Multiple treatments that can change the course of type 1 diabetes have been identified over the last several years through the efforts of TrialNet, the Immune Tolerance Network and others. Although these immune therapies can stop disease progression in those with elevated blood sugars, the effect has proven to be transient in most study subjects. The ongoing effort of Type 1 Diabetes TrialNet, its Clinical Centers and affiliates is to continue to develop better therapies to prevent and reverse type 1 diabetes in human subjects. The Barbara Davis Center and its affiliate network has been a central contributor to these efforts from the beginning of DPT-1 through TrialNet and we hope with renewal of our Clinical Center to be able to continue to push towards these aims as well as develop the next generation of physician-scientists who can build on the work accomplished so far. Our aim is not only to conduct excellent clinical research which can answer the main study questions being examined: most often metabolic - development of impaired glucose tolerance, overt diabetes or reduced C-peptide, but also to develop immune biomarkers which can help us better understand the pathogenesis of disease progression and identify secondary markers of responder groups that allow us to better tailor our therapies to achieve successful prevention of T1D.