Raman K. Marwaha

Vitamin D status of apparently healthy schoolgirls from two different socioeconomic strata in Delhi : relation to nutrition and lifestyle

Forty to fifty per cent of skeletal mass, accumulated during childhood and adolescence, is influenced by sunlight exposure, physical activity, lifestyle, endocrine status, nutrition and gender. In view of scarce data on association of nutrition and lifestyle with hypovitaminosis D in Indian children and adolescents, an in-depth study on 3,127 apparently healthy Delhi schoolgirls (6-18 years) from the lower (LSES, n 1,477) and upper socioeconomic strata (USES, n 1650) was carried out. These girls were subjected to anthropometry and clinical examination for hypovitaminosis D. Girls randomly selected from the two strata (LSES, n 193; USES, n 211) underwent detailed lifestyle, dietary, biochemical and hormonal assessment. Clinical vitamin D deficiency was noted in 11.5 % girls (12.4 % LSES, 10.7 % USES). USES girls had significantly higher BMI than LSES counterparts. Prevalence of biochemical hypovitaminosis D (serum 25-hydroxyvitamin D < 50 nmol/l) was seen in 90.8 % of girls (89.6 % LSES, 91.9 % USES, NS). Mean intake of energy, protein, fat, Ca, vitamin D and milk/milk products was significantly higher in USES than LSES girls. Conversely, carbohydrate, fibre, phytate and cereal intakes were higher in LSES than USES girls. Physical activity and time spent outdoors was significantly higher in LSES girls (92.8 v. 64 %, P = 0.000). Significant correlation between serum 25-hydroxyvitamin D and estimated sun exposure (r 0.185, P = 0.001) and percentage body surface area exposed (r 0.146, P = 0.004) suggests that these lifestyle-related factors may contribute significantly to the vitamin D status of the apparently healthy schoolgirls. Hence, in the absence of vitamin D fortification of foods, diet alone appears to have an insignificant role.

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes–associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10−9). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10−12) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.

Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey.

25-Hydroxy vitamin D (25(OH)D) deficiency is linked with predisposition to autoimmune type 1 diabetes and multiple sclerosis. Our objective was to assess the relationship between serum 25(OH)D levels and thyroid autoimmunity. Subjects included students, teachers and staff aged 16-60 years (total 642, 244 males, 398 females). Serum free thyroxine, thyroid-stimulating hormone (TSH), and thyroid peroxidase autoantibodies (TPOAb), intact parathyroid hormone and 25(OH)D were measured by electrochemiluminescence and RIA, respectively. Thyroid dysfunction was defined if (1) serum TSH > or = 5 microU/ml and TPOAb>34 IU/ml or (2) TSH > or = 10 microU/ml but normal TPOAb. The mean serum 25(OH)D of the study subjects was 17.5 (sd 10.2) nmol/l with 87 % having values < or = 25 nmol/l. TPOAb positivity was observed in 21 % of subjects. The relationship between 25(OH)D and TPOAb was assessed with and without controlling for age and showed significant inverse correlation (r - 0.08, P = 0.04) when adjusted for age. The prevalence of TPOAb and thyroid dysfunction were comparable between subjects stratified according to serum 25(OH)D into two groups either at cut-off of < or = 25 or >25 nmol/l or first and second tertiles. Serum 25(OH)D values show only weak inverse correlation with TPOAb titres. The presence of such weak association and narrow range of serum 25(OH)D did not allow us to interpret the present results in terms of quantitative cut-off values of serum 25(OH)D. Further studies in vitamin D-sufficient populations with wider range of serum 25(OH)D levels are required to substantiate the findings of the current study.

Vitamin D status in pregnant Indian women across trimesters and different seasons and its correlation with neonatal serum 25-hydroxyvitamin D levels

The present cross-sectional study was conducted to determine the vitamin D status of pregnant Indian women and their breast-fed infants. Subjects were recruited from the Department of Obstetrics, Armed Forces Clinic and Army Hospital (Research and Referral), Delhi. A total of 541 apparently healthy women with uncomplicated, single, intra-uterine gestation reporting in any trimester were consecutively recruited. Of these 541 women, 299 (first trimester, ninety-seven; second trimester, 125; third trimester, seventy-seven) were recruited in summer (April-October) and 242 (first trimester, fifty-nine, second trimester, ninety-three; third trimester, ninety) were recruited in winter (November-March) to study seasonal variations in vitamin D status. Clinical, dietary, biochemical and hormonal evaluations for the Ca-vitamin D-parathormone axis were performed. A subset of 342 mother-infant pairs was re-evaluated 6 weeks postpartum. Mean serum 25-hydroxyvitamin D (25(OH)D) of pregnant women was 23.2 (SD 12.2) nmol/l. Hypovitaminosis D (25(OH)D < 50 nmol/l) was observed in 96.3 % of the subjects. Serum 25(OH)D levels were significantly lower in winter in the second and third trimesters, while serum intact parathormone (iPTH) and alkaline phosphatase levels were significantly higher in winter in all three trimesters. A significant negative correlation was found between serum 25(OH)D and iPTH in mothers (r - 0.367, P = 0.0001) and infants (r - 0.56, P = 0.0001). A strong positive correlation was observed between 25(OH)D levels of mother-infant pairs (r 0.779, P = 0.0001). A high prevalence of hypovitaminosis D was observed in pregnancy, lactation and infancy with no significant inter-trimester differences in serum 25(OH)D levels.

