Progression likelihood score identifies substages of presymptomatic type 1 diabetes in childhood public health screening
Andreas Weiß, Jose Zapardiel‐Gonzalo, Franziska Voss, Manja Jolink, Joanna Stock, Florian Haupt, Kerstin Kick, Tiziana Welzhofer, Anja Heublein, Christiane Winkler, Peter Achenbach, Anette‐Gabriele Ziegler, Ezio Bonifacio, for the Fr1da-study group
Abstract
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 HbA 1c 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%). HbA 1c , 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. Graphical abstract