Moreover, HMGB1 is one of the endogenous ligands for TLR2, TLR4, and RAGE, while extracellular HMGB-1 binds to target receptors such as TLRs and RAGE, promoting nuclear translocation of transcription factors such as NF-kB [38] and is involved in the pathogenesis of diabetes [39] and renal ischemia–reperfusion injury [40]. This evidence concerns the gene HMGB1 and diabetes mellitus.