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Jacobsen, Laura M.; Larsson, Helena E.; Tamura, Roy N.; Vehik, Kendra; Clasen, Joanna; Sosenko, Jay; Hagopian, William A.; She, Jin-Xiong; Steck, Andrea K.; Rewers, Marian; Simell, Olli; Toppari, Jorma; Veijola, Riitta; Ziegler, Anette G.; Krischer, Jeffrey P.; Akolkar, Beena; Haller, Michael J.; Rewers, Marian; Bautista, Kimberly; Baxter, Judith; Bedoy, Ruth; Felipe-Morales, Daniel; Driscoll, Kimberly; Frohnert, Brigitte I.; Gallant, Marisa; Gesualdo, Patricia; Hoffman, Michelle; Karban, Rachel; Liu, Edwin; Norris, Jill; Samper-Imaz, Adela; Steck, Andrea; Waugh, Kathleen; Wright, Hali; Toppari, Jorma; Simell, Olli G.; Adamsson, Annika; Ahonen, Suvi; Hyoty, Heikki; Ilonen, Jorma.; Jokipuu, Sanna; Kallio, Tiina; Karlsson, Leena; Kahonen, Miia; Knip, Mikael; Kovanen, Lea; Koreasalo, Mirva; Kurppa, Kalle; Latva-aho, Tiina; Lonnrot, Maria; Mantymaki, Elina; Multasuo, Katja.; Niininen, Tiina; Niinisto, Sari; Nyblom, Mia; Rajala, Petra; Rautanen, Jenna.; Riikonen, Anne; Romo, Minna; Ronka, Juulia; Simell, Satu; Simell, Tuula; Sjoberg, Maija; Stenius, Aino; Leppanen, Maria; Vainionpaa, Sini.; Varjonen, Eeva; Veijola, Riitta; Virtanen, Suvi M.; Vaha-Makila, Mari; Akerlund, Mari; Lindfors, Katri; She, Jin-Xiong; Schatz, Desmond; Hopkins, Diane; Steed, Leigh; Bryant, Jennifer; Thomas, Jamie; Adams, Janey; Silvis, Katherine; Haller, Michael; Gardiner, Melissa; McIndoe, Richard; Sharma, Ashok; Anderson, Stephen W.; Jacobsen, Laura; Ziegler, Anette G.; Beyerlein, Andreas; Bonifacio, Ezio; Heublein, Anja; Hummel, Michael; Hummel, Sandra; Knopff, Annette; Koch, Charlotte; Koletzko, Sibylle; Ramminger, Claudia; Roth, Roswith.; Scholz, Marlon; Schulzik, Laura; Stock, Joanna; Warncke, Katharina; Wendel, Lorena; Winkler, Christiane; Lernmark, Ake; Agardh, Daniel; Aronsson, Carin Andren; Ask, Maria; Bremer, Jenny; Carlsson, Ulla-Marie; Cilio, Corrado; Ericson-Hallstrom, Emelie; Fors, Annika; Fransson, Lina; Gard, Thomas.; Bennet, Rasmus; Hansson, Carina; Hyberg, Susanne; Jisser, Hanna; Johansen, Fredrik; Jonsdottir, Berglind; Jovic, Silvija; Larsson, Helena Elding; Lindstrom, Marielle.; Lundgren, Markus; Mansson-Martinez, Maria; Markan, Maria; Melin, Jessica; Mestan, Zeliha; Nilsson, Caroline; Ottosson, Karin; Rahmati, Kobra; Ramelius, Anita; Salami, Falastin; Sibthorpe, Sara; Sjoberg, Anette; Sjoberg, Birgitta; Amboh, Evelyn Tekum; Torn, Carina; Wallin, Anne; Wimar, Asa; Aberg, Sofie; Hagopian, William A.; Killian, Michael; Crouch, Claire Cowen; Skidmore, Jennifer; Akramoff, Ashley; Banjanin, Jana; Chavoshi, Masumeh; Dunson, Kayleen; Hervey, Rachel; Levenson, Shana; Lyons, Rachel.; Meyer, Arlene; Mulenga, Denise; Schmitt, Davey; Schwabe, Julie; Becker, Dorothy; Franciscus, Margaret; Ellen, Mary; Smith, Dalmagro-Elias; Daftary, Ashi; Klein, Mary Beth; Yates, Chrystal; Krischer, Jeffrey P.; Austin-Gonzalez, Sarah; Avendano, Maryouri; Baethke, Sandra; Brown, Rasheedah; Burkhardt, Brant; Butterworth, Martha; Clasen, Joanna; Cuthbertson, David; Eberhard, Christopher; Fiske, Steven.; Garcia, Dena; Garmeson, Jennifer; Gowda, Veena; Heyman, Kathleen; Hsiao, Belinda; Laras, Francisco Perez; Lee, Hye-Seung; 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; Uusitalo, Ulla; Vehik, Kendra; Vijayakandipan, Ponni; Wood, Keith; Yang, Jimin; Ballard, Lori; Hadley, David.; McLeod, Wendy; Akolkar, Beena; Yu, Liping; Miao, Dongmei; Bingley, Polly; Williams, Alistair; Chandler, Kyla; Williams, Claire; George, Gifty; Grace, Sian; Gillard, Ben; Hagopian, William; Chavoshi, Masumeh; Erlich, Henry; Mack, Steven J.; Fear, Anna Lisa; Rich, Stephen S.; Chen, Wei-Min; Onengut-Gumuscu, Suna; Farber, Emily; Pickin, Rebecca Roche; Davis, John; Davis, Jordan; Gallo, Dan; Bonnie, Jessica; Campolieto, Paul; Ke, Sandra; Mulholland, Niveen; Bourcier, Kasia; Briese, Thomas; Johnson, Suzanne Bennett; Triplett, Eric (2019): Predicting progression to type 1 diabetes from ages 3 to 6 in islet autoantibody positive TEDDY children. In: Pediatric Diabetes, Vol. 20, No. 3: pp. 263-270
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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.

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