Folate, Vitamin B12 Tied to GDM Risk in Early Pregnancy

Gestational diabetes mellitus (GDM) is a common medical disorder in pregnancy, estimated to affect more than 20 million pregnancies worldwide, and causes significant short- and long-term consequences to both the women and their offspring.

Folate and B12 are essential micronutrients for the metabolism of single carbon atoms (known as 1-C metabolism) and these pathways are involved in DNA methylation and synthesis of amino acids, nucleic acids and lipids. Low vitamin B12 and low/high folate levels may contribute to GDM risk, but there is conflicting evidence.


Health Scientist at the Warwick Medical School (Coventry, UK) carried out a prospective, multi-center, multi-ethnic cohort study of 4,746 participants who were pregnant women aged between 18 and 45 years who were at less than 16 weeks of gestation. A random blood sample at booking and fasting and two hour blood samples at Oral Glucose Tolerance Test (OGTT) using 75 grams of anhydrous glucose after an overnight fast of at least 10 hours were taken.

Plasma glucose was determined by the hexokinase enzymatic method using a Synchron CX7 auto-analyzer (Beckman Coulter, Fullerton, CA, USA). Serum B12 and folate were measured by electro-chemiluminescent immunoassay (Roche Cobas analyzer, Roche Diagnostics, Burgess Hill, UK). Plasma total homocysteine (tHcy) was determined by stable isotopic dilution analysis using a Shimadzu HPLC system (Milton Keynes, UK) with an auto-sampler coupled to the detection system of an AB Sciex 6500 QTrap tandem mass spectrometer (liquid chromatography mass spectrometry [LCMS]) (Applied Biosystems, Warrington, UK).

The investigators reported that GDM prevalence was between 12.5% and 14.7%. Folate deficiency (1.3%) was rare but B12 insufficiency (42.3% at <220 pmol/L) and folate excess (36.5%) were common in early pregnancy. Early pregnancy median B12 levels were lower and folate levels higher, in women who were diagnosed with GDM at 26–28 weeks and B12 was negatively associated with fasting plasma glucose. Total homocysteine was inversely associated with blood glucose level and risk of GDM. The associations strengthened when adjusted for BMI, suggesting that the total homocysteine effect on blood glucose level/GDM is independent of BMI, B12 and folate.

The authors concluded that B12 insufficiency and folate excess were common in early pregnancy. Low B12 and high folate levels in early pregnancy were associated with small but statistically significant changes in maternal blood glucose level and higher relative risk (RR) of GDM. The findings warrant additional studies on the role of unmetabolized folic acid in glucose metabolism and investigating the effect of optimizing early pregnancy or pre-conception B12 and folate levels on subsequent hyperglycemia. The study was originally published on July 22, 2021 in the journal Diabetologia.

Related Links:
Warwick Medical School
Beckman Coulter
Roche Diagnostics
Shimadzu
Applied Biosystems