Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY)
Andrea K Steck, Kendra Vehik, Ezio Bonifacio, Ake Lernmark, Anette-G Ziegler, William A Hagopian, JinXiong She, Olli Simell, Beena Akolkar, Jeffrey Krischer, Desmond Schatz, Marian J Rewers, TEDDY Study Group, Marian Rewers, Kimberly Bautista, Judith Baxter, Ruth Bedoy, Daniel Felipe-Morales, Brigitte Frohnert, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Adela Samper-Imaz, Andrea Steck, Kathleen Waugh, Hali Wright, Jin-Xiong She, Desmond Schatz, Diane Hopkins, Leigh Steed, Jamie Thomas, Katherine Silvis, Michael Haller, Meena Shankar, Eleni Sheehan, Melissa Gardiner, Richard McIndoe, Haitao Liu, John Nechtman, Ashok Sharma, Joshua Williams, Gabriela Foghis, Stephen W Anderson, Anette G Ziegler, Andreas Beyerlein, Ezio Bonifacio, Michael Hummel, Sandra Hummel, Kristina Foterek, Mathilde Kersting, Annette Knopff, Sibylle Koletzko, Claudia Peplow, Roswith Roth, Joanna Stock, Elisabeth Strauss, Katharina Warncke, Christiane Winkler, Jorma Toppari, Olli G Simell, Annika Adamsson, Heikki Hyöty, Jorma Ilonen, Miia Kähönen, Mikael Knip, Annika Koivu, Mirva Koreasalo, Kalle Kurppa, Maria Lönnrot, Elina Mäntymäki, Katja Multasuo, Juha Mykkänen, Tiina Niininen, Mia Nyblom, Petra Rajala, Jenna Rautanen, Anne Riikonen, Minna Romo, Satu Simell, Tuula Simell, Ville Simell, Maija Sjöberg, Aino Stenius, Eeva Varjonen, Riitta Veijola, Suvi M Virtanen, Mari Åkerlund, Åke Lernmark, Daniel Agardh, Carin Andrén Aronsson, Maria Ask, Jenny Bremer, Ulla-Marie Carlsson, Corrado Cilio, Camilla Ekstrand, Emelie Ericson-Hallström, Lina Fransson, Thomas Gard, Joanna Gerardsson, Rasmus Håkansson, Monica Hansen, Gertie Hansson, Susanne Hyberg, Fredrik Johansen, Berglind Jonasdottir, Linda Jonsson, Helena Elding Larsson, Barbro Lernmark, Maria Månsson-Martinez, Maria Markan, Theodosia Massadakis, Jessica Melin, Zeliha Mestan, Kobra Rahmati, Anita Ramelius, Falastin Salami, Monica Sedig Järvirova, Sara Sibthorpe, Birgitta Sjöberg, Ulrica Swartling, Erika Trulsson, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, William A Hagopian, Xiang Yan, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Stephen Ayres, Kayleen Dunson, Diana Heaney, Rachel Hervey, Corbin Johnson, Rachel Lyons, Arlene Meyer, Denise Mulenga, Emma Schulte, Elizabeth Scott, Joshua Stabbert, John Willis, Dorothy Becker, Margaret Franciscus, MaryEllen Dalmagro-Elias Smith, Ashi Daftary, Mary Beth Klein, Chrystal Yates, Jeffrey P Krischer, Michael Abbondondolo, Sarah Austin-Gonzalez, Rasheedah Brown, Brant Burkhardt, Martha Butterworth, David Cuthbertson, Christopher Eberhard, Steven Fiske, Dena Garcia, Veena Gowda, David Hadley, Hye-Seung Lee, Shu Liu, Xiang Liu, Kristian Lynch, Jamie Malloy, Cristina McCarthy, Wendy McLeod, Chris Shaffer, Laura Smith, Susan Smith, Roy Tamura, Ulla Uusitalo, Kendra