S. C. Karat

Intrauterine exposure to maternal diabetes is associated with higher adiposity and insulin resistance and clustering of cardiovascular risk markers in Indian children

OBJECTIVE To test the hypothesis that maternal gestational diabetes increases cardiovascular risk markers in Indian children. RESEARCH DESIGN AND METHODS Anthropometry, blood pressure, and glucose/insulin concentrations were measured in 514 children at 5 and 9.5 years of age (35 offspring of diabetic mothers [ODMs], 39 offspring of diabetic fathers [ODFs]). Children of nondiabetic parents were control subjects. RESULTS At age 9.5 years, female ODMs had larger skinfolds (P < 0.001), higher glucose (30 min) and insulin concentrations, and higher homeostasis model assessment (HOMA) of insulin resistance and systolic blood pressure (P < 0.05) than control subjects. Male ODMs had higher HOMA (P < 0.01). Associations were stronger than at age 5 years. Female ODFs had larger skinfolds and male ODFs had higher HOMA (P < 0.05) than control subjects; associations were weaker than for ODMs. Associations between outcomes in control subjects and parental BMI, glucose, and insulin concentrations were similar for mothers and fathers. CONCLUSIONS The intrauterine environment experienced by ODMs increases diabetes and cardiovascular risk over genetic factors; the effects strengthen during childhood.

Maternal vitamin D status during pregnancy and body composition and cardiovascular risk markers in Indian children: the Mysore Parthenon Study–

BACKGROUND Metabolic consequences of vitamin D deficiency have become a recent research focus. Maternal vitamin D status is thought to influence musculoskeletal health in children, but its relation with offspring metabolic risk is not known. OBJECTIVE We aimed to examine the association between maternal vitamin D status and anthropometric variables, body composition, and cardiovascular risk markers in Indian children. DESIGN Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 28-32 wk gestation in 568 women who delivered at Holdsworth Memorial Hospital, Mysore, India. Anthropometric variables, glucose and insulin concentrations, blood pressure, and fasting lipid concentrations were measured in the offspring at 5 and 9.5 y of age. Muscle-grip strength was measured by using a hand-held dynamometer at age 9.5 y. Arm-muscle area was calculated as a measure of muscle mass. Fasting insulin resistance was calculated by using the homeostasis model assessment equation. RESULTS Sixty-seven percent of women had vitamin D deficiency [serum 25(OH)D concentration <50 nmol/L]. At ages 5 and 9.5 y, children born to vitamin D-deficient mothers had smaller arm-muscle area in comparison with children born to mothers without deficiency (P < 0.05). There was no difference in grip strength between offspring of women with and without vitamin D deficiency. At 9.5 y, children of vitamin D-deficient mothers had higher fasting insulin resistance than did children of nondeficient women (P = 0.04). There were no associations between maternal vitamin D status and other offspring risk factors at either age. CONCLUSION Intrauterine exposure to low 25(OH)D concentrations is associated with less muscle mass and higher insulin resistance in children.

Breastfeeding duration, age of starting solids and high BMI risk and adiposity in Indian children

This study utilized data from a prospective birth cohort study on 568 Indian children, to determine whether a longer duration of breastfeeding and later introduction of solid feeding were associated with a reduced higher body mass index (BMI) and less adiposity. Main outcomes were high BMI (>90th within-cohort sex-specific BMI percentile) and sum of skinfold thickness (triceps and subscapular) at age 5. Main exposures were breastfeeding (six categories from 1-4 to ≥21 months) and age of starting regular solid feeding (four categories from ≤3 to ≥6 months). Data on infant-feeding practices, socio-economic and maternal factors were collected by questionnaire. Birthweight, maternal and child anthropometry were measured. Multiple regression analysis that accounted for potential confounders demonstrated a small magnitude of effect for breastfeeding duration or introduction of solid feeds on the risk of high BMI but not for lower skinfold thickness. Breastfeeding duration was strongly negatively associated with weight gain (0-2 years) [adjusted β = -0.12 standard deviation, 95% confidence interval (CI): -0.19 to -0.05 per category change in breastfeeding duration, P = 0.001], and weight gain (0-2 years) was strongly associated with high BMI at 5 years (adjusted odds ratio = 3.8, 95% CI: 2.53-5.56, P < 0.001). In our sample, findings suggest that longer breastfeeding duration and later introduction of solids has a small reduction on later high BMI risk and a negligible effect on skinfold thickness. However, accounting for sampling variability, these findings cannot exclude the possibility of no effect at the population level.

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.

Testing the fetal overnutrition hypothesis; the relationship of maternal and paternal adiposity to adiposity, insulin resistance and cardiovascular risk factors in Indian children.

