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