Fig. 1.

Progression and staging of type 1 diabetes. Type 1 diabetes is characterized by a progressive loss of beta cell function (black dashed-dotted line) over time. As the disease progresses, beta cell function falls below the threshold (red dashed line) required to maintain glucose control creating a requirement for insulin replacement therapy. Type 1 diabetes may be staged over the course of its progression starting with stage 1 at which point 2 or more of the 4 commonly measured islet autoantibodies are detected with normoglycemia. Stage 2 is marked by the appearance of dysglycemia associated with loss of beta cell function in addition to the presence of autoantibodies. Stage 3 is defined by hyperglycemia requiring insulin. In the green boxes are categories of biomarkers which could be leveraged to refine the staging paradigm, improve prognostic predictions, or subset individuals within a given stage of disease. The specifics of these biomarkers are discussed in the text related to the relevant stage.