All our data indicates that (1) betatrophin may not control pancreatic β-cell expansion or regulate pancreatic β-cell function in T2DM patients; (2) irisin may not promote pancreatic β-cell proliferation or regulate pancreatic β-cell function through promoting the expression of betatrophin in humans; (3) the beneficial effect of irisin on glucose homeostasis may be due to other mechanisms, such as inducing browning of WAT [8, 10], rather than the direct effect on β-cell function. Here, FNDC5 is linked to type 2 diabetes mellitus.