Early Infant Diet and Islet Autoimmunity in the TEDDY Study
Authors: Uusitalo Ulla , Lee Hye-Seung , Andrén Aronsson Carin , Vehik Kendra , Yang Jimin , Hummel Sandra , Silvis Katherine , Lernmark Åke , Rewers Marian , Hagopian William , She Jin-Xiong , Simell Olli , Toppari Jorma , Ziegler Anette-G. , Akolkar Beena , Krischer Jeffrey , Virtanen Suvi M. , Norris Jill M. ,   The TEDDY Study Group, Rewers Marian , Bautista Kimberly , Baxter Judith , Bedoy Ruth , Felipe-Morales Daniel , Driscoll Kimberly , Frohnert Brigitte I. , Gallant Marisa , Gesualdo Patricia , Hoffman Michelle , Karban Rachel , Liu Edwin , Norris Jill , Samper-Imaz Adela , Steck Andrea , Waugh Kathleen , Wright Hali , Toppari Jorma , Simell Olli G. , Adamsson Annika , Ahonen Suvi , Hyöty Heikki , Ilonen Jorma , Jokipuu Sanna , Kallio Tiina , Karlsson Leena , Kähönenµ Miia , Knip Mikael , Kovanen Lea , Koreasalo Mirva , Kurppa Kalle , Latva-aho Tiina , Lönnrot Maria , Mäntymäki Elina , Multasuo Katja , Niininen Tiina , Niinistö Sari , Nyblom Mia , Rajala Petra , Rautanen Jenna , Riikonen Anne , Romo Minna , Rönkä Juulia , Simell Satu , Simell Tuula , Sjöberg Maija , Stenius Aino , Leppänen Maria , Vainionpää Sini , Varjonen Eeva , Veijola Riitta , Virtanen Suvi M. , Vähä-Mäkilä Mari , Åkerlund Mari , Lindfors Katri , She Jin-Xiong , Schatz Desmond , Hopkins Diane , Steed Leigh , Bryant Jennifer , Thomas Jamie , Adams Janey , Silvis Katherine , Haller Michael , Gardiner Melissa , McIndoe Richard , Sharma Ashok , Anderson Stephen W , Jacobsen Laura , Ziegler Anette G. , Beyerlein Andreas , Bonifacio Ezio , Heublein Anja , Hummel Michael , Hummel Sandra , Knopff Annette , Koch Charlotte , Koletzko Sibylle , Ramminger Claudia , Roth Roswith , Scholz Marlon , Schulzik Laura , Stock Joanna , Warncke Katharina , Wendel Lorena , Winkler Christiane , Lernmark Åke , Agardh Daniel , Aronsson Carin Andrén , Ask Maria , Bremer Jenny , Carlsson Ulla-Marie , Cilio Corrado , Ericson-Hallström Emelie , Fors Annika , Fransson Lina , Gard Thomas , Bennet Rasmus , Hansson Carina , Hyberg Susanne , Jisser Hanna , Johansen Fredrik , Jonsdottir Berglind , Jovic Silvija , Larsson Helena Elding , Lindström Marielle , Lundgren Markus , Månsson-Martinez Maria , Markan Maria , Melin Jessica , Mestan Zeliha , Nilsson Caroline , Ottosson Karin , Rahmati Kobra , Ramelius Anita , Salami Falastin , Sibthorpe Sara , Sjöberg Anette , Sjöberg Birgitta , Amboh Evelyn Tekum , Törn Carina , Wallin Anne , Wimar Åsa , Åberg Sofie , Hagopian William A. , Killian Michael , Crouch Claire Cowen , Skidmore Jennifer , Akramoff Ashley , Banjanin Jana , Chavoshi Masumeh , Dunson Kayleen , Hervey Rachel , Levenson Shana , Lyons Rachel , Meyer Arlene , Mulenga Denise , Schmitt Davey , Schwabe Julie , Becker Dorothy , Franciscus Margaret , Dalmagro-Elias Smith MaryEllen , Daftary Ashi , Klein Mary Beth , Yates Chrystal , Krischer Jeffrey P. , Austin-Gonzalez Sarah , Avendano Maryouri , Baethke Sandra , Brown Rasheedah , Burkhardt Brant , Butterworth Martha , Clasen Joanna , Cuthbertson David , Eberhard Christopher , Fiske Steven , Garcia Dena , Garmeson Jennifer , Gowda Veena , Heyman Kathleen , Hsiao Belinda , Perez Laras Francisco , Lee Hye-Seung , Liu Shu , Liu Xiang , Lynch Kristian , Maguire Colleen , Malloy Jamie , McCarthy Cristina , Merrell Aubrie , Meulemans Steven , Parikh Hemang , Quigley Ryan , Remedios Cassandra , Shaffer Chris , Smith Laura , Smith Susan , Sulman Noah , Tamura Roy , Uusitalo Ulla , Vehik Kendra , Vijayakandipan Ponni , Wood Keith , Yang Jimin , Abbondondolo Michael , Ballard Lori , Hadley David , McLeod Wendy , Akolkar Beena , Yu Liping , Miao Dongmei , Bingley Polly , Williams Alistair , Chandler Kyla , Williams Claire , George Gifty , Grace Sian , Gillard Ben , Hagopian William , Chavoshi Masumeh , Erlich Henry , Mack Steven J. , Fear Anna Lisa , Ke Sandra , Mulholland Niveen , Bourcier Kasia , Briese Thomas , Johnson Suzanne Bennett , Triplett Eric 
Published: January 2018

OBJECTIVE
To examine duration of breastfeeding and timing of complementary foods and risk of islet autoimmunity (IA).

RESEARCH DESIGN AND METHODS
The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,676 children with increased genetic risk of type 1 diabetes (T1D) in the U.S., Finland, Germany, and Sweden. This study included 7,563 children with at least 9 months of follow-up. Blood samples were collected every 3 months from birth to evaluate IA, defined as persistent, confirmed positive antibodies to insulin (IAAs), GAD, or insulinoma antigen-2. We examined the associations between diet and the risk of IA using Cox regression models adjusted for country, T1D family history, HLA genotype, sex, and early probiotic exposure. Additionally, we investigated martingale residuals and log-rank statistics to determine cut points for ages of dietary exposures.

RESULTS
Later introduction of gluten was associated with increased risk of any IA and IAA. The hazard ratios (HRs) for every 1-month delay in gluten introduction were 1.05 (95% CI 1.01, 1.10; P = 0.02) and 1.08 (95% CI 1.00, 1.16; P = 0.04), respectively. Martingale residual analysis suggested that the age at gluten introduction could be grouped as &lt;4, 4–9, and &gt;9 months. The risk of IA associated with introducing gluten before 4 months of age was lower (HR 0.68; 95% CI 0.47, 0.99), and the risk of IA associated with introducing it later than the age of 9 months was higher (HR 1.57; 95% CI 1.07, 2.31) than introduction between 4 and 9 months of age.

CONCLUSIONS
The timing of gluten-containing cereals and IA should be studied further.