PMID- 24034790 OWN - NLM STAT- MEDLINE DCOM- 20150110 LR - 20240422 IS - 1399-5448 (Electronic) IS - 1399-543X (Print) IS - 1399-543X (Linking) VI - 15 IP - 2 DP - 2014 Mar TI - Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. PG - 118-26 LID - 10.1111/pedi.12066 [doi] AB - OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tolerance test (OGTT), and (iii) risk for early T1D is related to country, population, human leukocyte antigen (HLA)-genotypes and immunological markers. METHODS: Autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2) and insulin (IAA) were analyzed from 3 months of age in children with genetic risk. Symptoms and laboratory values at diagnosis were obtained and reviewed for ADA criteria. RESULTS: The first 100 children to develop T1D, 33 first-degree relatives (FDRs), with a median age 2.3 yr (0.69-6.27), were diagnosed between September 2005 and November 2011. Although young, 36% had no symptoms and ketoacidosis was rare (8%). An OGTT diagnosed 9/30 (30%) children above 3 yr of age but only 4/70 (5.7%) below the age of 3 yr. FDRs had higher cumulative incidence than children from the general population (p < 0.0001). Appearance of all three autoantibodies at seroconversion was associated with the most rapid development of T1D (HR = 4.52, p = 0.014), followed by the combination of GADA and IAA (HR = 2.82, p < 0.0001). CONCLUSIONS: Close follow-up of children with genetic risk enables early detection of T1D. Risk factors for rapid development of diabetes in this young population were FDR status and initial positivity for GADA, IA-2, and IAA or a combination of GADA and IAA. CI - (c) 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Elding Larsson, Helena AU - Elding Larsson H AD - Department of Clinical Sciences, Lund University, Skane University Hospital SUS, Malmo, Sweden. FAU - Vehik, Kendra AU - Vehik K FAU - Gesualdo, Patricia AU - Gesualdo P FAU - Akolkar, Beena AU - Akolkar B FAU - Hagopian, William AU - Hagopian W FAU - Krischer, Jeffery AU - Krischer J FAU - Lernmark, Ake AU - Lernmark A FAU - Rewers, Marian AU - Rewers M FAU - Simell, Olli AU - Simell O FAU - She, Jin-Xiong AU - She JX FAU - Ziegler, Anette AU - Ziegler A FAU - Haller, Michael J AU - Haller MJ CN - TEDDY Study Group LA - eng GR - DK63865/DK/NIDDK NIH HHS/United States GR - UC4 DK063863/DK/NIDDK NIH HHS/United States GR - U01 DK063836/DK/NIDDK NIH HHS/United States GR - DK63790/DK/NIDDK NIH HHS/United States GR - UC4 DK063829/DK/NIDDK NIH HHS/United States GR - HHSN267200700014C/DK/NIDDK NIH HHS/United States GR - DK63863/DK/NIDDK NIH HHS/United States GR - DK63861/DK/NIDDK NIH HHS/United States GR - UC4 DK063865/DK/NIDDK NIH HHS/United States GR - DK63836/DK/NIDDK NIH HHS/United States GR - DK63829/DK/NIDDK NIH HHS/United States GR - U01 DK063829/DK/NIDDK NIH HHS/United States GR - UC4 DK095300/DK/NIDDK NIH HHS/United States GR - UC4 DK063821/DK/NIDDK NIH HHS/United States GR - UC4DK095300/DK/NIDDK NIH HHS/United States GR - UC4 DK063836/DK/NIDDK NIH HHS/United States GR - DK63821/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20130827 PL - Denmark TA - Pediatr Diabetes JT - Pediatric diabetes JID - 100939345 RN - 0 (Autoantibodies) RN - 0 (Histocompatibility Antigens) SB - IM MH - Autoantibodies/blood/genetics MH - Child MH - Child, Preschool MH - Cohort Studies MH - Diabetes Mellitus, Type 1/blood/*diagnosis/epidemiology/genetics MH - *Early Diagnosis MH - Epidemiologic Factors MH - Female MH - Gene-Environment Interaction MH - Genetic Predisposition to Disease MH - Histocompatibility Antigens/genetics MH - Humans MH - Infant MH - Male PMC - PMC3866211 MID - NIHMS502226 OTO - NOTNLM OT - TEDDY study OT - autoantibodies OT - diagnosis OT - follow-up studies OT - type 1 diabetes COIS- Conflict of Interest: The authors declare that there are no conflicts of interest to report regarding this study. FIR - Rewers, Marian IR - Rewers M FIR - Barriga, Katherine IR - Barriga K FIR - Bautista, Kimberly IR - Bautista K FIR - Baxter, Judith IR - Baxter J FIR - Eisenbarth, George IR - Eisenbarth G FIR - Frank, Nicole IR - Frank N FIR - Gesualdo, Patricia IR - Gesualdo P FIR - Hoffman, Michelle IR - Hoffman M FIR - Ide, Lisa IR - Ide L FIR - Karban, Rachel IR - Karban R FIR - Liu, Edwin IR - Liu E FIR - Norris, Jill IR - Norris J FIR - Waugh, Kathleen IR - Waugh K FIR - Samper-Imaz, Adela IR - Samper-Imaz A FIR - Steck, Andrea IR - Steck A FIR - She, Jin-Xiong IR - She JX FIR - Schatz, Desmond IR - Schatz D FIR - Hopkins, Diane IR - Hopkins D FIR - Steed, Leigh IR - Steed L FIR - Thomas, Jamie IR - Thomas J FIR - Silvis, Katherine IR - Silvis K FIR - Haller, Michael IR - Haller M FIR - Shankar, Meena IR - Shankar M FIR - Gardiner, Melissa IR - Gardiner M FIR - McIndoe, Richard IR - McIndoe R FIR - Liu, Haitao IR - Liu H FIR - Nechtman, John IR - Nechtman J FIR - Sharma, Ashok IR - Sharma A FIR - Williams, Joshua IR - Williams J FIR - Foghis, Gabriela IR - Foghis G FIR - Anderson, Stephen W IR - Anderson SW FIR - Ziegler, Anette G IR - Ziegler AG FIR - Beyerlein, Andreas IR - Beyerlein A FIR - Bonifacio, Ezio IR - Bonifacio E FIR - Henneberger, Lydia IR - Henneberger L FIR - Hummel, Michael IR - Hummel M FIR - Hummel, Sandra IR - Hummel S FIR - Foterek, Kristina IR - Foterek K FIR - Kersting, Mathilde IR - Kersting M FIR - Knopff, Annette IR - Knopff A FIR - Koletzko, Sibylle IR - Koletzko S FIR - Krause, Stephanie IR - Krause S FIR - Peplow, Claudia IR - Peplow C FIR - Pfluger, Maren IR - Pfluger M FIR - Roth, Roswith IR - Roth R FIR - Schenkel, Julia IR - Schenkel J FIR - Stock, Joanna IR - Stock J FIR - Strauss, Elisabeth IR - Strauss E FIR - Warncke, Katharina IR - Warncke K FIR - Winkler, Christiane IR - Winkler C FIR - Simell, Olli G IR - Simell OG FIR - Hyoty, Heikki IR - Hyoty H FIR - Ilonen, Jorma IR - Ilonen J FIR - Knip, Mikael IR - Knip M FIR - Lonnrot, Maria IR - Lonnrot M FIR - Mantymaki, Elina IR - Mantymaki E FIR - Mykkanen, Juha IR - Mykkanen J FIR - Nanto-Salonen, Kirsti IR - Nanto-Salonen K FIR - Niininen, Tiina IR - Niininen T FIR - Nyblom, Mia IR - Nyblom M FIR - Riikonen, Anne