Time to reframe the disease staging system for type 1 diabetes

Abstract

In 2015, introduction of a disease staging system offered a framework for benchmarking progression to clinical type 1 diabetes. This model, based on islet autoantibodies (stage 1) and dysglycaemia (stage 2) before type 1 diabetes diagnosis (stage 3), has facilitated screening and identification of people at risk. Yet, there are many limitations to this model as the stages combine a very heterogeneous group of individuals; do not have high specificity for type 1 diabetes; can occur without persistence (ie, reversion to an earlier risk stage); and exclude age and other influential risk factors. The current staging system also infers that individuals at risk of type 1 diabetes progress linearly from stage 1 to stage 2 and subsequently stage 3, whereas such movements are often more complex. With the approval of teplizumab by the US Food and Drug Administration in 2022 to delay type 1 diabetes in people at stage 2, there is a need to refine the definition and accuracy of type 1 diabetes staging. Theoretically, we propose that a type 1 diabetes risk calculator should incorporate any available demographic, genetic, autoantibody, metabolic, and immune data that could be continuously updated. Additionally, we call to action for the field to increase the breadth of knowledge regarding type 1 diabetes risk in non-relatives, adults, and individuals from minority populations.