Metabolite-related dietary patterns and the development of islet autoimmunity
Authors: Johnson Randi K. , Vanderlinden Lauren , DeFelice Brian C. , Kechris Katerina , Uusitalo Ulla , Fiehn Oliver , Sontag Marci , Crume Tessa , Beyerlein Andreas , Lernmark Åke , Toppari Jorma , Ziegler Anette-G. , She Jin-Xiong , Hagopian William , Rewers Marian , Akolkar Beena , Krischer Jeffrey , Virtanen Suvi M. , Norris Jill M. ,   The TEDDY Study Group, Bautista Kimberly , Baxter Judith , Felipe-Morales Daniel , Driscoll Kimberly , Frohnert Brigitte I. , Gallant Marisa , Gesualdo Patricia , Hoffman Michelle , Karban Rachel , Liu Edwin , Steck Andrea , Waugh Kathleen , Simell Olli G. , Adamsson Annika , Ahonen Suvi , Åkerlund Mari , Hekkala Anne , Holappa Henna , Hyöty Heikki , Ikonen Anni , Ilonen Jorma , Jäminki Sinikka , Jokipuu Sanna , Karlsson Leena , Kähönen Miia , Knip Mikael , Koivikko Minna-Liisa , Koreasalo Mirva , Kurppa Kalle , Kytölä Jarita , Latva-aho Tiina , Lindfors Katri , Lönnrot Maria , Mäntymäki Elina , Mattila Markus , Multasuo Katja , Mykkänen Teija , Niininen Tiina , Niinistö Sari , Nyblom Mia , Oikarinen Sami , Ollikainen Paula , Pohjola Sirpa , Rajala Petra , Rautanen Jenna , Riikonen Anne , Romo Minna , Ruohonen Suvi , Simell Satu , Sjöberg Maija , Stenius Aino , Tossavainen Päivi , Vähä-Mäkilä Mari , Vainionpää Sini , Varjonen Eeva , Veijola Riitta , Viinikangas Irene , 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. , Bonifacio Ezio , D’Angelo Miryam , 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 , Agardh Daniel , Aronsson Carin Andrén , Ask Maria , Bremer Jenny , Cilio Corrado , Ericson-Hallström Emelie , Fors Annika , Fransson Lina , Gard Thomas , Bennet Rasmus , Hansen Monika , 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 , Sjöberg Anette , Sjöberg Birgitta , Törn Carina , Wallin Anne , Wimar Åsa , Åberg Sofie , Killian Michael , Crouch Claire Cowen , Skidmore Jennifer , Akramoff Ashley , Chavoshi Masumeh , Dunson Kayleen , Hervey Rachel , Lyons Rachel , Meyer Arlene , Mulenga Denise , Radtke Jared , Romancik Matei , Schmitt Davey , Schwabe Julie , Zink Sarah , Austin-Gonzalez Sarah , Avendano Maryouri , Baethke Sandra , Brown Rasheedah , Burkhardt Brant , Butterworth Martha , Clasen Joanna , Cuthbertson David , Eberhard Christopher , Fiske Steven , Garmeson Jennifer , Gowda Veena , Heyman Kathleen , Hsiao Belinda , Karges Christina , Laras Francisco Perez , Lee Hye-Seung , Li Qian , 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 , Tewey Dena , Toth Michael , Vehik Kendra , Vijayakandipan Ponni , Wood Keith , Yang Jimin , Yu Liping , Miao Dongmei , Bingley Polly , Williams Alistair , Chandler Kyla , Ball Olivia , Kelland Ilana , Grace Sian , Ben Gillard  , Chavoshi Masumeh , Radtke Jared , Schwabe Julie , Wikoff Bill , Grapov Dmitry , Kind Tobias , Palazoglu Mine , Valdiviez Luis , Wancewicz Benjamin , Wohlgemuth Gert , Wong Joyce , Ke Sandra , Mulholland Niveen , Bourcier Kasia , Briese Thomas , Johnson Suzanne Bennett , Triplett Eric 
Published: October 2019

The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts.