reetta), Hiltunen, M. (Mikko), Peltola, J. (Jukka), Tienari, P. (Pentti), Rinne, J. (Juha), Ziemann, A. (Adam), Waring, J. (Jeffrey), Esmaeeli, S. (Sahar), Smaoui, N. (Nizar), Lehtonen, A. (Anne), Eaton, S. (Susan), Landenper, S. (Sanni), Michon, J. (John), Kerchner, G. (Geoff), Bowers, N. (Natalie), Teng, E. (Edmond), Eicher, J. (John), Mehta, V. (Vinay), Gormle, P. Y. (Padhraig Y.), Linden, K. (Kari), Whelan, C. (Christopher), Xu, F. (Fanli), Pulford, D. (David), Frkkil, M. (Martti), Pikkarainen, S. (Sampsa), Jussila, A. (Airi), Blomster, T. (Timo), Kiviniemi, M. (Mikko), Voutilainen, M. (Markku), Georgantas, B. (Bob), Heap, G. (Graham), Rahimov, F. (Fedik), Usiskin, K. (Keith), Maranville, J. (Joseph), Lu, T. (Tim), Oh, D. (Danny), Kalpala, K. (Kirsi), Miller, M. (Melissa), McCarthy, L. (Linda), Eklund, K. (Kari), Palomki, A. (Antti), Isomki, P. (Pia), Piri, L. (Laura), Kaipiainen-Seppnen, O. (Oili), Lertratanaku, A. (Apinya), Bing, D. C. (David Close Marla Hochfeld Nan), Gordillo, J. E. (Jorge Esparza), Mars, N. (Nina), Laitinen, T. (Tarja), Pelkonen, M. (Margit), Kauppi, P. (Paula), Kankaanranta, H. (Hannu), Harju, T. (Terttu), Greenberg, S. (Steven), Chen, H. (Hubert), Betts, J. (Jo), Ghosh, S. (Soumitra), Salomaa, V. (Veikko), Niiranen, T. (Teemu), Juonala, M. (Markus), Metsrinne, K. (Kaj), Khnen, M. (Mika), Junttila, J. (Juhani), Laakso, M. (Markku), Pihlajamki, J. (Jussi), Sinisalo, J. (Juha), Taskinen, M.-R. (Marja-Riitta), Tuomi, T. (Tiinamaija), Laukkanen, J. (Jari), Challis, B. (Ben), Peterson, A. (Andrew), Chu, A. (Audrey), Parkkinen, J. (Jaakko), Muslin, A. (Anthony), Joensuu, H. (Heikki), Meretoja, T. (Tuomo), Aaltonen, L. (Lauri), Auranen, A. (Annika), Karihtala, P. (Peeter), Kauppila, S. (Saila), Auvinen, P. (Pivi), Elenius, K. (Klaus), Popovic, R. (Relja), Schutzman, J. (Jennifer), Loboda, A. (Andrey), Chhibber, A. (Aparna), Lehtonen, H. (Heli), McDonough, S. (Stefan), Crohns, M. (Marika), Kulkarni, D. (Diptee), Kaarniranta, K. (Kai), Turunen, J. (Joni), Ollila, T. (Terhi), Seitsonen, S. (Sanna), Uusitalo, H. (Hannu), Aaltonen, V. (Vesa), Uusitalo-Jrvinen, H. (Hannele), Luodonp, M. (Marja), Hautala, N. (Nina), Strauss, E. (Erich), Chen, H. (Hao), Podgornaia, A. (Anna), Hoffman, J. (Joshua), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Hannula-Jouppi, K. (Katariina), Salmi, T. (Teea), Peltonen, S. (Sirkku), Koulu, L. (Leena), Harvima, I. (Ilkka), Wu, Y. (Ying), Choy, D. (David), Jalanko, A. (Anu), Kajanne, R. (Risto), Lyhs, U. (Ulrike), Kaunisto, M. (Mari), Davis, J. W. (Justin Wade), Quarless, D. (Danjuma), Petrovski, S. (Slav), Chen, C.-Y. (Chia-Yen), Bronson, P. (Paola), Yang, R. (Robert), Chang, D. (Diana), Bhangale, T. (Tushar), Holzinger, E. (Emily), Wang, X. (Xulong), Chen, X. (Xing), Auro, K. (Kirsi), Wang, C. (Clarence), Xu, E. (Ethan), Auge, F. (Franck), Chatelain, C. (Clement), Kurki, M. (Mitja), Karjalainen, J. (Juha), Havulinna, A. (Aki), Palin, K. (Kimmo), Palta, P. (Priit), Parolo, P. D. (Pietro Della Briotta), Zhou, W. (Wei), Lemmel, S. (Susanna), Rivas, M. (Manuel), Harju, J. (Jarmo), Lehisto, A. (Arto), Ganna, A. (Andrea), Llorens, V. (Vincent), Karlsson, A. (Antti), Kristiansson, K. (Kati), Hyvrinen, K. (Kati), Ritari, J. (Jarmo), Wahlfors, T. (Tiina), Koskinen, M. (Miika), Pylkäs, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Mantere, T. (Tuomo), Kangasniemi, E. (Eeva), Heikkinen, S. (Sami), Laakkonen, E. (Eija), Kononen, J. (Juha), Loukola, A. (Anu), Laiho, P. (Pivi), Sistonen, T. (Tuuli), Kaiharju, E. (Essi), Laukkanen, M. (Markku), Jrvensivu, E. (Elina), Lhteenmki, S. (Sini), Mnnikk, L. (Lotta), Wong, R. (Regis), Mattsson, H. (Hannele), Hiekkalinna, T. (Tero), Jimnez, M. G. (Manuel Gonzlez), Donner, K. (Kati), Prn, K. (KaIle), Nunez-Fontarnau, J. (Javier), Kilpelinen, E. (Elina), Sipi, T. P. (Timo P.), Brein, G. (Georg), Dada, A. (Alexander), Awaisa, G. (Ghazal), Shcherban, A. (Anastasia), Sipil, T. (Tuomas), Laivuori, H. (Hannele), Kiiskinen, T. (Tuomo), Siirtola, H. (Harri), Tabuenca, J. G. (Javier Gracia), Kallio, L. (Lila), Soini, S. (Sirpa), Pitknen, K. (Kimmo), and Kuopio, T. (Teijo)

