Impact of three different daily doses of vitamin D3 supplementation in healthy schoolchildren and adolescents from North India: a single-blind prospective randomised clinical trial.

In India, there is a lack of information about the adequate daily dose of vitamin D3 supplementation in school children. Hence, we undertook this study to evaluate the adequacy and efficacy of different doses of vitamin D3 in schoolchildren. A total of 1008 vitamin D-deficient (VDD) children, aged 6-16 years with serum 25-hydroxyvitamin D (25(OH)D) levels <50nmol/l, were cluster randomised into three groups (A-344, B-341 and C-232) for supplementation (600, 1000 and 2000 IU daily) of vitamin D3 under supervision for 6 months. Of the 1008 subjects who completed the study, 938 (93 %) were compliant. Baseline and post-supplementation fasting blood and urine samples were evaluated for Ca, phosphates, alkaline phosphatase, 25(OH)D and parathormone and urine Ca:creatinine ratio. The mean age of the subjects was 11·7 (sd 2·4) years, and the overall mean baseline serum 25(OH)D level was 24·3 (SD 9·5)nmol/l. Post-supplementation rise in serum 25(OH)D in compliant group was maximum with 2000 IU (70·0 (SD 30·0)nmol/l), followed by 1000 IU (46·8 (SD 22·5)nmol/l) and 600 IU (36·5 (SD 18·5)nmol/l), and serum 25(OH)D levels of ≥50nmol/l were achieved in 71·5, 81·8 and 92·9 % by groups A, B and C, respectively. Secondary hyperparathyroidism decreased from 31·7 to 8·4 % post-supplementation. Two participants developed hypercalciuria, but none developed hypercalcaemia. Children with VDD benefit maximum with the daily supplementation of 2000 IU of vitamin D3. Whether recommendations of 400 IU/d by Indian Council of Medical Research or 600 IU by Indian Academy of Pediatrics or Institute of Medicine would suffice to achieve vitamin D sufficiency in children with VDD remains debatable.

A randomised controlled trial comparing the efficacy of micellised and fat-soluble vitamin D3 supplementation in healthy adults.

Nanoemulsion formulation of vitamin D3 have been shown to have better bioavailability than the coarse emulsion preparation in vitro and in vivo animal studies. In the absence of randomised trial in humans, comparing the efficacy of nanotechnology-based miscellised vitamin D3 over conventional vitamin D3, we undertook this study. A total of 180 healthy adults were randomised to receive either micellised (DePura, group A) or conventional vitamin D3 (Calcirol, group B) at a monthly dose of 60 000 IU (1500µg) for 6 months. The outcome parameters were serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), Ca, phosphate, alkaline phosphatase and urinary Ca:creatinine ratio. A total of eighty-nine subjects in group A and seventy-seven in group B completed the trial. Subjects in both the groups had a significant increase in their serum 25(OH)D levels following supplementation (group A: 21·5 (sd 10·9) to 76·7 (sd 18·8) nmol/l (P<0·001); group B: 22·8 (sd 10·4) to 57·8 (sd 16·0) nmol/l (P<0·001)). Participants in micellised group had an additional increase of 20·2 (95 % CI 14·0, 26·4) nmol/l in serum 25(OH)D levels (P<0·001). The difference between the groups was 17·5 (95 % CI 11·8, 23·1) nmol/l, which remained statistically significant (P<0·001) even after adjustment for age and sex. Significant decline in mean serum PTH was observed in both the groups. No hypercalcaemia or hypercalciuria was noted. Although supplementation with both the preparations resulted in a significant rise in serum 25(OH)D levels, micellised vitamin D3 appeared to be more efficacious in achieving higher levels of serum 25(OH)D.

Relationship Between BMD and Prevalent Vertebral Fractures in Indian Women Older Than 50 Yr.

