Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study

C S Yajnik, S S Deshpande, A A Jackson, H Refsum, S Rao, D J Fisher, D S Bhat, S S Naik, K J Coyaji, C V Joglekar, N Joshi, H G Lubree, V U Deshpande, S S Rege, C H D Fall, C S Yajnik, S S Deshpande, A A Jackson, H Refsum, S Rao, D J Fisher, D S Bhat, S S Naik, K J Coyaji, C V Joglekar, N Joshi, H G Lubree, V U Deshpande, S S Rege, C H D Fall

Abstract

Aims/hypothesis: Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years.

Methods: In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years.

Results: Two-thirds of mothers had low vitamin B12 (<150 pmol/l), 90% had high MMA (>0.26 micromol/l) and 30% had raised tHcy concentrations (>10 micromol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B12 (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant.

Conclusions/interpretation: Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India.

Figures

Fig. 1
Fig. 1
The PMNS: a flow diagram to describe data collection and exclusions from the study. LMP Last menstrual period
Fig. 2
Fig. 2
Insulin resistance (HOMA-R) in the children at 6 years in relation to maternal vitamin B12 (18 weeks) and erythrocyte folate (28 weeks)
Fig. 3
Fig. 3
The groups of variables used in the PCAs are described in Statistical methods. The notation F1–F3 indicates the first to third principal components, or factors (F), derived from each group of variables. Lines connecting boxes indicate significant positive correlations (p < 0.01), and bold lines denote correlations significant at p < 0.001. Correlations labelled A–D are explained in the Results (PCA and conditional independence analysis). Veg Vegetables

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