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In The Pune Maternal Nutrition Study, vitamin B12 deficiency was seen in 65% of pregnant women, folate deficiency was rare. Maternal total homocysteine concentrations were inversely associated with offspring birthweight, and low vitamin B12 and high folate concentrations predicted higher offspring adiposity and insulin resistance. These findings guided a nested pre-conceptional randomised controlled trial ‘Pune Rural Intervention in Young Adolescents’. The interventions included: (1) vitamin B12+multi-micronutrients as per the United Nations International Multiple Micronutrient Antenatal Preparation, and proteins (B12+MMN), (2) vitamin B12 (B12 alone), and (3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference. Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex vitamins in the synthesis of nucleotides and S-adenosyl methionine, and the roles of vitamins A and D on gene expression, we propose that the multi-micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow-up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.

Neurocognitive development is a dynamic process over the life course and is influenced by intrauterine factors as well as later life environment. Using data from the Pune Maternal Nutrition Study from 1994 to 2008, we investigate the association of in utero, birth, and childhood conditions with offspring neurocognitive development in 686 participants of the cohort, at age 12 years. The life course exposure variables in the analysis include maternal pre-pregnancy size and nutrition during pregnancy, offspring birth measurements, nutrition and physical growth at age 12 years along with parental education and socio-economic status. We used the novel Bayesian Model Averaging (BMA) approach; which has been shown to have better predictive performance over traditional tests of associations. Our study employs eight standard neurocognitive tests that measure intelligence, working memory, visuo-conceptual and verbal learning, and decision-making/attention at 12 years of age. We control for nutritional-metabolic information based on blood measurements from the pregnant mothers and the children at 12 years of age. Our findings highlight the critical role of parental education and socio-economic background in determining child neurocognitive performance. Maternal characteristics (pre-pregnancy BMI, fasting insulin during pregnancy) and child height at 12 years were also robust predictors on the BMA. A range of early factors – such as maternal folate and ferritin concentrations during pregnancy, and child’s head circumference at birth – remained important determinants of some dimensions of child’s neurocognitive development, but their associations were not robust once we account for model uncertainty. Our results suggest that intrauterine influences on long- term neurocognitive outcomes may be potentially reversible by post-birth remediation. In addition to the current nutritional interventions, public health policy should also consider social interventions in children born into families with low socio-economic status to improve human capital.

BackgroundBased on studies in overweight-obese populations, it is tacitly assumed that maternal hyperglycemia is responsible for obesity-adiposity at birth and in later life.Study designTwo hospital based case control studies: 1) Neonatal outcomes, 2) Later life outcomes.MethodsWe studied associations of neonatal and later life obesity-adiposity [age and sex-adjusted BMI, waist circumference, skinfolds, and body fat percent by Dual energy X-ray Absorptiometry (DXA)] in offspring of mothers with diabetes (ODM) and those of mothers without diabetes (ONDM). Exposures were parental hyperglycemia and overweight-obesity.ResultsNeonatal study included 372 non-diabetic and 816 diabetic pregnancies [74 type 1 diabetes, 102 type 2 diabetes, 640 gestational diabetes (GDM)]. Mothers with type 1 diabetes were the youngest, thinnest, and with highest HbA1c. Maternal glycemia but not BMI was associated with neonatal obesity-adiposity. Thus, neonates of mothers with type 1 diabetes had highest ponderal index, abdominal circumference, and skinfolds.Later life study included 200 ODM (25 type 1 diabetes, 22 type 2 diabetes, 153 GDM) and 177 age, sex and socio-economic matched ONDM (2 to 26 y). Their obesity-adiposity was associated with bi-parental overweight-obesity in an additive manner, but not with parental diabetes. Offspring birth weight was also positively associated. Offspring of mothers with type 1 diabetes had the lowest and offspring of mothers with type 2 diabetes the highest obesity-adiposity.ConclusionNeonatal obesity-adiposity is driven by maternal glycemia while later life obesity-adiposity by bi-parental obesity. Our results provide a clear insight into pathogenesis of obesity-adiposity in the offspring.Article HighlightsIt is tacitly assumed that maternal diabetes is responsible for offspring obesity-adiposity.We examined the determinants of obesity-adiposity in intrauterine and in later life in children born to mothers with type 1, type 2 and GDM. Paternal influence was also investigated.Mothers with type 1 diabetes were the thinnest and most hyperglycemic. Their children were the most obese-adipose at birth but thinnest in later life. Later life obesity-adiposity was driven by bi-parental overweight-obesity, not by diabetes.Our findings suggest that strict maternal metabolic control during pregnancy will reduce macrosomia while targeting obesogenic family environment may reduce later life offspring obesity-adiposity.

