Progression likelihood score identifies substages of presymptomatic type 1 diabetes in childhood public health screening
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Aims/hypothesis: The aim of this study was to develop strategies that identify children from the general population who have late-stage presymptomatic type 1 diabetes and may, therefore, benefit from immune intervention. Methods: We tested children from Bavaria, Germany, aged 1.75–10 years, enrolled in the Fr1da public health screening programme for islet autoantibodies (n=154,462). OGTT and HbA1c were assessed in children with multiple islet autoantibodies for diagnosis of presymptomatic stage 1 (normoglycaemia) or stage 2 (dysglycaemia) type 1 diabetes. Cox proportional hazards and penalised logistic regression of autoantibody, genetic, metabolic and demographic information were used to develop a progression likelihood score to identify children with stage 1 type 1 diabetes who progressed to stage 3 (clinical) type 1 diabetes within 2 years. Results: Of 447 children with multiple islet autoantibodies, 364 (81.4%) were staged. Undiagnosed stage 3 type 1 diabetes, presymptomatic stage 2, and stage 1 type 1 diabetes were detected in 41 (0.027% of screened children), 30 (0.019%) and 293 (0.19%) children, respectively. The 2 year risk for progression to stage 3 type 1 diabetes was 48% (95% CI 34, 58) in children with stage 2 type 1 diabetes (annualised risk, 28%). HbA1c, islet antigen-2 autoantibody positivity and titre, and the 90 min OGTT value were predictors of progression in children with stage 1 type 1 diabetes. The derived progression likelihood score identified substages corresponding to ≤90th centile (stage 1a, n=258) and >90th centile (stage 1b, n=29; 0.019%) of stage 1 children with a 4.1% (95% CI 1.4, 6.7) and 46% (95% CI 21, 63) 2 year risk of progressing to stage 3 type 1 diabetes, respectively. Conclusions/interpretation: Public health screening for islet autoantibodies found 0.027% of children to have undiagnosed clinical type 1 diabetes and 0.038% to have undiagnosed presymptomatic stage 2 or stage 1b type 1 diabetes, with 50% risk to develop clinical type 1 diabetes within 2 years.
Details
Original language | English |
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Pages (from-to) | 2121-2131 |
Number of pages | 11 |
Journal | Diabetologia |
Volume | 65 |
Issue number | 12 |
Publication status | Published - 27 Aug 2022 |
Peer-reviewed | Yes |
External IDs
PubMed | 36028774 |
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ORCID | /0000-0002-8704-4713/work/141544362 |
Keywords
Research priority areas of TU Dresden
DFG Classification of Subject Areas according to Review Boards
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- Clinical trial modelling, Glucose tolerance, Immunotherapy, Islet autoantibodies, Population screening, Progression score, Public health screening, Type 1 diabetes, Diabetes Mellitus, Type 1/epidemiology, Public Health, Autoantibodies, Humans, Islets of Langerhans/metabolism, Disease Progression, Mass Screening, Child