Schematic representation of the balance of clinical trial activity in type 1 diabetes. Data are modeled onto a graphical representation of diabetes progression (adapted from reference [38]; reprinted with permission from Atkinson). Data are separated in two dimensions. First, according to stage of disease (primary prevention in the genetically at-risk before autoimmunity is apparent; secondary prevention when autoimmunity is present but no disease; and tertiary prevention or intervention when diabetes has been diagnosed but there is the opportunity to preserve C-peptide secretion); second, according to whether the therapy is antigen-specific (in black) or nonantigen-specific (in red). Underlined therapies are currently actively recruiting. The pie charts indicate the relative proportions of antigen-specific (black) and nonantigen-specific immunotherapy (red) in use at the different disease stages. DIPP, Diabetes Prediction and Prevention (39); APL, altered peptide ligand (40); ATG, anti-thymocyte globulin; CTLA-4Ig, cytotoxic T lymphocyte antigen-4 immunoglobulin; GCSF, granulocyte colony stimulating factor; HSCT, hematopoietic stem cell transplant; IFA, incomplete Freund's adjuvant; IL-1β, interleukin-1β; MMF/DZB, mycophenolate mofetil and daclizumab (41); α1-AT, α-1 antitrypsin; PBMC, peripheral blood mononuclear cell; TNF-α, tumor necrosis factor-α.