Ghattu V. Krishnaveni

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 <50u2009nmolu2009l−1) and 31% were below 28u2009nmolu2009l−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.

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

Aims and hypothesisVariants 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.MethodsWe 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.ResultsWe 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; pu2009=u20093u2009×u200910−5). 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 pu2009=u20090.06). 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; pu2009=u20094.0u2009×u200910−3), and also for waist circumference and other anthropometric variables.ConclusionsOur 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.

Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries

BACKGROUNDnLow- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30-40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain.nnnMETHODSnUsing extant longitudinal birth cohorts (n=19) with data on birthweight, gestational age and child anthropometry (12-60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth.nnnRESULTSnWe grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5-3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively.nnnCONCLUSIONSnThis analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.

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

Aims/hypothesisFTO 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.MethodsAll studies published on the association between FTO-rs9939609 (or proxy [r2u2009>u20090.98]) 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.ResultsThe FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (pu2009=u20099.0u2009×u200910−19), overweight by 1.13-fold/allele (pu2009=u20091.0u2009×u200910−11) and type 2 diabetes by 1.15-fold/allele (pu2009=u20095.5u2009×u200910−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, pu2009=u20096.6u2009×u200910−5). The FTO-rs9939609 minor allele increased BMI by 0.26xa0kg/m2 per allele (pu2009=u20092.8u2009×u200910−17), WHR by 0.003/allele (pu2009=u20091.2u2009×u200910−6), and body fat percentage by 0.31%/allele (pu2009=u20090.0005). 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/interpretationFTO 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.

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.

Low plasma vitamin B12 in pregnancy is associated with gestational ‘diabesity’ and later diabetes

Aims/hypothesisThis study was designed to test the hypothesis that low plasma vitamin B12 concentrations combined with high folate concentrations in pregnancy are associated with a higher incidence of gestational diabetes (GDM) and later diabetes.MethodsWomen (Nu2009=u2009785) attending the antenatal clinics of one hospital in Mysore, India, had their anthropometry, insulin resistance (homeostasis model assessment-2) and glucose tolerance assessed at 30xa0weeks’ gestation (100xa0g oral glucose tolerance test; Carpenter–Coustan criteria) and at 5xa0years after delivery (75xa0g OGTT; WHO, 1999). Gestational vitamin B12 and folate concentrations were measured in stored plasma samples.ResultsLow vitamin B12 concentrations (<150xa0pmol/l, B12 deficiency) were observed in 43% of women and low folate concentrations (<7xa0nmol/l) in 4%. B12-deficient women had higher body mass index (pu2009<u20090.001), sum of skinfold thickness (pu2009<u20090.001), insulin resistance (pu2009=u20090.02) and a higher incidence of GDM (8.7% vs 4.6%; OR 2.1, pu2009=u20090.02; pu2009=u20090.1 after adjusting for BMI) than non-deficient women. Among B12-deficient women, the incidence of GDM increased with folate concentration (5.4%, 10.5%, 10.9% from lowest to highest tertile, pu2009=u20090.04; p for interactionu2009=u20090.2). Vitamin B12 deficiency during pregnancy was positively associated with skinfold thickness, insulin resistance (pu2009<u20090.05) and diabetes prevalence at 5xa0year follow-up (pu2009=u20090.009; pu2009=u20090.008 after adjusting for BMI). The association with diabetes became non-significant after excluding women with previous GDM (pu2009=u20090.06).Conclusions/interpretationMaternal vitamin B12 deficiency is associated with increased adiposity and, in turn, with insulin resistance and GDM. Vitamin B12 deficiency may be an important factor underlying the high risk of ‘diabesity’ in south Asian Indians.

