The Relationship Between Folate, Vitamin B12 and Gestational Diabetes Mellitus with Proposed Mechanisms and Foetal Implications

The incidence of gestational diabetes mellitus (GDM) is rising, which warrants attention due to the associated complications during pregnancy and in the long term for both mother and offspring. Studies have suggested a relationship between maternal folate (vitamin B9) and vitamin B12 status and GDM risk. Seemingly the most problematic scenario occurs when there is B-vitamin imbalance, with high folate and low vitamin B12. This nutritional state can occur in vitamin B12 deficient women who exceed the recommended folic acid supplementation. However, the pathological mechanisms behind this relationship are currently unclear and are explored in this review article. A high folate/low B12 can lead to a functional folate deficiency through the methyl-trap phenomenon, impairing re-methylation of homocysteine and regeneration of folates for DNA synthesis and repair. Consequently elevated homocysteine concentration leads to endothelial dysfunction and oxidative stress. Vitamin B12 deficiency also leads to an impairment of the conversion of methylmalonyl-CoA to succinyl-CoA, which has been associated with insulin resistance. Insulin resistance is thought to contribute to the etiology of GDM. More studies are needed to confirm the impact of these and other mechanisms on disease development. However, it highlights a potential avenue for GDM risk modification through a vitamin B12 supplement and improvement of maternal metabolic health.