Altering the course of type 1 diabetes: an update on prevention and new‐onset clinical trials

Type 1 diabetes (T1D) results from autoimmune attack on the insulin producing pancreatic ß-cells. While there is ongoing research to artificially reproduce the critical function of the ß-cell with a closed loop system in which glucose sensing is tethered to insulin delivery, a Food and Drug Administration (FDA) approved clinical product has remained elusive. The definitive cure for T1D is to ensure that the necessary functional ß-cell mass remains. As ß-cell destruction is immune mediated, many efforts to halt this process have focused on immuno-modulatory and anti-inflammatory interventions. In theory, one could intervene at three different points in the course of diabetes to affect a cure: (i) prevention, before the development of diabetes; (ii) preservation, after the diagnosis, while some functional ßcell mass still remains; and (iii) replacement, for those who have had diabetes for an extended period of time, and who have no residual ßcell function (see Fig. 1). Promising efforts are underway at all three of these stages. This review will focus on the immuno-modulatory and anti-inflammatory interventions in the first two stages when there is still some ß-cell mass to preserve. However, these efforts may ultimately apply to ß-cell replacement, especially when stem cell approaches allow us to develop autologous ß-cell replacement, as these cells will remain under autoimmune attack. Hilary R. Thomasa and Stephen E. Gitelmanb aDepartment of Medicine and Diabetes Center, University of California, San Francisco, CA, USA; and bDepartment of Pediatrics and Diabetes Center, University of California, San Francisco, CA, USA