IR - Riikonen A FIR - Romo, Minna IR - Romo M FIR - Simell, Barbara IR - Simell B FIR - Simell, Tuula IR - Simell T FIR - Simell, Ville IR - Simell V FIR - Sjoberg, Maija IR - Sjoberg M FIR - Stenius, Aino IR - Stenius A FIR - Toppari, Jorma IR - Toppari J FIR - Varjonen, Eeva IR - Varjonen E FIR - Veijola, Riitta IR - Veijola R FIR - Virtanen, Suvi M IR - Virtanen SM FIR - Lernmark, Ake IR - Lernmark A FIR - Agardh, Daniel IR - Agardh D FIR - Andren-Aronsson, Carin IR - Andren-Aronsson C FIR - Ask, Maria IR - Ask M FIR - Bremer, Jenny IR - Bremer J FIR - Cilio, Corrado IR - Cilio C FIR - Ericson-Hallstrom, Emilie IR - Ericson-Hallstrom E FIR - Fransson, Lina IR - Fransson L FIR - Gard, Thomas IR - Gard T FIR - Gerardsson, Joanna IR - Gerardsson J FIR - Hansson, Gertie IR - Hansson G FIR - Hansen, Monica IR - Hansen M FIR - Hyberg, Susanne IR - Hyberg S FIR - Johansen, Fredrik IR - Johansen F FIR - Jonasdottir, Berglind IR - Jonasdottir B FIR - Karlsson, Ulla-Marie IR - Karlsson UM FIR - Larsson, Helena Elding IR - Larsson HE FIR - Lernmark, Barbro IR - Lernmark B FIR - Markan, Maria IR - Markan M FIR - Massadakis, Theodosia IR - Massadakis T FIR - Melin, Jessica IR - Melin J FIR - Mansson-Martinez, Maria IR - Mansson-Martinez M FIR - Nilsson, Anita IR - Nilsson A FIR - Rahmati, Kobra IR - Rahmati K FIR - Jarvirova, Monica Sedig IR - Jarvirova MS FIR - Sibthorpe, Sara IR - Sibthorpe S FIR - Sjoberg, Birgitta IR - Sjoberg B FIR - Swartling, Ulrica IR - Swartling U FIR - Trulsson, Erika IR - Trulsson E FIR - Torn, Carina IR - Torn C FIR - Wallin, Anne IR - Wallin A FIR - Wimar, Asa IR - Wimar A FIR - Aberg, Sofie IR - Aberg S FIR - Hagopian, William A IR - Hagopian WA FIR - Yan, Xiang IR - Yan X FIR - Killian, Michael IR - Killian M FIR - Crouch, Claire Cowen IR - Crouch CC FIR - Hay, Kristen M IR - Hay KM FIR - Ayres, Stephen IR - Ayres S FIR - Adams, Carissa IR - Adams C FIR - Bratrude, Brandi IR - Bratrude B FIR - Coughlin, David IR - Coughlin D FIR - Fowler, Greer IR - Fowler G FIR - Franco, Czarina IR - Franco C FIR - Hammar, Carla IR - Hammar C FIR - Heaney, Diana IR - Heaney D FIR - Marcus, Patrick IR - Marcus P FIR - Meyer, Arlene IR - Meyer A FIR - Mulenga, Denise IR - Mulenga D FIR - Scott, Elizabeth IR - Scott E FIR - Skidmore, Jennifer IR - Skidmore J FIR - Stabbert, Joshua IR - Stabbert J FIR - Stepitova, Viktoria IR - Stepitova V FIR - Williams, Nancy IR - Williams N FIR - Becker, Dorothy IR - Becker D FIR - Franciscus, Margaret IR - Franciscus M FIR - Dalmagro-Elias, MaryEllen IR - Dalmagro-Elias M FIR - Daftary, Ashi IR - Daftary A FIR - Krischer, Jeffrey P IR - Krischer JP FIR - Abbondondolo, Michael IR - Abbondondolo M FIR - Austin, Sarah IR - Austin S FIR - Brown, Rasheedah IR - Brown R FIR - Burkhardt, Brant IR - Burkhardt B FIR - Butterworth, Martha IR - Butterworth M FIR - Cuthbertson, David IR - Cuthbertson D FIR - Eberhard, Christopher IR - Eberhard C FIR - Fiske, Steven IR - Fiske S FIR - Gowda, Veena IR - Gowda V FIR - Hadley, David IR - Hadley D FIR - Lee, Hye-Seung IR - Lee HS