"What actually causes gestational diabetes was well researched between the 1940s and 1975, when a report(4) summarized the earlier research and then explained that gestational diabetes is caused by excessive amounts of xanthurenic acid, usually present in blood in very low levels.
But doesn't everyone's body chemistry make xanthurenic acid? (It's a metabolite of tryptophan.) Indeed, 100% of us have this body chemistry.
But why does all that extra estrogen cause only a minority of women's bodies to make lots more xanthurenic acid and develop gestational diabetes, when most women's bodies don't do that?
Table 2: Plasma xanthurenic acid
(XA) and pyridoxal-5'-phosphate (PLP) concentrations at the end of the vitamin B6-deficiency stage (-VB6-) and the other three stages of vitamin B6: normal (+VB6+), recovery (-VB6+), and excess (-VB6++).
With the high levels of estrogen during pregnancy, the weak enzymes falter and metabolize much more tryptophan than usual into xanthurenic acid and much less into melatonin, serotonin, and related molecules.
The researchers wrote: "Low vitamin B6 levels appear to alter metabolic pathways which result in a lowering of the biologic activity of endogenous insulin." In English: vitamin B6 strengthened specific weak enzymes so that less xanthurenic acid was available to "complex" with insulin, blocking its activity.
The 1975 and 1977 research was actually done more than two decades after several groups of researchers (7,8,9,10) had confirmed in the early 1950s that vitamin B6 returned levels of xanthurenic acid to normal.
Yoshino, "Xanthurenic acid inhibits metal ion-induced lipid peroxidation and protects NADP-isocitrate dehydrogenase from oxidative inactivation," Journal of Nutritional Science and Vitaminology, vol.
Nunes et al., "The antioxidant role of xanthurenic acid in the Aedes aegypti midgut during digestion of a blood meal," PLoS ONE, vol.