Associations of micronutrients and lipids with prediabetes and glycemic parameters in adolescent girls of the rural DERVAN cohort (DERVAN-9).

Background: We investigated the associations of micronutrients and lipids with prediabetes, glycemic parameters, and glycemic indices among the adolescent girls of the DERVAN (aDolescent and prEconception health peRspectiVe of Adult Non-communicable diseases) cohort study from rural India. Methods: We recruited 1,520 adolescent girls aged 16-18 years. We measured glycemic parameters (glucose, insulin and HbA1C), lipids (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides), and micronutrients (vitamin B12, folate, and vitamin D). Prediabetes was defined using American Diabetes Association criteria (fasting glucose ≥100 mg/dL or HbA1C ≥5.7%). Glycemic indices (insulin resistance, insulin sensitivity, and ß cell function) were calculated using the homeostasis model. Associations of prediabetes, glycemic parameters and glycemic indices with micronutrients and lipids were analyzed by multiple logistic regressions. Results: The median age and Body Mass Index (BMI) were 16.6 years and 17.6 kg/m2, respectively. Overall, 58% of girls had a low BMI. Median vitamin B12, folate, and vitamin D concentrations were 249.0 pg/mL, 6.1 ng/mL, and 14.2 ng/mL, respectively. The deficiencies observed were 32.1% for vitamin B12, 11.8% for folate, and 33.0% for vitamin D. Median total cholesterol, LDL, HDL, and triglyceride concentrations were 148.0 mg/dL, 81.5 mg/dL, 50.8 mg/dL, and 61.5 mg/dL, respectively. Elevated total cholesterol, LDL, and triglycerides were observed in 4.8, 4.0, and 3.8%, respectively, while low HDL was observed in 12.8%. Prediabetes was observed in 39.7% of the girls. Among lipids, total cholesterol and LDL were higher in girls with prediabetes (p < 0.01 for both). In a multivariate model containing cholesterol and vitamin B12/folate/vitamin D, prediabetes was associated with high cholesterol. Prediabetes was also associated with high LDL, independent of folate and vitamin D. Poor insulin secretion was high in those with low vitamin B12. Elevated insulin resistance was associated with low HDL. The likelihood of high insulin sensitivity was reduced in those with high triglycerides. The likelihood of poor ß cell function was high in those with high LDL. Statistical interactions between micronutrients and lipids for prediabetes and glycemic outcomes were not significant. Conclusion: There was a substantial deficiency of micronutrients and an absence of dyslipidemia. Our results indicate the need for lipid and micronutrient-based interventions in adolescence to improve glycemic outcomes. Maintaining adequate storage of not only micronutrients but also lipids in adolescent girls is likely to reduce diabetes risk in adulthood.

Prediabetes in rural adolescent girls from DERVAN cohort: data from the KONKAN region of the state of Maharashtra, India (DERVAN-4).

Background: India is witnessing an epidemic of type 2 diabetes. Overweight/obesity, overnutrition, physical inactivity, and family history are well-known risk factors for diabetes. We investigated the role of undernutrition in the development of diabetes among rural adolescent girls. Methods: DERVAN cohort study was set up in the KONKAN region of the western Indian state of Maharashtra. It enrolled 1,520 adolescent girls (16-18 years old at the time of enrollment). We measured glycemic parameters (glucose, insulin, and HbA1C) and body size using anthropometry and body composition using bioimpedance. Prediabetes was diagnosed using the American Diabetic Association (ADA) criteria. We also calculated various HOMA indices for insulin resistance (HOMA-IR), ß-cell function (HOMA-ß), insulin sensitivity (HOMA-S), and compensatory ß-cell response using a homeostasis model. BMI, body fat%, and waist circumferences were treated as exposures and all the glycemic parameters and indices as outcomes. Results: The median age of the subjects was 16.6 years. The median weight, height, and BMI were 40.7 kg, 151.7 cm, and 17.5 kg/m2, respectively. Prevalence of underweight was 28.8%, and stunting was observed in 30.4%. Thinness and obesity using BMI were observed in 58.4% and 4.2%, respectively. The median body fat% was 22.5, and excess body fat (>35%) was observed in 5.7%. The prevalence of prediabetes was 39.4%. Fasting insulin concentrations, HOMA-IR, and HOMA-ß showed a positive trend across body composition quartiles (p < 0.001). HOMA-S and compensatory ß-cell response showed an inverse trend (p < 0.001). Compared with prediabetic girls in the overweight/obese group, girls most undernourished group had lower median insulin concentrations (8.1 µIU/ml vs. 17.1 µIU/ml), lower HOMA-IR (1.1 vs. 2.3), and lower HOMA-ß (75.6 vs. 129.2) but higher sensitivity (87.4 vs. 43.7) (p < 0.001) for all. Conclusion: We have reported a high prevalence of prediabetes among rural adolescent girls with a very low prevalence of obesity. Prediabetes in obesity is driven by hyperinsulinemia and overworking of the pancreas while poor ß-cell function and poor insulin secretion are major drivers in the undernourished group. The high-risk diabetes screening programs are much needed for the undernourished populations. Caution should be exercised for planning the interventions as overfeeding (or overnutrition) is likely to put the populations at risk of development of obesity and insulin resistance.

