Type 1 diabetes mellitus prevention: present and future

Type 1 diabetes mellitus (T1DM) is a chronic disease with an increasing global incidence. The mortality associated with T1DM complications emphasizes the urgency of developing therapeutic strategies to prevent or delay the onset of T1DM. Historically, T1DM was solely described as a T cell-mediated disease. However, the role of β-cells as active participants in the immune-mediated damage is now well appreciated. Indeed, heterogeneity, vulnerability to stressors and the ability of β-cells to act as antigen-presenting cells has altered the perspective of what is necessary for effective disease prevention and ongoing β-cell preservation. Currently, teplizumab, an Fc-receptor non-binding humanized CD3-specific monoclonal antibody, is the only therapy approved by the FDA for the delay of T1DM onset. The intravenous administration, generalized immunosuppression and adverse effects mean that the transition to routine clinical practice is not without challenges. However, teplizumab could lead to the development of more accessible therapies. In this Review, we explore current and potential therapeutics for T1DM prevention. We offer alternative approaches, such as targeting the receptor for advanced glycation end products (RAGE). RAGE is a pattern recognition receptor that engages a wide range of ligands, including advanced glycation end products (AGEs; a family of molecules that includes the well described marker of long-term glucose concentrations, HbA_1c).