Background: To evaluate vitamin B12 and folate status in pregnancy and their relationship with maternal obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Methods: A retrospective case-control study of 344 women (143 GDM, 201 no-GDM) attending a district general hospital and that had B12 and folate levels measured in the early 3rd trimester was performed. Maternal history including early pregnancy body mass index (BMI) and neonatal data (birthweight, sex, and gestational age) was recorded for all subjects. Results: 26% of the cohort had B12 levels <150 pmol/L (32% vs. 22% in the two groups respectively, p < 0.05) while 1.5% were folate deficient. After adjusting for confounders, 1st trimester BMI was negatively associated with 3rd trimester B12 levels. Women with B12 insufficiency had higher odds of obesity and GDM (aOR (95% CI) 2.40 (1.31, 4.40), p = 0.004, and 2.59 (1.35, 4.98), p = 0.004, respectively), although the latter was partly mediated by BMI. In women without GDM, the lowest quartile of B12 and highest quartile of folate had significantly higher adjusted risk of fetal macrosomia (RR 5.3 (1.26, 21.91), p = 0.02 and 4.99 (1.15, 21.62), p = 0.03 respectively). Conclusion: This is the first study from the UK to show that maternal B12 levels are associated with BMI, risk of GDM, and additionally may have an independent effect on macrosomia. Due to the increasing burden of maternal obesity and GDM, longitudinal studies with B12 measurements in early pregnancy are needed to explore this link.

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

BackgroundMetformin, a standard therapy in type 2 diabetes, reduces vitamin B12 levels. Studies linking low vitamin B12 levels and cardiovascular disease are equivocal and suggest improving B12 levels may help in primary prevention. The role of vitamin B12 deficiency on cardiovascular risk factors, especially in type 2 diabetes has not been explored. The aim of this study is to investigate whether vitamin B12 deficiency in type 2 diabetes patients is associated with cardiovascular risk factors in two different ethnic groups in UK and India.MethodsType 2 diabetes patients from two secondary care diabetic centres (Europeans - UK and Indians - India) were studied. Serum vitamin B12, folate and biochemical parameters were measured.ResultsThe prevalence rates of vitamin B12 deficiency (<191 ng/L) were 27% and 12% in Europeans and Indians, respectively and higher in metformin treated type 2 diabetes patients. In linear regression analysis, after adjusting for all likely confounding factors, vitamin B12 independently associated with triglycerides in both the populations and cholesterol/HDL ratio in Indians. Logistic regression showed type 2 diabetes patients with vitamin B12 deficiency were at significantly higher odds of having coexisting coronary artery disease (CAD) in Europeans with similar but non-significant trend in Indians, after adjusting for all likely confounding factors.ConclusionsThe prevalence of vitamin B12 deficiency is common in type 2 diabetes patients and is associated with adverse lipid parameters. Type 2 diabetes management guidelines should include the recommendation for regular testing for B12 levels, especially for those on metformin.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-014-0129-4) contains supplementary material, which is available to authorized users.

Aims/hypothesis Gestational diabetes mellitus (GDM) is associated with an increased future risk of obesity in the offspring. Increased adiposity has been observed in the newborns of women with GDM. Our aim was to examine early fetal adiposity in women with GDM. Methods Obstetric and sonographic data was collated for 153 women with GDM and 178 controls from a single centre in Chennai, India. Fetal head circumference (HC), abdominal circumference (AC), femur length (FL) and biparietal diameter (BPD) were recorded at 11, 20 and 32 weeks. Anterior abdominal wall thickness (AAWT) as a marker of abdominal adiposity at 20 and 32 weeks was compared between groups. Adjustments were made for maternal age, BMI, parity, gestational weight gain, fetal sex and gestational age. Results Fetuses of women with GDM had significantly higher AAWT at 20 weeks (β 0.26 [95% CI 0.15, 0.37] mm, p < 0.0001) despite lower measures of HC, FL, BPD and AC. AAWT remained higher in the fetuses of women with GDM at 32 weeks (β 0.48 [0.30, 0.65] mm, p < 0.0001) despite similar measures for HC, FL, BPD and AC between groups. Both groups had similar birthweights at term. There was an independent relationship between fasting plasma glucose levels and AAWT after adjustment as described above. Conclusions/interpretation A 'thin but fat' phenotype signifying a disproportionate increase in adiposity despite smaller or similar lean body mass was observed in the fetuses of mothers with GDM, even at 20 weeks, thus pre-dating the biochemical diagnosis of GDM. Increased AAWT may serve as an early marker of GDM.