Aim/hypothesis Five subgroups were described in European diabetes patients using a data driven machine learning approach on commonly measured variables. We aimed to test the applicability of this phenotyping in Indian individuals with young-onset type 2 diabetes. Methods We applied the European-derived centroids to Indian individuals with type 2 diabetes diagnosed before 45 years of age from the WellGen cohort (n = 1612). We also applied de novo k-means clustering to the WellGen cohort to validate the subgroups. We then compared clinical and metabolic-endocrine characteristics and the complication rates between the subgroups. We also compared characteristics of the WellGen subgroups with those of two young European cohorts, ANDIS (n = 962) and DIREVA (n = 420). Subgroups were also assessed in two other Indian cohorts, Ahmedabad (n = 187) and PHENOEINDY-2 (n = 205). Results Both Indian and European young-onset type 2 diabetes patients were predominantly classified into severe insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severe insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to findings in Europeans (Swedish 26% vs 68%, Finnish 24% vs 71%, respectively). A higher proportion of SIDD compared with MOD was also seen in Ahmedabad (57% vs 33%) and in PHENOEINDY-2 (67% vs 23%). Both in Indians and Europeans, the SIDD subgroup was characterised by insulin deficiency and hyperglycaemia, MOD by obesity, SIRD by severe insulin resistance and MARD by mild metabolic-endocrine disturbances. In WellGen, nephropathy and retinopathy were more prevalent in SIDD compared with MOD while the latter had higher prevalence of neuropathy. Conclusions /interpretation Our data identified insulin deficiency as the major driver of type 2 diabetes in young Indians, unlike in young European individuals in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in type 2 diabetes in the young Indian population and suggest a need to review management strategies. Graphical abstract

Maternal nutrient availability and its transport through the placenta are crucial for fetal development. Nutrients are transported to the fetus via specific transporters present on the microvillous (MVM) and basal membrane (BM) of the placenta. Glucose is the most abundant nutrient transferred to the fetus and plays a key role in the fetal growth and development. The transfer of glucose across the human placenta is directly proportional to maternal glucose concentrations, and is mediated by glucose transporter family proteins (GLUTs). Maternal glucose concentration influences expression and activity of GLUTs in the MVM (glucose uptake) and BM (glucose delivery). Alteration in the number and function of these transporters may affect the growth and body composition of the fetus. The thin-fat phenotype of the Indian baby (low ponderal index, high adiposity) is proposed as a harbinger of future metabolic risk. We propose that placental function mediated through nutrient transporters contributes to the phenotype of the baby, specifically that glucose transporters will influence neonatal fat. This review discusses the role of various glucose transporters in the placenta in determining fetal growth and body composition, in light of the above hypothesis.

Background: Dietary vitamin B12 (B12) deficiency is common in Indians. Long-term compliance to tablet supplementation is poor in asymptomatic individuals. Objective: To study efficacy of B12 fortified nutrient bar and yogurt in improving plasma B12 concentrations in children and adults. Methods: Two double-blind, placebo-controlled directly observed therapy randomized controlled trials were conducted for 120 days: (1) Healthy children (10-13 years) were fed nutrient bar fortified with B12 (2 μg), multiple micronutrients B12 (1.8 μg) or placebo. (2) Healthy adults (18-50 years) were fed yogurt fortified with B12 (2 μg) or Propionibacterium (1 × 108 cfu/g) or placebo. B12, folate, homocysteine, and hemoglobin concentrations were measured before and post intervention. Results: We randomized 164 children and 118 adults; adherence was 96% and 82%, respectively. In children, B12 fortified bars increased B12 concentrations significantly above baseline (B12 alone +91 pmol/L, B12+ multiple micronutrients +82 pmol/L) compared to placebo. In adults, B12 fortified yogurt increased B12 significantly (+38 pmol/L) but Propionibacterium and placebo did not. In both trials, homocysteine fell significantly with B12 supplementation. Rise of B12 and fall of homocysteine were influenced by dose of B12 and folic acid. There was no significant difference in change of anthropometry and hemoglobin between groups. Conclusions: B12 fortified foods are effective in improving B12 status in Indian children and adults. They could be used to improve B12 status in the national programs for children, adolescents, and women of reproductive age. They could also be used as over-the-counter products.

With type 2 diabetes presenting at younger ages, there is a growing need to identify biomarkers of future glucose intolerance. A high (20%) prevalence of glucose intolerance at 18 years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. We investigated the potential of circulating microRNAs in risk stratification for future pre-diabetes in these women. Here, we provide preliminary longitudinal analyses of circulating microRNAs in normal glucose tolerant (NGT@18y, N = 10) and glucose intolerant (N = 8) women (ADA criteria) at 6, 12 and 17 years of their age using discovery analysis (OpenArray™ platform). Machine-learning workflows involving Lasso with bootstrapping/leave-one-out cross-validation identified microRNAs associated with glucose intolerance at 18 years of age. Several microRNAs, including miR-212-3p, miR-30e-3p and miR-638, stratified glucose-intolerant women from NGT at childhood. Our results suggest that circulating microRNAs, longitudinally assessed over 17 years of life, are dynamic biomarkers associated with and predictive of pre-diabetes at 18 years of age. Validation of these findings in males and remaining participants from the PMNS birth cohort will provide a unique opportunity to study novel epigenetic mechanisms in the life-course progression of glucose intolerance and enhance current clinical risk prediction of pre-diabetes and progression to type 2 diabetes.

Two thirds of all deaths in the world are due to non-communicable diseases (NCDs), and 80% of NCD deaths occur in low- and middle-income countries. Cardiovascular diseases, obesity and type 2 diabetes (T2D) are the major contributors to the global burden of NCDs. Studies in the life course evolution of these chronic diseases have highlighted an etiological role for factors which govern intrauterine and post-natal growth. Research in this field could off er a novel solution to the “primordial” prevention of conditions which are the most prominent killers in today’s world. These novel ideas arose from a series of studies by David Barker and his colleagues in the UK. They proposed that intrauterine undernutrition initiated a number of adaptations in the fetus which increased disease susceptibility in later life, especially when post-natal nutrition tended to be “excessive”. A developing fetus has the ability to grow in different ways depending on the surrounding (intrauterine) environment; this ability is called the “plasticity”. An unfavorable environment restricts the ability of the fetus to grow “wildly” and causes a permanent structural or functional change, known as “programming”. India is the world’s capital of low birth weight (lBW) babies, while at the same time it is evolving into one of the economic powers of the world. It was clear that research in India would shed important light on these new and exciting ideas.

