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.

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.

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.

Trier social stress test in Indian adolescents.

OBJECTIVE: To test the Trier Social Stress Test for children (TSST-C) in a cohort of Indian adolescents. DESIGN: Cohort study. SETTING: Holdsworth Memorial Hospital, Mysore, India. PARTICIPANTS: Adolescent children (N=273, 134 males; mean age 13.6 yrs) selected from an ongoing birth cohort; 269 completed the test. INTERVENTION: Performance of 5-minutes each of public- speaking and mental arithmetic tasks in front of two unfamiliar 'evaluators'. OUTCOME MEASURES: Salivary cortisol concentrations were measured at baseline and at regular intervals after the TSST-C. Continuous measurements of heart rate, finger blood pressure, stroke volume, cardiac output and systemic vascular resistance were carried out before, during and for 10 minutes after the TSST-C using a finger cuff. RESULTS: Cortisol concentrations [mean increment (SD): 6.1 (6.9) ng/mL], heart rate [4.6 (10.1) bpm], systolic [24.2 (11.6) mmHg] and diastolic blood pressure [16.5 (7.3) mmHg], cardiac output [0.6 (0.7) L/min], stroke volume [4.0 (5.6) mL] and systemic vascular resistance [225 (282) dyn.s/cm5] increased significantly (P<0.001) from baseline after inducing stress. CONCLUSIONS: The TSST-C produces stress responses in Indian adolescents of a sufficient magnitude to be a useful tool for examining stress physiology and its relationships to disease outcomes in this population.

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.

Mother's lifetime nutrition and the size, shape and efficiency of the placenta.

BACKGROUND: Studies have shown that the shape and size of the placenta at birth predict blood pressure in later life. The influences that determine placental morphology are largely unknown. We have examined the role of mother's body size. METHODS: We studied 522 neonates who were born in a maternity hospital in Mysore, South India. The weight of the placenta and the length and breadth of its surface, were measured after delivery. RESULTS: Higher maternal fat mass predicted a larger placental surface (p = 0.02), while larger maternal head circumference predicted a more oval placental surface (p = 0.03). Higher maternal fat mass and larger maternal head circumference were associated with greater placental efficiency, indicated by lower ratios of the length (p = 0.0003 and p = 0.0001 respectively) and breadth (p = 0.0002 and p < 0.0001) of the surface to birthweight. In a sub-sample of 51 mothers whose own birthweight was available, higher maternal birthweight was related to lower ratios of the length and breadth of the surface to birthweight (p = 0.01 and 0.002). Maternal height was unrelated to placental size or shape. CONCLUSIONS: Higher maternal fat mass, reflecting the mother's current nutritional state, and larger maternal head circumference, reflecting the mother's fetal/infant growth, are associated with changes in the shape and size of the placental surface and greater placental efficiency. We suggest that these associations reflect effects of the mother's nutrition at different stages of her lifecourse on the development of the placenta and on materno-placento-fetal transfer of nutrients.

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.

Prediction of body-fat percentage from skinfold and bio-impedance measurements in Indian school children.

BACKGROUND/OBJECTIVES: Few equations for calculating body-fat percentage (BF%) from field methods have been developed in South-Asian children. The objective of this study was to assess agreement between BF% derived from primary reference methods and that from skinfold equations and bio-impedance analysis (BIA) in Indian children. SUBJECTS/METHODS: We measured BF% in two groups of Indian children. In Pune, 570 rural children aged 6-8 years underwent dual-energy X-ray absorptiometry (DXA) scans. In Mysore (18)O in doubly labeled water was administered to 59 urban children aged 7-9 years. We conducted BIA at 50 kHz and anthropometry, including sub-scapular and triceps skinfold thicknesses. We used the published equations of Wickramasinghe, Shaikh, Slaughter and Dezenburg to calculate BF% from anthropometric data and the manufacturer's equation for BIA measurements. We assessed agreement with values derived from DXA and doubly labeled water using Bland-Altman analysis. RESULTS: Children were light and thin on average compared with international standards. There was poor agreement between the reference BF% values and those from all equations. Assumptions for Bland-Altman analysis were not met for Wickramasinghe, Shaikh and Slaughter equations. The Dezenberg equations under-predicted BF% for most children (mean difference in Pune -13.4, LOA -22.7, -4.0 and in Mysore -7.9, LOA (-13.7 and -2.2). The mean bias for the BIA equation in Pune was +5.0% and in Mysore +1.95%, and the limits of agreement were wide; -5.0, 15.0 and -7.8, 11.7 respectively. CONCLUSIONS: Currently available skinfold equations do not accurately predict BF% in Indian children. We recommend development of BIA equations in this population using a four-compartment model.

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.

The relationship of birthweight, muscle size at birth and post-natal growth to grip strength in 9-year-old Indian children: findings from the Mysore Parthenon study.

Foetal development may permanently affect muscle function. Indian newborns have a low mean birthweight, predominantly due to low lean tissue and muscle mass. We aimed to examine the relationship of birthweight, and arm muscle area (AMA) at birth and post-natal growth to handgrip strength in Indian children. Grip strength was measured in 574 children aged 9 years, who had detailed anthropometry at birth and every 6-12 months post-natally. Mean (standard deviation (s.d.)) birthweight was 2863 (446) g. At 9 years, the children were short (mean height s.d. -0.6) and light (mean weight s.d. -1.1) compared with the World Health Organization growth reference. Mean (s.d.) grip strength was 12.7 (2.2) kg (boys) and 11.0 (2.0) kg (girls). Weight, length and AMA at birth, but not skinfold measurements at birth, were positively related to 9-year grip strength (ß = 0.40 kg/s.d. increase in birthweight, P < 0.001; and ß = 0.41 kg/s.d. increase in AMA, P < 0.001). Grip strength was positively related to 9-year height, body mass index and AMA and to gains in these measurements from birth to 2 years, 2-5 years and 5-9 years (P < 0.001 for all). The associations between birth size and grip strength were attenuated but remained statistically significant for AMA after adjusting for 9-year size. We conclude that larger overall size and muscle mass at birth are associated with greater muscle strength in childhood, and that this is mediated mainly through greater post-natal size. Poorer muscle development in utero is associated with reduced childhood muscle strength.

