INS and type 2 diabetes mellitus: Methods: In silico hypothesis testing involved (1) the addition and qualification of proinsulin biology into a preexisting QSP model, (2) the creation and validation of virtual patients (VPs) for subpopulations of type 2 diabetics based on phenotypic traits, and (3) the simulation of clinical trials evaluating the therapeutic value of the conversion of circulating proinsulin to insulin in the VPs created.