OBJECTIVE We aimed to test the fetal overnutrition hypothesis by comparing the associations of maternal and paternal adiposity (sum of skinfolds) with adiposity and cardiovascular risk factors in children. DESIGN Children from a prospective birth cohort had anthropometry, fat percentage (bio-impedance), plasma glucose, insulin and lipid concentrations and blood pressure measured at 9.5 years of age. Detailed anthropometric measurements were recorded for mothers (at 3±2 weeks’ gestation) and fathers (5 years following the index pregnancy). SETTING Holdsworth Memorial Hospital, Mysore, India. SUBJECTS Children (n 504), born to mothers with normal glucose tolerance during pregnancy. RESULTS Twenty-eight per cent of mothers and 38% of fathers were overweight/ obese (BMI≥25.0 kg/m²), but only 4% of the children were overweight/obese (WHO age- and sex-specific BMI≥18.2 kg/m²). The children’s adiposity (BMI, sum of skinfolds, fat percentage and waist circumference), fasting insulin concentration and insulin resistance increased with increasing maternal and paternal sum of skinfolds adjusted for the child’s sex, age and socio-economic status. Maternal and paternal effects were similar. The associations with fasting insulin and insulin resistance were attenuated after adjusting for the child’s current adiposity. CONCLUSIONS In this population, both maternal and paternal adiposity equally predict adiposity and insulin resistance in the children. This suggests that shared family environment and lifestyle, or genetic/epigenetic factors, influence child adiposity. Our findings do not support the hypothesis that there is an intrauterine overnutrition effect of maternal adiposity in non-diabetic pregnancies, although we cannot rule out such an effect in cases of extreme maternal obesity, which is rare in our population.

Exposure to maternal gestational diabetes is associated with higher cardiovascular responses to stress in adolescent indians.

Context: Altered endocrinal and autonomic nervous system responses to stress may link impaired intra-uterine growth with later cardiovascular disease. Objective: To test the hypothesis that offspring of gestational diabetic mothers (OGDM) have high cortisol and cardiosympathetic responses during the Trier Social Stress Test for Children (TSST-C). Design: Adolescents from a birth cohort in India (n = 213; mean age, 13.5 y), including 26 OGDM, 22 offspring of diabetic fathers (ODF), and 165 offspring of nondiabetic parents (controls) completed 5 minutes each of public speaking and mental arithmetic tasks in front of two unfamiliar “evaluators” (TSST-C). Salivary cortisol concentrations were measured at baseline and at regular intervals after the TSST-C. Heart rate, blood pressure (BP), stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the test using a finger cuff; the beat-to-beat values were averaged for these periods. Results: Cortisol and cardiosympathetic parameters increased from baseline during stress (P < .001). OGDM had greater systolic BP (mean difference, 5.6 mm Hg), cardiac output (0.5 L/min), and stroke volume (4.0 mL) increases and a lower total peripheral resistance rise (125 dyn · s/cm5) than controls during stress. ODF had greater systolic BP responses than controls (difference, 4.1 mm Hg); there was no difference in other cardiosympathetic parameters. Cortisol responses were similar in all three groups. Conclusions: Maternal diabetes during pregnancy is associated with higher cardiosympathetic stress responses in the offspring, which may contribute to their higher cardiovascular disease risk. Further research may confirm stress-response programming as a predictor of cardiovascular risk in OGDM.

Cohort Profile: Mysore Parthenon Birth Cohort

The Mysore Parthenon Birth Cohort was established to examine the long-term effects of maternal glucose tolerance and nutritional status on cardiovascular disease risk factors in the offspring. During 1997-98, 830 of 1233 women recruited from the antenatal clinics of the Holdsworth Memorial Hospital (HMH), Mysore, India, underwent an oral glucose tolerance test. Of these, 667 women delivered live babies at HMH. Four babies with major congenital anomalies were excluded, and the remaining 663 were included for further follow-up. The babies had detailed anthropometry at birth and at 6-12-monthly intervals subsequently. Detailed cardiovascular investigations were done at ages 5, 9.5 and 13.5 years in the children, and in the parents at the 5-year and 9.5-year follow-ups. This ongoing study provides extensive data on serial anthropometry and body composition, physiological and biochemical measures, dietary intake, nutritional status, physical activity measures, stress reactivity measures and cognitive function, and socio-demographic parameters for the offspring. Data on anthropometry, cardiovascular risk factors and nutritional status are available for mothers during pregnancy. Anthropometry and risk factor measures are available for both parents at follow-up.

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

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.

Cohort profile: the 1934-66 Mysore birth records cohort in South India

Cohort Profile: The 1934–66 Mysore Birth Records Cohort in South India Murali Krishna,* Kumaran Kalyanaraman, SR Veena, GV Krishanveni, SC Karat, Vanessa Cox, Patsy Coakley, Kiran Nagaraj, Claudia Stein, BDR Paul, Martin Prince, Clive Osmond and Caroline HD Fall Early Career Research Fellow, Wellcome DBT India Alliance, India, Epidemiology Research Unit, CSI Holdsworth Memorial Hospital, Mysore, India, MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK, Division of Information, Evidence, Research and Innovation at WHO/ Europe, Copenhagen, Denmark and Institute of Psychiatry, Kings College, London, UK

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

There is evidence of a reduction in childrens 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.