Cord IGF-I concentrations in Indian newborns: associations with neonatal body composition and maternal determinants.

BACKGROUND: Indian newborns have been described as 'thin-fat' compared with European babies, but little is known about how this phenotype relates to the foetal growth factor IGF-I (insulin-like growth factor I) or its binding protein IGFBP-3. OBJECTIVE: To assess cord IGF-I and IGFBP-3 concentrations in a sample of Indian newborns and evaluate their associations with neonatal adiposity and maternal factors. METHODS: A prospective cohort study of 146 pregnant mothers with dietary, anthropometric and biochemical measurements at 28 and 34 weeks gestation. Neonatal weight, length, skin-folds, circumferences, and cord blood IGF-I and IGFBP-3 concentrations were measured at birth. RESULTS: Average cord IGF-I and IGFBP-3 concentrations were 46.6 (2.2) and 1269.4 (41) ng mL(-1) , respectively. Girls had higher mean IGF-I than boys (51.4 ng mL(-1) vs. 42.9 ng mL(-1) ; P < 0.03), but IGFBP-3 did not differ. Cord IGF-I was positively correlated with all birth size measures except length, and most strongly with neonatal sum-of-skin-folds (r = 0.50, P < 0.001). IGFBP-3 was positively correlated with ponderal index, sum-of-skin-folds and placenta weight (r = 0.21, 0.19, 0.16, respectively; P < 0.05). Of maternal demographic and anthropometric characteristics, only parity was correlated with cord IGF-I (r = 0.27, P < 0.001). Among dietary behaviours, maternal daily milk intake at 34 weeks gestation predicted higher cord IGF-I compared to no-milk intake (51.8 ng mL(-1) vs. 36.5 ng mL(-1) , P < 0.01) after controlling for maternal characteristics, placental weight, and newborn gestational age, sex, weight and sum-of-skin-folds. Sum-of-skin-folds were positively associated with cord IGF-I in this multivariate model (57.3 ng mL(-1) vs. 35.1 ng mL(-1) for highest and lowest sum-of skin-fold quartile, P < 0.001). IGFBP-3 did not show significant relationships with these covariates. CONCLUSION: In this Indian study, cord IGF-I concentration was associated with greater adiposity among newborns. Maternal milk intake may play a role in this relationship.

Child's homocysteine concentration at 2 years is influenced by pregnancy vitamin B12 and folate status.

Longitudinal studies investigating vitamin B12 and folate status of mothers and their offspring will provide a better understanding of intergenerational nutrition. During pregnancy and 2 years (2y) after delivery, we measured plasma vitamin B12 and folate concentrations in 118 women [aged (mean ± s.d.) 22.9 ± 3.9y] who attended a rural (n = 68) or an urban (n = 50) antenatal clinic in Pune, India. Cord blood vitamin B12 and folate were measured, and when the child was 2y total homocysteine (tHcy) was also measured. Demographic and diet measurements were recorded using standard methods. Pregnancy plasma vitamin B12 concentration at 34 weeks was low [median (25th, 75th), 115 (95, 147) pm]; 75% had low status (<150 pm). Plasma folate was high (mean ± s.d., 33 ± 21 nm); one had a folate concentration <7 pm. Cord plasma vitamin B12 and folate concentrations were higher than and positively associated with maternal concentrations. In stepwise regression, higher child vitamin B12 at 2y was predicted (total R 2 15.7%) by pregnancy vitamin B12 (std ß 0.201, R 2 7.7%), current consumption of cow's milk (std ß 0.194, R 2 3.3%) and whether breast feeding was stopped before 2y (std ß -0.234 R 2 7.2%). Child's 2y tHcy concentration was high (11.4 ± 3.6 µm) and predicted by lower pregnancy vitamin B12 (std ß -0.206, R 2 4.1%), lack of vitamin supplementation (std ß -0.256, R 2 5.6%) in pregnancy and whether currently breastfed (std ß 0.268, R 2 8.4%). Low maternal vitamin B12 status in pregnancy and prolonged breast-feeding results in disturbed one-carbon metabolism in offspring at 2y. Supplementation of women of child-bearing age, particularly during pregnancy and lactation, may improve the homocysteine status of these children.

Vitamin B12 and folate during pregnancy and offspring motor, mental and social development at 2 years of age.

Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (<150 pmol/l) and one mother was folate deficient during pregnancy. Maternal B12 at 28 and 34 weeks of gestation was associated with offspring B12 at 2 y (r = 0.29, r = 0.32, P < 0.001), but folate was not associated with offspring folate. At 2 y, motor development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.

Prediction of body-fat percentage from skinfold and bio-impedance measurements in Indian school children.

BACKGROUND/OBJECTIVES: Few equations for calculating body-fat percentage (BF%) from field methods have been developed in South-Asian children. The objective of this study was to assess agreement between BF% derived from primary reference methods and that from skinfold equations and bio-impedance analysis (BIA) in Indian children. SUBJECTS/METHODS: We measured BF% in two groups of Indian children. In Pune, 570 rural children aged 6-8 years underwent dual-energy X-ray absorptiometry (DXA) scans. In Mysore (18)O in doubly labeled water was administered to 59 urban children aged 7-9 years. We conducted BIA at 50 kHz and anthropometry, including sub-scapular and triceps skinfold thicknesses. We used the published equations of Wickramasinghe, Shaikh, Slaughter and Dezenburg to calculate BF% from anthropometric data and the manufacturer's equation for BIA measurements. We assessed agreement with values derived from DXA and doubly labeled water using Bland-Altman analysis. RESULTS: Children were light and thin on average compared with international standards. There was poor agreement between the reference BF% values and those from all equations. Assumptions for Bland-Altman analysis were not met for Wickramasinghe, Shaikh and Slaughter equations. The Dezenberg equations under-predicted BF% for most children (mean difference in Pune -13.4, LOA -22.7, -4.0 and in Mysore -7.9, LOA (-13.7 and -2.2). The mean bias for the BIA equation in Pune was +5.0% and in Mysore +1.95%, and the limits of agreement were wide; -5.0, 15.0 and -7.8, 11.7 respectively. CONCLUSIONS: Currently available skinfold equations do not accurately predict BF% in Indian children. We recommend development of BIA equations in this population using a four-compartment model.

Effect of physiological doses of oral vitamin B12 on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India.

BACKGROUND/OBJECTIVES: Vitamin B(12) (B(12)) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of B(12) and folic acid on plasma total homocysteine (tHcy) concentration. SUBJECTS/METHODS: A cluster randomized, placebo-controlled, double-blind, 2 x 3 factorial trial, using the family as the randomization unit. B(12) was given as 2 or 10 microg capsules, with or without 200 microg folic acid, forming six groups (B(0)F(0), B(2)F(0), B(10)F(0), B(0)F(200), B(2)F(200) and B(10)F(200)). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation. RESULTS: From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between B(12) and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B(0) vs. B(2) vs. B(10); and F(0) vs. F(200). At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: -7.8, -4.1) micromol/l in B(2), and by 7.1 (95% CI: -8.9, -5.4) micromol/l in B(10), compared to nonsignificant rise of 1.2 (95% CI: -0.5, 2.9) micromol/l in B(0). B(2) and B(10) did not differ significantly. In F(200), tHcy concentration decreased by 4.8 (95% CI: -6.3, -3.3) micromol/l compared to 2.8 (95% CI: -4.3, -1.2) micromol/l in F(0). CONCLUSION: Daily oral supplementation with physiological doses of B(12) is an effective community intervention to reduce tHcy. Folic acid (200 microg per day) showed no additional benefit, neither had any unfavorable effects.

Adiposity, inflammation and hyperglycaemia in rural and urban Indian men: Coronary Risk of Insulin Sensitivity in Indian Subjects (CRISIS) Study.

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-alpha 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.

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

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.

Body fat measurement in Indian men: comparison of three methods based on a two-compartment model.

