To further determine whether higher peripheral IGFBP3 levels favor islet injury in disease conditions such as diabetes, we challenged human islets with sera obtained from patients with either T1D or T2D, which are naturally enriched in IGFBP3 as compared to those of healthy subjects, in place of regular FBS, and confirmed increased Caspase 8 and decreased insulin mRNA expression (Fig. 3s, t). This evidence concerns the gene IGFBP3 and type 2 diabetes mellitus.