Impaired Glucose Tolerance

Impaired glucose tolerance is common in pregnancy and may be severe enough to be classified as diabetes mellitus (so-called gestational diabetes), which usually resolves on parturition. A number of studies have shown that supplements of 100 mg of vitamin B6 per day result in improved glucose tolerance (Rose et al., 1975).

As discussed in Section 9.5.4.2, estrogen metabolites inhibit kynureninase, and they also lead to reduced activity of kynurenine hydroxylase. As a result, in pregnancy or in response to (high-dose) oral contraceptives, tissue concentrations of kynurenine, hydroxykynurenine, xanthurenic, andkynurenic acids are higher than normal.

The impairment of glucose tolerance associated with high plasma levels of estrogens may be caused by a high plasma concentration of xanthurenic acid, which forms a biologically inactive complex with insulin (Kotake et al., 1975). The improvement following high doses of vitamin B6 could then be explained by reactivation of kynureninase that has been inactivated as a result of transamination (Section 9.3.1.5). However, animal studies have failed to demonstrate any effect of xanthurenic acid administration on glucose tolerance, and it has been suggested that the improvement in glucose tolerance in response to vitamin B6 was because of increased formation of quinolinic acid as a result of relief of the impairment of kynureninase activity (Adams et al., 1976). Quinolinic acid is an inhibitor of phosphoenolpyruvate carboxy-kinase, one of the key enzymes of gluconeogenesis, and the administration of tryptophan (to increase synthesis of quinolinic acid) has also been reported to improve glucose tolerance.

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