UNLABELLED: Obesity is a major risk factor for diabetes and related disorders. The current classification of obesity is based on body mass index (BMI, kg/m(2)), which is a surrogate for the total body fat. Since the relationship between BMI and body fat varies in different populations, an independent validation of the BMI-body fat relationship in the population of interest is desirable. OBJECTIVES: (1) To study the validity of field methods of measuring body fat (multiple skinfolds and bioimpedance) against a criterion method (deuterium dilution) and (2) To compare the prevalence of obesity (WHO 2000 criteria for BMI) with adiposity (body fat >25%) in middle-aged Indian men in rural and urban Pune. DESIGN: Community-based multistage stratified random sampling of middle-aged men from rural and urban Pune for study of body composition and cardiovascular risk. A third of these men, selected to represent wide BMI distribution, were studied for body fat measurements by specific methods. SUBJECTS: A total of 141 healthy men, approximately similar number from rural, urban slums and middle class from Pune. They were 39.3 (+/-6.2) y old and had a BMI of 21.9 (+/-3.7) kg/m(2). MEASUREMENTS: Anthropometry (height, weight and multiple skinfold thicknesses) by trained observers using standardised technique to calculate body fat by Durnin and Womersley's equation. Total body water and body fat by bioelectrical impedance analysis (BIA) and deuterium oxide dilution (D(2)O). RESULTS: Mean total body fat was 14.3 kg (23.0%) by anthropometry, 16.5 kg (26.0%) by BIA and 15.3 kg (24.6%) by D(2)O method. Although there was a good correlation between fat estimation by three methods (r= approximately 0.9, P<0.001 all), compared to D(2)O method anthropometry underestimated body fat by 1.0 kg and BIA overestimated fat by 1.2 kg (P<0.001 both). Using the standard cut-point of 25% body fat for 'adiposity' 29.5% rural, 46.0% slum and 75.0% middle class men were adipose. These proportions were considerably higher than the number of men who were 'preobese' (BMI> or =25-29.9 kg/m(2), 9.0% rural, 22.0% urban slums and 27.0% urban middle class) and 'obese' (BMI >30 kg/m(2), 4.0% urban slums, none in rural and urban middle class). CONCLUSION: We recommend that future studies assessing risk for chronic diseases in Indians should measure adiposity by anthropometry (multiple skinfolds) or BIA (calibrated for Indians) rather than relying only on BMI cut-points.

Characteristics of gestational diabetic mothers and their babies in an Indian diabetes clinic.

AIMS AND OBJECTIVES: To compare clinical and metabolic features of mothers with gestational diabetes (GDM) and their offspring with those in non-diabetic pregnancies at the King Edward Memorial Hospital, Pune, India. MATERIALS AND METHODS: Antenatal information was obtained from hospital records. GDM was diagnosed by 75 g OGTT (Oral Glucose Tolerance Test) in clinically high-risk women. Anthropometric measurements of mother and the babies were recorded within 24h of delivery and a maternal blood sample collected for hematological and biochemical measurements. RESULTS: Between the period Jan 1998 to December 2003,265 women with gestational diabetes were treated in our Unit. Forty nine percent had first-degree relatives with diabetes. Compared to non-diabetic mothers (n=215) GDM mothers were older (29.0 vs. 26.0y, p<0.001), more obese (body mass index- BMI 26.0 vs. 22.0 kg/m2, p<0.001), centrally obese (Waist hip ratio-WHR 0.89 vs 0.86, p<0.001), adipose (sum of 4 skinfolds 98.4 vs. 61.4 mm, p<0.001) and had higher blood pressure (127/80 vs. 122/70 mmHg, p<0.001). GDM mothers had higher concentrations of plasma triglycerides (195.0 vs. 153.0 mg/dl, p<0.01); blood hemoglobin (11.7 vs 10.9 g/dl, p<0.001) and higher platelet count but lower concentration of HDL cholesterol and albumin. Sixty percent GDM mothers and 34% of non-diabetic mothers were delivered by caesarean-section, 23% of GDM mothers delivered pre term (<37 wk). Despite the smaller gestation, babies of GDM mothers were heavier (BW 2950.0 vs. 2824.0g, p<0.001, adjusted for gender), longer (48.9 vs. 48.0 cm, p<0.01) and more adipose (sum of 2 skinfolds 10.5 vs. 8.5 mm). Only 5% of babies born to GDM mothers weighed > 4000 g but 30% were >90th centile of birth weight of babies born to non-diabetic mothers. Babies of GDM mothers suffered higher neonatal morbidity. CONCLUSIONS: GDM mothers in urban India are more obese and more adipose than non-diabetic mothers, frequently have a family history of diabetes and show metabolic features of insulin resistance syndrome, suggesting high cardiovascular risk. Neonates of GDM mothers are heavier, longer and more adipose than those born to non-diabetic mothers, and suffer higher neonatal morbidity.

Adiposity and hyperinsulinemia in Indians are present at birth.

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.