Background
Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10-18 years with an increased risk of developing type 1 diabetes.

Methods
Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes.

Findings
Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18 center dot 3 years (IQR 14 center dot 5-20 center dot 3). 442 (23 center dot 4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13 center dot 9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0 center dot 64 years (95% CI 0 center dot 34-0 center dot 95) for each 1-year increment of diagnosis age (Pearson's correlation coefficient 0 center dot 88, 95% CI 0 center dot 50-0 center dot 97, p=0 center dot 0020). The median interval between the last prediagnostic sample and diagnosis was 0 center dot 3 years (IQR 0 center dot 1-1 center dot 3) in the 227 participants who were autoantibody positive and 6 center dot 8 years (1 center dot 6-9 center dot 9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86-95) sensitive, with a positive predictive value of 66% (60-72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89-97) but lowered the positive predictive value to 55% (49-60).

Interpretation
Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials.