Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study
Authors: Thorsen Steffen U. , Liu Xiang , Kataria Yachana , Mandrup-Poulsen Thomas , Kaur Simranjeet , Uusitalo Ulla , Virtanen Suvi M. , Norris Jill M. , Rewers Marian , Hagopian William , Yang Jimin , She Jin-Xiong , Akolkar Beena , Rich Stephen , Aronsson Carin Andrén , Lernmark Åke , Ziegler Anette-Gabriele , Toppari Jorma , Krischer Jeffrey , Parikh Hemang M. , Ellervik Christina , Svensson Jannet ,   TEDDY Study Group, Rewers Marian , Barbour Aaron , Bautista Kimberly , Baxter Judith , Felipe-Morales Daniel , Frohnert Brigitte I. , Stahl Marisa , Gesualdo Patricia , Hoffman Michelle , Karban Rachel , Liu Edwin , Munoz Alondra , Norris Jill , O’Donnell Holly , Peacock Stesha , Shorrosh Hanan , Steck Andrea , Stern Megan , Waugh Kathleen , Toppari Jorma , Simell Olli G. , Adamsson Annika , Ahonen Suvi , Åkerlund Mari , Anttila Sirpa , Hakola Leena , Hekkala Anne , Honkanen Tiia , Hyöty Heikki , Ilonen Jorma , Koskenniemi Jaakko J. , Kähönen Miia , Knip Mikael , Koivikko Minna-Liisa , Kokkonen Katja , Koskinen Merja , Koreasalo Mirva , Kurppa Kalle , Kuusela Salla , Laiho Jutta , Latva-aho Tiina , Leppänen Laura , Lindfors Katri , Lönnrot Maria , Mäntymäki Elina , Mattila Markus , Miettinen Maija , Mykkänen Teija , Niininen Tiina , Niinistö Sari , Oikarinen Sami , Oinas Hanna-Leena , Ollikainen Paula , Othmani Zhian , Pitkänen Aino , Pohjola Sirpa , Rautanen Jenna , Riikonen Anne , Romo Minna , Rönkä Nelli , Simell Satu , Tossavainen Päivi , Vähä-Mäkilä Mari , Varjonen Eeva , Veijola Riitta , Viinikangas Irene , Vilmi Silja , Virtanen Suvi M. , McIndoe Richard , Schatz Desmond , Hopkins Diane , Haller Michael , Bernard Risa , Gardiner Melissa , Sharma Ashok , Jacobsen Laura , DePeiza Ashley , Hosford Jennifer , Petty Kennedy , Myers Leah , Ziegler Anette G. , Bonifacio Ezio , Gezginci Cigdem , Grätz Willi , Heublein Anja , Hohoff Eva , Hummel Sandra , Knopff Annette , Köger Melanie , Koletzko Sibylle , Ramminger Claudia , Roth Roswith , Schmidt Jennifer , Scholz Marlon , Stock Joanna , Warncke Katharina , Wendel Lorena , Winkler Christiane , Lernmark Åke , Agardh Daniel , Aronsson Carin Andrén , Bennet Rasmus , Cilio Corrado , Dahlberg Susanne , Fält Ulla , Goldman Tsubarah Malin , Ericson-Hallström Emelie , Fransson Lina , Gard Thomas , Halilovic Emina , Holmén Gunilla , Hyberg Susanne , Jonsdottir Berglind , Karimi Naghmeh , Elding Larsson Helena , Lindström Marielle , Lundgren Markus , Maziarz Marlena , Melin Jessica , Nilsson Caroline , Nordh Yohanna , Rahmati Kobra , Ramelius Anita , Salami Falastin , Sjöberg Anette , Tekum Amboh Evelyn , Törn Carina , Ulvenhag Ulrika , Wiktorsson Terese , Wimar Åsa , Hagopian William A. , Killian Michael , Cowen Crouch Claire , Skidmore Jennifer , Bowen Luka-Sophia , Metcalf Mikeil , Meyer Arlene , Meyer Jocelyn , Mulenga Denise , Powell Nole , Radtke Jared , Roy Shreya , Schmitt Davey , Tucker Preston , Becker Dorothy , Franciscus Margaret , Dalmagro-Elias Smith MaryEllen , Daftary Ashi , Klein Mary Beth , Yates Chrystal , Krischer Jeffrey P. , Adusumali Rajesh , Austin-Gonzalez Sarah , Avendano Maryouri , Baethke Sandra , Burkhardt Brant , Butterworth Martha , Cadigan Nicholas , Clasen Joanna , Counts Kevin , Gandolfo Laura , Garmeson Jennifer , Gowda Veena , Karges Christina , Liu Shu , Liu Xiang , Lynch Kristian , Malloy Jamie , Mramba Lazarus , McCarthy Cristina , Moreno Jose , Parikh Hemang M. , Remedios Cassandra , Shaffer Chris , Smith Susan , Sulman Noah , Tamura Roy , Tewey Dena , Thuma Henri , Toth Michael , Uusitalo Ulla , Vehik Kendra , Vijayakandipan Ponni , Wroble Melissa , Yang Jimin , Young Kenneth , Abbondondolo Michael , Ballard Lori , Brown Rasheedah , Cuthbertson David , Dankyi Stephen , Eberhard Christopher , Fiske Steven , Hadley David , Heyman Kathleen , Hsiao Belinda , Perez Laras Francisco , Lee Hye-Seung , Li Qian , Maguire Colleen , McLeod Wendy , Merrell Aubrie , Meulemans Steven , Quigley Ryan , Smith Laura , Akolkar Beena , Yu Liping , Miao Dongmei , Gillespie Kathleen , Chandler Kyla , Kelland Ilana , Ben Khoud Yassin , Randell Matthew , Rich Stephen S. , Chen Wei-Min , Onengut-Gumuscu Suna , Farber Emily , Roche Pickin Rebecca , Davis Jonathan , Davis Jordan , Gallo Dan , Bonnie Jessica , Campolieto Paul , Ke Sandra , Mulholland Niveen , Briese Thomas , Brusko Todd , Bennett Johnson Suzanne , McKinney Eoin , Pastinen Tomi , Ullitz Thorsen Steffen , Triplett Eric 
Published: March 2023

OBJECTIVE
To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).

RESEARCH DESIGN AND METHODS
In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.

RESULTS
We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.

CONCLUSIONS
Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.