Exciting research has happened in Pune since the publication in 2011 of our review on the role of maternal micronutrients in intrauterine programming of non-communicable diseases. We have completed a preconceptional micronutrient intervention in adolescents with the aim of improving the health of their offspring. This randomized controlled trial was based on our findings in the Pune Maternal Nutrition Study, and is called the Pune Rural Intervention in Young Adolescents (PRIYA) study. Interventions included: (1) vitamin B12 alone; (2) vitamin B12 with multi-micronutrients and milk powder; and (3) placebo. The vitamin B12 dose was 2 μg/day, to make it relevant in terms of physiology and public health. All groups received iron and folic acid as per the Indian national policy. A total of 557 adolescents (17 years of age, 291 boys and 266 girls) were enrolled; those with very low vitamin B12 levels were excluded and treated. Participants were carefully followed up to record marriages and pregnancies, and deliveries were attended to study neonatal outcomes. Very few of the boys married; by contrast, 182 of the girls married and 149 of them delivered a live child during the trial.

Hidden hunger is widespread in India. Individual dietary diversity score (IDDS) is a measure of the nutrient adequacy of the diet. The FAO has set guidelines for the measurement of dietary diversity: the IDDS and the minimum dietary diversity score for women (MDD-W) to assess nutritional deficiency, but validation against nutritional biomarkers is required. Using available data among rural youth (17 years) from the Pune Maternal Nutrition Study, the validity of DDS was assessed to measure deficiencies of vitamin B12, folate and Hb. Of the 355 boys and 305 girls, 19 % were classified as underweight, 57 % as vitamin B12 deficient (12 deficiency had a higher likelihood of an IDDS ≤ 4 (1·89; 95 % CI 1·24, 2·87) or an MDD-W ≤ 5 (1·40; 95 % CI 1·02, 1·94). Youth with anaemia were more likely to have an IDDS ≤ 4 (1·76; 95 % CI 1·01, 3·14) adjusted for socio-economic scores, BMI, energy intake and sex. Folate deficiency was low (3 %) and was not associated with either score. Youth with lowest plasma vitamin B12 and Hb infrequently or never consumed dairy products/non-vegetarian foods. These rural Indian youth were underweight, had low DDS and consumed foods low in good-quality proteins and micronutrients. Associations of DDS with circulating micronutrients indicate that DDS is a valid measure to predict vitamin B12 deficiency and anaemia.

Context Imbalances in maternal 1-carbon nutrients (vitamin B12, folate) have been shown to be associated with higher offspring cardiometabolic risk markers in India. Objective We examined the hypothesis that low plasma vitamin B12 (B12) and high folate and homocysteine concentrations in the mother are associated with higher hypothalamic–pituitary–adrenal axis (cortisol) and cardiovascular responses during the Trier Social Stress Test for Children (TSST-C) in an Indian birth cohort. Methods Adolescents (n = 264; mean age: 13.6 years), whose mothers’ plasma B12, folate and total homocysteine concentrations had been measured during pregnancy, completed 5-minutes each of public speaking and mental arithmetic tasks in front of 2 unfamiliar “judges” (TSST-C). Baseline and poststress salivary cortisol concentrations were measured. Heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the TSST-C using a finger cuff; beat-to-beat values were averaged for these periods, respectively. Results Maternal low B12 status (plasma B12 < 150 pmol/L) was associated with greater cortisol responses to stress in the offspring (P < .001). Higher homocysteine concentrations were associated with greater offspring heart rate response (P < .001). After adjustment for multiple comparisons, there were nonsignificant associations between higher maternal folate concentrations and offspring total peripheral resistance response (P = .01). Conclusion Our findings suggest that maternal 1-carbon nutritional status may have long-term programming implications for offspring neuroendocrine stress responses.

Background We here report the demographic and clinical profile of the patients enrolled in the Indian Council of Medical Research funded Registry of people with diabetes in India with young age at onset (YDR) from 1 January 2000 to 31 July 2011. Methods The YDR registry recruits all diabetes cases (newly diagnosed or treated) reporting on or after 1 January 2000 with age of diagnosis ≤25 years, and residing within the assigned geographical area of the reporting centres. A baseline proforma was used to obtain information on demographic and clinical details at registration. Results The registry has enrolled 5546 patients (49.5% male; 50.5% female) with youth onset diabetes from 205 reporting centres linked to 8 regional collaborating centres (RCC) across India. T1DM (63.9%; n = 3545) and T2DM (25.3%; n = 1401) were the commonest variants of youth onset diabetes, though their relative proportion varied across RCCs. The mean (SD) age at diagnosis for T1DM was 12.9 (6.5) years, while that for T2DM was 21.7 (3.7) years. Nearly half the T1DM patients were registered within 6 months of the onset of disease. Most cases of T2DM (47.3%) were registered after 3 years from their date of diagnosis. 56.1% of patients had at least one episode of hospitalization at registration. Conclusion The observations from YDR registry indicate the need to establish a surveillance system in India to monitor diabetes in youth, not only to understand its complex etiology and natural history but also due to its detrimental socio economic impact.