Subjects
Cardiovascular genetics, Genome-wide association studies
Abstract

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.

Published
2021

6. Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

Author

Zhou, Z, Jardine, M, Li, Q, Neuen, B, Cannon, C, De Zeeuw, D, Edwards, R, Levin, A, Mahaffey, K, Perkovic, V, Neal, B, Lindley, R, Guerrero, R, Aizenberg, D, Albisu, J, Alvarisqueta, A, Bartolacci, I, Berli, M, Bordonava, A, Calella, P, Cantero, M, Cartasegna, L, Cercos, E, Coloma, G, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, C, Cusumano, A, Douthat, W, Dran, R, Farias, E, Fernandez, M, Finkelstein, H, Fragale, G, Fretes, J, Garcia, N, Gastaldi, A, Gelersztein, E, Glenny, J, Gonzalez, J, Del Carmen Gonzalez Colaso, P, Goycoa, C, Greloni, G, Guinsburg, A, Hermida, S, Juncos, L, Klyver, M, Kraft, F, Krynski, F, Lanchiotti, P, De La Fuente, R, Marchetta, N, Mele, P, Nicolai, S, Novoa, P, Orio, S, Otreras, F, Oviedo, A, Raffaele, P, Resk, J, Rista, L, Papini, N, Sala, J, Santos, J, Schiavi, L, Sessa, H, Casabella, T, Ulla, M, Valdez, M, Vallejos, A, Villarino, A, Visco, V, Wassermann, A, Zaidman, C, Cheung, N, Droste, C, Fraser, I, Johnson, D, Mah, P, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, R, Da Costa, F, Amodeo, C, Turatti, L, Bregman, R, Sanches, F, Canani, L, Chacra, A, Borges, J, Vencio, S, Da Silva Franco, R, D'Avila, D, De Souza Portes, E, De Souza, P, Deboni, L, Filho, F, Neto, B, Gomes, M, Kohara, S, Keitel, E, Saraiva, J, Lisboa, H, De Carvalho Contieri, F, Milagres, R, Junior, R, De Brito, C, Hissa, M, Sabbag, A, Noronha, I, Panarotto, D, Filho, R, Pereira, M, Saporito, W, Scotton, A, Schuch, T, De Almeida, R, Ramos, C, Felicio, J, Thome, F, Hachmann, J, Yamada, S, Hayashida, C, Petry, T, Zanella, M, Andreeva, V, Angelova, A, Dimitrov, S, Genadieva, V, Genova-Hristova, G, Hristozov, K, Kamenov, Z, Koundurdjiev, A, Lozanov, L, Margaritov, V, Nonchev, B, Rangelov, R, Shinkov, A, Temelkova, M, Velichkova, E, Yakov, A, Aggarwal, N, Aronson, R, Bajaj, H, Cherney, D, Chouinard, G, Conway, J, Cournoyer, S, Daroza, G, De Serres, S, Dube, F, Goldenberg, R, Gupta, A, Gupta, M, Henein, S, Khandwala, H, Leiter, L, Madore, F, Mc-Mahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, N, Montenegro, M, Jorquera, J, Farina, M, Gajardo, V, Vejar, M, Chen, N, Chen, Q, Gan, S, Kong, Y, Li, D, Li, W, Li, X, Lin, H, Liu, J, Lu, W, Mao, H, Ren, Y, Song, W, Sun, J, Sun, L, Tu, P, Wang, G, Yang, J, Yin, A, Yu, X, Zhao, M, Zheng, H, Mendoza, J, Arcos, E, Avendano, J, Ruiz, J, Ortiz, L, Gonzalez, A, Triana, E, Higuera, J, Malaver, N, De Salazar, D, Rosero, R, Lozano, M, Cometa, L, Valenzuela, A, Alonso, R, Villegas, I, Yupanqui, H, Bartaskova, D, Barton, P, Belobradkova, J, Dohnalova, L, Drasnar, T, Ferkl, R, Halciakova, K, Klokocnikova, V, Kovar, R, Lastuvka, J, Lukac, M, Pesickova, S, Peterka, K, Pumprla, J, Rychlik, I, Saudek, F, Tesar, V, Valis, M, Weiner, P, Zemek, S, Alamartine, E, Borot, S, Cariou, B, Dussol, B, Fauvel, J, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, P, Thervet, E, Zaoui, P, Burst, V, Faghih, M, Faulmann, G, 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Abstract