The purpose of the study was to study the relationship of morphometric vertebral fractures with bone mineral density (BMD) in Indian women older than 50 yr. Four hundred fifteen healthy Indian women older than 50 yr (mean age: 62.8 yr) underwent lateral X-rays of the lumbar and thoracic spine. Genant's semiquantitative method was used to diagnose and classify morphometric vertebral fractures. BMD was measured by DXA at lumbar spine and total hip. Recruited subjects underwent anthropometric, biochemical, and hormonal evaluation. Vertebral fractures were present in 17.1% (95% confidence interval: 13.5, 20.8) subjects. Prevalence of osteoporosis based on BMD was 35.7%. By adding those with prevalent fractures, the number of women requiring therapy for osteoporosis would increase to 46.5%. The BMD measured at femur neck, total hip, and lumbar spine (L1eL4) was not found to be lower in women with vertebral fractures as compared with those without fractures. BMD was not found to be lower in women with vertebral fractures as compared with those without fractures. Significant number of additional subjects with BMD in the normal or osteopenic range become eligible for osteoporosis treatment when presence of vertebral fracture is used as an independent indication for such treatment.

Normative data of body fat mass and its distribution as assessed by DXA in Indian adult population.

Dual-energy X-ray absorptiometry (DXA) assessment of body fat mass is precise and highly correlated with under water weighing. In view of ethnic differences, we undertook this study to prepare normative data for body fat mass in apparently healthy adult Indians and correlate it with body mass index (BMI). This cross-sectional population-based study included 2347 subjects (male: 924; female: 1423) aged >20 yr who participated in a general health examination. They were evaluated for anthropometry and body fat mass by DXA. All subjects were categorized as overweight and obese based on standard BMI criteria. Mean age and BMI were 49.1 ± 18.2yr and 25.0 ± 4.7kg/m(2), respectively. Mean percent total and regional fat (trunk, arm, and leg) reached maximum in the age group of 30-40yr in males and 50-60yr in females. Females had significantly higher total and regional fat mass compared with males. Fat mass was positively correlated with age (r = 0.224; p < 0.00001) and BMI (r = 0.668; p < 0.00001). Prevalence of overweight and obesity was seen in 2119 (46.1%) and 536 (13.8%), respectively, according to World Health Organization definition and 64.0% and 31.1%, respectively, as per Indian guidelines. Percent total body fat mass (PTBFM) of 25% in males and 30% in females corresponds to BMI of 22.0kg/m(2) with sensitivity of >80% and specificity of >70% in receiver operating characteristic curve analysis. Body fat mass in Indians is higher than that in Western populations for a given age and BMI. PTBFM of 25% in males and 30% in females corresponds to BMI of 22kg/m(2) in Indians.

A Randomized controlled trial on safety and efficacy of single intramuscular versus staggered oral dose of 600 000IU Vitamin D in treatment of nutritional rickets.

OBJECTIVE: Comparison of efficacy and safety of two different regimens of vitamin D-600 000 IU as a single intramuscular dose, and 60 000IU orally once a week for 10 weeks-in treatment of nutritional rickets. METHODS: Children with nutritional rickets (age: 0.5-5 years, n = 61) were randomized to receive either 60 000IU vitamin D orally once a week for 10 weeks or 600 000IU single intramuscular injection. Serum calcium, phosphate, alkaline phosphatase, urinary calcium/creatinine ratio, serum 25 hydroxy vitamin D and radiological score were compared at 12-week follow-up. RESULTS: No difference was found in efficacy of the two regimens on comparing biochemical and radiological parameters. Serum 25 hydroxy vitamin D >100 ng/ml was found in two children in the oral group and one child in the intramuscular group. No child developed hypercalcemia or hypercalciuria after starting treatment. CONCLUSION: Staggered oral and one-time intramuscular administrations of 600 000IU vitamin D are equally effective and safe in treatment of nutritional rickets.

Efficacy of homeopathic intervention in subclinical hypothyroidism with or without autoimmune thyroiditis in children: an exploratory randomized control study.