Neurocognitive development is a dynamic process over the life course and is influenced by intrauterine factors as well as later life environment. Using data from the Pune Maternal Nutrition Study (PMNS) from 1994 to 2008, we investigate the association of in-utero, birth, and childhood conditions with offspring neurocognitive development in 686 participants of the cohort, at age 12 years. The life course exposure variables in the analysis include maternal pre-pregnancy size and nutrition during pregnancy, offspring birth measurements, nutrition and physical growth at age 12 years along with parental education and socio-economic status. We used the novel Bayesian Model Averaging (BMA) approach; which has been shown to have better predictive performance over traditional tests of associations. Our study employs 8 standard neurocognitive tests that measure intelligence, working memory, visuo-conceptual and verbal learning, and decision-making/attention at 12 years of age. We control for nutritional-metabolic information based on blood measurements from the pregnant mothers and the children at 12 years of age. Our findings highlight the critical role of parental education and socioeconomic background in determining child neurocognitive performance. Maternal characteristics (pre-pregnancy BMI, fasting insulin during pregnancy) and child height at 12 years were also robust predictors on the BMA. A range of early factors – such as maternal folate and ferritin concentrations during pregnancy, and child’s head circumference at birth – remained important determinants of some dimensions of child’s neurocognitive development, but their associations were not robust once we account for model uncertainty. Our results suggest that intrauterine influences on long term neurocognitive outcomes may be potentially reversible by post birth remediation. In addition to the current nutritional interventions, public health policy should also consider social interventions in children born into families with low socio-economic status to improve human capital.

Size at birth is known to be influenced by various fetal and maternal factors including genetic effects. South Asians have a high burden of low birthweight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic score (fGS) and maternal genetic score (mGS) from 196 birthweight-associated variants identified in Europeans and conducted association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6 years’ intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from above cohorts were compared with South Asians in UK BioBank and The Exeter Family Study of Childhood Health, a European ancestry cohort. Birthweight increased by 50.7g and 33.6g per standard deviation of fGS (p = 9.1x10-11) and mGS (p = 0.003) respectively in South Asians. A relatively weaker maternal genetic score effect compared to Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birthweight was strongly associated with body size in both childhood and adolescence (p = 3x10-5 - 1.9x10-51), however, fetal genetic score was associated with body size in childhood only (p < 0.01) and with head circumference, fasting glucose and triglycerides in adults (p < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birthweight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism partly explaining associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians.

Objectives: By convention, women's early marriage is considered a sociocultural decision sensitive to factors acting during adolescence such as poverty, early menarche, and less education. Few studies have examined broader risk factors in the natal household prior to marriage. We investigated whether biosocial markers of parental investment through the daughters' life-course were associated with early marriage risk in rural India. We used an evolutionary perspective to interpret our findings. / Materials and Methods: A prospective cohort recruited mothers at preconception. Children were followed from birth to age 21 years. Multivariable logistic regression models estimated odds ratios of marrying early (

Five subgroups were described in European diabetes patients using a data driven machine learning approach on commonly measured variables. We aimed to test the applicability of this phenotyping in Indian individuals with young-onset type 2 diabetes.We applied the European-derived centroids to Indian individuals with type 2 diabetes diagnosed before 45 years of age from the WellGen cohort (n = 1612). We also applied de novo k-means clustering to the WellGen cohort to validate the subgroups. We then compared clinical and metabolic-endocrine characteristics and the complication rates between the subgroups. We also compared characteristics of the WellGen subgroups with those of two young European cohorts, ANDIS (n = 962) and DIREVA (n = 420). Subgroups were also assessed in two other Indian cohorts, Ahmedabad (n = 187) and PHENOEINDY-2 (n = 205).Both Indian and European young-onset type 2 diabetes patients were predominantly classified into severe insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severe insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to findings in Europeans (Swedish 26% vs 68%, Finnish 24% vs 71%, respectively). A higher proportion of SIDD compared with MOD was also seen in Ahmedabad (57% vs 33%) and in PHENOEINDY-2 (67% vs 23%). Both in Indians and Europeans, the SIDD subgroup was characterised by insulin deficiency and hyperglycaemia, MOD by obesity, SIRD by severe insulin resistance and MARD by mild metabolic-endocrine disturbances. In WellGen, nephropathy and retinopathy were more prevalent in SIDD compared with MOD while the latter had higher prevalence of neuropathy.Our data identified insulin deficiency as the major driver of type 2 diabetes in young Indians, unlike in young European individuals in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in type 2 diabetes in the young Indian population and suggest a need to review management strategies.

ObjectiveHuman traits are heritable, and some of these including metabolic and lipid phenotypes show preferential parental transmissions, or parent-of-origin effects. These have been mostly studied in populations comprising adults. We aimed to investigate heritability and parent-of-origin effects on cardiometabolic and anthropometric traits in a birth-cohort with serial measurements to assess if these effects manifested at an early age.Research design and methodsWe investigated heritability and parent-of-origin effects on cardiometabolic and anthropometric traits in the Pune Maternal Nutrition Study (PMNS) wherein offspring and parents were studied from birth and followed-up for 18 years. Heritability was estimated by calculating association between mid-parental phenotypes and offspring. Maternal and paternal effects on offspring phenotype were modelled by regression after adjusting for age, sex and BMI. Parent-of-origin effects were calculated by the difference between maternal and paternal effects.ResultsAnthropomorphic traits and cardiometabolic traits were robustly heritable. Parent-of-origin effects were observed for glycemic traits at both 6- and 12-years, with a paternal effect at 6-years which transitioned to a maternal effect at 12-years. For insulin and HOMA-S, a negative maternal effect transitioned to a positive one at 12-years. For HOMA-B, a paternal effect at 6-years transitioned to a maternal one at 12-years. Lipid traits consistently showed stronger maternal influence while anthropometric traits did not show any parental biases.ConclusionsOur study highlights that parental programming of cardiometabolic traits is evident from early childhood and can transition during puberty. Further studies are needed to determine the mechanisms of underlying such effects.