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect

Published
2021

8. Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data

Author

Cardwell, C. R., Stene, L. C., Joner, G., Davis, E. A., Cinek, O., Rosenbauer, J., Ludvigsson, J., Castell, C., Svensson, J., Goldacre, M. J., Waldhoer, T., Polanska, J., Gimeno, S. G. A., Chuang, L.-M., Parslow, R. C., Wadsworth, E. J. K., Chetwynd, A., Pozzilli, P., Brigis, G., Urbonaitė, B., Šipetić, S., Schober, E., Ionescu-Tirgoviste, C., de Beaufort, C. E., Stoyanov, D., Buschard, K., and Patterson, C. C.

Published
2010
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23. Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups Results From the Randomized CREDENCE Trial

Author

Mahaffey, KW, Jardine, MJ, Bompoint, S, Cannon, CP, Neal, B, Heerspink, HJL, Charytan, DM, Edwards, R, Agarwal, R, Bakris, G, Bull, S, Capuano, G, de Zeeuw, D, Greene, T, Levin, A, Pollock, C, Sun, T, Wheeler, DC, Yavin, Y, Zhang, H, Zinman, B, Rosenthal, N, Brenner, BM, Perkovic, V, Ahuad Guerrero, RA, Aizenberg, D, Pablo Albisu, J, Alvarisqueta, A, Bartolacci, I, Alberto Berli, M, Bordonava, A, Calella, P, Cecilia Cantero, M, Rodolfo Cartasegna, L, Cercos, E, Cecilia Coloma, G, Colombo, H, Commendatore, V, Cuadrado, J, Alberto Cuneo, C, Maria Cusumano, A, Guillermo Douthat, W, Dario Dran, R, Farias, E, Florencia Fernandez, M, Finkelstein, H, Fragale, G, Osvaldo Fretes, J, Horacio Garcia, N, Gastaldi, A, Gelersztein, E, Archibaldo Glenny, J, Pablo Gonzalez, J, Gonzalez Colaso, PDC, Goycoa, C, Cristian Greloni, G, Guinsburg, A, Hermida, S, Isaias Juncos, L, Isabel Klyver, M, Kraft, F, Krynski, F, Virginia Lanchiotti, P, Alfonso Leon de la Fuente, R, Marchetta, N, Mele, P, Nicolai, S, 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Abstract

BACKGROUND: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). METHODS: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. RESULTS: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). CONCLUSIONS: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.

Published
2019

30. 4348Cluster analysis of cardiovascular risk phenotypes in patients with type 2 diabetes and established atherosclerotic cardiovascular disease: a potential approach to precision medicine

Author

Sharma, A, primary, Zheng, Y, additional, Ezekowitz, J A, additional, Westerhout, C M, additional, Goodman, S G, additional, Armstrong, P W, additional, Buse, J B, additional, Green, J B, additional, Kaufman, K D, additional, McGuire, D K, additional, Ambrosio, G, additional, Chuang, L M, additional, Lopes, R D, additional, Peterson, E D, additional, and Holman, R R, additional

Published
2018
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32. Breast-feeding and childhood-onset type 1 diabetes: A pooled analysis of individual participant data from 43 observational studies

