How do we improve adolescent diet and physical activity in India and sub-Saharan Africa? Findings from the Transforming Adolescent Lives through Nutrition (TALENT) consortium.

OBJECTIVE: Adolescent diet, physical activity and nutritional status are generally known to be sub-optimal. This is an introduction to a special issue of papers devoted to exploring factors affecting diet and physical activity in adolescents, including food insecure and vulnerable groups. SETTING: Eight settings including urban, peri-urban and rural across sites from five different low- and middle-income countries. DESIGN: Focus groups with adolescents and caregivers carried out by trained researchers. RESULTS: Our results show that adolescents, even in poor settings, know about healthy diet and lifestyles. They want to have energy, feel happy, look good and live longer, but their desire for autonomy, a need to 'belong' in their peer group, plus vulnerability to marketing exploiting their aspirations, leads them to make unhealthy choices. They describe significant gender, culture and context-specific barriers. For example, urban adolescents had easy access to energy dense, unhealthy foods bought outside the home, whereas junk foods were only beginning to permeate rural sites. Among adolescents in Indian sites, pressure to excel in exams meant that academic studies were squeezing out physical activity time. CONCLUSIONS: Interventions to improve adolescents' diets and physical activity levels must therefore address structural and environmental issues and influences in their homes and schools, since it is clear that their food and activity choices are the product of an interacting complex of factors. In the next phase of work, the Transforming Adolescent Lives through Nutrition consortium will employ groups of adolescents, caregivers and local stakeholders in each site to develop interventions to improve adolescent nutritional status.

Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

Comparing BMI with skinfolds to estimate age at adiposity rebound and its associations with cardio-metabolic risk markers in adolescence.

BACKGROUND: Body mass index (BMI) reaches a nadir in mid-childhood, known as the adiposity rebound (AR). Earlier AR is associated with a higher risk of cardio-vascular diseases in later life. Skinfolds, which are a more direct measure of adiposity, may give better insight into the relationship between childhood adiposity and later obesity and cardio-metabolic risk. OBJECTIVE: We aimed to assess whether AR corresponds to a rebound in skinfolds, and compare associations of BMI-derived AR and skinfold-derived AR with cardio-metabolic risk markers in adolescence. METHODS: We used penalised splines with random coefficients to estimate BMI and skinfold trajectories of 604 children from the Mysore Parthenon Birth Cohort. Age at AR was identified using differentiation of the BMI and skinfold growth curves between 2 and 10 years of age. At 13.5 years, we measured blood pressure, and glucose, insulin and lipid concentrations. RESULTS: BMI and skinfolds had different growth patterns. Boys reached BMI-derived AR earlier than skinfold-derived AR (estimated difference: 0.41 years; 95% CI:[0.23, 0.56]), whereas the opposite was observed in girls (estimated difference: -0.71 years; 95% CI:[-0.90, -0.54]). At 13.5 years, children with earlier BMI-derived AR had higher BMI (-0.58 SD per SD increase of AR; 95%CI:[-0.65, -0.52]), fat mass (-0.44; 95%CI:[-0.50, -0.37]), insulin resistance (HOMA-IR: -0.20; 95%CI:[-0.28, -0.12]) and systolic blood pressure (-0.20; 95%CI:[-0.28, -0.11]), and lower HDL-cholesterol (0.12; 95%CI:[0.04, 0.21]). The associations were independent of BMI at time of rebound, but were fully explained by fat mass at 13.5 years. Similar associations were found for skinfold-derived AR. CONCLUSION: BMI-derived adiposity rebound predicts later cardio-metabolic risk markers similarly to that derived from skinfolds, a direct measure of adiposity.

Size at birth, morning cortisol and cardiometabolic risk markers in healthy Indian children.

OBJECTIVE: Prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis may link reduced foetal growth with higher adult chronic disease risk. South Asians have a high prevalence of low birth weight and a thin-fat phenotype, which is associated with subsequent type 2 diabetes and the metabolic syndrome. Altered HPA activity could be one of the pathological processes underlying this link. METHODS: Plasma morning cortisol and corticosteroid-binding globulin (CBG) concentrations were determined in 528 children aged 9·5 years from a prospective birth cohort in India. They had detailed anthropometry at birth, and current measurements of anthropometry, plasma glucose, insulin and lipid concentrations and blood pressure. Insulin resistance (Homeostasis Model Assessment) and insulin secretion (the 30-min insulin increment) were also assessed. RESULTS: None of the birth measurements were associated with cortisol concentrations, but both birth weight (P = 0·03) and length (P = 0·004) were inversely associated with CBG concentrations. Cortisol concentrations were inversely associated with current body mass index (P = 0·02), and positively associated with glucose (fasting: P < 0·001; 30-min: P = 0·002) concentrations, and systolic blood pressure (P = 0·005), but not insulin resistance or the insulin increment. CONCLUSION: Higher morning cortisol is associated with higher cardiometabolic risk markers in Indian children. Although cortisol concentrations did not appear to be related to birth size, small size at birth was associated with higher CBG levels, and may be one of the processes by which foetal undernutrition affects adult health. The findings suggest a need for dynamic testing of HPA axis activity (such as measuring stress responses).