Diurnal variation in salivary progesterone in fertile Indian women.

Research question: Is there a diurnal variation in salivary progesterone levels during menstrual cycle among Indian women? Design: A longitudinal study was carried out to measure progesterone in saliva among small cross-sectional sample (n = 31) of fertile Indian women of reproductive age comprising young adults (18-25 years, n = 11), adults (26-38 years, n = 9) and middle aged (39-45 years, n = 11). Saliva samples were collected twice daily (morning and evening) across the entire menstrual cycle of 31 women. Results: Mean ages at enrolment and menarche were 30.6 years and 13.6 years respectively. Fifty-five percent of the women were married. The menstrual cycle range was 20-40 days. After controlling for age and menstrual cycle length, statistically significant diurnal variation in progesterone levels was observed across menstrual cycles with high levels in the morning. Conclusions: This is the first report on salivary progesterone in subjects with Indian ethnicity and could have clinical implications for designing point of care kits for menstrual cycle management, fertility and reproduction.

What shapes adolescents' diet and physical activity habits in rural Konkan, India? Adolescents' and caregivers' perspectives.

OBJECTIVE: To explore, adolescents' and caregivers' perspectives, about shaping of diet and physical activity habits in rural Konkan, India. DESIGN: Five focus group discussions (FGD) were conducted with adolescents and two with caregivers. Data were analysed using thematic analysis. SETTING: FGD were conducted in secondary schools located in remote rural villages in the Ratnagiri district, Konkan region, Maharashtra, India. PARTICIPANTS: Forty-eight adolescents were recruited including twenty younger (10-12 years) and twenty-eight older (15-17 years) adolescents. Sixteen caregivers (all mothers) were also recruited. RESULTS: Three themes emerged from discussion: (i) adolescents' and caregivers' perceptions of the barriers to healthy diet and physical activity, (ii) acceptance of the status quo and (iii) salience of social and economic transition. Adolescents' basic dietary and physical activity needs were rarely met by the resources available and infrastructure of the villages. There were few opportunities for physical activity, other than performing household chores and walking long distances to school. Adolescents and their caregivers accepted these limitations and their inability to change them. Increased use of digital media and availability of junk foods marked the beginning of a social and economic transition. CONCLUSION: FGD with adolescents and their caregivers provided insights into factors influencing adolescent diet and physical activity in rural India. Scarcity of basic resources limited adolescent diet and opportunities for physical activity. To achieve current nutritional and physical activity recommendations for adolescents requires improved infrastructure in these settings, changes which may accompany the current Indian social and economic transition.

Is small placenta a risk for low birth weight in KOKAN? (Data from a coastal region in the state of Maharashtra, India).

