Erschienen:
Springer Science and Business Media LLC, 2022
Erschienen in:
Diabetologia, 65 (2022) 12, Seite 2121-2131
Sprache:
Englisch
DOI:
10.1007/s00125-022-05780-9
ISSN:
0012-186X;
1432-0428
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Aims/hypothesis</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>We tested children from Bavaria, Germany, aged 1.75–10 years, enrolled in the Fr1da public health screening programme for islet autoantibodies (<jats:italic>n</jats:italic>=154,462). OGTT and HbA<jats:sub>1c</jats:sub> 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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>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<jats:sub>1c</jats:sub>, 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, <jats:italic>n</jats:italic>=258) and >90th centile (stage 1b, <jats:italic>n</jats:italic>=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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions/interpretation</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Graphical abstract</jats:title>
</jats:sec>