Charudatta V. Joglekar

Neonatal anthropometry: the thin–fat Indian baby. The Pune Maternal Nutrition Study

OBJECTIVE: To examine body size and fat measurements of babies born in rural India and compare them with white Caucasian babies born in an industrialised country.DESIGN: Community-based observational study in rural India, and comparison with data from an earlier study in the UK, measured using similar methods.SUBJECTS: A total of 631 term babies born in six rural villages, near the city of Pune, Maharashtra, India, and 338 term babies born in the Princess Anne Hospital, Southampton, UK.MEASUREMENTS: Maternal weight and height, and neonatal weight, length, head, mid-upper-arm and abdominal circumferences, subscapular and triceps skinfold thicknesses, and placental weight.RESULTS: The Indian mothers were younger, lighter, shorter and had a lower mean body mass index (BMI) (mean age, weight, height and BMI: 21.4 y, 44.6 kg, 1.52 m, and 18.2 kg/m2) than Southampton mothers (26.8 y, 63.6 kg, 1.63 m and 23.4 kg/m2). They gave birth to lighter babies (mean birthweight: 2.7 kg compared with 3.5 kg). Compared to Southampton babies, the Indian babies were small in all body measurements, the smallest being abdominal circumference (s.d. score: −2.38; 95% CI: −2.48 to −2.29) and mid-arm circumference (s.d. score: −1.82; 95% CI: −1.89 to −1.75), while the most preserved measurement was the subscapular skinfold thickness (s.d. score: −0.53; 95% CI: −0.61 to −0.46). Skinfolds were relatively preserved in the lightest babies (below the 10th percentile of birthweight) in both populations.CONCLUSIONS: Small Indian babies have small abdominal viscera and low muscle mass, but preserve body fat during their intrauterine development. This body composition may persist postnatally and predispose to an insulin-resistant state.

Newborn size, infant and childhood growth, and body composition and cardiovascular disease risk factors at the age of 6 years: the Pune Maternal Nutrition Study

Objective:To study associations of size and body proportions at birth, and growth during infancy and childhood, to body composition and cardiovascular disease (CVD) risk factors at the age of 6 years.Design:The Pune Maternal Nutrition Study, a prospective population-based study of maternal nutrition and CVD risk in rural Indian children.Methods:Body composition and CVD risk factors measured in 698 children at 6 years were related to body proportions and growth from birth.Measurements:Anthropometry was performed every 6 months from birth. At 6 years, fat and lean mass (dual X-ray absorptiometry) and CVD risk factors (insulin resistance, blood pressure, glucose tolerance, plasma lipids) were measured.Results:Compared with international references (NCHS, WHO) the children were short, light and thin (mean weight <−1.0 s.d. at all ages). Larger size and faster growth in all body measurements from birth to 6 years predicted higher lean and fat mass at 6 years. Weight and height predicted lean mass more strongly than fat mass, mid-upper arm circumference (MUAC) predicted them both approximately equally and skinfolds predicted only fat mass. Neither birthweight nor the ‘thin-fat’ newborn phenotype, was related to CVD risk factors. Smaller MUAC at 6 months predicted higher insulin resistance (P<0.001) but larger MUAC at 1 year predicted higher systolic blood pressure (P<0.001). After infancy, higher weight, height, MUAC and skinfolds, and faster growth of all these parameters were associated with increased CVD risk factors.Conclusions:Slower muscle growth in infancy may increase insulin resistance but reduce blood pressure. After infancy larger size and faster growth of all body measurements are associated with a more adverse childhood CVD risk factor profile. These rural Indian children are growing below international ‘norms’ for body size and studies are required in other populations to determine the generalizability of the findings.

Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of Type 2 diabetes and related traits in Indians

Diabet. Med. 29, 121–127 (2012)

Maternal homocysteine in pregnancy and offspring birthweight: epidemiological associations and Mendelian randomization analysis

