The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening
AuthorJacobsen, LM; Bocchino, L; Evans-Molina, C; DiMeglio, L; Goland, R; Wilson, DM; Atkinson, MA; Aye, T; Russell, WE; Wentworth, JM; ...
University of Melbourne Author/sWentworth, John
Document TypeJournal Article
CitationsJacobsen, L. M., Bocchino, L., Evans-Molina, C., DiMeglio, L., Goland, R., Wilson, D. M., Atkinson, M. A., Aye, T., Russell, W. E., Wentworth, J. M., Boulware, D., Geyer, S. & Sosenko, J. M. (2020). The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening. DIABETOLOGIA, 63 (3), pp.588-596. https://doi.org/10.1007/s00125-019-05047-w.
Access StatusAccess this item via the Open Access location
Open Access URLAccepted version
AIMS/HYPOTHESIS: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. METHODS: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1-49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. RESULTS: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. CONCLUSIONS/INTERPRETATION: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.
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