Attenuation of islet-specific T cell responses is associated with C-peptide improvement in autoimmune type 2 diabetes patients.

The clinical efficacy of peroxisome proliferator-activated receptor gamma ( PPAR-γ) agonists in cell-mediated autoimmune diseases results from down-regulation of inflammatory cytokines and autoimmune effector cells. T cell islet autoimmunity has been demonstrated to be common in patients with phenotypic type 2 diabetes mellitus ( T2DM) and islet-specific T cells ( T+) to be correlated positively with more severe beta cell dysfunction. We hypothesized that the beneficial effects of the PPAR-γ agonist, rosiglitazone, therapy in autoimmune T2DM patients is due, in part, to the immunosuppressive properties on the islet-specific T cell responses. Twenty-six phenotypic T2DM patients positive for T cell islet autoimmunity ( T+) were identified and randomized to rosiglitazone ( n = 12) or glyburide ( n = 14). Beta cell function, islet-specific T cell responses, interleukin ( IL)-12 and interferon ( IFN)-γ responses and islet autoantibodies were followed for 36 months. Patients treated with rosiglitazone demonstrated significant ( P < 0·03) down-regulation of islet-specific T cell responses, although no change in response to tetanus, a significant decrease ( P < 0·05) in IFN-γ production and significantly ( P < 0·001) increased levels of adiponectin compared to glyburide-treated patients. Glucagon-stimulated beta cell function was observed to improve significantly ( P < 0·05) in the rosiglitazone-treated T2DM patients coinciding with the down-regulation of the islet-specific T cell responses. In contrast, beta cell function in the glyburide-treated T2DM patients was observed to drop progressively throughout the study. Our results suggest that down-regulation of islet-specific T cell autoimmunity through anti-inflammatory therapy may help to improve beta cell function in autoimmune phenotypic T2DM patients. [ABSTRACT FROM AUTHOR]