Over several decades, studies have described the progression of autoimmune 
diabetes, from the first appearance of autoantibodies until, and after, the 
diagnosis of clinical disease with hyperglycaemia and insulin dependence. 
Despite the improved management of type 1 diabetes with exogenous insulin, most 
patients do not meet clinical glycaemic goals, and diabetes remains an important 
medical problem that affects children and adults. Clinical and preclinical 
studies have suggested strategies to prevent the diagnosis of type 1 diabetes in 
people at risk, but the outcomes of previous clinical trials have not met their 
primary endpoints of disease prevention or delay. The results from the TN-10 
teplizumab prevention trial show that the diagnosis of type 1 diabetes can be 
delayed by treatment with a FcR non-binding monoclonal antibody to CD3 in people 
at high risk for disease. This Series paper discusses how this clinical 
achievement raises new questions about for whom, and when, immunological 
strategies might be developed to prevent type 1 diabetes, and how to achieve 
this goal.