Ng K, Stavropoulos H, Anand V, et al. - Islet autoantibody type-specific titer thresholds defined in this study can significantly improve type 1 diabetes risk stratification among children.

• A total of 24,662 children at elevated genetic or familial risk to develop islet autoimmunity and diabetes were followed in prospective cohort studies in Finland, Germany, Sweden, and the U.S.

• There were 1,604 children with confirmed positivity, and markedly different 5-year diabetes risks linked with IAA (autoantibodies against insulin)(n = 909), GADA (GAD antibodies)(n = 1076), and IA-2A (insulinoma-associated antigen 2) (n = 714) were evident, when stratified by quartiles of titer, ranging from 19% (GADA 1st quartile) to 60% (IA-2A 4th quartile).

• For each autoantibody, the minimum titer related to a maximum difference in 5-year risk varied, corresponding to the 58.6th, 52.4th, and 10.2nd percentile of children specifically positive for each of IAA, GADA, and IA-2A, respectively.

• The 5-year risk granted by single (n = 954) and multiple (n = 527) autoantibodies could be stratified from 6 to 75%, employing these autoantibody type-specific titer thresholds in the 1,481 children with all autoantibodies examined.

• Effective identification of children with a ≥50% 5-year risk was enabled by the thresholds, when considering age-specific autoantibody screening (57–65% positive predictive value and 56–74% sensitivity for ages 1–5 years).

• The significance of links between the three autoantibody titers and diabetes risk was corroborated in the multivariable analysis.