@article{d2283a1514174dde94e7fbe7249f22e3,
title = "Predicting progression to type 1 diabetes from ages 3 to 6 in islet autoantibody positive TEDDY children",
abstract = "Objective: The capacity to precisely predict progression to type 1 diabetes (T1D) in young children over a short time span is an unmet need. We sought to develop a risk algorithm to predict progression in children with high-risk human leukocyte antigen (HLA) genes followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Methods: Logistic regression and 4-fold cross-validation examined 38 candidate predictors of risk from clinical, immunologic, metabolic, and genetic data. TEDDY subjects with at least one persistent, confirmed autoantibody at age 3 were analyzed with progression to T1D by age 6 serving as the primary endpoint. The logistic regression prediction model was compared to two non-statistical predictors, multiple autoantibody status, and presence of insulinoma-associated-2 autoantibodies (IA-2A). Results: A total of 363 subjects had at least one autoantibody at age 3. Twenty-one percent of subjects developed T1D by age 6. Logistic regression modeling identified 5 significant predictors - IA-2A status, hemoglobin A1c, body mass index Z-score, single-nucleotide polymorphism rs12708716_G, and a combination marker of autoantibody number plus fasting insulin level. The logistic model yielded a receiver operating characteristic area under the curve (AUC) of 0.80, higher than the two other predictors; however, the differences in AUC, sensitivity, and specificity were small across models. Conclusions: This study highlights the application of precision medicine techniques to predict progression to diabetes over a 3-year window in TEDDY subjects. This multifaceted model provides preliminary improvement in prediction over simpler prediction tools. Additional tools are needed to maximize the predictive value of these approaches.",
keywords = "autoantibodies, metabolic, pediatric, prediction, type 1 diabetes",
author = "{The TEDDY study group} and Jacobsen, {Laura M.} and Larsson, {Helena E.} and Tamura, {Roy N.} and Kendra Vehik and Joanna Clasen and Jay Sosenko and Hagopian, {William A.} and She, {Jin Xiong} and Jin-Xiong She and Marian Rewers and Olli Simell and Jorma Toppari and Riitta Veijola and Ziegler, {Anette G.} and Krischer, {Jeffrey P.} and Beena Akolkar and Haller, {Michael J.}",
note = "Funding Information: The TEDDY Study Group 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 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), 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 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 TR001082). Dr. Xiang Liu assisted in the classification tree prediction using report. Funding Information: NIH/NCATS Clinical and Translational Science Award University of Colorado, Grant/Award Number: UL1 TR001082; NIH/NCATS Clinical and Translational Science Award University of Florida, Grant/Award Number: UL1 TR000064; TEDDY Study group funding grants, Grant/Award Number: U01 DK63863, U01 DK63836, U01 DK63790 UC4 DK106955, UC4 DK112243, UC4 DK117483 Contract No. HHSN267200700014CU01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865UC4 DK106955, UC4 DK112243, UC4 DK117483UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865UC4 DK63863, UC4 DK95300, UC4 DK100238; University of Florida; Florida State University; Columbia University; University of Virginia; Funding Information: The TEDDY Study Group 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 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), 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 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 TR001082). Dr. Xiang Liu assisted in the classification tree prediction using report. The TEDDY Study Group: Colorado Clinical Center: Marian Rewers, M.D., Ph.D., PI1,4,5,6,10,11, Kimberly Bautista12, Judith Baxter9,10,12,15, Ruth Bedoy2, Daniel Felipe-Morales, Kimberly Dris-coll, Ph.D.9, Brigitte I. Frohnert, M.D.2,14, Marisa Gallant, M.D.13, Patricia Gesualdo2,6,12,14,15, Michelle Hoffman12,13,14, Rachel Karban12, Edwin Liu, M.D.13, Jill Norris, Ph.D.2,3,12, Adela Samper-Imaz, Andrea Steck, M.D.3,14, Kathleen Waugh6,7,12,15, Hali Wright12. University of Colorado, Anschutz Medical Campus, Barbara Davis Center for Childhood Diabetes. Finland Clinical Center: Jorma Toppari, M.D., Ph.D., PI¥^1,4,11,14, Olli G. Simell, M.D., Ph.D., Annika Adamsson, Ph.D.^12, Suvi Ahonen*,±,§, Heikki Hy{\"o}ty, M.D., Ph.D.*,±,6, Jorma. Ilonen, M.D., Ph.D.¥,¶,3, Sanna Jokipuu^, Tiina Kallio^, Leena Karlsson^, Miia K{\"a}h{\"o}nenμ,¤, Mikael Knip, M.D., Ph.D.*,±,5, Lea Kovanen*±§, Mirva Koreasalo*,±,§,2, Kalle Kurppa, M.D., Ph.D.*,±,13, Tiina Latva-ahoμ,¤, Maria L{\"o}nnrot, M.D., Ph.D.*,±,6, Elina M{\"a}ntym{\"a}ki^, Katja. Multasuoμ,¤ Tiina Niininen±,*,12, Sari Niinist{\"o}±,§,2, Mia Nyblom*±, Petra Rajala^, Jenna. Rautanen±,§, Anne Riikonen* ± §, Minna Romo^, Juulia R{\"o}nk{\"a}μ,¤, Satu Simell, M.D., Ph.D.¥,13,Tuula Simell, Ph.D.¥,12, Maija Sj{\"o}berg¥,^,12,14, Aino Steniusμ,12, Maria Lepp{\"a}nen^, Sini. Vainionp{\"a}{\"a}^, Eeva Varjonen¥,^,12, Riitta Veijola, M.D., Ph.D.μ,¤,14, Suvi M. Virtanen, M.D., Ph.D.*,±,§,2, Mari V{\"a}h{\"a}-M{\"a}kil{\"a}^, Mari {\AA}kerlund*,±,§, Katri Lindfors, Ph.D.*,13,¥University of Turku, *University of Tampere, μUniversity of Oulu, ^Turku University Hospital, Hospital. District of Southwest Finland, ±Tampere University Hospital, ¤Oulu University Hospital, §National Institute for Health and Welfare, Finland, ¶University of Kuopio. Georgia/Florida Clinical Center: Jin-Xiong She, Ph.D., PI1,3,4,11, Desmond Schatz, M.D.*4,5,7,8, Diane Hopkins12, Leigh Steed12,13,14,15, Jennifer Bryant, Jamie Thomas*6,12, Janey Adams*12, Katherine Silvis2, Michael Haller, M.D.*14, Melissa Gardiner, Richard McIndoe, Ph.D., Ashok Sharma, Stephen W. Anderson, M.D.^, Laura Jacobsen, M.D.*14. Center for Biotechnology and Genomic Medicine, Augusta University. *University of Florida. ^Pediatric Endocrine Associates, Atlanta. Germany Clinical Center: Anette G. Ziegler, M.D., PI1,3,4,11, Andreas Beyerlein, Ph.D.2, Ezio Bonifacio Ph.D.*,5, Anja Heu-blein, Michael Hummel, M.D.13, Sandra Hummel, Ph.D.2, Annette Knopff7, Charlotte Koch, Sibylle Koletzko, M.D.¶13, Claudia Rammin-ger, Roswith. Roth, Ph.D.9, Marlon Scholz, Laura Schulzik2, Joanna Stock9,12,14, Katharina Warncke, M.D.14, Lorena Wendel, Christiane Winkler, Ph.D.2,12,15. Forschergruppe Diabetes e.V. and Institute of Diabetes Research, Helmholtz Zentrum M{\"u}nchen, Forschergruppe Diabetes, and Klinikum rechts der Isar, Technische Universit{\"a}t M{\"u}nchen. *Center for Regenerative Therapies, TU Dresden, ¶Dr. von Hauner Children's Hospital, Department of Gastroenterology, Ludwig Maximillians University Munich. Sweden Clinical Center: {\AA}ke Lern-mark, Ph.D., PI1,3,4,5,6,8,10,11,15, Daniel Agardh, M.D., Ph.D.13, Carin Andr{\'e}n Aronsson, Ph.D.2,12,13, Maria Ask, Jenny Bremer, Ulla-Marie Carlsson, Corrado Cilio, Ph.D., M.D.5, Emelie Ericson-Hallstr{\"o}m, Annika Fors, Lina Fransson, Thomas. Gard, Rasmus Bennet, Carina Hansson, Susanne Hyberg, Hanna Jisser, Fredrik Johansen, Berglind Jonsdottir, M.D., Silvija Jovic, Helena Elding Larsson, M.D., Ph.D. 6,14, Marielle. Lindstr{\"o}m, Markus Lundgren, M.D.14, Maria M{\aa}nsson-Martinez, Maria Markan, Jessica. Melin12, Zeliha Mestan, Caroline Nilsson, Karin Ottosson, Kobra Rahmati, Anita Ramelius, Falastin Salami, Sara Sibthorpe, Anette Sj{\"o}berg, Birgitta Sj{\"o}berg, Evelyn Tekum Amboh, Carina T{\"o}rn, Ph.D.3,15, Anne Wallin, {\AA}sa Wimar14, Sofie {\AA}berg. Lunds Universitet. Washington Clinical Center: William A. Hagopian, M.D., Ph.D., PI1,3,4,5,6,7,11,13,14, Michael Killian6,7,12,13, Claire Cowen Crouch12,14,15, Jennifer Skidmore2, Ashley Akramoff, Jana Banjanin, Masumeh Chavoshi, Kayleen Dunson, Rachel Hervey, Shana Leven-son, Rachel. Lyons, Arlene Meyer, Denise Mulenga, Davey Schmitt, Julie Schwabe. Pacific Northwest. Research Institute. Pennsylvania Satellite Center: Dorothy Becker, M.D., Margaret Franciscus, MaryEl-len. Dalmagro-Elias Smith2, Ashi Daftary, M.D., Mary Beth Klein, Chrystal Yates. Children's. Hospital of Pittsburgh of UPMC. Data Coordinating Center: Jeffrey P. Krischer, Ph.D.,PI1,4,5,10,11, Sarah Austin-Gonzalez, Maryouri Avendano, Sandra Baethke, Rasheedah Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",
year = "2019",
month = may,
doi = "10.1111/pedi.12812",
language = "English (US)",
volume = "20",
pages = "263--270",
journal = "Pediatric Diabetes",
issn = "1399-543X",
publisher = "Blackwell Munksgaard",
number = "3",
}