High prevalence of polycystic ovary syndrome characteristics in girls with euthyroid chronic lymphocytic thyroiditis: a case–control study

OBJECTIVE The aim was to find the prevalence of polycystic ovary syndrome (PCOS) phenotype in adolescent euthyroid girls with chronic lymphocytic thyroiditis (CLT). DESIGN This was a prospective case-control study as part of an ongoing community-wide thyroid survey in Indian schools. METHODS One hundred and seventy-five girls with euthyroid CLT and 46 age-matched non-CLT girls underwent clinical, biochemical, hormonal, and ultrasonographic evaluation for diagnosis of PCOS by Rotterdam 2003 criteria. All subjects underwent serum sampling for LH, FSH, testosterone, DHEAS, free thyroxine, TSH, and anti-thyroid peroxidase (TPO) antibodies. Oral glucose tolerance test (OGTT) was undertaken for plasma glucose and insulin. RESULTS Significantly higher prevalence of PCOS was noted in girls with euthyroid CLT when compared to their control counterparts (46.8 vs 4.3%, P=0.001). The CLT girls had higher body mass index, waist circumference, and systolic blood pressure (P=0.001). Mean number of menstrual cycles/year was 8.4+/-3.5 vs 10.1+/-1.4, and mean Ferriman-Gallwey score was 11.9+/-3.5 vs 3.0+/-2.4 (P=0.001) in cases versus controls respectively. The fasting and postprandial glucose and serum cholesterol were also higher in the cases (P=0.001). Homeostasis model assessment-insulin resistance was 4.4+/-4.2 vs 2.3+/-2.7 in the cases versus controls (P=0.001). CONCLUSION Higher prevalence of PCOS characteristics in euthyroid CLT girls when compared to controls suggest possible role of autoimmune phenomenon in the etiopathogenesis of PCOS. Further studies are required to understand the pathogenic link between these two disorders.

Vitamin D Nutritional Status of Exclusively Breast Fed Infants and Their Mothers

BACKGROUND Vitamin D nutrition has a profound effect on the development of an infant. Vitamin D status of mothers and their infants are closely correlated. While hypovitaminosis D has emerged as a significant public health problem across all age groups, there is limited information of this condition in lactating mothers and their breast fed infants. AIM To evaluate the vitamin D status of lactating mothers and their breast fed infants. SUBJECTS AND METHODS 180 healthy lactating mothers and exclusively breast fed infants, 2-24 weeks old, were recruited for the study. The mother-infant pairs underwent concurrent clinical, biochemical and hormonal evaluation for calcium-vitamin D-PTH axis. RESULTS The mean serum 25(OH)D values in lactating mothers was 27.2 +/- 14.6 nmol/l (10.9 +/- 5.8 ng/ml), while that of their infants was 28.9 +/- 20.8 nmol/l (11.6 +/- 8.3 ng/ml). Serum 25(OH)D levels <25 nmol/l (10 ng/ml) were found in 47.8% of the mothers and 43.2% of the infants. Among these, elevated PTH levels (>54 pg/ml) were seen in 59.3% of the mothers and 69.6% of the infants. A highly significant negative correlation was found between serum 25(OH)D and PTH in mothers (r = -0.480, p = 0.01) and their infants (r = -0.431, p = 0.01). A strong positive correlation was seen of 25(OH)D levels in mother-infant pairs (r = 0.324, p = 0.001). CONCLUSIONS A high prevalence of vitamin D deficiency was found in lactating mothers and their exclusively breast fed infants. Infants born to mothers with hypovitaminosis D had 3.8 times higher risk of developing hypovitaminosis D as compared to those born to mothers with normal vitamin D levels.

Common Variants of IL6, LEPR, and PBEF1 Are Associated With Obesity in Indian Children

The increasing prevalence of obesity in urban Indian children is indicative of an impending crisis of metabolic disorders. Although perturbations in the secretion of adipokines and inflammatory molecules in childhood obesity are well documented, the contribution of common variants of genes encoding them is not well investigated. We assessed the association of 125 common variants from 21 genes, encoding adipocytokines and inflammatory markers in 1,325 urban Indian children (862 normal weight [NW group] and 463 overweight/obese [OW/OB group]) and replicated top loci in 1,843 Indian children (1,399 NW children and 444 OW/OB children). Variants of four genes (PBEF1 [rs3801266] [P = 4.5 × 10−4], IL6 [rs2069845] [P = 8.7 × 10−4], LEPR [rs1137100] [P = 1.8 × 10−3], and IL6R [rs7514452] [P = 2.1 × 10−3]) were top signals in the discovery sample. Associations of rs2069845, rs1137100, and rs3801266 were replicated (P = 7.9 × 10−4, 8.3 × 10−3, and 0.036, respectively) and corroborated in meta-analysis (P = 2.3 × 10−6, 3.9 × 10−5, and 4.3 × 10−4, respectively) that remained significant after multiple testing corrections. These variants also were associated with quantitative measures of adiposity (weight, BMI, and waist and hip circumferences). Allele dosage analysis of rs2069845, rs1137100, and rs3801266 revealed that children with five to six risk alleles had an approximately four times increased risk of obesity than children with less than two risk alleles (P = 1.2 × 10−7). In conclusion, our results demonstrate the association of the common variants of IL6, LEPR, and PBEF1 with obesity in Indian children.

A study of insulin resistance by HOMA-IR and its cut-off value to identify metabolic syndrome in urban Indian adolescents.

Objective: Insulin resistance (IR) and associated metabolic abnormalities are increasingly being reported in the adolescent population. Cut-off value of homeostasis model of assessment IR (HOMA-IR) as an indicator of metabolic syndrome (MS) in adolescents has not been established. This study aimed to investigate IR by HOMA-IR in urban Indian adolescents and to establish cut-off values of HOMA-IR for defining MS. Methods: A total of 691 apparently healthy adolescents (295 with normal body mass index (BMI), 205 overweight, and 199 obese) were included in this cross-sectional study. MS in adolescents was defined by International Diabetes Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. IR was calculated using the HOMA model. Results: Mean height, waist circumference (WC), waist/hip ratio (WHR), waist/height ratio (WHtR), and blood pressure were significantly higher in boys as compared to girls. The HOMA-IR values increased progressively from normal weight to obese adolescents in both sexes. Mean HOMA-IR values increased progressively according to sexual maturity rating in both sexes. HOMA-IR value of 2.5 had a sensitivity of >70% and specificity of >60% for MS. This cut-off identified larger number of adolescents with MS in different BMI categories (19.7% in normal weight, 51.7% in overweight, and 77.0% in obese subjects) as compared to the use of IDF or ATP III criteria for diagnosing MS. Odds ratio for having IR (HOMA-IR of >2.5) was highest with WHtR (4.9, p <0.0001) and WC (4.8, p <0.0001), compared to WHR (3.3, p <0.0001). Conclusions: In Indian adolescents, HOMA-IR increased with sexual maturity and with progression from normal to obese. A HOMA-IR cut-off of 2.5 provided the maximum sensitivity and specificity in diagnosing MS in both genders as per ATP III and IDF criteria. Conflict of interest:None declared.

Role of Calcium Deficiency in Development of Nutritional Rickets in Indian Children: A Case Control Study

CONTEXT Nutritional rickets is usually attributed to vitamin D deficiency. Studies from some tropical countries have postulated low dietary intake of calcium as the cause of nutritional rickets. Both vitamin D and dietary calcium deficiency are highly prevalent in India. Information on their relative contribution in the development of rickets in Indian children is limited. OBJECTIVE The aim was to study the role of calcium and vitamin D deficiency in causation of nutritional rickets in young Indian children. DESIGN AND METHODS In a case-control study, 67 children with nutritional rickets and 68 age- and sex-matched healthy controls were compared for demographic factors, nutritional status, sun exposure (UV score), dietary calcium and phytate intake (for subjects not breast-fed at presentation), and biochemical parameters [serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxyvitamin D (25OHD), and PTH]. RESULTS Mean intake of calcium (204±129 vs. 453±234 mg/d; P<0.001) and proportion of calcium from dairy sources (41.7 vs. 88.6%; P<0.001) were significantly lower in cases vs. controls. The dietary intake of phytate was also significantly higher in cases (P=0.01). Median serum 25OHD level (interquartile range) in both cases and controls was in the range of deficiency [13.7 (10; 17.9) and 19.4 (12.3; 24.6) ng/ml, respectively]. There was no significant difference in the serum 25OHD level (P=0.08) or sun exposure as measured by UV score (P=0.39) among the cases and controls. In cases with rickets, significant negative correlations were seen between dietary calcium intake and radiological score (r=-0.28; P=0.03) and PTH (r=-0.26; P=0.02). No correlation was found between serum 25OHD level and radiological score or biochemical parameters of rickets. CONCLUSIONS Rickets develops when low dietary calcium intake coexists with a low or borderline vitamin D nutrition status.

Genetic Variant of AMD1 Is Associated with Obesity in Urban Indian Children

Background Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI). We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children. Methodology/Principal Findings We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW) and 463 over-weight/obese (OW/OB) children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB) in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [OR = 1.41, P = 1.5×10-4] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [OR = 1.28, P = 4.2×10-3] and meta-analysis [OR = 1.35, P = 1.9×10-6]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis. Conclusions/Significance Our study provides first evidence for the association of AMD1 variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken.