Aside from universal concerns regarding immuno-reactivity for any type of transplanted non-autologous material, the eventual dysfunction of transplanted hPSC-derived β-like cells because of prolonged glucolipotoxicity, as well as IAPP deposit toxicity from the continued insulin resistance in peripheral tissues, represents the main challenge for β cell transplants in T2D. This evidence concerns the gene INS and type 2 diabetes mellitus.