Uptake pattern of training programs over two decades at an International Ophthalmic Training Institute in India.

Purpose: Inadequacy of trained human resources is a critical challenge for eye-care delivery worldwide. Recognizing this, the World Health Organization (WHO) and the International Agency for Prevention of Blindness had identified the development of human resources as one of the focal areas in the global initiative "Vision 2020: The Right to Sight." The global action plan of the WHO also emphasized the need for trained workforce for ensuring comprehensive eye-care services. We aimed to present the uptake pattern of training programs offered at a high-volume training institute in India. Methods: We did a retrospective analysis of data related to training programs conducted between 2000 and 2019. Trainees included ophthalmologists, allied ophthalmic personnel, and eye-care management professionals from all over the world. We analyzed the overall growth over the 20 years in the WHO regions. The uptake patterns were also analyzed across four segments of 5-year-periods by the type of training. Results: Overall, 9091 trainees from 118 countries attended training in over 40 courses that included long- and short-term clinical training for ophthalmologists (54.2%) and short-term training for eye-care managers (29.5%), allied ophthalmic personnel (6.2%), and eye-care technicians (10.2%). The majority of the trainees (81.3%) came from the Southeast Asian region, of which 87.4% were from India. Most (98.3%) of the trainees belonged to developing countries. We found an overall average growth of 4.8% in the training uptake across the four 5-year segments over the 20 years. Conclusion: Comparatively better representation of trainees from the developing countries is encouraging as the prevalence of blindness and visual impairment is higher in those countries, warranting improved eye-care delivery. Given the strong influence of distance and associated costs of accessing training, the development of similar institutes in other regions might help enhance the global efforts to eliminate needless blindness.

Periconceptional diet and the risk of gestational diabetes in south Indian women: findings from the BAngalore Nutrition Gestational diabetes LiFEstyle Study (BANGLES).

BACKGROUND: Gestational diabetes can predispose two generations-a mother and her child-to a higher risk of obesity and type 2 diabetes. Culture-specific strategies to prevent gestational diabetes are required. BANGLES investigated the associations between women's periconceptional diet and gestational diabetes risk. METHODS: BANGLES was a prospective observational study (n=785), in which women of various socioeconomic status were recruited at 5-16 weeks' gestation in Bangalore, India. Periconceptional diet was recalled at recruitment, using a validated 224-item food frequency questionnaire, that was reduced to 21 food groups for the food group-gestational diabetes analysis, and 68 food groups for the principal component analysis for a diet pattern-gestational diabetes analysis. Diet-gestational diabetes associations were examined using multivariate logistic regression, adjusting for a priori confounders determined from the literature. Gestational diabetes was assessed by a 75 g oral glucose tolerance test at 24-28 weeks' gestation, applying 2013 WHO criteria. FINDINGS: Women who consumed whole-grain cereals (adjusted odds ratio [OR] 0·58, 95% CI 0·34-0·97, p=0·03); had moderate egg consumption (>1-3 times per week) compared with less than once per week (adjusted OR 0·54, 95% CI 0·34-0·86, p=0·01); and a higher weekly intake of pulses and legumes (adjusted OR 0·81, 95% CI 0·66-0·98, p=0·03), nuts and seeds (adjusted OR 0·77, 95% CI 0·63-0·94, p=0·01), and fried and fast food (adjusted OR 0·72, 95% CI 0·59-0·89, p=0·002) had a lower gestational diabetes. None of these associations was significant after correction for multiple testing. A high-diversity, urban diet pattern characterised by diverse home-cooked and processed foods and associated with older, affluent, educated, urban women was associated with a lower risk (adjusted OR 0·80, 95% CI 0·64-0·99, p=0·04). BMI was the strongest risk factor for gestational diabetes and possibly mediated the diet pattern-gestational diabetes associations. INTERPRETATION: The same food groups that were associated with a lower gestational diabetes risk were components of the high-diversity, urban diet pattern. One healthy diet pattern might not be relevant to India. Findings support global recommendations to encourage women to attain a healthy pre-pregnancy BMI, increase diet diversity to prevent gestational diabetes, and have policies to increase food affordability. FUNDING: Schlumberger Foundation.

DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)-height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children's SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC.

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.

AIMS/HYPOTHESIS: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS: All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS: The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/INTERPRETATION: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.

Glucose tolerance and insulin resistance in Indian children: relationship to infant feeding pattern.

AIMS/HYPOTHESIS: Our objective was to examine whether longer duration of breast-feeding and later introduction of complementary foods are associated with lower glucose concentrations and insulin resistance (IR-HOMA) in Indian children. METHODS: Breast-feeding duration (six categories from <3 to ≥18 months) and age at introduction of complementary foods (four categories from <4 to ≥6 months) were recorded at 1, 2 and 3 year follow-up of 568 children from a birth cohort in Mysore, India. At 5 and 9.5 years of age, 518 children were assessed for glucose tolerance and IR-HOMA. RESULTS: All the children were initially breast-fed; 90% were breast-fed for ≥6 months and 56.7% started complementary foods at or before the age of 4 months. Each category increase in breast-feeding duration was associated with lower fasting insulin concentration (ß = -0.05 pmol/l [95% CI -0.10, -0.004]; p = 0.03) and IR-HOMA (ß = -0.05 [95% CI -0.10, -0.001]; p = 0.046) at 5 years, adjusted for the child's sex, age, current BMI, socioeconomic status, parent's education, rural/urban residence, birthweight and maternal gestational diabetes status. Longer duration of breastfeeding was associated with higher 120-min glucose concentration at 5 years (ß = 0.08 mmol/l [95% CI 0.001, 0.15; p = 0.03]) but lower 120-min glucose concentration at 9.5 years (ß = -0.09 [95% CI -0.16, -0.03]; p = 0.006). Age at starting complementary foods was unrelated to the children's glucose tolerance and IR-HOMA. CONCLUSIONS/INTERPRETATION: Within this cohort, in which prolonged breast-feeding was the norm, there was evidence of a protective effect of longer duration of breast-feeding against glucose intolerance at 9.5 years. At 5 years longer duration of breast-feeding was associated with lower IR-HOMA.

Assessment of the Effect of Bone Density on Implant Stability: A Clinical Study.

BACKGROUND: In this study, we determined the effect of bone density on implant stability. METHODOLOGY: Two hundred and sixty dental implant sites in 128 patients were assessed for resonance frequency analysis (RFA) following implant insertion, at 6 months and 12 months. The implant stability quotient (ISQ) was determined. RESULTS: The mean ± standard deviation bone density in anterior mandible was 862.8 ± 203.4 Hounsfield units (HU), in posterior mandible was 528.4 ± 115.6 HU, in anterior maxilla was 594.2 ± 95.2 HU, and in posterior maxilla was 438.1 ± 110.2 HU. The mean insertion torque in successful implants was 38.2 ± 7.1 Ncm and in failed implants was 22.4 ± 4.2 Ncm. The mean RFA value in successful implants was 65.4 ± 5.8 and in failed implants was 45.8 ± 4.1 ISQ. A statistically significant (P < 0.05) difference was obtained. CONCLUSION: Within the limitation of the study, we observed that successful implants exhibited higher RFA and insertion torque and were higher into failed implants suggesting a correlation of bone quality and implant stability parameters.

What stresses adolescents? A qualitative study on perceptions of stress, stressors and coping mechanisms among urban adolescents in India.