OBJECTIVE India is a double world capital of early-life undernutrition and type 2 diabetes. We aimed to characterize life course growth and metabolic trajectories in those developing glucose intolerance as young adults in the Pune Maternal Nutrition Study (PMNS). RESEARCH DESIGN AND METHODS PMNS is a community-based intergenerational birth cohort established in 1993, with serial information on parents and children through pregnancy, childhood, and adolescence. We compared normal glucose-tolerant and glucose-intolerant participants for serial growth, estimates of insulin sensitivity and secretion (HOMA and dynamic indices), and β-cell compensation accounting for prevailing insulin sensitivity. RESULTS At 18 years (N = 619), 37% of men and 20% of women were glucose intolerant (prediabetes n = 184; diabetes n = 1) despite 48% being underweight (BMI CONCLUSIONS Inadequate compensatory insulin secretory response to decreasing insulin sensitivity in early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia from childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally.

BackgroundNutritional interventions during the first 1000 days of life improves lifelong health. Better pre-conceptional maternal nutrition improves the nutrition of the early embryo. Vitamins B12 and folate are important for fetal neural development. Vitamin B12 deficiency is common in India.MethodsIn the Pune Rural Intervention in Young Adolescents (PRIYA) adolescents (N=557, 226 females) were provided with vitamin B12 (2µg/day) with or without multiple micronutrients, or a placebo, from preconception until delivery. All groups received mandatory iron and folic acid. We used the Bayley’s Scale of Infant Development (BSID-III) at 24-42 months of age to investigate effects on offspring neurodevelopment. We examined cord blood concentrations of brain-derived neurotropic factor (BDNF).ResultsParticipants in the three groups had similar baseline B12 levels. These improved in the B12 supplemented groups at pre-conceptional and pregnancy (28 weeks gestation) measurements, reflected in higher cord holo-TC levels compared to the placebo. Neurodevelopmental outcomes are available for 74 children. Offspring in the B12 alone group (n=21) performed better than the placebo (n=27) on cognition (p=0.044) and language (p=0.020) domains (adjusted for maternal baseline B12 levels). There were no differences between the B12+MMN (n=26) and placebo group. Cord blood BDNF levels were highest in the B12 alone group (not statistically significant).ConclusionPre-conceptional vitamin B12 supplementation improved maternal B12 status and offspring neurodevelopment at 2 years of age. The usefulness of cord BDNF as a marker of brain development needs further investigation. Our results highlight the importance of intervening in the pre-conceptional period.

IntroductionThe Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that intrauterine and early life exposures significantly influence fetal development and risk for disease in later life. Evidence from prospective birth cohorts suggests a role for maternal B12 and folate in influencing neurocognitive outcomes in the offspring. In the Indian setting, B12 deficiency is common during the pregnancy while rates of folate deficiency are lower. The long-term influences of maternal nutrition during the pregnancy on adult neurocognitive outcomes have not been examined. The Pune Maternal Nutrition Study (PMNS) is a preconceptional birth cohort into its 24th year and is considered a unique resource to study the DOHaD hypothesis. We found an association between maternal B12 status in pregnancy and child’s neurocognitive status at 9 years of age. We now plan to assess neurocognitive function and MRI measurements of brain structural–functional connectivity at young adult age to study its association with maternal nutritional exposures during the pregnancy.Methods and analysisAs part of ongoing prospective follow-up in young adults of the PMNS at the Diabetes Unit, KEM Hospital Research Center, Pune India, the following measurements will be done: neurocognitive performance (Standardised Tests of Intelligence, Verbal and Visual Memory, Attention and Executive Functions), temperament (Adult Temperament Questionnaire), psychopathology (Brief Symptom Inventory and Clinical Interview on Mini Neuropsychiatric Interview 7.0). Brain MRI for structural T1, resting-state functional connectivity and diffusion tensor imaging will be performed on a subset of the cohort (selected based on exposure to a lower or higher maternal B12 status at 18 weeks of pregnancy).Ethics and disseminationThe study is approved by Institutional ethics committee of KEM Hospital Research Center, Pune. The results will be shared at national and international scientific conferences and published in peer-reviewed scientific journals.Trial registration numberNCT03096028

In The Pune Maternal Nutrition Study, vitamin B12 deficiency was seen in 65% of pregnant women, folate deficiency was rare. Maternal total homocysteine concentrations were inversely associated with offspring birthweight, and low vitamin B12 and high folate concentrations predicted higher offspring adiposity and insulin resistance. These findings guided a nested pre-conceptional randomized controlled trial ‘Pune Rural Intervention in Young Adolescents (PRIYA)’. The interventions included: 1) vitamin B12+multi-micronutrients the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) and proteins (B12+MMN), 2) vitamin B12 (B12 alone), and 3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference. Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex vitamins in the synthesis of nucleotides and S-Adenosyl Methionine, and the roles of vitamins A and D on gene expression, we propose that the multi-micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.

