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 B 12 , 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 B 12 , 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 B 12 (<150 pmol/l), 90% had high MMA (>0.26 μmol/l) and 30% had raised tHcy concentrations (>10 μmol/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 B 12 (18 weeks; p=0.03) predicted higher HOMA-R in the Diabetologia (2008)

One third of the Indian babies are of low birth weight (<2.5 kg), and this is attributed to maternal undernutrition. We therefore examined the relationship between maternal nutrition and birth size in a prospective study of 797 rural Indian women, focusing on macronutrient intakes, dietary quality and micronutrient status. Maternal intakes (24-h recall and food frequency questionnaire) and erythrocyte folate, serum ferritin and vitamin C concentrations were measured at 18 +/- 2 and 28 +/- 2 wk gestation. Mothers were short (151.9 +/- 5.1 cm) and underweight (41.7 +/- 5.1 kg) and had low energy and protein intakes at 18 wk (7.4 +/- 2.1 MJ and 45.4 +/- 14.1 g) and 28 wk (7.0 +/- 2.0 MJ and 43.5 +/- 13.5 g) of gestation. Mean birth weight and length of term babies were also low (2665 +/- 358 g and 47.8 +/- 2.0 cm, respectively). Energy and protein intakes were not associated with birth size, but higher fat intake at wk 18 was associated with neonatal length (P < 0.001), birth weight (P < 0.05) and triceps skinfold thickness (P < 0.05) when adjusted for sex, parity and gestation. However, birth size was strongly associated with the consumption of milk at wk 18 (P < 0.05) and of green leafy vegetables (P < 0.001) and fruits (P < 0.01) at wk 28 of gestation even after adjustment for potentially confounding variables. Erythrocyte folate at 28 wk gestation was positively associated with birth weight (P < 0.001). The lack of association between size at birth and maternal energy and protein intake but strong associations with folate status and with intakes of foods rich in micronutrients suggest that micronutrients may be important limiting factors for fetal growth in this undernourished community.

We studied body size and cord blood leptin and insulin concentrations in newborn urban Indian (Pune, India) and white Caucasian (London, UK) babies to test the hypothesis that the adiposity and hyperinsulinemia of Indians are present at birth. Indian babies (n = 157) were lighter in weight compared with white Caucasian babies [n = 67; median weight, 2805 g vs. 3475 g, respectively; P < 0.001, adjusted for gestational age and sex; -1.52 SD score; confidence interval (CI), -1.66, -1.42] and had smaller abdominal (-2.39 SD score; CI, -2.52, -2.09), midarm (-1.47 SD score; CI, -1.58, -1.34), and head (-1.23 SD score; CI, -1.42, -1.13) circumferences. However, their skinfolds were relatively preserved: subscapular (central) skinfold (-0.32 SD score; CI, -0.43, -0.20) was better preserved than triceps (peripheral) skinfold (-0.86 SD score; CI, -0.97, -0.75). Cord plasma leptin (median, 6.2 ng/ml Pune and 6.4 ng/ml London) and insulin (median, 34.7 pmol/liter Pune and 20.8 pmol/liter London) concentrations were comparable in the two populations but were higher in Indians when adjusted for birth weight, confirming relative adiposity and hyperinsulinemia of Indian babies. Indian mothers were smaller in all respects, compared with white Caucasian mothers, except subscapular skinfold, which was similar in the two populations. Our results support the intrauterine origin of adiposity, central adiposity, and hyperinsulinemia in Indians. Further research should concentrate on elucidating genetic and environmental influences on fetal growth and body composition. Prevention of insulin resistance syndrome in Indians will need to address regulation of fetal growth in addition to prevention of obesity in later life.

Objective: To describe the relationship of the mother's physical activity to the birth size of her baby in a rural Indian population. Design: Prospective observational study. Setting: Six villages near Pune, Maharashtra, India. Subjects: A total of 797 women were studied after excluding abortions and termination of pregnancies (112), foetal anomalies (8), multiple pregnancies (3), incomplete pre-pregnancy anthropometry (14) and pregnancies detected later than 21 weeks of gestation (168). Method: An activity questionnaire was developed after focus group discussions and incorporated community-specific activities. It was validated against an observer-maintained diary. Activity scores were derived using published data on energy costs to weight the contributions of various activities. It was then administered to assess physical activity at 18 ( AE 2) and 28 ( AE 2) weeks of gestation. Outcome measures: Birth outcome, maternal weight gain and neonatal anthropometry. Results: The activity questionnaire was used to classify women into light, moderate and heavy activity categories. Maternal activity did not influence the incidence of prematurity or stillbirth, or the duration of gestation. It was inversely related to maternal weight gain up to 28 weeks of gestation (P ¼ 0.002). Higher maternal activity in early, as well as mid gestation, was associated with lower mean birth weight (P ¼ 0.05 and 0.02, respectively ), and smaller neonatal head circumference (P ¼ 0.005 and 0.009) and mid-arm circumference (P ¼ 0.03 and 0.01) after adjusting for the effect of major confounding factors. Conclusions: The Findings suggest that excessive maternal activity during pregnancy is associated with smaller foetal size in rural India, The approach described for developing an activity questionnaire has potential for adoption in other settings.

Aims/hypothesis The aim of this study was to investigate whether the higher prevalence of insulin resistance and glucose intolerance in urban compared with rural Indian men is related to their higher adiposity (percentage body fat) and the associated inflammatory state. Methods We studied 149 rural, 142 urban slum and 150 urban middle-class male residents (age 30-50 years), who were selected by stratified random sampling. We measured body fat (bioimpedance), waist circumference, glucose tolerance (75 g OGTT), insulin resistance [homeostasis model assessment (HOMA-IR)], beta cell function (insulinogenic index) and inflammatory markers (total leucocyte count, IL-6, TNF-α and C-reactive protein). Results Adiposity, waist circumference, HOMA-IR, insulinogenic index and both fasting and 120 min plasma glucose concentrations increased progressively from rural through to urban slum and urban middle-class men. Inflammatory markers were higher in urban than in rural men. Adiposity was strongly related to HOMA-IR (r=0.57, p<0.001) and to insulinogenic index and glycaemic parameters (r=0.25, p<0.001 for both). Adiposity explained approximately two thirds of the difference in HOMA-IR between the urban middle-class men and the rural and slum residents, but its contribution to the difference in insulinogenic index and 120 min plasma glucose concentration was not significant. Inclusion of C-reactive protein, IL-6 and total leucocyte count in the models did not further explain these results, nor did the inclusion of waist circumference. There was a significant residual difference after these adjustments. Conclusions/interpretation Adiposity is a major contributor to the difference in insulin resistance between rural and urban Indian men; there was no additional contribution from inflammation or central obesity. Other unmeasured factors also seem to contribute to the metabolic differences between rural and urban men.