Calcifediol boosts efficacy of ChAdOx1 nCoV-19 vaccine by upregulating genes promoting memory T cell responses.

The ChAdOx1 nCoV-19 (COVISHIELD) vaccine has emerged as a pivotal tool in the global fight against the COVID-19 pandemic. In our previous study eligible subjects were supplemented with calcifediol, a direct precursor to the biologically active form of vitamin D, calcitriol with an objective to enhance the immunogenicity of the COVISHIELD vaccine. Herein we investigated the effects of calcifediol supplementation on gene expression profiles in individuals who received the COVISHIELD vaccine. Peripheral blood mononuclear cells were isolated from vaccinated individuals with and without calcifediol supplementation at baseline, 3rd and 6th month, and the gene expression profiles were analyzed using high-throughput sequencing. The results revealed distinct patterns of gene expression associated with calcifediol supplementation, suggesting potential molecular mechanisms underlying the beneficial effects of calcifediol in improving the efficacy of COVISHIELD vaccine via augmentation of T cell activation, proliferation and T cell memory responses. Additionally, there was upregulation of NOD like receptor, JAK/STAT and TGF beta signaling pathways. Calcifediol supplementation in vaccinated individuals also downregulated the pathways related to the Coronavirus disease. Taken together, our findings provide valuable insights into the interplay between vitamin D receptor (VDR) signaling and vaccine-induced immune responses and offer another approach in improving vaccination induced antiviral responses.

Impact of BMI on serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with calcifediol supplementation in young adults: a longitudinal study.

BACKGROUND: High body mass index (BMI) is a risk factor for vitamin D deficiency. The rise in serum 25-hydroxyvitamin D [25(OH)D] concentrations following cholecalciferol supplementation is suboptimal, owing to adipose tissue sequestration and/or volumetric dilution. Calcifediol is a proven potent oral alternative for vitamin D supplementation, but whether BMI adversely affects its efficacy in raising 25(OH)D concentrations, is not well known. MATERIAL AND METHODS: Adults with serum concentrations of 25(OH)D < 30 ng/mL were recruited and stratified as normal, overweight, or obese using WHO criteria. Baseline evaluation included 25(OH)D, parathyroid hormone (PTH), and total 1,25-dihydroxyvitamin D [1,25(OH)2D] based on BMI category (n = 883). A subset of participants was supplemented with 50 µg calcifediol (n = 193) and assessed for the rise in serum concentrations of 25(OH)D at 3- and 6-months following supplementation. RESULTS: Participants were stratified as obese (11.2%), overweight (32.1%), or normal weight (56.7%). There were no significant baseline differences in serum concentrations of 25(OH)D among the groups (13.1 ± 6.4 vs 12.8 ± 6.8 vs 11.6 ± 6.6 ng/mL, p = 0.62). Similarly, PTH or 1,25(OH)2D concentrations were not different among the groups. On follow-up, 25(OH)D concentrations increased in all three groups at 3 and 6 months from baseline. The increase in 25(OH)D was 74.4 ng/mL (IQR 35.3-115.3) in obese, followed by overweight 62.2 ng/mL (18.1-98.7) and normal weight groups 47.1 ng/mL (17.5-89.7) at 3 months. 1,25(OH)2D also increased in all groups, without any significant intergroup differences (p > 0.05). CONCLUSION: BMI does not impede the rise in 25(OH)D concentrations following supplementation with calcifediol in young adults with vitamin D deficiency.

Normative data for insulin-like growth factor-1 (IGF-1) in healthy children and adolescents from India.

BACKGROUND: Serum IGF-1 is an important biochemical tool to diagnose and monitor GH-related disorders. However, ethnic-specific Indian data following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage-specific normative data for IGF-1 in healthy Indian children and adolescents. METHODS: A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. RESULTS: We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, peak and higher IGF-1 values. The reference interval (2.5th-97.5th percentile) was broader during peri-pubertal ages, indicating a higher physiological variability. CONCLUSION: This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents.

Efficacy, safety, and dose-response effects of calcifediol supplementation on 25-hydroxyvitamin D, parathyroid hormone, and 1,25-dihydroxyvitamin D levels in healthy adults: An open-label, interventional pilot study.

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent across the globe. Cholecalciferol (Vitamin D3) fails to attain sufficient serum concentrations of 25-hydroxyvitamin D (25(OH)D) in a significant proportion of supplemented individuals. Calcifediol (25-hydroxyvitamin D3) is less studied in healthy adults and its effects on 25(OH)D, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25(OH)2D) at higher doses are not well known. MATERIALS AND METHODS: The study was an open-label, interventional trial recruiting consecutive participants with VDD who were allocated to receive either 2 capsules (50 µg-group) or 1 capsule (25 µg-group) daily doses of calcifediol. Baseline assessment included clinicodemographic parameters, dietary calcium, calcemic (calcium, inorganic phosphate, albumin, alkaline phosphatase, urine spot calcium/creatinine), and hormonal parameters (25(OH)D, PTH, and 1,25(OH)2D). Participants were followed up at 4 and 8 weeks with repeat assessments of calcemic and hormonal parameters. RESULTS: There were 64 participants, 35 (50 µg-group) and 29 (25 µg-group), without any significant difference in any of the baseline parameters. 97.1% participants in the 50 µg-group (at 4 and 8 weeks) and 93.1% (at 4 weeks) and 96.5% (at 8 weeks) in the 25 µg-group attained 25(OH)D sufficiency (≥30 ng/ml) with calcifediol. The mean serum 25(OH)D was 84.0 ± 27.7 ng/ml in the 50 µg-group and 58.0 ± 23.6 ng/ml in the 25 µg-group group at 4 weeks, which later rose to 94.3 ± 21.8 ng/ml and 76.0 ± 16.4 ng/ml, respectively, at 8 weeks. PTH levels decreased in both groups at both time points. 1,25(OH)2D rose significantly in both groups at 4 and 8 weeks but was not significantly different between both groups. There was no case of incident hypercalcemia or symptomatic nephrolithiasis. CONCLUSION: Calcifediol is a safe and efficacious alternative for oral Vitamin D supplementation in young adults. Increment in 25(OH)D levels is rapid and dose-dependent.