Background: In India, stress levels are increasing steadily among youth. We aimed to explore the factors that contribute to psychological stress and coping strategies among adolescents in Mysore, India to inform the development of an intervention. Methods: We recruited 16 volunteers in Mysore, India including 6 younger (12-15 years; 3 girls) and 10 older adolescents/ young adults (17-25 years; 5 girls) using a purposive sampling technique. Older adolescents were recruited from ongoing birth cohort study, and the younger adolescents by word-of-mouth from the community. Individual in-depth interviews were carried out based on a semi-structured interview guide comprising open-ended questions. The interviews were analysed to derive themes and emerging constructs related to stress and coping strategies.  Results: Adolescents generally perceived stress in their daily lives. Family conflicts and academic pressures were the main triggers for increased stress. Issues around peer relationships, and social position were also important contributors. Adolescents reported that they had robust coping strategies. These included stress release through rationalising and acceptance of the situation, distraction activities, spirituality, and self-comforting methods. However, they felt the need for further support from their family, and the society in general. In particular they expressed the need for a space to share their concerns and obtain guidance through healthy discussions with adults.      Conclusions: Our study indicates that adolescents in India are exposed to a wide range of stressors in their daily lives. The conflict between 'traditional' society's opinions of what adolescents should do and the new age adolescents' aspirations for autonomy to find 'informed' solutions for their issues may hinder the stress management efforts. Moving forward, we propose to develop a culturally acceptable intervention tool that accommodates adolescents' perspectives and psychosocial context.

Childhood cognitive ability: relationship to gestational diabetes mellitus in India.

AIMS/HYPOTHESIS: Our aim was to test the hypothesis that gestational diabetes mellitus (GDM) in mothers is associated with poorer cognitive ability in their offspring in India. METHODS: During 1997 to 1998 maternal GDM status was assessed by OGTT at 30 +/- 2 weeks of gestation. Between 2007 and 2008, at a mean age of 9.7 years, 515 children (32 offspring of GDM mothers [ODM]; 483 offspring of non-GDM mothers [controls]) from the Mysore Parthenon birth cohort underwent cognitive function assessment using tests from the Kaufman Assessment Battery for Children--Second Edition and additional tests measuring learning, long-term storage/retrieval, short-term memory, reasoning, attention and concentration, and visuo-spatial and verbal abilities. RESULTS: Compared with controls, ODM scored higher in tests for learning, long-term retrieval/storage (p = 0.008), reasoning (p = 0.02), verbal ability (p = 0.01), and attention and concentration (p = 0.003). In multiple regression, adjusted for the child's age, sex, gestation, neonatal weight and head circumference, maternal age, parity and BMI, and the parent's socioeconomic status, education and rural/urban residence, this difference remained significant only for learning, long-term retrieval/storage (beta = 0.4 SD (95% CI 0.01-0.75); p = 0.04) and verbal ability (beta = 0.5 SD (95% CI 0.09-0.83); p = 0.02), and not with other test scores. CONCLUSIONS/INTERPRETATION: In this population of healthy Indian children, there was no evidence of lower cognitive ability in ODM. In fact some cognitive scores were higher in ODM.

Low plasma vitamin B12 in pregnancy is associated with gestational 'diabesity' and later diabetes.

AIMS/HYPOTHESIS: This study was designed to test the hypothesis that low plasma vitamin B(12) concentrations combined with high folate concentrations in pregnancy are associated with a higher incidence of gestational diabetes (GDM) and later diabetes. METHODS: Women (N = 785) attending the antenatal clinics of one hospital in Mysore, India, had their anthropometry, insulin resistance (homeostasis model assessment-2) and glucose tolerance assessed at 30 weeks' gestation (100 g oral glucose tolerance test; Carpenter-Coustan criteria) and at 5 years after delivery (75 g OGTT; WHO, 1999). Gestational vitamin B(12) and folate concentrations were measured in stored plasma samples. RESULTS: Low vitamin B(12) concentrations (<150 pmol/l, B(12) deficiency) were observed in 43% of women and low folate concentrations (<7 nmol/l) in 4%. B(12)-deficient women had higher body mass index (p < 0.001), sum of skinfold thickness (p < 0.001), insulin resistance (p = 0.02) and a higher incidence of GDM (8.7% vs 4.6%; OR 2.1, p = 0.02; p = 0.1 after adjusting for BMI) than non-deficient women. Among B(12)-deficient women, the incidence of GDM increased with folate concentration (5.4%, 10.5%, 10.9% from lowest to highest tertile, p = 0.04; p for interaction = 0.2). Vitamin B(12) deficiency during pregnancy was positively associated with skinfold thickness, insulin resistance (p < 0.05) and diabetes prevalence at 5 year follow-up (p = 0.009; p = 0.008 after adjusting for BMI). The association with diabetes became non-significant after excluding women with previous GDM (p = 0.06). CONCLUSIONS/INTERPRETATION: Maternal vitamin B(12) deficiency is associated with increased adiposity and, in turn, with insulin resistance and GDM. Vitamin B(12) deficiency may be an important factor underlying the high risk of 'diabesity' in south Asian Indians.

FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians.

