The importance of quantitating islet autoimmunity though the measurement of the islet-reactive T cells is emphasized by the reports estimating that up to 15–20% of newly diagnosed autoimmune T1D patients are autoantibody-negative [62]. Furthermore, approximately 9% of autoantibody-negative T1D patients

carry the highest-risk human leucocyte antigen (HLA) genotype DR3–DQ2/DR4–DQ8, suggesting strongly that these patients had autoimmune diabetes but were undetected with autoantibody testing alone [62]. Similarly, a subgroup of Japanese autoimmune diabetes patients, known as fulminant type 1 diabetes, have been reported to be autoantibody-negative but demonstrate islet-specific T cell responses [63]. In phenotypic T2D patients, we identified the presence of a subgroup

of phenotypic T2D patients who are autoantibody-negative, but demonstrate islet-specific autoimmunity with islet-reactive T cells similar to classic Ivacaftor in vivo T1D patients www.selleckchem.com/products/cx-4945-silmitasertib.html [60]. These T cell islet-reactive positive phenotypic T2D patients also demonstrated a more severe β cell lesion than the patients who had not yet developed islet-reactive T cell responses [60], thus implicating the islet-reactive T cells in T2D patients in the β cell functional demise associated with T2D pathogenesis. Moreover, these studies demonstrate further the importance of assaying for islet autoimmune T cell responses when determining the presence of islet autoimmunity in T2D patients. Therefore, it appears that islet autoimmune disease may be involved in the continued β cell functional demise associated with the progressive nature of T2D disease. However, is the islet autoimmunity that develops in T2D the same as the islet autoimmunity which develops in T1D? Comparing islet autoantibodies associated with T1D and T2D patients

suggests potential differences. The most common islet autoantibodies found in childhood T1D patients are islet cell autoantibodies (ICA), glutamate decarboxylase autoantibodies (GADAb), insulinoma-associated antigen-2 autoantibodies Rucaparib (IA-2), zinc transporter autoantibodies (ZnT8) and insulin autoantibodies (IAA), with many patients demonstrating positivity for multiple islet autoantibodies. In fact, positivity for an increasing number of islet autoantibodies is associated with a progressively greater risk of developing T1D [64–67]. In contrast, for phenotypic T2D patients, GADAb and ICA are much more common than IAA, IA-2 and ZnT8 autoantibodies and singular positivity for either ICA or GADAb is more characteristic of autoimmune phenotypic T2D patients [68–73]. One important issue to stress is the islet autoantibodies used to categorize and identify autoimmune T2D patients are islet autoantibodies identified originally in T1D patients. Therefore, there may be other islet autoantibodies specific to autoimmunity in phenotypic T2 diabetes that have not yet been identified which would classify them more accurately. In support of this concept, Seissler et al.