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

Summary 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