AIMS AND HYPOTHESIS: Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune. METHODS: We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India. RESULTS: We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13-1.40; p = 3 x 10(-5)). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01-0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09-0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06-1.37; p = 4.0 x 10(-3)), and also for waist circumference and other anthropometric variables. CONCLUSIONS: Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes.

Adiposity and Cortisol Response to Stress in Indian Adolescents.

OBJECTIVE: We examined associations of different adiposity measures with cortisol responses during the Trier Social Stress Test for children (TSST-C). DESIGN: Descriptive study. SETTING: Holdsworth Memorial Hospital, Mysore, India. PARTICIPANTS: Adolescents aged 13.5y from a birth cohort were recruited (N=269, 133 boys). METHODS: The stressor (TSST-C) was 5-minutes each of public speaking and mental arithmetic tasks in front of two unfamiliar 'judges'. Salivary cortisol concentrations were measured at baseline and at regular intervals after TSST-C. Weight, height, sub scapular and triceps skinfold thickness, and waist and hip circumference were measured, and percentage body fat was estimated (fat%; bioimpedance). Body mass index (BMI) and Waist-to-hip ratio (WHR) were calculated. All variables were converted into within-cohort SD scores before analysis. Stress-induced change in cortisol concentrations from baseline (cortisol response) was examined in relation to adiposity. RESULTS: Stress increased cortisol concentrations significantly from baseline (mean (SD): 5.5 (6.4) ng/mL; P<0.001). Higher WHR was associated with lower cortisol response at 20 and 30-minutes after stress (~0.13 SD decrease in cortisol response per SD higher WHR, P<0.05). Higher fat% was also associated with lower cortisol response only in girls 20-minutes post-stress (0.23 SD lower response per SD higher fat%, P=0.004). Sum of skinfold thickness and BMI were not associated with cortisol responses. CONCLUSION: Abdominal adiposity is associated with reduced hypothalamic-pituitary-adrenal axis reactivity to stress in this adolescent population.

Life course programming of stress responses in adolescents and young adults in India: Protocol of the Stress Responses in Adolescence and Vulnerability to Adult Non-communicable disease (SRAVANA) Study.

Background: Early life nutrition may affect individuals' susceptibility to adult non-communicable diseases (NCD). Psychological stress is a well-recognised NCD risk factor. Recent evidence suggests that impaired foetal nutrition alters neuro-endocrine pathways, and hypothalamic-pituitary-adrenal axis feedback systems, resulting in abnormal stress responses, and NCD risk. This study aims to examine adolescent cortisol and cardiovascular stress responses in relation to maternal nutrition and contemporaneous NCD risk markers. Methods: The study sample will be drawn from three well-established birth cohorts in India; the Parthenon cohort, Mysore (N=550, age~20y), the SARAS KIDS prenatal intervention cohort, Mumbai (N=300, age~10-12y) and the Pune Rural Intervention in Young Adults/ PRIYA cohort, Pune (N=100, age~22y). We will perform the 'Trier Social Stress Test (TSST)', a well-accepted stress-test module which involves participants performing 5-minutes each of public speaking and mental arithmetic tasks in front of unfamiliar 'judges' (stressor). Repeated measures of salivary cortisol and autonomic cardiovascular outcomes relative to the stressor will be assessed. Measures of psychological stress, cognitive function, blood pressure, glucose-insulin metabolism and depression will be carried out. Mechanistic studies including DNA methylation in gluco-corticoid receptor ( NR3C1) and 11ß-HSD2 gene loci and neuroimaging will be carried out in a subsample. Qualitative interviews and focus group discussions in a subsample of the Parthenon cohort will explore the perception of stress and stressors among the youth. We will convert repeated measures into time-weighted averages before analysis. We will carry out multivariable regression analysis to test the associations. We will further refine the analyses using the mixed-model regression and conditional analyses for the association with repeated measures.   Ethics and dissemination: This study has been approved by the research ethics committee of CSI Holdsworth Memorial Hospital, Mysore. The findings will be disseminated locally and at international meetings, and reports will be submitted to open access peer reviewed journals.

Developmental origins of diabetes-an Indian perspective.