KOKAN region is characterized by undernutrition across all stages of lifecycle. Developmental Origins of Health & Disease hypothesis suggests that environmental influences in the early period of growth and development can contribute to the risks of noncommunicable diseases (NCD) in adulthood. Newborns and placentas of 815 pregnant mothers delivered in a rural hospital were studied. We tested the hypothesis that low placental weight will be associated with low birth weight (LBW). Mothers had a mean age of 26 years and were smaller in size at delivery [mean height of 152.1 cm (±6.1 cm), weight 52 kg (±10.2 kg), body mass index (BMI) 22.5 kg/m2 (±4.1 kg/m2)]. Mean placental weight was 488 g (±120 g). Mean birth weight, length, and head circumference of the newborn were 2.54 kg (±0.5 kg), 46.3 cm (±3.1 cm), and 32.7 cm (±1.7 cm), respectively. Prevalence of LBW, stunting, and small head size was 41.6%, 42.2%, and 18.2%, respectively. Maternal height, weight, and BMI at delivery were all positively associated with placental weight (p < 0.01 for all). Mothers with placentas in the lowest placental weight tertile had an increased likelihood of producing an LBW baby [OR 7.7, 95% CI (5.0, 11.8)], a stunted baby [OR 1.9 (1.4, 2.9)], or a baby with a small head circumference [OR 2.4 (1.4, 4.0)]. Mothers in the lowest height tertile had odds of producing a LBW baby [OR 1.8 95% CI (1.2, 2.7)] or a stunted baby [OR 1.6 (1.1, 2.3)]. There is a need to improve the nutritional status of women in KOKAN region which may reduce the risk of NCD.

Birth weight, childhood and adolescent growth and diabetes risk factors in 21-year-old Asian Indians: the Pune Children's Study.

Our objective was to investigate associations of body size (birth weight and body mass index (BMI)) and growth in height, body fat (adiposity) and lean mass during childhood and adolescence, with risk markers for diabetes in young South Asian adults. We studied 357 men and women aged 21 years from the Pune Children's Study birth cohort. Exposures were 1) birth weight, 21-year BMI, both of these mutually adjusted, and their interaction, and 2) uncorrelated conditional measures of growth in height and proxies for gain in adiposity and lean mass from birth to 8 years (childhood) and 8 to 21 years (adolescence) constructed from birth weight, and weight, height, and skinfolds at 8 and 21 years. Outcomes were plasma glucose and insulin concentrations during an oral glucose tolerance test and derived indices of insulin resistance and secretion. Higher 21-year BMI was associated with higher glucose and insulin concentrations and insulin resistance, and lower disposition index. After adjusting for 21-year BMI, higher birth weight was associated with lower 120-min glucose and insulin resistance, and higher disposition index. In the growth analysis, greater adiposity gain during childhood and adolescence was associated with higher glucose, insulin and insulin resistance, and lower disposition index, with stronger effects from adolescent gain. Greater childhood lean gain and adolescent height gain were associated with lower 120-min glucose and insulin. Consistent with other studies, lower birth weight and higher childhood weight gain increases diabetes risk. Disaggregation of weight gain showed that greater child/adolescent adiposity gain and lower lean and height gain may increase risk.

Do components of adult height predict body composition and cardiometabolic risk in a young adult South Asian Indian population? Findings from a hospital-based cohort study in Pune, India: Pune Children's Study.

OBJECTIVES: We investigated whether the relationship between components of height and cardiovascular disease (CVD) risk may be explained by body composition. We also examined relationships between parental heights and offspring CVD risk. DESIGN: A cohort study using cross-sectional data. SETTING: A secondary care hospital setting in Pune, India. PARTICIPANTS: We studied 357 young adults and their parents in the Pune Children's Study. Primary and secondary outcomes: we measured weight, total height, leg length, sitting height, plasma glucose, insulin and lipids, and blood pressure (BP). Total and regional lean and fat mass were measured by dual X-ray absorptiometry. RESULTS: Leg length was inversely related, and sitting height was directly related to BMI. Total height and leg length were directly related to lean mass, while sitting height was directly related to both lean and fat mass. Leg length was inversely related to systolic BP and 120 min glucose, independent of lean and fat mass. Sitting height was directly related to systolic BP and triglycerides; these relationships were attenuated on adjustment for lean and fat mass. When examined simultaneously, greater leg length was protective and greater sitting height was associated with a more detrimental CVD risk profile. CONCLUSIONS: Shorter adult leg length and greater sitting height are associated with a more adverse CVD risk factor profile. The mechanisms need further study, but our findings suggest a role for lean and fat mass.

aDolescent and prEconception health peRspectiVe of Adult Non-communicable diseases (DERVAN): protocol for rural prospective adolescent girls cohort study in Ratnagiri district of Konkan region of India (DERVAN-1).