INTRODUCTION: The decision to treat subclinical hypothyroidism (SCH) with or without autoimmune thyroiditis (AIT) in children, presents a clinical dilemma. This study was undertaken to evaluate the efficacy of individualized homeopathy in these cases. METHODS: The study is an exploratory, randomized, placebo controlled, single blind trial. Out of 5059 school children (06-18 years) screened for thyroid disorders, 537 children had SCH/AIT and 194 consented to participate. Based on primary outcome measures (TSH and/or antiTPOab) three major groups were formed: Group A - SCH + AIT (n = 38; high TSH with antiTPOab+), Group B - AIT (n = 47; normal TSH with antiTPOab+) and Group C - SCH (n = 109; only high TSH) and were further randomized to two subgroups-verum and control. Individualized homeopathy or identical placebo was given to respective subgroup. 162 patients completed 18 months of study. RESULTS: Baseline characteristics were similar in all the subgroups. The post treatment serum TSH (Group A and C) returned to normal limits in 85.94% of verum and 64.29% of controls (p < 0.006), while serum AntiTPOab titers (Group A and B) returned within normal limits in 70.27%of verum and 27.02%controls (p < 0.05). Eight children (10.5%) progressed to overt hypothyroidism (OH) from control group. CONCLUSION: A statistically significant decline in serum TSH values and antiTPOab titers indicates that the homeopathic intervention has not only the potential to treat SCH with or without antiTPOab but may also prevent progression to OH.

Strong influence of variants near MC4R on adiposity in children and adults: a cross-sectional study in Indian population.

Common variants near melanocortin 4 receptor (MC4R) gene are shown to be associated with adiposity but have varied effects in different age groups. Among Indians, studies have shown association of these variants with obesity in adults, but their association in children is yet to be confirmed. We evaluated association of rs17782313 and rs12970134 near MC4R with adiposity and related traits in Indians including 1362 children and 4077 adults (consisting of 2049 diabetic and 2028 nondiabetic adult subjects). Both variants rs17782313 and rs12970134 showed strong association with adiposity measures (weight, body mass index and waist circumference) in children (P-range 7.6 × 10(-5)-3.8 × 10(-12)) and nominal association in nondiabetic adults (P-range 0.05-0.003). Effect sizes on adiposity measures in children (ß range 0.22-0.26 Z-score) were ~3-fold higher compared with adults (ß range 0.06-0.08). The minor alleles of both variants showed borderline association (P-range 0.08-0.04) with risk of type 2 diabetes in adults. Meta-analysis of rs12970134 in >12 000 Indian adults corroborated its association with adiposity (P≤2.2 × 10(-9)), homeostasis model assessment-estimated insulin resistance (P=4.0 × 10(-5)) and type 2 diabetes (P=0.003) with only moderate heterogeneity, suggesting similar effect on adult Indians residing in different geographical regions. In conclusion, the study demonstrates association of variants near MC4R with obesity and related traits in Indian children and adults, with higher impact during childhood.

Impact of body mass index on thyroid functions in Indian children.

OBJECTIVE: There is controversy about the relation of thyroid functions and body mass index. The present study was aimed to assess the relationship between thyroid function and body mass index in Indian school children. DESIGN: Population survey. PATIENTS: Data were collected from 25 schools in 19 cities across five different geographical zones of India. Children, who consented, were evaluated for anthropometry and blood tests. Children were categorized as overweight and obese based on standard BMI criteria. MEASUREMENTS: Serum samples were analysed for free T3, free T4, TSH and anti-TPO antibodies. RESULTS: A total of 13,691 children in the age group of 5-18 years formed the study population. The mean age and mean BMI were 11·9 ± 3·0 years and 18·48 ± 3·89 kg/m² respectively. Among these, 2119 (15·5%) children were overweight and 536 (3·9%) were obese. Subclinical hypothyroidism was present in 943 (6·9%) children.FT3 and TSH levels increased and FT4 levels decreased with increasing BMI in euthyroid boys and girls. Prevalence of SCH was significantly higher in obese/overweight children (9·0%, vs 6·5%; P = 0·034) as compared with normal BMI children. CONCLUSIONS: Serum FT3 and TSH were positively while FT4 was negatively associated with BMI in apparently healthy euthyroid children.

