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High folate, low vitamin B12 levels amplify gestational diabetes risk

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February 20, 2019

Gestational diabetes risk can be increased by an imbalance in folate and vitamin B12 concentrations during pregnancy, according to findings published in the Journal of Diabetes.

“Recently, the role of folate and vitamin B12 on the development of [gestational diabetes] has emerged as a field of interest,” Qiang Zhang, PhD, an associate professor in the department of occupational and environmental health at the School of Public Health at Tianjin Medical University in China, and colleagues wrote. “Folate and vitamin B12 are metabolically entwined during 1-carbon metabolism. Both serve as cofactors in the synthesis of methionine from homocysteine (Hcy). Growing evidence indicates that Hcy concentrations are significantly elevated among women with [gestational diabetes].”

Zhang and colleagues recruited 406 pregnant women (mean age, 29.4 years) from the Beichen District Women’s and Children’s Health Center in Tianjin, China, for a cross-sectional study that aimed to analyze the potential link between gestational diabetes and folate and vitamin B12 levels. Each participant underwent a 75-g oral glucose tolerance test between 24 and 28 weeks of gestation to screen for gestational diabetes. At the screening time, folate, vitamin B12 and glucose concentrations were measured.

The researchers found a positive association between folate concentration and both 1-hour plasma glucose (P = .002) and 2-hour plasma glucose (P = .001), and also found a similar association between high folate to vitamin B12 ratios and high plasma glucose, both at 1 hour (P = .031) and 2 hours (P = .02). An opposite association was found for 1-hour plasma glucose and 2-hour plasma glucose with vitamin B12 levels, but not to a significant degree.

For participants with folate levels of 12.2 ng/mL or more, there was higher risk for gestational diabetes (OR = 1.98; 95% CI, 1-3.9) compared with those with lower levels. Conversely, gestational diabetes risk was negatively linked to vitamin B12 levels, with the lowest risk seen in participants with 306 pg/mL or more (OR = 0.3; 95% CI, 0.15-0.6), compared with those with 234 pg/mL to 306 pg/mL (OR = 0.63; 95% CI, 0.35-1.12) and those with less than 234 pg/mL, who were used as reference. Combining these two concentrations revealed that higher folate to vitamin B ratios increased gestational diabetes risk, especially for those with ratios of 41.03 or greater (OR = 3.08; 95% CI, 1.63-5.83) compared with a ratio of less than 26.67, which was used as reference.


The researchers also examined whether age or prepregnancy BMI had any additive effect on gestational diabetes risk. Older women with higher folate concentrations (OR = 2.03; 95% CI, 1.01-4.07), lower vitamin B12 concentrations (OR = 2.43; 95% CI, 1.07-5.51) and higher folate to vitamin B12 ratios (OR = 2.13; 95% CI, 1.09-4.15) had much higher risk than younger women with lower levels of each factor. In addition, participants with high prepregnancy BMI and low levels of vitamin B12 levels were at increased risk for gestational diabetes (OR = 2.92; 95% CI, 1.35-6.3) compared with participants with lower prepregnancy BMI and high vitamin B12 levels.

“Our findings lend further support to the hypothesis that B vitamin status during pregnancy may play an important role in maternal metabolic disease, especially in women of older age and with higher [prepregnancy] BMI,” the researchers wrote. “It may be time to consider vitamin B12 supplementation together with optimal use of folic acid supplements during pregnancy, especially in women with advanced age and higher BMI.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.

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