INTRODUCTION: Precise impact of nutritional insufficiencies in adolescence as a risk factor for non-communicable diseases (NCD) in later life as adults remains largely unknown.We are conducting research into the effects of nutrition on adolescent girls of Ratnagiri district by a prospective cohort study (aDolescent and prEconception health peRspectiVe of Adult Non-communicable diseases cohort). Our study focuses on the physical health, nutritional parameters and cognitive profiles of adolescent girls, during the prenatal and postnatal period and we aim to follow this cohort and their offspring for 20 years. METHODS AND ANALYSIS: Cohort recruitment began in June 2019. Our aim is to recruit more than 1500 adolescent girls, age 16-18 years, over a period of 3 years. The recruit's cognition, diet and physical activity will be recorded. The following investigations will be performed: body composition by anthropometry and bioimpedence, and blood pressure, fasting blood sample to measure glucose, insulin, lipids, micronutrients and hormones, abdominal ultrasonography to measure liver, pancreas and kidneys.A biorepository has been created for long-term storage of blood, urine and saliva samples for future analysis. By this longitudinal study, we aim to identify the effects of malnutrition on the behavioural and biological measures in adolescent subjects and evaluate if these are associated with the onset of NCDs in adulthood. ETHICS AND DISSEMINATION: Institutional Ethic Committee (IEC) of BKL Walawalkar Rural Medical College and Hospital has granted the permission to carry out the study. IEC is registered with Government of India. Its registration code is EC/755/INST/MH/2015/RR-18. It is not a clinical trial but as required we have also registered the study on Clinical Trial Registry of India (CTRI). The registration code is CTRI/2019/04/018453.Appropriate written informed consent and assent are obtained from the parents and the adolescent girls, respectively. We plan to publish our results in peer-reviewed journals.

Menarche among rural adolescent girls in Dervan (Data from the KONKAN region of the state of Maharashtra, India).

CONTEXT: Associations between age at menarche and risk of type 2 diabetes and cardiovascular disease are well established in adults. But little is known about these risks in adolescents. AIM: To examine the association between age at menarche and anthropometric indicators, and also examine nutrition among the rural adolescent girls of KONKAN region. SETTING AND DESIGN: We investigated 1,071 school going adolescent girls who underwent holistic education and various clinical investigations as a part of community program. Age at menarche was recorded and anthropometric measurements were performed. Macronutrient intake was estimated by 24 h recall. STATISTICAL ANALYSIS USED: We used trend statistics and logistic regression to examine the association. RESULTS: A total of 813 girls had attained menarche. Mean age at menarche was 13.0 years. When compared with premenarchal girls anthropometric parameters were significantly higher in postmenarchal girls (P < 0.05 for all) and the prevalence of stunting and thinness was lower (P < 0.001 for both). There was a decreasing trend for weight (P < 0.001), BMI (P < 0.001), and waist circumference (P < 0.05) with increasing age of onset of menarche, and increasing trend for stunting and thinness (P < 0.001 for both). More than 65% of the girls were eating below the recommended daily allowance of calories, protein, and fat. Adolescents with late onset of menarche had increased likelihood of stunting (P < 0.01) and thinness (P < 0.001). CONCLUSIONS: Adolescent girls in the KONKAN region with late menarche are thin and stunted. There is an urgent need to improve nutritional status of adolescent girls from KONKAN as malnutrition can affect the onset of menarche.

Nutritional Status and Psychological Impairment in Rural Adolescent Girls: Pilot Data From "KOKAN" Region of Western India.

