Association of maternal vitamin B12 and folate levels in early pregnancy with gestational diabetes: a prospective UK cohort study (PRiDE study)

Abstract

Aims/hypothesis The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide in all ethnic groups. Low vitamin B12 and low/high folate levels may contribute to GDM risk, but there is conflicting evidence. Our aim is to assess the relationships of early pregnancy vitamin B12 and folate levels with the risk of GDM status at 26–28 weeks of gestation. Methods This was a prospective, multi-centre, multi-ethnic cohort study (n = 4746) in the UK. Participants who were eligible to be selectively screened as per the National Institute for Health and Care Excellence (NICE) criteria were included in the study. Results GDM prevalence was 12.5% by NICE and 14.7% by International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. 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. B12 was negatively associated with fasting plasma glucose (1 SD: −0.06 mmol/l; 95% CI −0.04, −0.08; p < 0.0001) and 2 h plasma glucose levels (−0.07 mmol/l; 95% CI −0.02, −0.12; p = 0.004). Higher B12 was associated with 14.4% lower RR of IADPSG-GDM (0.856; 95% CI 0.786, 0.933; p = 0.0004) after adjusting for key confounders (age, parity, smoking status, ethnicity, family history, household income and folate status). Approximately half of this association was mediated through BMI. Folate was positively associated with 2 h plasma glucose levels (0.08 mmol/l; 95% CI 0.04, 0.13; p = 0.0005) but its relationship with fasting plasma glucose was U-shaped (quadratic β: 0.011; p = 0.05). Higher folate was associated with 11% higher RR of IADPSG-GDM (adjusted RR 1.11; 95% CI 1.036, 1.182; p = 0.002) (age, parity, smoking status, ethnicity, family history, household income and B12 status). Although no interactions were observed for B12 and folate (as continuous variables) with glucose levels and GDM risk, a low B12–high folate combination was associated with higher blood glucose level and risk of IADPSG-GDM (adjusted RR 1.742; 95% CI 1.226, 2.437; p = 0.003). Conclusions/interpretation 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 RR of GDM. Our findings warrant additional studies on the role of unmetabolised folic acid in glucose metabolism and investigating the effect of optimising early pregnancy or pre-conception B12 and folate levels on subsequent hyperglycaemia. Trial registration: ClinicalTrials.gov NCT03008824. Graphical abstract

Associations of Maternal rs1801131 Genotype in MTHFR and Serum Folate and Vitamin B12 with Gestational Diabetes Mellitus in Chinese Pregnant Women

“…We found that serum folate levels are positively correlated with blood glucose levels and significantly associated with GDM risk in a dose-response manner. Our findings were consistent with recently published results [ 16 , 36 ], which indicated that higher maternal folate during pregnancy is associated with increased GDM risk.…”

“…However, inconsistent findings were found for prepregnancy habitual intakes of folate in the Nurse’s Health Study [ 11 ]. Although folic acid intake evaluated via the questionnaire may not accurately reflect folate levels in pregnant women, serum and red blood cell folate levels have also been associated with GDM [ 10 , 16 ]. Our preliminary study indicated that higher folate levels in mid-pregnancy can slightly increase maternal GDM risk [ 17 ].…”

“…Since these nutrients are interrelated in OCM, several studies have explored the combined effects of folate and B 12 on GDM. Studies from Singapore and UK revealed that B 12 insufficiency coupled with excess folate was associated with a higher risk of GDM [ 15 , 16 ]. Similar results were obtained in our previous study with a small sample size.…”

A Brief Review on Vitamin B12 Deficiency Looking at Some Case Study Reports in Adults

“…Currently, research suggests that there are disease implications associated with vitamin B 12 deficiency, especially in vegetarian populations [15][16][17], in pregnancy [18,19], in the elderly [20], and in developing countries [19].…”

Maternal Glucose and LDL-Cholesterol Levels Are Related to Placental Leptin Gene Methylation, and, Together With Nutritional Factors, Largely Explain a Higher Methylation Level Among Ethnic South Asians

“…Also, vitamin D has effects on genome wide DNA methylation levels and was recently reported to influence long-chain polyunsaturated fatty acids and oxidative stress in the placenta via one-carbon metabolism (37). The relations between nutritional factors and the methylation of regulatory cytokines in placenta is likely very complicated, where not only the level of each nutritional factor itself, but also the combination of different factors may be important (38,39). Differences in vitamin levels could also be proxy measures of other complex life-style factors.…”