A prospective study specific on patients with DM and CLTI showed that lower Klotho protein and higher fibroblast growth factor 23 levels measured at baseline were independently associated with major adverse cardiovascular and limb-related events at 1 year, suggesting a modulating role for these proteins in the atherosclerotic pathways and possible targets for future anti-atherosclerotic drugs.26 This evidence concerns the gene FGF23 and diabetes mellitus.