Vehik, Ponni Vijayakandipan, Keith Wood, Jimin Yang, Beena Akolkar, Kasia Bourcier, Thomas Briese, Suzanne Bennett Johnson, Steve Oberste, Eric Triplett, Liping Yu, Dongmei Miao, Polly Bingley, Alistair Williams, Kyla Chandler, Saba Rokni, Joanna Boldison, Jacob Butterly, Gabriella Carreno, Claire Caygill, Ivey Geoghan, Anna Long, Molly Payne, James Pearson, Sophie Ridewood, Rebecca Wyatt, Elisabeth Aardal Eriksson, Ing-Marie Lundgren, Ewa Lönn Karlsson, Dzeneta Nezirevic Dernroth, Iris Erlund, Irma Salminen, Jouko Sundvall, Jaana Leiviskä, Mari Lehtonen, Randie R Little, Alethea L Tennill, Henry Erlich, Steven J Mack, Anna Lisa Fear, Oliver Fiehn, Bill Wikoff, Brian Defelice, Dmitry Grapov, Tobias Kind, Mine Palazoglu, Luis Valdiviez, Benjamin Wancewicz, Gert Wohlgemuth, Joyce Wong, Joseph F Petrosino, Santica M Marcovina, Vinod P Gaur, Richard D Smith, Thomas O Metz, Charles Ansong, Bobbie-Jo Webb-Robertson, Hugh D Mitchell, Heather Higgins, Sandra Ke, Jin-Xiong She, Richard McIndoe, Haitao Liu, John Nechtman, Yansheng Zhao, Na Jiang, Stephen S Rich, Wei-Min Chen, Suna Onengut-Gumuscu, Emily Farber, Rebecca Roche Pickin, Jordan Davis, Dan Gallo, Jessica Bonnie, Paul Campolieto, Andrea K Steck, Kendra Vehik, Ezio Bonifacio, Ake Lernmark, Anette-G Ziegler, William A Hagopian, JinXiong She, Olli Simell, Beena Akolkar, Jeffrey Krischer, Desmond Schatz, Marian J Rewers, TEDDY Study Group, Marian Rewers, Kimberly Bautista, Judith Baxter, Ruth Bedoy, Daniel Felipe-Morales, Brigitte Frohnert, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Adela Samper-Imaz, Andrea Steck, Kathleen Waugh, Hali Wright, Jin-Xiong She, Desmond Schatz, Diane Hopkins, Leigh Steed, Jamie Thomas, Katherine Silvis, Michael Haller, Meena Shankar, Eleni Sheehan, Melissa Gardiner, Richard McIndoe, Haitao Liu, John Nechtman, Ashok Sharma, Joshua Williams, Gabriela Foghis, Stephen W Anderson, Anette G Ziegler, Andreas Beyerlein, Ezio Bonifacio, Michael Hummel, Sandra Hummel, Kristina Foterek, Mathilde Kersting, Annette Knopff, Sibylle Koletzko, Claudia Peplow, Roswith Roth, Joanna Stock, Elisabeth Strauss, Katharina Warncke, Christiane Winkler, Jorma Toppari, Olli G Simell, Annika Adamsson, Heikki Hyöty, Jorma Ilonen, Miia Kähönen, Mikael Knip, Annika Koivu, Mirva Koreasalo, Kalle Kurppa, Maria Lönnrot, Elina Mäntymäki, Katja Multasuo, Juha Mykkänen, Tiina Niininen, Mia Nyblom, Petra Rajala, Jenna Rautanen, Anne Riikonen, Minna Romo, Satu Simell, Tuula Simell, Ville Simell, Maija Sjöberg, Aino Stenius, Eeva Varjonen, Riitta Veijola, Suvi M Virtanen, Mari Åkerlund, Åke Lernmark, Daniel Agardh, Carin Andrén Aronsson, Maria Ask, Jenny Bremer, Ulla-Marie Carlsson, Corrado Cilio, Camilla Ekstrand, Emelie Ericson-Hallström, Lina Fransson, Thomas Gard, Joanna Gerardsson, Rasmus Håkansson, Monica Hansen, Gertie Hansson, Susanne