The dose-effect correlation between Caspase 8 and cell death upon IGFBP3 exposure (Supplementary Fig. 4a–c) and the abrogation of the Caspase-8-associated beta-cell apoptosis obtained through the depletion of IGFBP3 from the T1D/T2D serum or with the use of an anti-IGFBP3 monoclonal antibody during the serum challenge of beta cells, further reinforced our findings (Supplementary Fig. 4d–f). This evidence concerns the gene CASP8 and type 2 diabetes mellitus.