Higher Maternal Plasma Folate but Not Vitamin B-12 Concentrations during Pregnancy Are Associated with Better Cognitive Function Scores in 9- to 10- Year-Old Children in South India

Folate and vitamin B-12 are essential for normal brain development. Few studies have examined the relationship of maternal folate and vitamin B-12 status during pregnancy and offspring cognitive function. To test the hypothesis that lower maternal plasma folate and vitamin B-12 concentrations and higher plasma homocysteine concentrations during pregnancy are associated with poorer neurodevelopment, 536 children (aged 9-10 y) from the Mysore Parthenon birth cohort underwent cognitive function assessment during 2007-2008 using 3 core tests from the Kaufman Assessment Battery, and additional tests measuring learning, long-term storage/retrieval, attention and concentration, and visuo-spatial and verbal abilities. Maternal folate, vitamin B-12, and homocysteine concentrations were measured at 30 +/- 2 wk gestation. During pregnancy, 4% of mothers had low folate concentrations (<7 nmol/L), 42.5% had low vitamin B-12 concentrations (<150 pmol/L), and 3% had hyperhomocysteinemia (>10 micromol/L). The childrens cognitive test scores increased by 0.1-0.2 SD per SD increase across the entire range of maternal folate concentrations (P < 0.001 for all), with no apparent associations at the deficiency level. The associations with learning, long-term storage/retrieval, visuo-spatial ability, attention, and concentration were independent of the parents education, socioeconomic status, religion, and the childs sex, age, current size, and folate and vitamin B-12 concentrations. There were no consistent associations of maternal vitamin B-12 and homocysteine concentrations with childhood cognitive performance. In this Indian population, higher maternal folate, but not vitamin B-12, concentrations during pregnancy predicted better childhood cognitive ability. It also suggests that, in terms of neurodevelopment, the concentration used to define folate deficiency may be set too low.

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

BACKGROUNDnMetabolic 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.nnnOBJECTIVEnWe aimed to examine the association between maternal vitamin D status and anthropometric variables, body composition, and cardiovascular risk markers in Indian children.nnnDESIGNnSerum 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.nnnRESULTSnSixty-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.nnnCONCLUSIONnIntrauterine exposure to low 25(OH)D concentrations is associated with less muscle mass and higher insulin resistance in children.

Glucose tolerance in pregnancy in South India: relationships to neonatal anthropometry

Background.u2002 The incidence of type 2 diabetes is increasing worldwide, most rapidly in developing countries such as India. Exposure as a fetus to maternal gestational diabetes is thought to be a risk factor for developing the disease. This study was set up to determine the incidence of gestational diabetes mellitus in one urban maternity unit in South India and to examine its effect on the offsprings neonatal anthropometry, childhood growth, and glucose/insulin metabolism. This paper reports neonatal outcomes.

Association between maternal folate concentrations during pregnancy and insulin resistance in Indian children

Aims/hypothesisIn an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points.MethodsWe measured plasma vitamin B12, folate and homocysteine concentrations at 30u2009±u20092xa0weeks’ gestation in 654 women who delivered at one hospital. Neonatal anthropometry was recorded, and the children’s glucose and insulin concentrations were measured at 5, 9.5 and 13.5xa0years of age. Insulin resistance was estimated using HOMA of insulin resistance (HOMA-IR).ResultsMaternal homocysteine concentrations were inversely associated with all neonatal anthropometric measurements (pu2009<u20090.05), and positively associated with glucose concentrations in the children at 5 (30xa0min; pu2009=u20090.007) and 9.5xa0years of age (120xa0min; pu2009=u20090.02). Higher maternal folate concentrations were associated with higher HOMA-IR in the children at 9.5 (pu2009=u20090.03) and 13.5xa0years of age (pu2009=u20090.03). Maternal vitamin B12 concentrations were unrelated to offspring outcomes.Conclusions/interpretationMaternal vitamin B12 status did not predict insulin resistance in our cohort. However, associations of maternal homocysteine and folate concentrations with birth size, and with childhood insulin resistance and glycaemia in the offspring, suggest a role for nutritionally driven disturbances in one-carbon metabolism in fetal programming of diabetes.