INS and Insulin resistance: Though the role of PDXK mutations in diabetes mellitus is purely speculative at this stage of our research, nevertheless, based on the effects of PDXK variants on AGEs, we favor the idea that pathophysiology of hyperglycemia might be linked to a combination of impaired insulin action on target tissues (i.e. insulin resistance) and reduced beta cell function, as it has been hypothesized for mutations of APPL1 gene associated to monogenic diabetes29.