The association between visceral fat accumulation caused by high-dose folic acid supplementation in the first trimester and gestational diabetes mellitus: protocol for a nested case-control study in a cohort study

Excess folic acid (FA) supplementation intake among women in child-bearing age, which may lead to an increase in the amount of unmetabolized FA in the bloodstream. Whereas, research on the relationship between high-dose FA and gestational diabetes mellitus (GDM) was lacking, and the potential mechanisms were still unclear. This is an ongoing cohort which is part of the Qingdao Women and Children’s Hospital Health Cohort, China. In total, 4000 pregnant women were recruited in gestational weeks 9–13+6, and were followed across pregnancy (16 ± 1, 20 ± 1, 24–28 weeks of gestation). Participants would undergo questionnaires investigation, physical measurement, red blood cell folate, serum folate, serum vitamin B12 and methylmalonic acid detection in early pregnancy. Serum liver X receptors α (LXR-α) and sterol regulatory element-binding protein 1 c (SREBP-1c) levels were tested from Down’s syndrome screening at 16 weeks of gestation on the basis of a nested case-control study. GDM was based on 75-g oral glucose tolerance test at 24–28 weeks’ gestation. The levels of red blood cell folate, serum folate, LXR-α/SREBP-1c and visceral fat (VF) depth between pregnant women with GDM and without GDM will be analyzed. Our findings could help shed light on the role of high-dose FA regulating LXR- α / SREBP-1c to induce VF accumulation in the pathogenesis of GDM. We anticipated that inform clinical recommendations based on VF depth with precise FA supplementation intake. The trial is prospectively recorded at the CHiCTR registry (Trial ID: ChiCTR2300070781). Date recorded: 23/04/2023.