The serum proinsulin-to-C-peptide ratio has been demonstrated to be predictive of type 1 diabetes, with higher fasted ratio in progressors ~1 year before clinical onset of type 1 diabetes in the TNPTP cohort [49] and others [50] as a consequence of derailed insulin processing but appeared to change little over time [8]. This evidence concerns the gene INS and type 1 diabetes mellitus.