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.

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.

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.

Cognitive function and disability in late life: an ecological validation of the 10/66 battery of cognitive tests among community-dwelling older adults in South India.

BACKGROUND: The 10/66 Dementia Research Group developed and validated a culture and education fair battery of cognitive tests for diagnosis of dementia in population-based studies in low-income and middle-income countries including India. AIMS: This study examined the association between individual domains of the 10/66 battery of cognitive tests and 'disability' and 'functional impairment' in community-dwelling older adults in South India. METHODS: One hundred twenty-nine adults aged 60-90 years residing in Karunapura, in the city of Mysore, were interviewed in their own homes. Cognitive functioning was measured by administering the 10/66 battery of cognitive tests that composes of Community Screening Instrument for Dementia (CSI'D' COGSCORE), verbal fluency (VF) and word list memory recall (WLMR). A reliable informant was interviewed to ascertain if the subject's cognitive problems have resulted in functional impairment. Disability was measured by WHO Disability Schedule-II (DAS). RESULTS: The women had significantly lower CSI'D' COGSCORE score when compared with men (p = 0.002). The presence of 'functional impairment' resulting from cognitive decline was significantly associated with lower scores on VF (p = 0.03), WLMR (p = 0.03) and CSI'D' COGSCOREs (p < 0.01). There was a significant inverse association between WHO DAS II score and WLMR (p = 0.004), VF (0.006) and CSI'D' COGSCORE scores (p ≤ 0.001) even after adjusting for self-reported ischaemic heart disease, stroke, chronic obstructive airway disease, hypertension and diabetes. CONCLUSIONS: Lower scores on individual domains of the 10/66 battery of cognitive tests are associated with higher levels of disability and functional impairment in community-dwelling older adults. These culture and education fair tests are suitable for use in population-based research in India. Copyright © 2015 John Wiley & Sons, Ltd.

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).

Birth size and physical activity in a cohort of Indian children aged 6-10 years.

There is evidence of a reduction in children's physical activity in India in the last decade. Our objective was to assess whether size and body composition at birth are associated with physical activity in school-aged children. Children from a prospective observational cohort study born in Mysore, South India between 1997 and 1998 (n = 663) had neonatal anthropometric measurements made within 72 h of delivery [weight, mid-upper arm circumference (MUAC), chest, abdomen and head circumference, crown-heel, crown-buttock and leg length, triceps and subscapular skinfolds]. At 6-10 years, children (n = 449) were asked to wear AM7164 or GT1M Actigraph accelerometers for 7 days. Body composition was measured within 6 months of activity monitoring. Arm muscle area at birth and time of activity monitoring was calculated from MUAC and skinfold measurements. Activity outcome measures were: mean accelerometer counts per minute (cpm); counts per day and proportion of time spent in moderate and vigorous activity. The mean (S.D.) number of days with ≥500 min of recorded accelerometer data was 7.0 (1.1). Linear regression models showed no significant associations between any of the neonatal anthropometric measures and the activity variables. Body fat percentage at 7.5 years was negatively associated with all activity variables (B = -4.69, CI: -7.31, -2.07 for mean cpm). In conclusion, this study showed no associations between body size and skinfold thickness at birth and objectively measured physical activity in childhood.

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.

Adiposity, insulin resistance and cardiovascular risk factors in 9-10-year-old Indian children: relationships with birth size and postnatal growth.

Lower birthweight, and rapid childhood weight gain predict elevated cardiovascular risk factors in children. We examined associations between serial, detailed, anthropometric measurements from birth to 9.5 years of age and cardiovascular risk markers in Indian children. Children (n = 663) born at the Holdsworth Memorial Hospital, Mysore, India were measured at birth and 6-12 monthly thereafter. At 9.5 years, 539 (255 boys) underwent a 2-h oral glucose tolerance test, and blood pressure (BP) and fasting lipid concentrations were measured. Insulin resistance was calculated using the HOMA equation. These outcomes were examined in relation to birth measurements and changes in measurements (growth) during infancy (0-2 years), 2-5 years and 5-9.5 years using conditional s.d. scores. Larger current weight, height and skinfold thickness were associated with higher risk markers at 9.5 years (P < 0.05). Lower weight, smaller length and mid-arm circumference at birth were associated with higher fasting glucose concentrations at 9.5 years (P ⩽ 0.01). After adjusting for current weight/height, there were inverse associations between birthweight and/or length and insulin concentrations, HOMA, systolic and diastolic BP and plasma triglycerides (P < 0.05). Increases in conditional weight and height between 0-2, 2-5 and 5-9.5 years were associated with higher insulin concentrations, HOMA and systolic BP. In conclusion, in 9-10-year-old Indian children, as in other studies, cardiovascular risk factors were highest in children who were light or short at birth but heavy or tall at 9 years. Greater infant and childhood weight and height gain were associated with higher risk markers.

Accelerometers for measuring physical activity behavior in Indian children.

OBJECTIVE: To examine the validity of accelerometers for characterizing habitual physical activity patterns in Indian children. DESIGN: Cohort study. SETTING: Holdsworth Memorial Hospital, Mysore. SUBJECTS: Children (N=103, mean age 6.6 years) selected from an ongoing birth cohort study. METHODS: Physical activity was measured over 7 days using accelerometers (MTI Actigraph) and concurrent parent-maintained activity diaries. Actigraph counts per minute representing sedentary (<10), light (< 400), moderate (<3000) and vigorous activity were determined using a structured activity session in a separate group of 10 children. In 46 children chosen for validating accelerometers, time spent in different activity levels according to diaries was determined. Energy Expenditure (EE) was calculated from diaries using a factorial method. RESULTS: Ninety-eight children wore the monitor for > or = 4 days. Total counts and time spent in different activity levels were similar in boys and girls (P>0.2). Among 46 children chosen for comparisons, time spent in sedentary (r =0.48, P=0.001), light (r=0.70, P<0.001) and moderate activities (r=0.29, P=0.054) according to diaries correlated with those derived from counts, and total Actigraph counts correlated with EE (r=0.42, P=0.004). Bland-Altman analysis showed systematic bias, and wide limits of agreement between these methods for time spent in different activity levels. CONCLUSIONS: Accelerometers are a well tolerated and objective way of measuring activity behavior in free-living children. Though accelerometer counts correlate with time spent in activity of varying intensity and energy expenditure derived from parent-maintained diaries, wide limits of agreement show that the limitations of accelerometers need to be recognized in interpreting the data that they generate.

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.