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Observational Study
. 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)

Andrea K Steck  1 , Kendra Vehik  2 , Ezio Bonifacio  3 , Ake Lernmark  4 , Anette-G Ziegler  5 , William A Hagopian  6 , JinXiong She  7 , Olli Simell  8 , Beena Akolkar  9 , Jeffrey Krischer  2 , Desmond Schatz  10 , Marian J Rewers  11 ; TEDDY Study Group
Collaborators, Affiliations
Observational Study

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

Andrea K Steck et al. Diabetes Care. 2015 May.

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.

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Figures

Figure 1
Figure 1
Progression to diabetes in children with confirmed autoantibodies (N = 577). Ab+, antibody positive.
Figure 2
Figure 2
Progression to diabetes in children expressing one, two, or three autoantibodies by family history. Ab+, antibody positive; GP, general population.
See this image and copyright information in PMC

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