In fact, therapeutic interventions with insulin or oral hypoglycemic agents have been associated with decreased risk of PC with improved glucose metabolism [73,74,75]; additionally, higher PaSC activity was observed in patients with DM, which in the setting of hyperinsulinemia potentiates the desmoplastic response and accentuates transforming growth factor beta1 (TGF-β1) signaling contributing to PC development [64,75,76,77,78]. This evidence concerns the gene INS and pachyonychia congenita.