Predicting Islet Cell Autoimmunity and Type 1 Diabetes: An 8-Year TEDDY Study Progress Report
Authors: Jeffrey P. Krischer, Xiang Liu, Kendra Vehik, Beena Akolkar, William A. Hagopian, Marian J. Rewers, Jin-Xiong She, Jorma Toppari, Anette-G. Ziegler, Åke Lernmark, Marian Rewers, Kimberly Bautista, Judith Baxter, Daniel Felipe-Morales, Kimberly Driscoll, Brigitte I. Frohnert, Marisa Gallant, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Andrea Steck, Kathleen Waugh, Jorma Toppari, Olli G. Simell, Annika Adamsson, Suvi Ahonen, Mari Åkerlund Anne Hekkala, Henna Holappa, Heikki Hyöty, Anni Ikonen, Jorma Ilonen, Sinikka Jäminki, Sanna Jokipuu, Leena Karlsson, Miia Kähönen, Mikael Knip, Minna-Liisa Koivikko, Mirva Koreasalo, Kalle Kurppa, Jarita Kytölä, Tiina Latva-aho, Katri Lindfors, Maria Lönnrot, Elina Mäntymäki, Markus Mattila, Katja Multasuo, Teija Mykkänen, Tiina Niininen, Sari Niinistö, Mia Nyblom, Sami Oikarinen, Paula Ollikainen, Sirpa Pohjola, Petra Rajala, Jenna Rautanen, Anne Riikonen, Minna Romo, Suvi Ruohonen, Satu Simell, Maija Sjöberg, Aino Stenius, Päivi Tossavainen, Mari Vähä-Mäkilä, Sini Vainionpää, Eeva Varjonen, Riitta Veijola, Irene Viinikangas, Suvi M. Virtanen, Jin-Xiong She, Desmond Schatz, Diane Hopkins, Leigh Steed, Jennifer Bryant, Katherine Silvis, Michael Haller, Melissa Gardiner, Richard McIndoe, Ashok Sharma, Stephen W. Anderson, Laura Jacobsen, John Marks, P.D. Towe, Anette G. Ziegler, Ezio Bonifacio, Miryam D'Angelo, Anita Gavrisan, Cigdem Gezginci, Anja Heublein, Verena Hoffmann, Sandra Hummel, Andrea Keimer, Annette Knopff, Charlotte Koch, Sibylle Koletzko, Claudia Ramminger, Roswith Roth, Marlon Scholz, Joanna Stock, Katharina Warncke, Lorena Wendel, Christiane Winkler, Åke Lernmark, Daniel Agardh, Carin Andrén Aronsson, Maria Ask, Jenny Bremer, Corrado Cilio, Emelie Ericson-Hallström, Annika Fors, Lina Fransson, Thomas Gard, Rasmus Bennet, Monika Hansen, Susanne Hyberg, Hanna Jisser, Fredrik Johansen, Berglind Jonsdottir, Silvija Jovic, Helena Elding Larsson, Marielle Lindström, Markus Lundgren, Maria Månsson-Martinez, Maria Markan, Jessica Melin, Zeliha Mestan, Caroline Nilsson, Karin Ottosson, Kobra Rahmati, Anita Ramelius, Falastin Salami, Anette Sjöberg, Birgitta Sjöberg, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, William A. Hagopian, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Ashley Akramoff, Masumeh Chavoshi, Kayleen Dunson, Rachel Hervey, Rachel Lyons, Arlene Meyer, Denise Mulenga, Jared Radtke, Matei Romancik, Davey Schmitt, Julie Schwabe, Sarah Zink, Dorothy Becker, Margaret Franciscus, MaryEllen Dalmagro-Elias Smith, Ashi Daftary, Mary Beth Klein, Chrystal Yates, Jeffrey P. Krischer, Sarah Austin-Gonzalez, Maryouri Avendano, Sandra Baethke, Rasheedah Brown, Brant Burkhardt, Martha Butterworth, Joanna Clasen, David Cuthbertson, Christopher Eberhard, Steven Fiske, Jennifer Garmeson, Veena Gowda, Kathleen Heyman, Belinda Hsiao, Christina Karges, Francisco Perez Laras, Hye-Seung Lee, Qian Li, Shu Liu, Xiang Liu, Kristian Lynch, Colleen Maguire, Jamie Malloy, Cristina McCarthy, Aubrie Merrell, Steven Meulemans, Hemang Parikh, Ryan Quigley, Cassandra Remedios, Chris Shaffer, Laura Smith, Susan Smith, Noah Sulman, Roy Tamura, Dena Tewey, Michael Toth, Ulla Uusitalo, Kendra Vehik, Ponni Vijayakandipan, Keith Wood, Jimin Yang, Liping Yu, Dongmei Miao, Polly Bingley, Alistair Williams, Kyla Chandler, Olivia Ball, Ilana Kelland, Sian Grace, Ben Gillard, William Hagopian, Masumeh Chavoshi, Jared Radtke, Julie Schwabe, Henry Erlich, Steven J. Mack, Anna Lisa Fear, Sandra Ke, Niveen Mulholland, Stephen S. Rich, Wei-Min Chen, Suna Onengut-Gumuscu, Emily Farber, Rebecca Roche Pickin, Jonathan Davis, Jordan Davis, Dan Gallo, Jessica Bonnie, Paul Campolieto, Beena Akolkar, Kasia Bourcier, Thomas Briese, Suzanne Bennett Johnson, Eric Triplett
Journal: Diabetes Care (2019)

OBJECTIVE Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D. RESULTS HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden’s index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762). CONCLUSIONS Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.