Research in context
Evidence before this study
To search for the evidence published before this study, we searched PubMed using the search terms “pediatric islet autoantibodies”, “public health screening islet autoantibodies”, and “population-based prediction of type 1 diabetes” for articles published between Jan 1, 2012, and May 1, 2022 (date of last search). Most childhood type 1 diabetes cases appear in people with high HLA genetic risk, but about a quarter of cases have lower HLA risk. Islet autoantibodies are known to precede diagnosis and can reveal people at greatest future risk of type 1 diabetes. Knowing islet autoantibodies status in advance can prevent most diabetic ketoacidosis at onset, and immunotherapy applied in individuals who are islet autoantibodies positive can significantly delay onset. Multiple-islet autoantibodies mark the greatest risk as do islet autoantibodies appearing in early childhood. However, autoimmunity might evolve over time, and people initially with single-islet autoantibodies, or with islet autoantibodies appearing later in childhood, can also progress to clinical disease. Most large studies to date have followed up children at high HLA or familial risk via frequent islet autoantibodies testing throughout childhood. Although sensitive and specific, these approaches are not cost-effective for prediction of population-wide type 1 diabetes.
Added value of this study
Our results show that testing at only two ages (2 years and 6 years) is sufficient to detect a large majority of cases occurring by age 15 years. We found that including children who were positive for single-islet autoantibodies provided a key part of this sensitivity, especially children younger than 6 years. Our results, although primarily from children who were prescreened for elevated genetic risk, suggest that this strategy might apply even in those at lower HLA risk. Another key finding was that two-age islet-autoantibody testing might have different optimal ages in different geographical regions.
Implications of all the available evidence
Our results show that an efficient, initial autoantibody testing strategy might be sufficient in predicting type 1 diabetes diagnosis before the age of 15 years and raises the possibility that similar population-wide screening for future type 1 diabetes is possible.