Abstract
The regulatory approval and growing pipeline of disease-modifying therapies for presymptomatic type 1 diabetes have sparked an increase in screening for the presence of islet autoantibodies in individuals who may not have yet developed clinical symptoms of disease. The staging system that is currently employed to define type 1 diabetes diagnosis in presymptomatic and symptomatic phases is based on the presence of islet autoantibodies and glycemic status. Here, we make the case to consider using C-peptide values to provide context for glycemia. Inclusion of C-peptide could result in better prediction of progression to clinical disease and more specificity for features typically associated with type 1 diabetes (and, thus, be less susceptible to confounding influences on glycemia like age and insulin resistance). It also could more rapidly identify responses to disease-modifying therapies. The implementation and translation of these findings will be key to long-term success in type 1 diabetes prediction and disease modification strategies.