Nithya Sukumar

Prevalence of vitamin B-12 insufficiency during pregnancy and its effect on offspring birth weight: a systematic review and meta-analysis.

BACKGROUND Vitamin B-12 and folate are micronutrients essential for normal embryogenesis. Vitamin B-12 insufficiency in pregnancy is high in certain parts of the world, such as India, and although this has been linked to low birth weight (LBW) in these populations, the relation between vitamin B-12 and birth weight (BW) elsewhere is unknown. OBJECTIVES We performed a systematic review to assess 1) the worldwide prevalence of vitamin B-12 insufficiency in pregnancy and 2) its association with BW. DESIGN A search of 5 electronic databases was performed to identify eligible articles. Random-effects meta-analysis was conducted according to geographic regions and pregnancy trimesters for the prevalence subreview and by categorical measures of BW. RESULTS A total of 57 and 23 articles were included for the prevalence and BW subreviews, respectively. The pooled estimates of vitamin B-12 insufficiency were 21%, 19%, and 29% in the first, second, and third trimesters, respectively, with high rates for the Indian subcontinent and the Eastern Mediterranean. The large heterogeneity between studies was partially addressed by creating a standardized score for each study (mean vitamin B-12 insufficiency ÷ cutoff value), which internally corrected for geographic region, trimester, and assay type. Twelve of the 13 longitudinal studies included showed a decrease in mean or median vitamin B-12 across trimesters. Pooled analysis showed nonsignificantly lower maternal vitamin B-12 concentrations in LBW than in normal-BW infants and higher odds of LBW with lower vitamin B-12 values (adjusted OR: 1.70; 95% CI: 1.16, 2.50), but studies from India largely contributed to the latter. CONCLUSIONS Our review indicates that vitamin B-12 insufficiency during pregnancy is common even in nonvegetarian populations and that concentrations of vitamin B-12 decrease from the first to the third trimester. There is no consistent association between vitamin B-12 insufficiency and LBW. However, given the long-term risks of LBW, this observation warrants further cohort studies and randomized controlled trials.

Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes

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.

Vitamin B12 Status among Pregnant Women in the UK and Its Association with Obesity and Gestational Diabetes

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.

Vitamin B12 status in women of childbearing age in the UK and its relationship with national nutrient intake guidelines: results from two National Diet and Nutrition Surveys

Objective To assess serum B12, folate and the associated homocysteine (Hcy) levels among women of childbearing age in the UK and examine their association with dietary intake in relation to the UK Recommended Nutrient Intakes (RNIs) for B12 and folate. Design Cross-sectional study. Setting Data from two publicly available National Diet and Nutrition Surveys (NDNS 2000/2001 and 2008/2012) were used. These were population-based surveys of randomly selected samples of adults which were carried out in their households. Participants Women of childbearing age (aged 19–39 years), representative of the UK population. Those who were pregnant or breastfeeding were excluded. Outcome measures The associations between micronutrient intakes and blood levels of B12, folate and Hcy were assessed by correlation and stepwise linear regression. B12 intake was divided into quintiles and plotted against blood B12 and Hcy concentrations to determine the threshold of any associations. Results 299 women from the first NDNS cohort had complete intake and biomarker data. The prevalence of serum vitamin B12 (≤150 pmol/L) and serum folate (≤10 nmol/L) deficiency and hyperhomocysteinemia (≥12 µmol/L) was 12.4%, 6.4% and 21.2%, respectively, despite seemingly adequate B12 intakes (median 3.8 μg/day, 96% consumed more than the UK RNI of 1.5 μg/day). B12 concentrations increased across all quintiles of intake with serum levels in quintiles 4 and 5 (median intake 4.9 and 7.1 μg/day, respectively) significantly higher than quintile 1. However, Hcy concentrations levelled off between quintiles 4 and 5. Comparison of micronutrient intake between the two surveys found that folate intake has reduced in the more recent cohort. Conclusions The UK RNI for B12 intake should be increased for women of childbearing age with intakes of around 5–7 μg/day likely to be associated with stable biomarker levels. B12 levels should also be measured in women preconceptionally or in early pregnancy given the high rates of deficiency.

Reduced GLP-1 Secretion at 30 Minutes After a 75g Oral Glucose Load is Observed in Gestational Diabetes Mellitus: A Prospective Cohort Study

Glucagon-like peptide 1 (GLP-1) levels may be reduced in type 2 diabetes, but whether a similar impairment exists in gestational diabetes mellitus (GDM) has not been established. We studied this in a prospective cohort study of pregnant women (n = 144) during oral glucose tolerance test (OGTT). GLP-1, glucose, and insulin were sampled at 30-min intervals during a 2-h 75-g OGTT, and indices of insulin secretion and sensitivity were calculated. In a nested case-control study, women with GDM (n = 19) had 12% lower total GLP-1 secretion area under the curve (AUC) compared with control subjects matched for age, ethnicity, and gestational age (n = 19), selected from within the lowest quartile of glucose120 min values in our cohort. GDM had lower GLP-1 response in the first 30 min (19% lower GLP-130 min and 17% lower AUC0–30 min) after adjustment for possible confounders. Their glucose levels began to diverge at 30 min of the OGTT with increasing insulin levels, and by 120 min, their insulin levels were three times higher. In a secondary cohort of 57 women that included “high-normal” glucose120 min values, low GLP-1 AUC0–30 min was independently associated with lower indices of insulin secretion and sensitivity. In conclusion, we have observed that women with GDM have lower GLP-1 response at 30 min of an OGTT and hyperglycemia at 120 min despite significant hyperinsulinemia.