Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study
Author:
Thorsen Steffen U.12, Liu Xiang3ORCID, Kataria Yachana4, Mandrup-Poulsen Thomas1ORCID, Kaur Simranjeet2, Uusitalo Ulla3ORCID, Virtanen Suvi M.567ORCID, Norris Jill M.8ORCID, Rewers Marian9, Hagopian William10ORCID, Yang Jimin11ORCID, She Jin-Xiong11, Akolkar Beena12, Rich Stephen13ORCID, Aronsson Carin Andrén14ORCID, Lernmark Åke14ORCID, Ziegler Anette-Gabriele15ORCID, Toppari Jorma16ORCID, Krischer Jeffrey3, Parikh Hemang M.3, Ellervik Christina171819, Svensson Jannet217ORCID, 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 XiangORCID, 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,
Affiliation:
1. 1Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark 2. 2Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Herlev, Herlev, Denmark 3. 3Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 4. 4Department of Pathology and Laboratory Medicine, Boston University, Boston, MA 5. 5Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland 6. 6Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland 7. 7Center for Child Health Research, Tampere University and University Hospital and Research, Development and Innovation Centre, Tampere University Hospital, Tampere, Finland 8. 8Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 9. 9Pacific Northwest Research Institute, Seattle, WA 10. 10Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO 11. 11Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 12. 12National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 13. 13Center for Public Health Genomics and Department of Public Health Sciences, University of Virginia, Charlottesville, VA 14. 14Department of Clinical Sciences, Lund University Clinical Research Centre, Skåne University Hospital, Malmö, Sweden 15. 15Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany 16. 16Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, and Department of Pediatrics, Turku University Hospital, Turku, Finland 17. 17Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark 18. 18Department of Pathology, Harvard Medical School, Boston, MA 19. 19Department of Laboratory Medicine, Boston Children’s Hospital, Boston, MA
Abstract
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.
Funder
Fabrikant Vilhelm Pedersen og Hustrus mindelegat
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
3 articles.
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