Author

Cardwell, C.R. Stene, L.C. Ludvigsson, J. Rosenbauer, J. Cinek, O. Svensson, J. Perez-Bravo, F. Memon, A. Gimeno, S.G. Wadsworth, E.J.K. Strotmeyer, E.S. Goldacre, M.J. Radon, K. Chuang, L.-M. Parslow, R.C. Chetwynd, A. Karavanaki, K. Brigis, G. Pozzilli, P. Urbonaite, B. Schober, E. Devoti, G. Sipetic, S. Joner, G. Ionescu-Tirgoviste, C. De Beaufort, C.E. Harrild, K. Benson, V. Savilahti, E. Ponsonby, A.-L. Salem, M. Rabiei, S. Patterson, C.C.

Abstract

OBJECTIVE - To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS - Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS - Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64- 0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies;OR = 0.87, 95%CI 0.75 -1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I 2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I 2 = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS - The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies. © 2012 by the American Diabetes Association.

Published
2012

33. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

Author

Cho, YS, Chen, C-H, Hu, C, Long, J, Hee Ong, RT, Sim, X, Takeuchi, F, Wu, Y, Go, MJ, Yamauchi, T, Chang, Y-C, Kwak, SH, Ma, RCW, Yamamoto, K, Adair, LS, Aung, T, Cai, Q, Chang, L-C, Chen, Y-T, Gao, Y, Hu, FB, Kim, H-L, Kim, S, Kim, YJ, Lee, JJ-M, Lee, NR, Li, Y, Liu, JJ, Lu, W, Nakamura, J, Nakashima, E, Ng, DP-K, Tay, WT, Tsai, F-J, Wong, TY, Yokota, M, Zheng, W, Zhang, R, Wang, C, So, WY, Ohnaka, K, Ikegami, H, Hara, K, Cho, YM, Cho, NH, Chang, T-J, Bao, Y, Hedman, AK, Morris, AP, McCarthy, MI, Takayanagi, R, Park, KS, Jia, W, Chuang, L-M, Chan, JCN, Maeda, S, Kadowaki, T, Lee, J-Y, Wu, J-Y, Teo, YY, Tai, ES, Shu, XO, Mohlke, KL, Kato, N, Han, B-G, and Seielstad, M