BACKGROUND Disturbed one-carbon (1-C) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established. METHODS We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study (PMNS, Pune, India) and Parthenon Cohort Study (Mysore, India). We tested for evidence of causality within a Mendelian randomization framework, using a methylenetetrahydrofolatereductase (MTHFR) gene variant rs1801133 (earlier known as 677C→T) by instrumental variable and triangulation analysis, separately and using meta-analysis. RESULTS Median (IQR) homocysteine concentration and mean (SD) birthweight were 8.6 µmol/l (6.7,10.8) and 2642 g (379) in the PMNS and 6.0 µmol/l (5.1,7.1) and 2871 g (443) in the Parthenon study. Offspring birthweight was inversely related to maternal homocysteine concentration-PMNS: -22 g/SD [95% confidence interval (CI): (-50, 5), adjusted for gestational age and offspring gender]; Parthenon: -57 g (-92, -21); meta-analysis: -40 g (-62, -17)]. Maternal risk genotype at rs1801133 predicted higher homocysteine concentration [PMNS: 0.30 SD/allele (0.14, 0.46); Parthenon: 0.21 SD (0.02, 0.40); meta-analysis: 0.26 SD (0.14, 0.39)]; and lower birthweight [PMNS: -46 g (-102, 11, adjusted for gestational age, offspring gender and rs1801133 genotype); Parthenon: -78 g (-170, 15); meta-analysis: -61 g (-111, -10)]. Instrumental variable and triangulation analysis supported a causal association between maternal homocysteine concentration and offspring birthweight. CONCLUSIONS Our findings suggest a causal role for maternal homocysteine (1-C metabolism) in fetal growth. Reducing maternal homocysteine concentrations may improve fetal growth.

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

Background/Objectives:Vitamin B12 (B12) 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 B12 and folic acid on plasma total homocysteine (tHcy) concentration.Subjects/Methods:A cluster randomized, placebo-controlled, double-blind, 2 × 3 factorial trial, using the family as the randomization unit. B12 was given as 2 or 10 μg capsules, with or without 200 μg folic acid, forming six groups (B0F0, B2F0, B10F0, B0F200, B2F200 and B10F200). 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 B12 and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B0 vs. B2 vs. B10; and F0 vs. F200. At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: −7.8, −4.1) μmol/l in B2, and by 7.1 (95% CI: −8.9, −5.4) μmol/l in B10, compared to nonsignificant rise of 1.2 (95% CI: −0.5, 2.9) μmol/l in B0. B2 and B10 did not differ significantly. In F200, tHcy concentration decreased by 4.8 (95% CI: −6.3, −3.3) μmol/l compared to 2.8 (95% CI: −4.3, −1.2) μmol/l in F0.Conclusion:Daily oral supplementation with physiological doses of B12 is an effective community intervention to reduce tHcy. Folic acid (200 μg per day) showed no additional benefit, neither had any unfavorable effects.

Increases in Plasma Holotranscobalamin Can Be Used to Assess Vitamin B-12 Absorption in Individuals with Low Plasma Vitamin B-12

Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 microg (n = 191) or 2 microg (n = 122) of cyanocobalamin at 6-h intervals. A rise in plasma holo-TC of > or =15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 concentration was <150 pmol/L in 48% of participants; holo-TC was <35 pmol/L in 98% and total homocysteine was high in 50% of participants (>10 micromol/L in children and >15 micromol/L in adults). In the 10 microg group, the plasma holo-TC concentration increased by 4.8-fold from (mean +/- SD) 9.3 +/- 7.0 pmol/L to 53.8 +/- 25.9 pmol/L and in the 2 microg group by 2.2-fold from 11.1 +/- 8.5 pmol/L to 35.7 +/- 19.3 pmol/L. Only 10% of the participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status.

Maternal and paternal height and BMI and patterns of fetal growth: The Pune Maternal Nutrition Study

We examined the differential associations of each parents height and BMI with fetal growth, and examined the pattern of the associations through gestation. Data are from 557 term pregnancies in the Pune Maternal Nutrition Study. Size and conditional growth outcomes from 17 to 29 weeks to birth were derived from ultrasound and birth measures of head circumference, abdominal circumference, femur length and placental volume (at 17 weeks only). Parental height was positively associated with fetal head circumference and femur length. The associations with paternal height were detectible earlier in gestation (17–29 weeks) compared to the associations with maternal height. Fetuses of mothers with a higher BMI had a smaller mean head circumference at 17 weeks, but caught up to have larger head circumference at birth. Maternal but not paternal BMI, and paternal but not maternal height, were positively associated with placental volume. The opposing associations of placenta and fetal head growth with maternal BMI at 17 weeks could indicate prioritisation of early placental development, possibly as a strategy to facilitate growth in late gestation. This study has highlighted how the pattern of parental–fetal associations varies over gestation. Further follow-up will determine whether and how these variations in fetal/placental development relate to health in later life.