Correlation between bone mineral density measured by peripheral and central dual energy X-ray absorptiometry in healthy Indian children and adolescents aged 10-18 years.

There are few large-scale studies on the utility of peripheral dual energy X-ray absorptiometry (pDXA) in children. As central dual energy X-ray absorptiometry (cDXA) equipment is not commonly available in the developing world, we assessed the correlation of bone mineral density (BMD) with cDXA and pDXA in children to determine the optimal Z-score thresholds of pDXA for predicting two predefined Z-score cutoffs (≤-1, ≤-2) of cDXA in 844 subjects (441 boys, 403 girls) aged 10-18 years. The BMD of antero-posterior lumbar spine (L1-L4), proximal femur and forearm was measured by cDXA, while the peripheral BMD of forearm and calcaneus was estimated using pDXA. The correlation was statistically significant at all sites (p<0.01). The coefficients ranged from 0.56 to 0.79 in boys and 0.17 to 0.32 in girls. A significant positive correlation was observed between BMD by pDXA and cDXA in Indian children, with a strong gender difference in both the extent of correlation and the ability of peripheral BMD to predict central BMD.

Efficacy of vitamin D loading doses on serum 25-hydroxy vitamin D levels in school going adolescents: an open label non-randomized prospective trial.

AIM: Vitamin D deficiency (VDD) among adolescents is a major health problem in India. The aim of this study was to assess the efficacy of therapeutic/loading doses of vitamin D supplementation on serum 25-hydroxy vitamin D (25OHD) levels in vitamin D deficient adolescents. METHODS: A total of 482 out of the 511 subjects recruited for the study were divided into three groups, each group receiving 60,000 IU of vitamin D3 weekly for 4, 6 and 8 weeks followed by 600 IU daily for 12 weeks, respectively. Clinical evaluation was followed by estimation of biochemical markers and serum 25OHD levels. RESULTS: VDD was observed in 94.8% of adolescents. All three vitamin D loading doses were equally efficacious in achieving vitamin D sufficiency >75 nmol/L (>30 ng/mL) in more than 90% subjects in the three groups. Mean 25OHD levels in groups 2 and 3 following maintenance therapy were 67.5±16.5 nmol/L (27.0±6.6 ng/mL) and 70.0±21.8 nmol/L (28.0±8.7 ng/mL), respectively. CONCLUSION: Supplementing 60,000 IU of vitamin D3 per week for 4-8 weeks, followed by 600 IU daily through fortified milk, is an effective strategy for achieving vitamin D sufficiency in Indian adolescents.

Management of nutritional rickets in Indian children: a randomized controlled trial.

