Distinct Growth Phases in Early Life Associated With the Risk of Type 1 Diabetes: The TEDDY Study
Authors: Xiang Liu, Kendra Vehik, Yangxin Huang, Helena Elding Larsson, Jorma Toppari, Anette G. Ziegler, Jin-Xiong She, Marian Rewers, William A. Hagopian, Beena Akolkar, Jeffrey P. Krischer, Marian Rewers, Aaron Barbour, Kimberly Bautista, Judith Baxter, Daniel Felipe-Morales, Kimberly Driscoll, Brigitte I. Frohnert, Marisa Stahl, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Edwin Liu, Jill Norris, Stesha Peacock, Hanan Shorrosh, Andrea Steck, Megan Stern, Erica Villegas, Kathleen Waugh, Jorma Toppari, Olli G. Simell, Annika Adamsson, Suvi Ahonen, Mari Åkerlund, Leena Hakola, Anne Hekkala, Henna Holappa, Heikki Hyöty, Anni Ikonen, Jorma Ilonen, Sinikka Jäminki, Sanna Jokipuu, Leena Karlsson, Jukka Kero, Miia Kähönen, Mikael Knip, Minna-Liisa Koivikko, Merja Koskinen, Mirva Koreasalo, Kalle Kurppa, Jarita Kytölä, Tiina Latva-aho, Katri Lindfors, Maria Lönnrot, Elina Mäntymäki, Markus Mattila, Maija Miettinen, Katja Multasuo, Teija Mykkänen, Tiina Niininen, Sari Niinistö, Mia Nyblom, Sami Oikarinen, Paula Ollikainen, Zhian Othmani, Sirpa Pohjola, Petra Rajala, Jenna Rautanen, Anne Riikonen, Eija Riski, Miia Pekkola, Minna Romo, Satu 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, 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, Rasmus Bennet, Corrado Cilio, Helene Engqvist, Emelie Ericson-Hallström, Annika Fors, Lina Fransson, Thomas Gard, Monika Hansen, Hanna Jisser, Fredrik Johansen, Berglind Jonsdottir, Silvija Jovic, Helena Elding Larsson, Marielle Lindström, Markus Lundgren, Marlena Maziarz, Maria Månsson-Martinez, Maria Markan, Jessica Melin, Zeliha Mestan, Caroline Nilsson, Karin Ottosson, Kobra Rahmati, Anita Ramelius, Falastin Salami, Anette Sjöberg, Birgitta Sjöberg, Malin Svensson, Carina Törn, Anne Wallin, Åsa Wimar, Sofie Åberg, William A. Hagopian, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Masumeh Chavoshi, Rachel Hervey, Rachel Lyons, Arlene Meyer, Denise Mulenga, Jared Radtke, Matei Romancik, Davey Schmitt, 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, Stephen Dankyi, 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, 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, Michael Abbondondolo, Lori Ballard, David Hadley, Wendy McLeod, Steven Meulemans, Liping Yu, Dongmei Miao, Polly Bingley, Alistair Williams, Kyla Chandler, Olivia Ball, Ilana Kelland, Sian Grace, William Hagopian, Masumeh Chavoshi, Jared Radtke, Sarah Zink, 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 (2020)

OBJECTIVE This study investigates two-phase growth patterns in early life and their association with development of islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS The Environmental Determinants of Diabetes in the Young (TEDDY) study followed 7,522 genetically high-risk children in Sweden, Finland, Germany, and the U.S. from birth for a median of 9.0 years (interquartile range 5.7–10.6) with available growth data. Of these, 761 (10.1%) children developed IA and 290 (3.9%) children were diagnosed with T1D. Bayesian two-phase piecewise linear mixed models with a random change point were used to estimate children’s individual growth trajectories. Cox proportional hazards models were used to assess the effects of associated growth parameters on the risks of IA and progression to T1D. RESULTS A higher rate of weight gain in infancy was associated with increased IA risk (hazard ratio [HR] 1.09 [95% CI 1.02, 1.17] per 1 kg/year). A height growth pattern with a lower rate in infancy (HR 0.79 [95% CI 0.70, 0.90] per 1 cm/year), higher rate in early childhood (HR 1.48 [95% CI 1.22, 1.79] per 1 cm/year), and younger age at the phase transition (HR 0.76 [95% CI 0.58, 0.99] per 1 month) was associated with increased risk of progression from IA to T1D. A higher rate of weight gain in early childhood was associated with increased risk of progression from IA to T1D (HR 2.57 [95% CI 1.34, 4.91] per 1 kg/year) in children with first-appearing GAD autoantibody only. CONCLUSIONS Growth patterns in early life better clarify how specific growth phases are associated with the development of T1D.