Laboratory studies have clearly shown that Klotho plays a protective role in kidney, cardiovascular and retina through anti-oxidation, anti-inflammation, anti-fibrosis and regulation of metabolic signaling pathways (such as Nrf2, Wnt/β-catenin, PI3K/Akt, TGF-β/Smad, etc.), providing a theoretical basis for the intervention of diabetes-related organ damage. This evidence concerns the gene NFE2L2 and diabetes mellitus.