FIR - Liu, Shu IR - Liu S FIR - Lynch, Kristian IR - Lynch K FIR - Malloy, Jamie IR - Malloy J FIR - McCarthy, Cristina IR - McCarthy C FIR - McLeod, Wendy IR - McLeod W FIR - Smith, Laura IR - Smith L FIR - Smith, Susan IR - Smith S FIR - Tamura, Roy IR - Tamura R FIR - Uusitalo, Ulla IR - Uusitalo U FIR - Vehik, Kendra IR - Vehik K FIR - Washington, Earnest IR - Washington E FIR - Yang, Jimin IR - Yang J FIR - Akolkar, Beena IR - Akolkar B FIR - Bourcier, Kasia IR - Bourcier K FIR - Briese, Thomas IR - Briese T FIR - Johnson, Suzanne Bennett IR - Johnson SB FIR - Oberste, Steve IR - Oberste S FIR - Triplett, Eric IR - Triplett E FIR - Yu, Liping IR - Yu L FIR - Miao, Dongmei IR - Miao D FIR - Bingley, Polly IR - Bingley P FIR - Williams, Alistair IR - Williams A FIR - Chandler, Kyla IR - Chandler K FIR - Rokni, Saba IR - Rokni S FIR - Long, Anna IR - Long A FIR - Boldison, Joanna IR - Boldison J FIR - Butterly, Jacob IR - Butterly J FIR - Broadhurst, Jessica IR - Broadhurst J FIR - Carreno, Gabriella IR - Carreno G FIR - Curnock, Rachel IR - Curnock R FIR - Easton, Peter IR - Easton P FIR - Geoghan, Ivey IR - Geoghan I FIR - Goode, Julia IR - Goode J FIR - Pearson, James IR - Pearson J FIR - Reed, Charles IR - Reed C FIR - Ridewood, Sophie IR - Ridewood S FIR - Wyatt, Rebecca IR - Wyatt R FIR - Eriksson, Elisabeth Aardal IR - Eriksson EA FIR - Karlsson, Ewa Lonn IR - Karlsson EL FIR - Erlund, Iris IR - Erlund I FIR - Salminen, Irma IR - Salminen I FIR - Sundvall, Jouko IR - Sundvall J FIR - Leiviska, Jaana IR - Leiviska J FIR - Lehtonen, Mari IR - Lehtonen M FIR - Little, Randie R IR - Little RR FIR - Tennill, Alethea L IR - Tennill AL FIR - Erlich, Henry IR - Erlich H FIR - Bugawan, Teodorica IR - Bugawan T FIR - Alejandrino, Maria IR - Alejandrino M FIR - Fiehn, Oliver IR - Fiehn O FIR - Wikoff, Bill IR - Wikoff B FIR - Kind, Tobias IR - Kind T FIR - Palazoglu, Mine IR - Palazoglu M FIR - Wong, Joyce IR - Wong J FIR - Wohlgemuth, Gert IR - Wohlgemuth G FIR - She, Jin-Xiong IR - She JX FIR - Petrosino, Joseph F IR - Petrosino JF FIR - Marcovina, Santica M IR - Marcovina SM FIR - Higgins, Heather IR - Higgins H FIR - Ke, Sandra IR - Ke S FIR - McIndoe, Richard IR - McIndoe R FIR - Liu, Haitao IR - Liu H FIR - Nechtman, John IR - Nechtman J FIR - Zhao, Yansheng IR - Zhao Y FIR - Jiang, Na IR - Jiang N FIR - Onengut-Gumuscu, Suna IR - Onengut-Gumuscu S FIR - Rich, Stephen S IR - Rich SS FIR - Chen, Wei-Min IR - Chen WM FIR - Farber, Emily IR - Farber E FIR - Pickin, Rebecca Roche IR - Pickin RR FIR - Davis, Jordan IR - Davis J FIR - Gallo, Dan IR - Gallo D EDAT- 2013/09/17 06:00 MHDA- 2015/01/13 06:00 PMCR- 2015/03/01 CRDT- 2013/09/17 06:00 PHST- 2013/03/27 00:00 [received] PHST- 2013/06/24 00:00 [revised] PHST- 2013/06/28 00:00 [accepted] PHST- 2013/09/17 06:00 [entrez] PHST- 2013/09/17 06:00 [pubmed] PHST- 2015/01/13 06:00 [medline] PHST- 2015/03/01 00:00 [pmc-release] AID - 10.1111/pedi.12066 [doi] PST - ppublish SO - Pediatr Diabetes. 2014 Mar;15(2):118-26. doi: 10.1111/pedi.12066. Epub 2013 Aug 27.