Low plasma vitamin B12 in pregnancy is associated with gestational 'diabesity' and later diabetes

Aims/hypothesis This study was designed to test the hypothesis that low plasma vitamin B-12 concentrations combined with high folate concentrations in pregnancy are associated with a higher incidence of gestational diabetes (GDM) and later diabetes. Methods Women (N=785) attending the antenatal clinics of one hospital in Mysore, India, had their anthropometry, insulin resistance (homeostasis model assessment-2) and glucose tolerance assessed at 30 weeks' gestation (100 g oral glucose tolerance test; Carpenter-Coustan criteria) and at 5 years after delivery (75 g OGTT; WHO, 1999). Gestational vitamin B-12 and folate concentrations were measured in stored plasma samples. Results Low vitamin B-12 concentrations (<150 pmol/l, B-12 deficiency) were observed in 43% of women and low folate concentrations (<7 nmol/l) in 4%. B-12-deficient women had higher body mass index (p<0.001), sum of skinfold thickness (p<0.001), insulin resistance (p=0.02) and a higher incidence of GDM (8.7% vs 4.6%; OR 2.1, p=0.02; p=0.1 after adjusting for BMI) than non-deficient women. Among B-12-deficient women, the incidence of GDM increased with folate concentration (5.4%, 10.5%, 10.9% from lowest to highest tertile, p=0.04; p for interaction=0.2). Vitamin B-12 deficiency during pregnancy was positively associated with skinfold thickness, insulin resistance (p<0.05) and diabetes prevalence at 5 year follow-up (p=0.009; p=0.008 after adjusting for BMI). The association with diabetes became non-significant after excluding women with previous GDM (p=0.06). Conclusions/interpretation Maternal vitamin B-12 deficiency is associated with increased adiposity and, in turn, with insulin resistance and GDM. Vitamin B-12 deficiency may be an important factor underlying the high risk of 'diabesity' in south Asian Indians.