First, irisin levels in circulation were described to be lower than normal in patients with T2D,23 which exhibit increased risk of osteoporosis and bone fractures,25 and in subjects who suffered from osteoporotic fractures.26,27 Second, it was suggested that irisin secreted by exercised skeletal muscle could induce osteogenesis at the bone–muscle interface. Here, FNDC5 is linked to type 2 diabetes mellitus.