‘Thrifty phenotype’ hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.Anthropometric data was available on 7–34 year-old twins (n=209, 97 males) and singletons (n=182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birth weight (2420 vs 3100 g, pAfrican populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socioeconomic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.

OBJECTIVES: Background: The FUT2 gene is responsible for the secretion of ABO blood type antigens into the body fluids (saliva, mucous, urine, tears, breast milk, sweat, and semen). Those who secrete the antigens into body fluids are call secretors, those who do not are called non-secretors. Hypothesis: GWAS studies have reported FUT gene variants to be associated with circulating vitamin-B12 (Vit-B12) concentrations. Missense mutations in the FUT2 gene result in a non-secretor phenotype. Thus, the secretory status of an individual may affect circulating vitamin-B12 concentrations over and above the genotype. METHODS: Materials and Methods: We included 780 participants (271 children, 282 mothers, and 227 fathers) from Pune Maternal Nutrition Study (PMNS). We measured the secretor status of individuals in saliva by hemagglutination test. A total of eight genetic variants including six SNPs from the FUT2 gene (rs492602, rs681343, rs281377, rs601338, rs1800027, and rs602662) and two SNPs from the FUT6 gene (rs3760776 and rs3760775) from our previous GWAS study were correlated with circulating vitamin-B12 levels. We tested the associations of FUT gene variants with secretor status phenotype and of the secretor phenotype with circulating vit-B12, folate, and ferritin concentrations in addition to H.pylori antibody levels. RESULTS: Results and Discussion: We found 33% of participants were non-secretors compared to 20% reported in Western Caucasian populations. Non-secretors had higher vitamin-B12 concentrations but not of folate and ferritin, vitamin-B12 associations were over and above FUT genotypes. Non-secretors showed a higher response to Vit-B12 supplementation. We found a FUT2 haplotype () to be strongly associated with Vit-B12 concentrations and non-secretor status. Non-secretors had lower H.pylori antibody concentrations. FUT6 genotype and haplotype were associated with Vit-B12 concentrations but not with secretor status and H.pylori antibody levels. CONCLUSIONS: Our data suggest that secretor status may influence Vit-B12 concentrations through susceptibility to H.pylori infection and possibly other gut microbiota. A higher frequency of non-secretors in Indians could offer a selective advantage against Vit-B12 deficiency. FUNDING SOURCES: BBSRC, UK; MRC, UK; WELLCOME TRUST, UK; DBT, India; ICMR India

Background: Decrease in insulin sensitivity in late gestation is thought to promote fetal growth in humans. Methods: Cohorts with serial glucose and insulin measurements during pregnancy were included in this study. These include two Indian (n=248), a Mexican (n=115), two European (n=326) and an American (n=32) cohort. HOMA-S was correlated with neonatal weight. Results: Indian mothers were short & thin (153.7 cm, 48.8 kg and 20.2 kg/m2) and gained 5.9 kg between first and third trimesters, babies were 2720g. Mexican mothers were short (156cm, 63 kg and BMI 25.1kg/m2) and gained 7.5 kg, babies were 2955g. European mothers were tall and obese (168.0 cm, 95.5 kg and 33.7 kg/m2), gained 7.4 kg and babies were 3640g. In Indian mothers, FPG progressively decreased with increasing gestation with a small (15%) increase in insulin concentrations, HOMA-S remained stable. In Mexican and European mothers FPG remained stable, insulin increased (>50%) and HOMA-S decreased (>30%). American mothers showed the classic increase in HOMA-S in early pregnancy and a fall in late gestation (Figure 1). In Indian and Mexican mothers HOMA-S was not associated with offspring birth weight while in European cohorts, it was inversely associated. Conclusion: Chronic maternal undernutrition (stunting) and failure to reduce insulin sensitivity in late gestation may contribute to poor fetal growth in India and Mexico. Mechanistic studies are warranted. Disclosure S. Deshpande-joshi: None. O. Perichart-perera: Other Relationship; Self; IFA CELTICS, Nestle. M. Van poppel: None. C. A. Vinter: None. D. M. Jensen: None. G. Desoye: None. P. Catalano: None. C. S. Yajnik: None. H. Damle: None. M. K. Deshmukh: None. D. Bhat: None. N. S. Memane: None. A. A. Bhalerao: None. R. Ladkat: None. P. Tiwari: None. S. R. Otiv: None.

Background: Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature. Objectives: The consortium will investigate the effects of preconception exposures on four sets of outcomes: (1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes. Population: A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation. Design: The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages. Methods: Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors. Preliminary results: Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data. Conclusions: The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.

The Developmental Origins of Health and Disease (DOHaD) paradigm posits that a mismatch between circumstances at or around conception and in later life leads to metabolic dysregulation and the development of obesity and diabetes. In this review we highlight three strands of evidence: prospective studies of patterns of growth from birth to adulthood, historical studies of exposure to famine at defined points during gestation and early life, and nutrition intervention studies. We conclude that, while much is still unknown, it is becoming clearer that the combination of early-life undernutrition and later development of obesity is associated with increased risk of diabetes. There is a need to support public health programmes aimed at intergenerational (primordial) prevention of diabetes and other non-communicable disease.