Published
2011

34. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Author

Mahajan, A, Go, MJ, Zhang, W, Below, JE, Gaulton, KJ, Ferreira, T, Horikoshi, M, Johnson, AD, Ng, MCY, Prokopenko, I, Saleheen, D, Wang, X, Zeggini, E, Abecasis, GR, Adair, LS, Almgren, P, Atalay, M, Aung, T, Baldassarre, D, Balkau, B, Bao, Y, Barnett, AH, Barroso, I, Basit, A, Been, LF, Beilby, J, Bell, GI, Benediktsson, R, Bergman, RN, Boehm, BO, Boerwinkle, E, Bonnycastle, LL, Burtt, N, Cai, Q, Campbell, H, Carey, J, Cauchi, S, Caulfield, M, Chan, JCN, Chang, L-C, Chang, T-J, Chang, Y-C, Charpentier, G, Chen, C-H, Chen, H, Chen, Y-T, Chia, K-S, Chidambaram, M, Chines, PS, Cho, NH, Cho, YM, Chuang, L-M, Collins, FS, Cornelis, MC, Couper, DJ, Crenshaw, AT, van Dam, RM, Danesh, J, Das, D, de Faire, U, Dedoussis, G, Deloukas, P, Dimas, AS, Dina, C, Doney, ASF, Donnelly, PJ, Dorkhan, M, van Duijn, C, Dupuis, J, Edkins, S, Elliott, P, Emilsson, V, Erbel, R, Eriksson, JG, Escobedo, J, Esko, T, Eury, E, Florez, JC, Fontanillas, P, Forouhi, NG, Forsen, T, Fox, C, Fraser, RM, Frayling, TM, Froguel, P, Frossard, P, Gao, Y, Gertow, K, Gieger, C, Gigante, B, Grallert, H, Grant, GB, Groop, LC, Groves, CJ, Grundberg, E, Guiducci, C, Hamsten, A, Han, B-G, Hara, K, Hassanali, N, Hattersley, AT, Hayward, C, Hedman, AK, Herder, C, Hofman, A, Holmen, OL, Hovingh, K, Hreidarsson, AB, Hu, C, Hu, FB, Hui, J, Humphries, SE, Hunt, SE, Hunter, DJ, Hveem, K, Hydrie, ZI, Ikegami, H, Illig, T, Ingelsson, E, Islam, M, Isomaa, B, Jackson, AU, Jafar, T, James, A, Jia, W, Joeckel, K-H, Jonsson, A, Jowett, JBM, Kadowaki, T, Kang, HM, Kanoni, S, Kao, WHL, Kathiresan, S, Kato, N, Katulanda, P, Keinanen-Kiukaanniemi, SM, Kelly, AM, Khan, H, Khaw, K-T, Khor, C-C, Kim, H-L, Kim, S, Kim, YJ, Kinnunen, L, Klopp, N, Kong, A, Korpi-Hyovalti, E, Kowlessur, S, Kraft, P, Kravic, J, Kristensen, MM, Krithika, S, Kumar, A, Kumate, J, Kuusisto, J, Kwak, SH, Laakso, M, Lagou, V, Lakka, TA, Langenberg, C, Langford, C, Lawrence, R, Leander, K, Lee, J-M, Lee, NR, Li, M, Li, X, Li, Y, Liang, J, Liju, S, Lim, W-Y, Lind, L, Lindgren, CM, Lindholm, E, Liu, C-T, Liu, JJ, Lobbens, S, Long, J, Loos, RJF, Lu, W, Luan, J, Lyssenko, V, Ma, RCW, Maeda, S, Maegi, R, Mannisto, S, Matthews, DR, Meigs, JB, Melander, O, Metspalu, A, Meyer, J, Mirza, G, Mihailov, E, Moebus, S, Mohan, V, Mohlke, KL, Morris, AD, Muehleisen, TW, Mueller-Nurasyid, M, Musk, B, Nakamura, J, Nakashima, E, Navarro, P, Peng-Keat, N, Nica, AC, Nilsson, PM, Njolstad, I, Noethen, MM, Ohnaka, K, Ong, TH, Owen, KR, Palmer, CNA, Pankow, JS, Park, KS, Parkin, M, Pechlivanis, S, Pedersen, NL, Peltonen, L, Perry, JRB, Peters, A, Pinidiyapathirage, JM, Platou, CGP, Potter, S, Price, JF, Qi, L, Radha, V, Rallidis, L, Rasheed, A, Rathmann, W, Rauramaa, R, Raychaudhuri, S, Rayner, NW, Rees, SD, Rehnberg, E, Ripatti, S, Robertson, N, Roden, M, Rossin, EJ, Rudan, I, Rybin, D, Saaristo, TE, Salomaa, V, Saltevo, J, Samuel, M, Sanghera, DK, Saramies, J, Scott, J, Scott, LJ, Scott, RA, Segre, AV, Sehmi, J, Sennblad, B, Shah, N, Shah, S, Shera, AS, Shu, XO, Shuldiner, AR, Sigurdsson, G, Sijbrands, E, Silveira, A, Sim, X, Sivapalaratnam, S, Small, KS, So, WY, Stancakova, A, Stefansson, K, Steinbach, G, Steinthorsdottir, V, Stirrups, K, Strawbridge, RJ, Stringham, HM, Sun, Q, Suo, C, Syvanen, A-C, Takayanagi, R, Takeuchi, F, Tay, WT, Teslovich, TM, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Tikkanen, E, Trakalo, J, Tremoli, E, Trip, MD, Tsai, FJ, Tuomi, T, Tuomilehto, J, Uitterlinden, AG, Valladares-Salgado, A, Vedantam, S, Veglia, F, Voight, BF, Wang, C, Wareham, NJ, Wennauer, R, Wickremasinghe, AR, Wilsgaard, T, Wilson, JF, Wiltshire, S, Winckler, W, Wong, TY, Wood, AR, Wu, J-Y, Wu, Y, Yamamoto, K, Yamauchi, T, Yang, M, Yengo, L, Yokota, M, Young, R, Zabaneh, D, Zhang, F, Zhang, R, Zheng, W, Zimmet, PZ, Altshuler, D, Bowden, DW, Cho, YS, Cox, NJ, Cruz, M, Hanis, CL, Kooner, J, Lee, J-Y, Seielstad, M, Teo, YY, Boehnke, M, Parra, EJ, Chambers, JC, Tai, ES, McCarthy, MI, Morris, AP, Mahajan, A, Go, MJ, Zhang, W, Below, JE, Gaulton, KJ, Ferreira, T, Horikoshi, M, Johnson, AD, Ng, MCY, Prokopenko, I, Saleheen, D, Wang, X, Zeggini, E, Abecasis, GR, Adair, LS, Almgren, P, Atalay, M, Aung, T, Baldassarre, D, Balkau, B, Bao, Y, Barnett, AH, Barroso, I, Basit, A, Been, LF, Beilby, J, Bell, GI, Benediktsson, R, Bergman, RN, Boehm, BO, Boerwinkle, E, Bonnycastle, LL, Burtt, N, Cai, Q, Campbell, H, Carey, J, Cauchi, S, Caulfield, M, Chan, JCN, Chang, L-C, Chang, T-J, Chang, Y-C, Charpentier, G, Chen, C-H, Chen, H, Chen, Y-T, Chia, K-S, Chidambaram, M, Chines, PS, Cho, NH, Cho, YM, Chuang, L-M, Collins, FS, Cornelis, MC, Couper, DJ, Crenshaw, AT, van Dam, RM, Danesh, J, Das, D, de Faire, U, Dedoussis, G, Deloukas, P, Dimas, AS, Dina, C, Doney, ASF, Donnelly, PJ, Dorkhan, M, van Duijn, C, Dupuis, J, Edkins, S, Elliott, P, Emilsson, V, Erbel, R, Eriksson, JG, Escobedo, J, Esko, T, Eury, E, Florez, JC, Fontanillas, P, Forouhi, NG, Forsen, T, Fox, C, Fraser, RM, Frayling, TM, Froguel, P, Frossard, P, Gao, Y, Gertow, K, Gieger, C, Gigante, B, Grallert, H, Grant, GB, Groop, LC, Groves, CJ, Grundberg, E, Guiducci, C, Hamsten, A, Han, B-G, Hara, K, Hassanali, N, Hattersley, AT, Hayward, C, Hedman, AK, Herder, C, Hofman, A, Holmen, OL, Hovingh, K, Hreidarsson, AB, Hu, C, Hu, FB, Hui, J, Humphries, SE, Hunt, SE, Hunter, DJ, Hveem, K, Hydrie, ZI, Ikegami, H, Illig, T, Ingelsson, E, Islam, M, Isomaa, B, Jackson, AU, Jafar, T, James, A, Jia, W, Joeckel, K-H, Jonsson, A, Jowett, JBM, Kadowaki, T, Kang, HM, Kanoni, S, Kao, WHL, Kathiresan, S, Kato, N, Katulanda, P, Keinanen-Kiukaanniemi, SM, Kelly, AM, Khan, H, Khaw, K-T, Khor, C-C, Kim, H-L, Kim, S, Kim, YJ, Kinnunen, L, Klopp, N, Kong, A, Korpi-Hyovalti, E, Kowlessur, S, Kraft, P, Kravic, J, Kristensen, MM, Krithika, S, Kumar, A, Kumate, J, Kuusisto, J, Kwak, SH, Laakso, M, Lagou, V, Lakka, TA, Langenberg, C, Langford, C, Lawrence, R, Leander, K, Lee, J-M, Lee, NR, Li, M, Li, X, Li, Y, Liang, J, Liju, S, Lim, W-Y, Lind, L, Lindgren, CM, Lindholm, E, Liu, C-T, Liu, JJ, Lobbens, S, Long, J, Loos, RJF, Lu, W, Luan, J, Lyssenko, V, Ma, RCW, Maeda, S, Maegi, R, Mannisto, S, Matthews, DR, Meigs, JB, Melander, O, Metspalu, A, Meyer, J, Mirza, G, Mihailov, E, Moebus, S, Mohan, V, Mohlke, KL, Morris, AD, Muehleisen, TW, Mueller-Nurasyid, M, Musk, B, Nakamura, J, Nakashima, E, Navarro, P, Peng-Keat, N, Nica, AC, Nilsson, PM, Njolstad, I, Noethen, MM, Ohnaka, K, Ong, TH, Owen, KR, Palmer, CNA, Pankow, JS, Park, KS, Parkin, M, Pechlivanis, S, Pedersen, NL, Peltonen, L, Perry, JRB, Peters, A, Pinidiyapathirage, JM, Platou, CGP, Potter, S, Price, JF, Qi, L, Radha, V, Rallidis, L, Rasheed, A, Rathmann, W, Rauramaa, R, Raychaudhuri, S, Rayner, NW, Rees, SD, Rehnberg, E, Ripatti, S, Robertson, N, Roden, M, Rossin, EJ, Rudan, I, Rybin, D, Saaristo, TE, Salomaa, V, Saltevo, J, Samuel, M, Sanghera, DK, Saramies, J, Scott, J, Scott, LJ, Scott, RA, Segre, AV, Sehmi, J, Sennblad, B, Shah, N, Shah, S, Shera, AS, Shu, XO, Shuldiner, AR, Sigurdsson, G, Sijbrands, E, Silveira, A, Sim, X, Sivapalaratnam, S, Small, KS, So, WY, Stancakova, A, Stefansson, K, Steinbach, G, Steinthorsdottir, V, Stirrups, K, Strawbridge, RJ, Stringham, HM, Sun, Q, Suo, C, Syvanen, A-C, Takayanagi, R, Takeuchi, F, Tay, WT, Teslovich, TM, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Tikkanen, E, Trakalo, J, Tremoli, E, Trip, MD, Tsai, FJ, Tuomi, T, Tuomilehto, J, Uitterlinden, AG, Valladares-Salgado, A, Vedantam, S, Veglia, F, Voight, BF, Wang, C, Wareham, NJ, Wennauer, R, Wickremasinghe, AR, Wilsgaard, T, Wilson, JF, Wiltshire, S, Winckler, W, Wong, TY, Wood, AR, Wu, J-Y, Wu, Y, Yamamoto, K, Yamauchi, T, Yang, M, Yengo, L, Yokota, M, Young, R, Zabaneh, D, Zhang, F, Zhang, R, Zheng, W, Zimmet, PZ, Altshuler, D, Bowden, DW, Cho, YS, Cox, NJ, Cruz, M, Hanis, CL, Kooner, J, Lee, J-Y, Seielstad, M, Teo, YY, Boehnke, M, Parra, EJ, Chambers, JC, Tai, ES, McCarthy, MI, and Morris, AP