INTRODUCTION: Rickets is usually attributed to vitamin D deficiency. However, recent studies have implicated dietary calcium deficiency in its etiology. Information on relative efficacy of calcium, vitamin D or both together in healing of rickets is limited. OBJECTIVE: To study effect of treatment with calcium, vitamin D or a combination of these two on healing of nutritional rickets in young children. DESIGN: Randomized controlled trial. METHODS: Sixty-seven cases of nutritional rickets in the age group of 6 months to 5 years were randomly allocated to receive vitamin D (600 000 IU single intramuscular dose), calcium (75 mg/kg/day elemental calcium orally) or a combination of the above two for a period of 12 weeks. The demographic parameters, nutritional status, dietary calcium and phytate intake were assessed for all. Radiographs (wrist and knee) and biochemical parameters (serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxycholecalciferol and parathyroid hormone) were evaluated at baseline, 6 and 12 weeks for evidence of healing. RESULTS: Mean dietary intake of calcium in all cases was low (204 ± 129 mg/day). Mean serum 25-hydroxycholecalciferol D level was 15.9 ± 12.4 ng/ml, and 82.1% of patients had serum vitamin D levels <20 ng/ml, indicative of vitamin D deficiency. After 6 and 12 weeks of treatment, radiological and biochemical evidence of healing rickets was observed in all treatment groups, albeit to a variable extent. The combined end point of normal serum alkaline phosphatase and complete radiological healing at 12 weeks was observed in 50% subjects on combination therapy as compared with 15.7% subjects on vitamin D alone and 11.7% on calcium alone. CONCLUSIONS: Children with rickets had a low serum vitamin D level and a low dietary calcium intake. The best therapeutic response was seen with a combination of vitamin D and calcium than either of them given alone. TRIAL REGISTRATION NUMBER: CTRI/2010/091/000448.

Thyroid status two decades after salt iodization: country-wide data in school children from India.

OBJECTIVE: Country-wide evaluation of thyroid disorders in school children following two decades of universal salt iodization (USI) has not been carried out till date. This study was planned with aim to assess thyroid status of school children two decades after the launch of USI programme. DESIGN: Population survey. PATIENTS: We collected data from 25 schools in 19 cities across five different geographical zones of India. Those children who were evaluated for anthropometry, and goitre status by palpation formed 'total population'. Children who consented to give blood samples were defined as 'study population'. MEASUREMENTS: Serum free T3, free T4, TSH, anti-TPO antibody and thyroid ultrasound. RESULTS: A total of 38,961 children aged 5-15 years formed total population. Goitre rate was 15.5% while thyroid hypoechogenicity was found in 4404 (11.3%) children. In the study population (13,790 children), 2258 (16.4%) had goitre, 505 (3.7%) had positive anti-TPO antibody titres, 1001 (7.3%) had hypothyroidism (TSH > 5.2 µIU/ml) and 41 (0.3%) had thyrotoxicosis (TSH < 0.1 µIU/ml). Among goitrous children, 203 (9.0%) had anti-TPO positivity, 365 (16.1%) had hypoechogenicity of thyroid and either of these were present in 488 (21.6%) children. CONCLUSIONS: Endemic goitre in school children persisted nationwide, despite more than two decades of USI programme. Thyroid autoimmunity only partially explains the increase in goitre prevalence.

Role of B12 and homocysteine status in determining BMD and bone turnover in young Indians.

Vitamin B(12) (B(12)) deficiency and hyperhomocysteinemia (HHcy) are independent risk factors for low bone mineral density (BMD) and fracture risk. We studied the role of HHcy and B(12) deficiency in determining the peak bone mass in Indians. Randomly selected 151 healthy young adult subjects (females 100, mean age: 26 yr) underwent evaluation of dietary intake of calcium and B(12); sun exposure; estimation of BMD by dual-energy X-ray absorptiometry at total hip, forearm, and lumbar spine; serum 25(OH)D(3); intact parathyroid hormone; B(12); homocysteine (Hcy); and bone turnover markers (BTMs) serum crosslaps, N-mid osteocalcin, and bone-specific alkaline phosphatase. Hypovitaminosis D (serum 25OHD(3)<20 ng/mL) and serum ALP level >150 IU/L were seen in 83% and 27%, respectively. Median serum B(12) and Hcy levels were 140 pg/mL (interquartile range [IQR]: 72-230 pg/mL) and 18 µmol/L (IQR 14-32 µmol/L); B(12) deficiency (serum B(12)<200 pg/mL) and HHcy (serum Hcy>30 µmol/L) were present in 71% and 68%, respectively. Low BMD (Z-score <-2.0) was present in 17% of subjects. There was no significant correlation between serum Hcy, folate, B(12), BTM, and BMD. BMD was predicted by height, weight, and body mass index. Young Indian healthy adults have high prevalence of hypovitaminosis D, B(12) deficiency, and HHcy. There is no correlation of serum B(12), folate, and Hcy status with BTMs and BMD in young, healthy, vegetarian Indian adults. Anthropometric variables predict BMD in young Indians.