Type 2 diabetes has rapidly developed into a major public health problem in south Asia (defined here as Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka) in recent decades. During this period, major lifestyle changes associated with economic transition, industrialisation, urbanisation, and globalisation have been key determinants in the increasing burden of non-communicable diseases. A decline in nutrition quality, reduced physical activity, and increased sedentary behaviours are reflected in the increasing prevalence of type 2 diabetes and related risk factors in the region. The International Diabetes Federation 2017 estimates of the prevalence of diabetes in adults in the region range from 4·0% in Nepal to 8·8% in India. The prevalence of overweight ranges from 16·7% in Nepal to 26·1% in Sri Lanka, and the prevalence of obesity ranges from 2·9% in Nepal to 6·8% in Sri Lanka. An increasing proportion of children, adolescents, and women are overweight or obese, leading to a heightened risk of type 2 diabetes. Ethnic south Asians present with greater metabolic risk at lower levels of BMI compared with other ethnic groups (referred to as the south Asian phenotype), with type 2 diabetes often developing at a younger age, and with rapid progression of diabetic complications. Because of the presence of multiple risk factors and a body composition conducive to the development of type 2 diabetes, south Asians should be aggressively targeted for prevention. In this Series paper, we detail trends in the prevalence of diabetes in the region and address major determinants of the disease in the context of nutrition and physical activity transitions and the south Asian phenotype.

AimsMaternal diabetes in pregnancy increases offspring obesity and diabetes risk. We investigated body size and composition, and glucose tolerance in offspring born to Indian diabetic mothers (ODM) and to non-diabetic mothers (ONDM), and studied maternal and paternal determinants.MethodsWe compared the physical characteristics, body composition (Dual energy X-ray Absorptiometry) and glycemia of ODMs and matched ONDMs. Overweight-obesity was defined using International Obesity Task Force (IOTF) for 2-18 years (cutoff of BMI > 25 kg/m2) and World Health Oraganization (WHO) criteria for >18 years (BMI > 25 kg/m2). Glycemic measures included capillary blood glucose measurement in children =10 years. We calculated separate SD scores for capillary fasting, capillary random and venous fasting plasma glucose. Those above median SD score were classified as glucose intolerant. We evaluated insulin sensitivity (Homeostatic Model Assessment HOMA-S and Matsuda index), beta cell function (HOMA-β and insulinogenic index) and β-cell compensatory response (Disposition Index: [Log (Insulinogenic index) + Log (Matsuda index)]). We studied the association of maternal and paternal body size and glycemia with outcomes in the child.ResultsWe studied 200 ODMs of 176 diabetic mothers (133 GDM, 21 type 2 diabetes, 22 type 1 diabetes), and 177 ONDMs at an average of 9.7 years after delivery. ODMs were heavier, more adipose and more glucose intolerant than ONDMs. Differences for body size parameters were more prominent in males and they also had a wider spectrum of metabolic abnormalities. Three (4%) ODM were receiving treatment for diabetes (diagnosed between 10-25 years of age). On OGTT, the older ODMs (>= 10 years) had higher prevalence of glucose intolerance (1 DM, 14 IFG, 12 IGT and 4 both IFG and IGT) compared to ONDM, (0 DM, 7 IFG, 9 IGT and 1 both IFG and IGT). None of the diabetic and pre-diabetic ODMs, including children of type 1 diabetic mothers, were positive for circulating GAD or ZnT8 antibodies.Younger ODMs (Type 2 diabetic and GDM mothers were heavier compared to type 1 diabetic mothers, and their children were more likely to be overweight-obese. Children of type 1 diabetic mothers were glucose intolerant despite lack of overweight-obesity. In addition, fathers had an independent influence on the child’s phenotype, especially for overweight-obesity. Maternal hyperglycemia during pregnancy had an overriding influence on offspring glucose intolerance.ConclusionsODMs were more overweight-obese and glucose intolerant compared to ONDMs. We propose that these two outcomes in the ODMs are independently programmed by respective parental phenotypes. Preventive strategies will need to be informed by these findings. Studies of genetic and epigenetic mechanisms involved in fetal programming of body size and glycemia will further help our understanding.Research in ContextWhat is already known about this subject?India has experienced a rapid escalation of diabetes in young individuals including diabetes in pregnancy. Short-term effects of maternal hyperglycemia on the offspring are well known.What is the key question?There is little data on long-term effects of maternal hyperglycemia on offspring body size and cardiometabolic risk factors. We compared these in the offspring of diabetic mothers compared to those of non-diabetic mothers. We also sought differences within types of diabetes (type 1, type 2, GDM) and studied paternal determinants of these outcomes.What are the new findings?Type 1 diabetic mothers were thinnest and most hyperglycemic; type 2 diabetic mothers were most overweight-obese, GDM mothers were intermediate. Gestational maternal hyperglycemia was the overriding determinant of offspring hyperglycemia. Maternal hyperglycemia predicted offspring glucose intolerance but not overweight obesity; maternal overweight-obesity predicted offspring overweight-obesity but not hyperglycemia, suggesting an uncoupling of these phenotypes often considered congruent. Fathers had an additive influence on offspring size.How might this impact on clinical practice in the foreseeable future?Knowing the relative independence of influences on body size and metabolic outcomes will inform strategies of their primordial and primary prevention. Establishing genetic and epigenetic mechanisms will help.