Abstract

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Published
2014

38. Breast-Feeding and Childhood-Onset Type 1 Diabetes A pooled analysis of individual participant data from 43 observational studies

Author

Cardwell, CR, Stene, LC, Ludvigsson, J, Rosenbauer, J, Cinek, O, Svensson, J, Perez-Bravo, F, Memon, A, Gimeno, SG, Wadsworth, EJK, Strotmeyer, ES, Goldacre, MJ, Radon, K, Chuang, L-M, Parslow, RC, Chetwynd, A, Karavanaki, K, Brigis, G, Pozzilli, P, Urbonaite, B, Schober, E, Devoti, G, Sipetic, S, Joner, G, Ionescu-Tirgoviste, C, de Beaufort, CE, Harrild, K, Benson, V, Savilahti, E, Ponsonby, A-L, Salem, M, Rabiei, S, Patterson, CC, Cardwell, CR, Stene, LC, Ludvigsson, J, Rosenbauer, J, Cinek, O, Svensson, J, Perez-Bravo, F, Memon, A, Gimeno, SG, Wadsworth, EJK, Strotmeyer, ES, Goldacre, MJ, Radon, K, Chuang, L-M, Parslow, RC, Chetwynd, A, Karavanaki, K, Brigis, G, Pozzilli, P, Urbonaite, B, Schober, E, Devoti, G, Sipetic, S, Joner, G, Ionescu-Tirgoviste, C, de Beaufort, CE, Harrild, K, Benson, V, Savilahti, E, Ponsonby, A-L, Salem, M, Rabiei, S, and Patterson, CC

Abstract

OBJECTIVE: To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS: Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS: Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS: The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

Published
2012

39. Birth order and childhood type 1 diabetes risk: A pooled analysis of 31 observational studies

Author

Cardwell, C. R., Stene, L. C., Joner, G., Bulsara, M. K., Cinek, O., Rosenbauer, J., Ludvigsson, J., Svensson, J., Goldacre, M. J., Waldhoer, T., Jarosz-Chobot, P., Gimeno, S. G., Chuang, L.-M., Roberts, C. L., Parslow, R. C., Wadsworth, E. J., Chetwynd, A., Brigis, G., Urbonaite, B., Šipetić, S., Schober, E., Devoti, G., Ionescu-Tirgoviste, C., De Beaufort, Carine, Stoyanov, D., Buschard, K., Radon, K., Glatthaar, C., Patterson, C. C., Cardwell, C. R., Stene, L. C., Joner, G., Bulsara, M. K., Cinek, O., Rosenbauer, J., Ludvigsson, J., Svensson, J., Goldacre, M. J., Waldhoer, T., Jarosz-Chobot, P., Gimeno, S. G., Chuang, L.-M., Roberts, C. L., Parslow, R. C., Wadsworth, E. J., Chetwynd, A., Brigis, G., Urbonaite, B., Šipetić, S., Schober, E., Devoti, G., Ionescu-Tirgoviste, C., De Beaufort, Carine, Stoyanov, D., Buschard, K., Radon, K., Glatthaar, C., and Patterson, C. C.

Abstract

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results: Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second-or later born children became apparent [fully adjusted OR=0.90 95% confidence interval (CI) 0.83-0.98; P=0.02] but this association varied markedly between studies (I2=67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children <5years of age (n=25 studies, maternal age adjusted OR=0.84 95% CI 0.75, 0.93; I2=23%). Conclusion: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged <5 years. This finding could reflect increased exposure to infections in early life in later born children. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.

