INS and gestational diabetes: As mentioned above, given that intracerebroventricular infusion of FGF21 promotes insulin sensitivity by a similar mechanism [18], we hypothesize that the higher plasma FGF21 in the background of essentially similar CSF FGF21 levels (lower CSF/plasma FGF21 ratio) in GDM subjects may indicate a central failure in this compensatory response through either dysfunctional transport of circulating FGF21 through the BBB into the CSF or disordered metabolism of FGF21 within the CSF as discussed above.