Establishment of age-specified bone mineral density reference range for Indian females using dual-energy X-ray absorptiometry.

We undertook this study to establish age-specified bone mineral density (BMD) reference range for Indian females using dual-energy X-ray absorptiometry. BMD at multiple skeletal sites was measured in 2034 healthy women aged 18--85yr. The effect of anthropometry and biochemical parameters on BMD was determined. Peak BMD was observed between 30 and 35yr at the hip, lumbar spine, and radius. Significant positive correlation of height and weight with BMD was observed at 33% radius, femur neck, and lumbar spine, whereas significant negative correlation was seen between serum alkaline phosphatase (ALP) and serum parathyroid hormone levels with BMD at aforementioned sites. On multivariate regression analysis, age, weight, and serum ALP were the most consistent contributors to variance in the BMD. Compared with age-matched US females, BMD of lumbar spine was significantly lower for our subjects in all age groups. Prevalence of osteoporosis among women aged older than 50yr was significantly higher based on Caucasian T-scores as opposed to using peak BMD/standard deviation values from the population under review at lumbar spine but not at femoral neck.

Effects of sports training & nutrition on bone mineral density in young Indian healthy females.

BACKGROUND & OBJECTIVES: Peak bone mass, a major determinant of osteoporosis is influenced by genetic, nutritional, lifestyle and hormonal factors. This study was designed to evaluate the impact of sports training on dietary intake and bone mineral and metabolic parameters in young healthy Indian females. METHODS: Healthy female college going students (N=186, sportswomen, 90; controls 96) in the age group of 18-21 yr, residing in New Delhi (India) were evaluated for anthropometry, biochemistry (serum total and ionic calcium, phosphorus, total alkaline phosphatase, 25-hydroxyvitamin D & parathyroid hormone), diet, physical activity and lifestyle. Bone mineral density (BMD) at hip, forearm and lumbar spine were studied using central DXA. RESULTS: Sports related physical activity (3 vs. 0 h/day, P < 0.001) and direct sunlight exposure (120 vs. 30 min/day, P < 0.001) were significantly higher in sportswomen than in controls with sedentary lifestyle. Significantly higher intake of all macronutrients (energy, protein, carbohydrates and fat) and dietary calcium was noted in the diets of sportswomen. Mean serum 25(OH)D levels were significantly higher (53.0 ± 18.9 vs. 12.9 ± 7.7 nmol/l; P < 0.001) while PTH (35.3 ± 17.6 vs. 51.7 ± 44.9 pg/ml; P < 0.001) and ALP levels (194.0 ± 51.0 vs. 222.1 ± 51.4 IU/l; P<0.001) were significantly lower in sportswomen when compared to controls. No significant difference was found in ionized calcium and inorganic phosphorus in the two groups. Significantly higher (P < 0.001) total BMD and BMD at all sites except femur neck were found in sportswomen than controls (P < 0.001). INTERPRETATION & CONCLUSIONS: Physical activity, optimal nutrition and adequate sun exposure are vital for attaining peak bone mass.

Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization.

We undertook this study to characterize peak bone density and evaluate its determinants in a healthy cohort of young adult male paramilitary personnel. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 473 healthy men aged 21-40 yr. The effect of anthropometry and biochemical parameters on BMD was determined. Mean BMD values of L1-L4, forearm, total hip, and femoral neck were 1.170+/-0.137, 0.755+/-0.089, 1.129+/-0.130, and 1.115+/-0.133 g/cm(2), respectively. BMD values for 31- to 40-yr age group were lower than those of 20- to 30-yr age group except for forearm, which was higher in the former. Significant positive correlation was observed between height, weight, and body mass index with BMD. On multivariate regression analysis, weight was the most consistent contributor to variance in the BMD. Compared with age-matched US males, BMD of total hip and femoral neck were higher for Indian paramilitary personnel by 3.58% and 4.2%, whereas lumbar spine BMD was lower by 4.1%. In conclusion, peak BMD in healthy Indian males was achieved by 30 yr of age at lumbar spine and hip, with weight being the most consistent contributor to variance in BMD. Peak BMD in this population was comparable to that reported in white US males.