Marked Gender Difference in Plasma Total Homocysteine Concentrations in Indian Adults with low Vitamin B12

CONTEXT Plasma total homocysteine (tHcy) is higher in men than women. OBJECTIVE To explore the gender differences in tHcy in relation to determinants of one-carbon metabolism in Indian people with low B₁₂ and adequate folate. SETTING The study took place in rural and urban areas of Pune, India. DESIGN AND PARTICIPANTS Participants were 441 men from the cross-sectional Coronary Risk of Insulin Sensitivity in Indian Subjects study (CRISIS) and premenopausal wives of 146 men (median ages 38 and 34 years, respectively). MAIN OUTCOME MEASURES Gender difference in fasting tHcy in relation to plasma albumin and creatinine concentrations, lifestyle factors, diet and lean mass, plasma B₁₂ and red cell folate (RCF) was assessed. RESULTS Prevalence of high tHcy (> 15 µmol/L, median 14.4 µM) was 40 %, low B12 (< 150 pmol/L, 114 pmol/L) 66 %, and low RCF (< 283 nmol/L, 525 nmol/L) 8 %. Men had higher (1.8x) plasma tHcy concentrations (16.2 µmol/L) than women (9.5 µmol/L). Only 50 % of the gender difference was explained by age, lean mass, B₁₂, and RCF. The difference remained after controlling for other explanatory variables. Women with a tHcy of 9.3 µM had the same B₁₂ concentration (129 pmol/L) as men with a tHcy of 15 µM; and for a tHcy of 10.0 µmol/L women had the same RCF concentration (533 nmol/L) as men with a tHcy of 15 µmol/L. CONCLUSIONS Adult Indian women have markedly lower tHcy concentrations compared to men. This suggests a lower threshold for supplementation to improve reproductive and cardiovascular outcomes.

Circulating lipids and cardiovascular risk in newly diagnosed non‐insulin‐dependent diabetic subjects in India

Circulating concentrations of total cholesterol, triglycerides, non‐esterified fatty acids (NEFA), glycerol, and 3‐hydroxybutyrate (3‐HB) were measured in 133 subjects with normal glucose tolerance (NGT), 78 with impaired‐glucose‐tolerance (IGT) and 189 non‐insulin dependent (Type 2) diabetic (NIDDM) patients. Plasma cholesterol concentration was similar in the three groups; NGT (4.2 (2.3–7.5) mmol l−1 , median (range)), IGT (4.7 (2.7–6.3)) and NIDDM (4.3 (2.3–6.9)). Plasma triglycerides (NGT 0.88 (0.37–2.80), IGT 1.26 (0.43–3.82) and NIDDM 1.38 (0.62–3.91) mmol l−1 ) and NEFA (NGT 0.81 (0.29–1.58), IGT 1.02 (0.33–1.87) and NIDDM 1.02 (0.48–2.77) mmol l−1 ) were higher in the two hyperglycaemic groups, but blood 3‐HB concentration was similar in the three groups. Plasma cholesterol concentration in these subjects is lower than that reported in white Caucasians in the UK and USA and migrant Indian NIDDM patients in the UK. In NIDDM patients plasma cholesterol concentration was related to age, body mass index (BMI), and plasma glucose concentration while plasma triglyceride concentration was related to plasma NEFA and insulin (IRI) concentration. Evidence of ischaemia on electrocardiography in patients with diabetes was associated with higher age, blood pressure, plasma triglyceride, glucose, and IRI concentrations. © 1997 by John Wiley & Sons, Ltd.

Conventional and novel cardiovascular risk factors and markers of vascular damage in rural and urban Indian men.

BACKGROUND India is undergoing rapid epidemiological and nutritional transition largely as a consequence of rapid urbanisation. We investigated conventional and novel cardiovascular risk factors in rural and urban Indian men and studied their association with markers of vascular damage. METHODS We randomly selected and studied 149 rural, 142 urban slum residents and 150 urban middle class middle aged Indian men. We measured conventional (obesity, blood pressure, lipids, smoking habits) and novel (proinflammatory and prothrombotic factors) cardiovascular risk factors and markers of vascular damage (carotid intima media thickness (IMT), von Willebrand Factor (vWF), e-selectin). RESULTS There was a progressive increase in most of the conventional cardiovascular (CV) risk factors from rural to slum to urban middle class men. Plasminogen activator inhibitor-1 (PAI-1), platelet count, total homocysteine and C-reactive protein showed similar patterns. Carotid IMT was similar in the three groups; vWF was highest in rural and e-selectin in slum men. Adjusting for location, age explained 17%, obesity 3% and conventional risk factors 1% of the variance in carotid IMT, whilst novel cardiovascular risk factors were without any significant impact. CONCLUSIONS Urbanisation increases obesity related as well as prothrombotic and proinflammatory CV risk factors in Indian men, but appears not to impact on IMT.