Background: Adolescence is a period during which psychological foundations are laid down as well as consolidated. Not much information is available on rural Indian adolescent girls and their psychological health. Methods: We did a pilot survey of psychological health of 80 adolescent girls residing at KOKAN region of western India. Psychological health was evaluated using Youth Paediatric Symptom Checklist (Y-PSC) consisting of 35 items with maximum score of 70. Girls with a score >30 were classified as psychologically impaired. In addition we also collected random blood sample and measured the micronutrients. Macronutrient intake was estimated by 24 h recall. Results: The mean age of the girls was 14 years with a standard deviation of 1.5. In all 35/76 (46.1%) could be classified as psychologically impaired. There was a high prevalence of micronutrient deficiencies with varying degrees. More than 65% were deficient in calcium, zinc and folic acid. About 22% were anemic and 36% were vitamin B1 deficient. More than 75% had a low recommended dietary allowance (RDA) of macronutrients. Those with poor serum calcium concentration had higher psychological score (p < 0.05). Fat and calcium intakes were inversely associated with psychological score (p < 0.05 and p < 0.001 respectively). Odds ratios for psychological impairment were significant for those with low calcium levels [1.47 (95% CI 1.21, 4.31)], and for those with low calcium intake 1.43 (1.08, 3.19) and low iron intake 3.04 (1.02, 9.26). Conclusion: Our pilot data has shown the urgent need to improve the nutrition of adolescent girls, which could improve their psychological health.

GWAS identifies population-specific new regulatory variants in FUT6 associated with plasma B12 concentrations in Indians.

Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (P = 1.2 × 10-23) and rs78060698 (P = 8.3 × 10-17) in FUT6 to be associated with circulating B12 concentrations. Although in-silico analysis replicated both variants in Europeans, differences in the effect allele frequency, effect size and the linkage disequilibrium structure of credible set variants with the reported variants suggest population-specific characteristics in this region. We replicated previously reported variants rs602662, rs601338 in FUT2, rs3760776, rs708686 in FUT6, rs34324219 in TCN1 (all P < 5 × 10-8), rs1131603 in TCN2 (P = 3.4 × 10-5), rs12780845 in CUBN (P = 3.0 × 10-3) and rs2270655 in MMAA (P = 2.0 × 10-3). Circulating B12 concentrations in the PMNS and Parthenon study showed a significant decline with increasing age (P < 0.001), however, the genetic contribution to B12 concentrations remained constant. Luciferase reporter and electrophoretic-mobility shift assay for the FUT6 variant rs78060698 using HepG2 cell line demonstrated strong allele-specific promoter and enhancer activity and differential binding of HNF4α, a key regulator of expression of various fucosyltransferases. Hence, the rs78060698 variant, through regulation of fucosylation may control intestinal host-microbial interaction which could influence B12 concentrations. Our results suggest that in addition to established genetic variants, population-specific variants are important in determining plasma B12 concentrations.

The Pune Rural Intervention in Young Adolescents (PRIYA) study: design and methods of a randomised controlled trial.

BACKGROUND: The Pune Maternal Nutrition Study (PMNS) was established to prospectively study the relationship of maternal nutrition to fetal growth and later cardiometabolic risk in the offspring. High homocysteine and low vitamin B12 levels in pregnancy predicted lower birthweight and higher insulin resistance at 6 years in the offspring. B12 deficiency was widespread in this population, due to low dietary intake. We therefore commenced a community-based intervention study with the underlying hypothesis that vitamin B12 supplementation of adolescent members of the PMNS cohort will improve birth weight, B12 status, and reduce future diabetes risk, in their offspring. METHODS: The individually randomised controlled trial commenced in September 2012, with boys and girls randomized into 3 groups, to receive daily for at least 3 years or until the birth of their first child: 1) vitamin B12 2 µg; or 2) vitamin B12 2 µg plus multiple micronutrients (MMN) plus 20 g of milk powder or 3) placebo. Iron and folic acid is given to all participants. Compliance is assessed by monthly supplement counts. Adverse events are recorded using a standardised questionnaire. The primary outcome is cord blood B12 concentration; based on 180-200 pregnancies in the girls, the study has ~80% power to detect a 0.5 SD change in newborn B12, in the B12 supplementation groups compared with controls, at the 5% significance level. Primary analysis will be by intention to treat. DISCUSSION: Our study tests a primordial prevention strategy through an intergenerational intervention started pre-conceptionally in both boys and girls using physiological doses of micronutrients to improve immediate pregnancy-related and long-term cardio metabolic outcomes. The results will have significant public health implications in a setting with widespread B12 deficiency but relative folate sufficiency. The randomised controlled trial design allows us to be confident that our findings will be causally relevant. TRIAL REGISTRATION: ISRCTN 32921044, applied on 14/09/2012. CTRI 2012/12/003212, registered on 02/12/2012. Retrospectively registered.