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.

Relationship between physical activity measured using accelerometers and energy expenditure measured using doubly labelled water in Indian children.

BACKGROUND/OBJECTIVES: To test the association between physical activity measured using accelerometer counts (Actigraph) and energy expenditure (EE) measured using the doubly labelled water (DLW) method in free-living children in India. The aim of this study was to explore the usefulness of Actigraphs in estimating EE. SUBJECTS/METHODS: Total EE (TEE) was measured in 58 children aged 8-9 years over a period of 2 weeks using the DLW technique. Physical activity level (PAL) was estimated from TEE, and the basal metabolic rate was predicted from weight. Physical activity was measured simultaneously using the Actigraph accelerometers (MTI AM7164 and GT1M). TEE was also calculated from the Actigraph counts using a published equation. RESULTS: TEE (mean: 6.6 vs 5.7 MJ, P=0.04) and Actigraph counts (counts/minute: 557 vs 465, P=0.02; total counts: 445 534 vs 354 748, P=0.004) were higher in boys than in girls. There were no significant correlations between either total Actigraph counts (r=0.15, P=0.3) or counts/minute (r=0.18, P=0.2), and TEE estimated using DLW. Similarly, there were no significant correlations between Actigraph counts and PAL (r=0.10, P=0.5; r=0.17, P=0.2, respectively). The Bland-Altman analysis showed poor agreement between TEE estimated using the DLW method and TEE derived from the Actigraph equation. CONCLUSIONS: Activity measured using Actigraph accelerometers was not related to TEE and PAL derived using the DLW technique in children in Mysore. Actigraphs may not be useful in predicting EE in this setting, but may be better used for judging activity patterns.

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.

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.

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.

Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size.

BACKGROUND/OBJECTIVES: Vitamin D is required for bone growth and normal insulin secretion. Maternal hypovitaminosis D may impair fetal growth and increase the risk of gestational diabetes. We have related maternal vitamin D status in pregnancy to maternal and newborn glucose and insulin concentrations, and newborn size, in a South Indian population. SUBJECTS/METHODS: Serum 25 hydroxy vitamin D (25(OH)D) concentrations, glucose tolerance, and plasma insulin, proinsulin and 32-33 split proinsulin concentrations were measured at 30 weeks gestation in 559 women who delivered at the Holdsworth Memorial Hospital, Mysore. The babies' anthropometry and cord plasma glucose, insulin and insulin precursor concentrations were measured. RESULTS: In total 66% of women had hypovitaminosis D (25(OH)D concentrations <50 nmol l(-1)) and 31% were below 28 nmol l(-1). There was seasonal variation in 25(OH)D concentrations (P<0.0001). There was no association between maternal 25(OH)D and gestational diabetes (incidence 7% in women with and without hypovitaminosis D). Maternal 25(OH)D concentrations were unrelated to newborn anthropometry or cord plasma variables. In mothers with hypovitaminosis D, higher 25(OH)D concentrations were associated with lower 30-min glucose concentrations (P=0.03) and higher fasting proinsulin concentrations (P=0.04). CONCLUSIONS: Hypovitaminosis D at 30 weeks gestation is common in Mysore mothers. It is not associated with an increased risk of gestational diabetes, impaired fetal growth or altered neonatal cord plasma insulin secretory profile.

Relationships of maternal and paternal birthweights to features of the metabolic syndrome in adult offspring: an inter-generational study in South India.

AIMS/HYPOTHESIS: The association between lower birthweight and metabolic syndrome may result from fetal undernutrition (fetal programming hypothesis) and/or genes causing both low birthweight and insulin resistance (fetal insulin hypothesis). We studied associations between the birthweight of parents and metabolic syndrome in the offspring. METHODS: We identified men and women (aged 35-68 years), who had been born in Holdsworth Memorial Hospital, Mysore, India. We also identified the offspring (20-46 years) of these men and women. In total, 283 offspring of 193 mothers and 223 offspring of 144 fathers were studied. Investigations included anthropometry, oral glucose tolerance, plasma insulin and lipid concentrations and blood pressure. The metabolic syndrome was defined using WHO criteria. RESULTS: Among the offspring, lower birthweight was associated with an increased risk of glucose intolerance (impaired glucose tolerance, impaired fasting glucose or type 2 diabetes) and higher cholesterol and triacylglycerol concentrations (p < 0.05 for all adjusted for sex and age). Most outcomes in the offspring, including most individual components of the metabolic syndrome, were unrelated to parental birthweight. However, both maternal and paternal birthweight were inversely related to offspring metabolic syndrome (odds ratio [OR] 0.36 [95% CI: 0.13-1.01] per kg, p = 0.053 for mother-offspring pairs; OR 0.26 [0.07-0.93], p = 0.04 for father-offspring pairs, adjusted for offspring age, sex, BMI and socioeconomic status). Maternal birthweight was inversely related to offspring systolic blood pressure (beta = -2.5 mmHg [-5.00 to 0.03] per kg maternal birthweight; p = 0.052). CONCLUSIONS/INTERPRETATION: Factors in both parents may influence the risk of metabolic syndrome in their offspring. There are several possible explanations, but the findings are consistent with the fetal insulin (genetic) hypothesis.

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.