Hyberg, Fredrik Johansen, Berglind Jonasdottir, Linda Jonsson, Helena Elding Larsson, Barbro Lernmark, Maria Månsson-Martinez, Maria Markan, Theodosia Massadakis, Jessica Melin, Zeliha Mestan, Kobra Rahmati, Anita Ramelius, Falastin Salami, Monica Sedig Järvirova, Sara Sibthorpe, Birgitta Sjöberg, Ulrica Swartling, Erika Trulsson, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, William A Hagopian, Xiang Yan, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Stephen Ayres, Kayleen Dunson, Diana Heaney, Rachel Hervey, Corbin Johnson, Rachel Lyons, Arlene Meyer, Denise Mulenga, Emma Schulte, Elizabeth Scott, Joshua Stabbert, John Willis, Dorothy Becker, Margaret Franciscus, MaryEllen Dalmagro-Elias Smith, Ashi Daftary, Mary Beth Klein, Chrystal Yates, Jeffrey P Krischer, Michael Abbondondolo, Sarah Austin-Gonzalez, Rasheedah Brown, Brant Burkhardt, Martha Butterworth, David Cuthbertson, Christopher Eberhard, Steven Fiske, Dena Garcia, Veena Gowda, David Hadley, Hye-Seung Lee, Shu Liu, Xiang Liu, Kristian Lynch, Jamie Malloy, Cristina McCarthy, Wendy McLeod, Chris Shaffer, Laura Smith, Susan Smith, Roy Tamura, Ulla Uusitalo, Kendra Vehik, Ponni Vijayakandipan, Keith Wood, Jimin Yang, Beena Akolkar, Kasia Bourcier, Thomas Briese, Suzanne Bennett Johnson, Steve Oberste, Eric Triplett, Liping Yu, Dongmei Miao, Polly Bingley, Alistair Williams, Kyla Chandler, Saba Rokni, Joanna Boldison, Jacob Butterly, Gabriella Carreno, Claire Caygill, Ivey Geoghan, Anna Long, Molly Payne, James Pearson, Sophie Ridewood, Rebecca Wyatt, Elisabeth Aardal Eriksson, Ing-Marie Lundgren, Ewa Lönn Karlsson, Dzeneta Nezirevic Dernroth, Iris Erlund, Irma Salminen, Jouko Sundvall, Jaana Leiviskä, Mari Lehtonen, Randie R Little, Alethea L Tennill, Henry Erlich, Steven J Mack, Anna Lisa Fear, Oliver Fiehn, Bill Wikoff, Brian Defelice, Dmitry Grapov, Tobias Kind, Mine Palazoglu, Luis Valdiviez, Benjamin Wancewicz, Gert Wohlgemuth, Joyce Wong, Joseph F Petrosino, Santica M Marcovina, Vinod P Gaur, Richard D Smith, Thomas O Metz, Charles Ansong, Bobbie-Jo Webb-Robertson, Hugh D Mitchell, Heather Higgins, Sandra Ke, Jin-Xiong She, Richard McIndoe, Haitao Liu, John Nechtman, Yansheng Zhao, Na Jiang, Stephen S Rich, Wei-Min Chen, Suna Onengut-Gumuscu, Emily Farber, Rebecca Roche Pickin, Jordan Davis, Dan Gallo, Jessica Bonnie, Paul Campolieto
Abstract
Objective: While it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined.
Research design and methods: The Environmental Determinants of Diabetes in the Young (TEDDY) study has observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months.
Results: Life table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P < 0.0001]). The mean GADA level did not significantly affect the risk of diabetes.
Conclusions: In the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Source: PubMed