Published
2011

40. Birthweight and the risk of childhood-onset type 1 diabetes:a meta-analysis of observational studies using individual patient data

Author

Cardwell, C. R., Stene, L. C., Joner, G., Davis, E. A., Cinek, O., Rosenbauer, J., Ludvigsson, J., Castell, C., Svensson, J., Goldacre, M. J., Waldhoer, T., Polanska, J., Gimeno, S. G. A., Chuang, L. -M., Parslow, R. C., Wadsworth, E. J. K., Chetwynd, A., Pozzilli, P., Brigis, G., Urbonaite, B., Sipetic, S., Schober, E., Ionescu-Tirgoviste, C., de Beaufort, C. E., Stoyanov, D., Buschard, K., Patterson, C. C., Cardwell, C. R., Stene, L. C., Joner, G., Davis, E. A., Cinek, O., Rosenbauer, J., Ludvigsson, J., Castell, C., Svensson, J., Goldacre, M. J., Waldhoer, T., Polanska, J., Gimeno, S. G. A., Chuang, L. -M., Parslow, R. C., Wadsworth, E. J. K., Chetwynd, A., Pozzilli, P., Brigis, G., Urbonaite, B., Sipetic, S., Schober, E., Ionescu-Tirgoviste, C., de Beaufort, C. E., Stoyanov, D., Buschard, K., and Patterson, C. C.

Abstract

We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p = 0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p = 0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p = 0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.

Published
2010

41. Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data

Author

Cardwell, C R, Stene, L C, Joner, G, Davis, E A, Cinek, O, Rosenbauer, J, Ludvigsson, J, Castell, C, Svensson, J, Goldacre, M J, Waldhoer, T, Polanska, J, Gimeno, S G A, Chuang, L-M, Parslow, R C, Wadsworth, E J K, Chetwynd, A, Pozzilli, P, Brigis, G, Urbonaite, B, Sipetic, S, Schober, E, Ionescu-Tirgoviste, C, de Beaufort, C E, Stoyanov, D, Buschard, K, Patterson, C C, Cardwell, C R, Stene, L C, Joner, G, Davis, E A, Cinek, O, Rosenbauer, J, Ludvigsson, J, Castell, C, Svensson, J, Goldacre, M J, Waldhoer, T, Polanska, J, Gimeno, S G A, Chuang, L-M, Parslow, R C, Wadsworth, E J K, Chetwynd, A, Pozzilli, P, Brigis, G, Urbonaite, B, Sipetic, S, Schober, E, Ionescu-Tirgoviste, C, de Beaufort, C E, Stoyanov, D, Buschard, K, and Patterson, C C

Abstract

Udgivelsesdato: 2010-Apr, AIMS/HYPOTHESIS: We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. METHODS: Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders.Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. RESULTS: Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p=0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p=0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p=0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. CONCLUSIONS/INTERPRETATION: Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.

Published
2010

42. Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies

Author

Cardwell, C. R., primary, Stene, L. C., additional, Joner, G., additional, Bulsara, M. K., additional, Cinek, O., additional, Rosenbauer, J., additional, Ludvigsson, J., additional, Svensson, J., additional, Goldacre, M. J., additional, Waldhoer, T., additional, Jarosz-Chobot, P., additional, Gimeno, S. G., additional, Chuang, L.-M., additional, Roberts, C. L., additional, Parslow, R. C., additional, Wadsworth, E. J., additional, Chetwynd, A., additional, Brigis, G., additional, Urbonaite, B., additional, Sipetic, S., additional, Schober, E., additional, Devoti, G., additional, Ionescu-Tirgoviste, C., additional, de Beaufort, C. E., additional, Stoyanov, D., additional, Buschard, K., additional, Radon, K., additional, Glatthaar, C., additional, and Patterson, C. C., additional

Published
2010
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49. The Diabcare-Asia 1998 Study -Outcomes on Control and Complications in Type 1 and Type 2 Diabetic Patients

Author

Nitiyanant, W., primary, Tandhanand, S., additional, Mahtab, H., additional, Zhu, X. X., additional, Pan, C. Y., additional, Raheja, B. S., additional, Sathe, S. R., additional, Soegondo, S., additional, Soewondo, P., additional, Kim, Y. S., additional, Embong, M., additional, Lantion-Ang, L., additional, Lim-Abraham, M. A., additional, Lee, W. W. R., additional, Wijesuriya, M., additional, Tai, T. Y, additional, Chuang, L. M, additional, Le, H. L., additional, Cockram, C., additional, Jorgensen, L. N., additional, and Yeo, J. P., additional

Published
2002
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