CD28 and type 1 diabetes mellitus: Notably, CTLA-4 Ig has been demonstrated to block CD28-mediated costimulatory signaling, with success in recent onset type 1 diabetes at delaying loss of C-peptide (62, 63), endorsing the potential utility of therapeutics such as CD226 blockade in modulating T cell costimulation for the prevention or reversal of type 1 diabetes.