Aim/HypothesisFive subgroups were described in European diabetes patients using a data driven machine learning approach on commonly measured variables. We aimed to test the applicability of this phenotyping in Indian young-onset type 2 diabetes patients.MethodsWe applied the European derived centroids to the Indian type 2 diabetes patients diagnosed before 45 years of age from the WellGen (n = 1612) cohort. We also applied de novo k-means clustering to the WellGen cohort to validate the subgroups. We then compared clinical and metabolic-endocrine characteristics and the complication rates between the subgroups. We also compared characteristics of the WellGen subgroups with those of two young European cohorts ANDIS (n= 962) and DIREVA (n=420). Subgroups were also assessed in two other Indian cohorts, Ahmedabad (n = 187) and PHENOEINDY-2 (n = 205).ResultsBoth Indian and European young type 2 diabetes patients were predominantly classified into severely insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severely insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to figures in Europeans (Swedish: 26% vs 68%, Finnish: 24% vs 71% respectively). A higher proportion of SIDD compared to MOD was also seen in Ahmedabad (57% vs 33%) and in PHENOEINDY-2 (67% vs 23%). Both in Indians and Europeans, the SIDD subgroup was characterized by insulin deficiency and hyperglycemia, MOD by obesity, SIRD by severe insulin resistance and MARD by mild metabolic-endocrine disturbances. In WellGen, nephropathy and retinopathy were more prevalent in SIDD compared to MOD while the latter had higher prevalence of neuropathy.Conclusions /InterpretationOur data identified insulin deficiency as the major driver of type 2 diabetes in young Indians, unlike in young European patients in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in young Indian type 2 diabetes, and suggest a need to review management strategies.

We recently reported genetic variants associated with birth weight and their effect on future cardiometabolic risk in Europeans. Despite a higher burden of low birth weight and cardiometabolic disorders, such studies are lacking in South Asians. We generated fetal and maternal genetic scores (fGS and mGS) from 196 birth weight-associated variants identified in Europeans and conducted association analysis with various birth measures and serially measured anthropometric and cardiometabolic traits from seven Indian and Bangladeshi cohorts. Although fGS and mGS were comparable to Europeans, birth weight was substantially smaller suggesting strong environmental constraints on fetal growth in South Asians. Birth weight increased by 50.7g and 33.6g per standard deviation fGS (P=9.1×10−11) and mGS (P=0.003) in South Asians. The fGS was further associated with childhood body size and head circumference, fasting glucose, and triglycerides in adults (P

BackgroundVitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy.MethodsA systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsOf the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT’s -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT’s) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring.ConclusionIn the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia.Systematic Review Registration[website], identifier [registration number]

BACKGROUND Gestational diabetes mellitus (GDM) can adversely affect the health of the developing foetus. Women of South Asian origin are particularly at risk of developing GDM. Insulin resistance (IR) contributes to the aetiology of GDM, and whilst studies have shown associations of vitamin B12 (B12) and folate status with GDM and IR, only a limited number of B12 and folate markers have been used. OBJECTIVE To use a comprehensive panel of B12 and folate markers to examine their association with IR in pregnant women with diet-controlled GDM and normal glucose tolerance (NGT). METHODS In this cross-sectional study, 59 British-Bangladeshi women (24 GDM and 35 NGT) with a mean age 29 years, BMI 26.7 kg/m2 and gestational age 33 weeks were recruited. Serum total B12, holotranscobalamin, folate, methylmalonic acid, plasma homocysteine and 5-methyltetrahydrofolate, and red cell folate (RCF) were measured along with other parameters. Independent sample t-test and chi-squared test were used to assess differences in markers between GDM and NGT women. Spearman's test was used to look for correlations. A simple multiple regression analysis was used to investigate if markers of B12 and folate status predicted IR, using the homeostatic model assessment of insulin resistance (HOMA-IR), adjusting for age, GDM status and BMI. RESULTS There were no differences in concentrations of B12 and folate markers between GDM and NGT women. In Spearman's analysis HOMA-IR correlated negatively with total serum B12 (P

We recently reported genetic variants associated with birth weight and their effect on future cardiometabolic risk in Europeans. Despite a higher burden of low birth weight and cardiometabolic disorders, such studies are lacking in South Asians. We generated fetal and maternal genetic scores (fGS and mGS) from 196 birth weight-associated variants identified in Europeans and conducted association analysis with various birth measures and serially measured anthropometric and cardiometabolic traits from seven Indian and Bangladeshi cohorts. Although fGS and mGS were comparable to Europeans, birth weight was substantially smaller suggesting strong environmental constraints on fetal growth in South Asians. Birth weight increased by 50.7g and 33.6g per standard deviation fGS (P=9.1x10-11) and mGS (P=0.003) in South Asians. The fGS was further associated with childhood body size and head circumference, fasting glucose, and triglycerides in adults (P

Maternal nutrient availability and its transport through the placenta are crucial for fetal development. Nutrients are transported to the fetus via specific transporters present on the microvillous (MVM) and basal membrane (BM) of the placenta. Glucose is the most abundant nutrient transferred to the fetus and plays a key role in the fetal growth and development. The transfer of glucose across the human placenta is directly proportional to maternal glucose concentrations, and is mediated by glucose transporter family proteins (GLUTs). Maternal glucose concentration influences expression and activity of GLUTs in the MVM (glucose uptake) and BM (glucose delivery). Alteration in the number and function of these transporters may affect the growth and body composition of the fetus. The thin-fat phenotype of the Indian baby (low ponderal index, high adiposity) is proposed as a harbinger of future metabolic risk. We propose that placental function mediated through nutrient transporters contributes to the phenotype of the baby, specifically that glucose transporters will influence neonatal fat. This review discusses the role of various glucose transporters in the placenta in determining fetal growth and body composition, in light of the above hypothesis.