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Diabetes Care. 2015 May;38(5):808-13. doi: 10.2337/dc14-2426. Epub 2015 Feb 9.

Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY).

Collaborators (236)

Rewers M, Bautista K, Baxter J, Bedoy R, Felipe-Morales D, Frohnert B, Gesualdo P, Hoffman M, Karban R, Liu E, Norris J, Samper-Imaz A, Steck A, Waugh K, Wright H, She JX, Schatz D, Hopkins D, Steed L, Thomas J, Silvis K, Haller M, Shankar M, Sheehan E, Gardiner M, McIndoe R, Liu H, Nechtman J, Sharma A, Williams J, Foghis G, Anderson SW, Ziegler AG, Beyerlein A, Bonifacio E, Hummel M, Hummel S, Foterek K, Kersting M, Knopff A, Koletzko S, Peplow C, Roth R, Stock J, Strauss E, Warncke K, Winkler C, Toppari J, Simell OG, Adamsson A, Hyöty H, Ilonen J, Kähönen M, Knip M, Koivu A, Koreasalo M, Kurppa K, Lönnrot M, Mäntymäki E, Multasuo K, Mykkänen J, Niininen T, Nyblom M, Rajala P, Rautanen J, Riikonen A, Romo M, Simell S, Simell T, Simell V, Sjöberg M, Stenius A, Varjonen E, Veijola R, Virtanen SM, Åkerlund M, Lernmark Å, Agardh D, Aronsson CA, Ask M, Bremer J, Carlsson UM, Cilio C, Ekstrand C, Ericson-Hallström E, Fransson L, Gard T, Gerardsson J, Håkansson R, Hansen M, Hansson G, Hyberg S, Johansen F, Jonasdottir B, Jonsson L, Larsson HE, Lernmark B, Månsson-Martinez M, Markan M, Massadakis T, Melin J, Mestan Z, Rahmati K, Ramelius A, Salami F, Järvirova MS, Sibthorpe S, Sjöberg B, Swartling U, Trulsson E, Törn C, Wallin A, Wimar Å, Åberg S, Hagopian WA, Yan X, Killian M, Crouch CC, Skidmore J, Ayres S, Dunson K, Heaney D, Hervey R, Johnson C, Lyons R, Meyer A, Mulenga D, Schulte E, Scott E, Stabbert J, Willis J, Becker D, Franciscus M, Smith MD, Daftary A, Klein MB, Yates C, Krischer JP, Abbondondolo M, Austin-Gonzalez S, Brown R, Burkhardt B, Butterworth M, Cuthbertson D, Eberhard C, Fiske S, Garcia D, Gowda V, Hadley D, Lee HS, Liu S, Liu X, Lynch K, Malloy J, McCarthy C, McLeod W, Shaffer C, Smith L, Smith S, Tamura R, Uusitalo U, Vehik K, Vijayakandipan P, Wood K, Yang J, Akolkar B, Bourcier K, Briese T, Johnson SB, Oberste S, Triplett E, Yu L, Miao D, Bingley P, Williams A, Chandler K, Rokni S, Boldison J, Butterly J, Carreno G, Caygill C, Geoghan I, Long A, Payne M, Pearson J, Ridewood S, Wyatt R, Eriksson EA, Lundgren IM, Karlsson EL, Dernroth DN, Erlund I, Salminen I, Sundvall J, Leiviskä J, Lehtonen M, Little RR, Tennill AL, Erlich H, Mack SJ, Fear AL, Fiehn O, Wikoff B, Defelice B, Grapov D, Kind T, Palazoglu M, Valdiviez L, Wancewicz B, Wohlgemuth G, Wong J, Petrosino JF, Marcovina SM, Gaur VP, Smith RD, Metz TO, Ansong C, Webb-Robertson BJ, Mitchell HD, Higgins H, Ke S, She JX, McIndoe R, Liu H, Nechtman J, Zhao Y, Jiang N, Rich SS, Chen WM, Onengut-Gumuscu S, Farber E, Pickin RR, Davis J, Gallo D, Bonnie J, Campolieto P.

Author information

1
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO andrea.steck@ucdenver.edu.
2
Pediatric Epidemiology Center, University of South Florida, Tampa, FL.
3
Technische Universität Dresden, Dresden, Germany.
4
Lund University/Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
5
Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany; Klinikum rechts der Isar, Technische Universität München, München, Germany; and Forschergruppe Diabetes e.V., Neuherberg, Germany.
6
Pacific Northwest Diabetes Research Institute, Seattle, WA.
7
Medical College of Georgia, Georgia Regents University, Augusta, GA.
8
Department of Pediatrics, University of Turku, Turku, Finland.
9
Division of Diabetes, Endocrinology, & Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
10
University of Florida, Gainesville, FL.
11
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO.

Abstract

OBJECTIVE:

While it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined.

RESEARCH DESIGN AND METHODS:

The Environmental Determinants of Diabetes in the Young (TEDDY) study has observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months.

RESULTS:

Life table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P < 0.0001]). The mean GADA level did not significantly affect the risk of diabetes.

CONCLUSIONS:

In the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive.

PMID:
25665818
PMCID:
PMC4407751
DOI:
10.2337/dc14-2426
[Indexed for MEDLINE]
Free PMC Article

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