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. The gene discussed is FGF21; the disease is gestational diabetes.