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.

Associations of trunk fat depots with insulin resistance, ß cell function and glycaemia--a multiple technique study.

OBJECTIVE: Central (truncal) adiposity is associated strongly with insulin resistance and diabetes. There are very few reports comparing methods of trunk fat measurement in their ability to predict glycaemia and insulin resistance. We report a comparative analysis of different trunk fat measurements in predicting glycaemia and insulin resistance in middle aged Indian men. MATERIALS AND METHODS: Trunk fat measurements were performed using anthropometry, magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) on 128 men. Additional measurements were taken to characterise insulin resistance (Matsuda index) and beta cell function (Insulinogenic Index), glycaemia (fasting and 120 min glucose concentrations). Using residual approach we compared the ability of different trunk fat measurement techniques to predict insulin resistance, beta cell function and glycaemia. RESULTS: There was a strong association between trunk fat measures from each technique with glycaemia and insulin resistance indices but not with the Insulinogenic Index. Insulin resistance and glycaemia, were best predicted using anthropometric measurements, notably by waist circumference and subscapular skinfold thickness. Neither MRI measures of trunk or visceral fat nor DXA trunk fat added significantly. CT liver density contributed to some extent to predict insulin resistance and 120 min glucose after anthropometric measurements. CONCLUSIONS: Our results suggest that, in Indian men, anthropometric measurements are good predictors of glycaemia and insulin resistance. Other complex measurements such as MRI, DXA and CT make only a small addition to the prediction. This finding supports the application of anthropometry for determining trunk fat in clinical and epidemiological settings.

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.

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.

Vitamin B12 and folic acid supplementation and plasma total homocysteine concentrations in pregnant Indian women with low B12 and high folate status.

Maternal vitamin B12 deficiency and hyperhomocysteinemia predict poor pregnancy outcome, foetal adiposity and insulin resistance. In India amongst practicing clinicians and policy makers there is little appreciation of widespread vitamin B12 deficiency. We investigated 163 (86 rural, 77 urban) pregnant women attending antenatal clinics in a rural health centre and a referral hospital in the city of Pune, at 17, 28, and 34 weeks gestation for vitamin supplements, and circulating concentrations of vitamin B12, folate, and total homocysteine. At enrolment 80% rural and 65% urban women had low vitamin B12 but only two rural women had low folate concentrations. During pregnancy 85% rural and 95% of urban women received folic acid; 12% rural and 84% urban women also received vitamin B12. In women receiving no supplementation (n=17) plasma vitamin B12 and folate did not change from 17 to 34 weeks gestation, but homocysteine increased (p<0.05). Homocysteine concentrations at 34 weeks gestation in women receiving only folic acid (n=71, mean 8.4 (95% CI 7.8, 9.1) micromol/L) were comparable to the unsupplemented group (9.7 (7.3, 12.7), p=0.15), but women who received a total dose of >1000 microg of vitamin B12 up to 34 weeks (n=42, all with folic acid) had lower concentrations (6.7 (6.0, 7.4), p<0.001). Increasing dose of vitamin B12 (rs=-0.31, p=0.006) but not folic acid (rs=-0.19, p=0.11) was associated with lower plasma total homocysteine concentration. In vitamin B12 insufficient, folate replete pregnant women, vitamin B12 supplementation is associated with a reduction of plasma total homocysteine concentration in late pregnancy.

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

We examined the differential associations of each parent's 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.