American Diabetes Association
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HLA genotype and probiotics modify the association between timing of solid food introduction and islet autoimmunity in the TEDDY Study

posted on 2023-08-14, 21:09 authored by William Hagopian, Ulla Uusitalo, Lazarus K. Mramba, Carin Andrén Aronsson, Kendra Vehik, Jimin Yang, Sandra Hummel, Åke Lernmark, Marian Rewers, Richard McIndoe, Jorma Toppari, Anette G. Ziegler, Beena Akolkar, Jeffrey P. Krischer, Suvi M. Virtanen, Jill M. Norris


To study the interaction between HLA genotype, early probiotic exposure, and timing of complementary foods in relation to risk of islet autoimmunity (IA).

Research design and methods

The TEDDY study prospectively follows 8,676 children with increased genetic risk of type 1 diabetes. We used Cox regression model adjusting for potential confounders to study early feeding and the risk of IA in a sample of 7,770 children


Any solid food introduced early (<6 months) was associated with increased risk of IA if the child had the HLA DR3/4 genotype and no probiotic exposure during the first year of life. Rice introduced at 4-5.9 months compared to later in the U.S. was associated with increased risk of IA.


Timing of solid food introduction, including rice, may be associated with IA in HLA DR3/4 children not exposed to probiotics. The microbiome composition under these exposure combinations requires further study.


The TEDDY Study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, U01 DK128847, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. This work is supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


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