Effect of Vitamin D Supplementation on Bone Turnover Markers in Children and Adolescents from North India.

OBJECTIVES: Vitamin D is known to play an important role in bone mineral metabolism. Its deficiency may affect growth and status of bone markers in children. Hence, we undertook to study the status of bone markers in children with vitamin D deficiency (VDD) and impact of vitamin D3 supplementation on them. MATERIALS AND METHODS: Total 468 out of 615 children and adolescents with VDD, who were given either of the three doses (600, 1000, and 2000) of vitamin D supplementation, were included in the study. These 468 children with pre- and postsupplementation preserved samples with available anthropometry, serum biochemistry, 25-hydroxy-vitamin D, and parathormone were evaluated for bone formation (procollagen type 1 amino-terminal propeptide [P1NP]) and resorption (ß-cross laps [CTx]) markers. RESULTS: The mean age and body mass index of these children were 11.3 ± 2.3 years (boys: 11.5 ± 2.4; girls: 12.2 ± 1.2 years; P = 0.03) and 18.1 ± 3.8 kg/m2 (boys: 18.2 ± 3.9; girls: 17.6 ± 3.2 kg/m2; P = 0.208), respectively. There were 8.8% subjects with severe, 42.7% with moderate, and 48.5% with mild VDD. There was a significant decline in serum P1NP (from 691 ± 233 ng/ml to 640 ± 259 ng/ml, P < 0.001) and CTx (from 1.67 ± 0.53 ng/ml to 1.39 ± 0.51 ng/ml, P < 0.001) following supplementation. Though decline in serum P1NP and CTx levels was observed in both boys and girls, among all three supplementation groups and VDD categories, the effect was more marked in serum CTx than P1NP levels. CONCLUSIONS: Vitamin D supplementation in VDD children resulted in decrease in both bone formation (P1NP) and resorption (CTx). The impact, however, was more marked on bone resorption than bone formation.

Normative range of blood biochemical parameters in urban Indian school-going adolescents.

Adolescence is the most critical phase of human growth that radically alters physiology of the body and wherein any inconsistency can lead to serious health consequences in adulthood. The timing and pace at which various developmental events occur during adolescence is highly diverse and thus results in a drastic change in blood biochemistry. Monitoring the physiological levels of various biochemical measures in ample number of individuals during adolescence can call up for an early intervention in managing metabolic diseases in adulthood. Today, only a couple of studies in different populations have investigated blood biochemistry in a small number of adolescents however, there is no comprehensive biochemical data available worldwide. In view, we performed a cross-sectional study in a sizeable group of 7,618 Indian adolescents (3,333 boys and 4,285 girls) aged between 11-17 years to inspect the distribution of values of common biochemical parameters that generally prevails during adolescence and we observed that various parameters considerably follow the reported values from different populations being 3.56-6.49mmol/L (fasting glucose), 10.60-199.48pmol/L (insulin), 0.21-3.22nmol/L (C-peptide), 3.85-6.25% (HbA1c), 2.49-5.54mmol/L (total cholesterol), 1.16-3.69mmol/L (LDL), 0.78-1.85mmol/L (HDL), 0.33-2.24mmol/L (triglycerides), 3.56-11.45mmol/L (urea), 130.01-440.15µmol/L (uric acid) and 22.99-74.28µmol/L (creatinine). Barring LDL and triglycerides, all parameters differed significantly between boys and girls (p< 0.001). Highest difference was seen for uric acid (p = 1.3 x10-187) followed by C-peptide (p = 6.6 x10-89). Across all ages during adolescence, glycemic and nitrogen metabolites parameters varied markedly with gender. Amongst lipid parameters, only HDL levels were found to be significantly associated with gender following puberty (p< 0.001). All parameters except urea, differed considerably in obese and lean adolescents (p< 0.0001). The present study asserts that age, sex and BMI are the essential contributors to variability in blood biochemistry during adolescence. Our composite data on common blood biochemical measures will benefit future endeavors to define reference intervals in adolescents especially when the global availability is scarce.

Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at CETP Locus in Indians.

Indians, a rapidly growing population, constitute vast genetic heterogeneity to that of Western population; however they have become a sedentary population in past decades due to rapid urbanization ensuing in the amplified prevalence of metabolic syndrome (MetS). We performed a genome-wide association study (GWAS) of MetS in 10,093 Indian individuals (6,617 MetS and 3,476 controls) of Indo-European origin, that belong to our previous biorepository of The Indian Diabetes Consortium (INDICO). The study was conducted in two stages-discovery phase (N = 2,158) and replication phase (N = 7,935). We discovered two variants within/near the CETP gene-rs1800775 and rs3816117-associated with MetS at genome-wide significance level during replication phase in Indians. Additional CETP loci rs7205804, rs1532624, rs3764261, rs247617, and rs173539 also cropped up as modest signals in Indians. Haplotype association analysis revealed GCCCAGC as the strongest haplotype within the CETP locus constituting all seven CETP signals. In combined analysis, we perceived a novel and functionally relevant sub-GWAS significant locus-rs16890462 in the vicinity of SFRP1 gene. Overlaying gene regulatory data from ENCODE database revealed that single nucleotide polymorphism (SNP) rs16890462 resides in repressive chromatin in human subcutaneous adipose tissue as characterized by the enrichment of H3K27me3 and CTCF marks (repressive gene marks) and diminished H3K36me3 marks (activation gene marks). The variant displayed active DNA methylation marks in adipose tissue, suggesting its likely regulatory activity. Further, the variant also disrupts a potential binding site of a key transcription factor, NRF2, which is known for involvement in obesity and metabolic syndrome.

Role of Parathyroid Hormone in Determination of Fat Mass in Patients with Vitamin D Deficiency.

BACKGROUND: Obesity has become a global epidemic and it is rising is Asia. Vitamin D deficiency (VDD) is widely prevalent in the Indian subcontinent. Studies have linked VDD to obesity and shown correlation between parathyroid hormone (PTH), 25-hydroxy Vitamin D (25(OH)D), and fat mass (FM). However, studies on the role of PTH among subjects with VDD are lacking. OBJECTIVE: The objective of this study is to study the role of PTH in the determination of FM in participants with VDD. SUBJECTS: Five hundred and fifty-one adults (m:247, f:304) were included in this study. MATERIALS AND METHODS: Total and regional (trunk, arm, and leg) FM was assessed by dual X-ray absorptometry. Biochemical and hormonal parameters such as calcium, phosphorus, alkaline phosphatase, ionic calcium, 25(OH)D, and PTH were also analyzed. RESULTS: The mean age of the study population was 58.8 ± 15.8 years (Male: [63.3 ± 13.1], Female: [55.2 ± 16.9]). FM and body mass index were significantly lower in females with higher levels of serum 25(OH)D. Total FM was negatively correlated with serum 25(OH)D (r = -0.363, P < 0.0001) and positively correlated with serum PTH (r: 0.262, P < 0.0001) in females only. Females with VDD and secondary hyperparathyroidism had higher FM than those with normal PTH. CONCLUSIONS: Females with VDD had higher total and regional FM. However, this correlation was evident only in those with high serum PTH levels, suggesting a potential role of PTH in the accumulation of FM.