Association of Folic Acid Supplementation, Dietary Folate Intake and Serum Folate Levels with Risk of Gestational Diabetes Mellitus: A Matched Case-Control Study

Zhu, Liyuan; ZHOU, Ya; Fu, Yueqi; Sun, Wanxiao; Jing, Chen; Yu, Ningning; Zhao, Mingqiu

doi:10.3177/jnsv.69.28

Cited by 1 publication

(6 citation statements)

References 40 publications

(42 reference statements)

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“…Multiple studies have been conducted to investigate the association between FA intake, circulating folate levels, MTHFR polymorphisms, and the risk of GDM. [10][11][12][13][14][15][16][17] However, there is currently no consensus on the relationship between FA intake and GDM. 18 Some studies have provided evidence supporting the connection between pregnancies lacking FA supplementation and an increased risk of GDM.…”

Section: Discussionmentioning

confidence: 99%

“…18 Some studies have provided evidence supporting the connection between pregnancies lacking FA supplementation and an increased risk of GDM. 10,11 Conversely, contradictory findings have suggested that excessive FA intake may also be associated with a higher risk of GDM. 15,16 We did not find a correlation between FA intake and GDM.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies have been conducted to investigate the association between FA intake, circulating folate levels, MTHFR polymorphisms, and the risk of GDM 10–17 . However, there is currently no consensus on the relationship between FA intake and GDM 18 .…”

Section: Discussionmentioning

confidence: 99%

“…9 Furthermore, there is a correlation between FA supplementation and an altered risk of GDM. [10][11][12][13][14][15][16][17] Several studies have demonstrated that pregnancies without FA supplementation are linked to an increased risk of GDM, 10,11 while contrasting evidence has recently emerged suggesting that excessive FA intake and elevated circulating folate levels may be associated with an elevated risk of GDM. [12][13][14][15][16][17] The discrepancies in the findings could be due to the use of different indicators to assess the folate status, as well as the influence of factors such as ethnicity, vitamin B 12 status in the studied population, and imprecise estimation of FA intake.…”

Section: Introductionmentioning

confidence: 99%

“…The world health organisation has long attached great importance to adequate periconceptional synthetic folic acid (FA) supplementation due to its crucial protective role against foetal neural tube defects (NTDs) 9 . Furthermore, there is a correlation between FA supplementation and an altered risk of GDM 10–17 . Several studies have demonstrated that pregnancies without FA supplementation are linked to an increased risk of GDM, 10,11 while contrasting evidence has recently emerged suggesting that excessive FA intake and elevated circulating folate levels may be associated with an elevated risk of GDM 12–17 .…”

Section: Introductionmentioning

confidence: 99%

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Gestational diabetes mellitus is associated with distinct folate‐related metabolites in early and mid‐pregnancy: A prospective cohort study

Zheng,

Zhang,

Zhang

et al. 2024

Diabetes Metabolism Res

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AimsThis study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype.Materials and MethodsA prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5‐methyltetrahydrofolate (5‐MTHF), 5, 10‐methylene‐tetrahydrofolate (5,10‐CH2‐THF), 5‐ formyltetrahydrofolate (5‐CHO‐THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5‐MTHF, and methylmalonic acid (MMA), were determined at 6–17 weeks and 20–26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75‐g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders.ResultsThe study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01–1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23–2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04–1.88)] in early pregnancy, and RBC 5‐MTHF [aOR (95% CI) = 1.48 (1.10–2.00)], RBC 5,10‐CH2‐THF [aOR (95% CI) = 1.55 (1.15–2.10)], and plasma 5‐MTHF [aOR (95% CI) = 1.36 (1.00–1.86)] in mid‐pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1‐h and 2‐h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5‐ MTHF and 5,10‐CH2‐THF, and plasma 5‐ MTHF in mid‐pregnancy are positively associated with the 1‐h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM.ConclusionsElevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5‐MTHF and 5,10‐CH2‐THF and plasma 5‐MTHF during mid‐pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.

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