The developmental origins of health disease (DOHaD) hypothesis proposes that altered environmental influences (nutrition, metabolism, pollutants, stress and so on) during critical stages of fetal growth predisposes individuals to diabetes and other non-communicable disease in later life. This phenomenon is thought to reflect permanent effects ('programming') of unbalanced fetal development on physiological systems. Intrauterine programming may underlie the characteristic Indian 'thin-fat' phenotype and the current unprecedented epidemic of diabetes on the backdrop of multigenerational maternal undernutrition in the country. India has been at the forefront of the DOHaD research for over two decades. Both retrospective and prospective birth cohorts in India provide evidence for the role of impaired early-life nutrition on the later diabetes risk. These studies show that in a transitioning country such as India, maternal undernutrition (of micronutrients) and overnutrition (gestational diabetes) co-exist, and expose the offspring to disease risk through multiple pathways. Currently, the Indian scientists are embarking on complex mechanistic and intervention studies to find solutions for the diabetes susceptibility of this population. However, a few unresolved issues in this context warrant continued research and a cautious approach.

Birth size, risk factors across life and cognition in late life: protocol of prospective longitudinal follow-up of the MYNAH (MYsore studies of Natal effects on Ageing and Health) cohort.

INTRODUCTION: For late-life neurocognitive disorders, as for other late-life chronic diseases, much recent interest has focused on the possible relevance of Developmental Origins of Health and Disease (DOHaD). Programming by undernutrition in utero, followed by overnutrition in adult life may lead to an increased risk, possibly mediated through cardiovascular and metabolic pathways. This study will specifically examine, if lower birth weight is associated with poorer cognitive functioning in late life in a south Indian population. METHODS AND ANALYSIS: From 1934 onwards, the birth weight, length and head circumference of all babies born in the CSI Holdsworth Memorial Hospital, Mysore, India, were recorded in obstetric notes. Approximately 800 men and women from the Mysore Birth Records Cohort aged above 55 years, and a reliable informant for each, will be asked to participate in a single cross-sectional baseline assessment for cognitive function, mental health and cardiometabolic disorders. Participants will be assessed for hypertension, type-2 diabetes and coronary heart disease, nutritional status, health behaviours and lifestyles, family living arrangements, economic status, social support and social networks. Additional investigations include blood tests (for diabetes, insulin resistance, dyslipidaemia, anaemia, vitamin B12 and folate deficiency, hyperhomocysteinemia, renal impairment, thyroid disease and Apolipoprotein E genotype), anthropometry, ECG, blood pressure, spirometry and body composition (bioimpedance). We will develop an analysis plan, first using traditional univariate and multivariable analytical paradigms with independent, dependent and mediating/confounding/interacting variables to test the main hypotheses. ETHICS AND DISSEMINATION: This study has been approved by the research ethics committee of CSI Holdsworth Memorial Hospital. The findings will be disseminated locally and at international meetings, and will be published in open access peer reviewed journals.

Truncal adiposity is present at birth and in early childhood in South Indian children.

OBJECTIVES: Muscle-thin but adipose ('thin-fat') body composition of south Asian adults contributes to their high risk of type 2 diabetes. Studies in Pune, India showed that this phenotype is present at birth. We aimed to determine if south Indian babies have a 'thin-fat' phenotype and if this persists in childhood. DESIGN: Prospective cohort study. SETTING: Holdsworth Memorial Hospital, Mysore, India. SUBJECTS: Children (n = 663) whose mothers were recruited from the antenatal clinics. METHODS: Weight, length, head, mid-upper-arm, abdominal circumferences; triceps and subscapular skinfolds were measured at birth, one and four years, and compared with white Caucasian babies born in Southampton, UK (birth), and UK and Dutch growth standards (one and four years). RESULTS: Mysore babies were lighter (2983 g vs 3472 g; -1.10 SD, CI -1.16, -1.02) and smaller in all body measurements than UK neonates (P < 0.001). The deficit was greatest for mid-upper-arm (-1.07 SD), head (-0.89 SD) and abdominal circumferences (-0.73 SD), and least for length (-0.25 SD) and subscapular skinfold thickness (-0.19 SD). Predictors of skinfold thickness were maternal body mass index (P < 0.001) and socio-economic status (P = 0.05). At four years, subscapular skinfold thickness was larger than UK (+0.18 SD, CI +0.11, +0.25; P < 0.001) and Dutch standards (+0.61 SD, CI +0.51, +0.71; P < 0.001), despite all other body measurements remaining smaller. Predictors of 4-year skinfold thickness were neonatal skinfold thickness (P = 0.001) and maternal insulin concentrations (P = 0.05). CONCLUSIONS: Mysore newborns have a 'thin-fat' phenotype. This may reflect the action of genes and/or the 'maternal environment'. The phenotype persists in childhood, and may be the forerunner of a diabetogenic adult phenotype.