Normative Data on Dehydroepiandrosterone Sulphate (DHEAS) and its Attributes in Healthy Indian Children and Adolescents.

Dehydroepiandrosterone sulphate (DHEAS), the biochemical indicator of adrenarche and pubarche, is of paramount importance in the evaluation of puberty-related disorders. The reference range of DHEAS should be ethnicity, age, sex, pubarche and Tanner stage specific. Anthropometry, puberty assessment and hormonal parameters were estimated using electrochemiluminescence assay. Bone age was estimated using the BoneXpert software. Of 2191 healthy Indian children aged 5-18 y screened at Chandigarh, 1919 were included in the final analysis (994 boys). The median DHEAS levels at pubarche stage P2 were 82.10 (55.0-129.0) g/dl in girls and 132.50 (95.12-205.50) g/dl in boys. By ROC analysis, the level of DHEAS at pubarche was 63.7 g/dl (sensitivity 72.6%, specificity 64.4%) in girls and 82.2 g/dl (sensitivity 81.8%, specificity 68.8%) in boys. The median age at adrenarche was 9.5 y in both sexes. On multivariate regression analysis; bone age, body mass index (BMI), gonadal steroids, and insulin-like growth factor-1 (IGF-1) significantly correlated with serum DHEAS levels in either sex.

An open-label, randomized, crossover study to evaluate the bioavailability of nanoemulsion versus conventional fat-soluble formulation of cholecalciferol in healthy participants.

Background: Nanoemulsion preparations of cholecalciferol available in the market claim to have better bioavailability than the conventional fat-soluble cholecalciferol. However, limited data are available in humans for such preparations. We, therefore, compared the relative bioavailability of two formulations of 60,000 IU cholecalciferol (nanoemulsion oral solution, water-miscible vitamin D3 [test] vs soft gelatin capsules [reference]) in healthy adult participants. Methods: In this randomized, open-label, two sequence, single-dose, two-way crossover study (CTRI/2018/05/013839), Indian participants aged 18-45 years received single dose of nanoemulsion and capsule formulations, under fasting conditions. Blood samples collected over 120 h were assessed to determine cholecalciferol concentrations. Pharmacokinetic parameters (area under the concentration-time curve up to 120 h [AUC0-120h], maximum observed drug concentration [Cmax], time to reach maximum drug concentration [Tmax], terminal half-life [T½el], and terminal elimination rate constant [Kel]) were estimated using baseline corrected data and analyzed using analysis of variance. Results: Among the 24 eligible participants, the relative bioavailability of nanoemulsion was significantly higher than the capsules by 36% (p = 0.0001) based on AUC0-120h. Similarly, Cmax of the nanoemulsion was significantly higher by 43% (p = 0.0001) than that of the capsules. The intra-participant variability for AUC0-120h and Cmax were 23.22% and 26.51%, respectively. The Tmax, T½el, and Kel were comparable for both the formulations. No adverse effects were noted with either of the two formulations. Conclusions: Nanoemulsion oral solution of cholecalciferol showed a greater bioavailability compared with soft gelatin capsules, under fasting conditions, in healthy human participants.

Daily v. weekly oral vitamin D3 therapy for nutritional rickets in Indian children: a randomised controlled open-label trial.

The aim of the study was to compare the efficacy of daily v. weekly oral vitamin D3 therapy in radiological healing of nutritional rickets. Children 6 months to 12 years (n 132) diagnosed with nutritional rickets were randomised into three groups (n 44): group A - 2000 IU daily vitamin D3 for 12 weeks, B - 60 000 IU weekly for 3 weeks, C - 60 000 IU weekly for 6 weeks. Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and X-ray score were estimated at baseline and 12 weeks (endline). The proportion of children who achieved complete radiological healing at endline was compared between three groups by χ2 and delta change in laboratory parameters by ANOVA (parametric data) or Kruskal Wallis test (non-parametric data), respectively. Baseline 25(OH)D ≤ 20 ng/ml was seen in 119 (90·2 %), hyperparathyroidism in 90 (68·8 %) and hypocalcaemia in 96 (72·7 %). A total of 120/132 children completed the study. Complete radiological healing seen in 30 (75 %) in group A, 23 (60·5 %) in group B and 26 (61·9 %) in group C; P = 0·15, with comparable endline X-ray scores; P = 0·31. The median (interquartile range (IQR)) delta X-ray score (baseline-endline) was 7 (4,9), 5 (2·25, 6) and 6 (4,7) in groups A, B and C, respectively; P = 0·019. Median (IQR) 25(OH)D endline levels in groups A, B and C were 50·0 (26·5, 66·5), 42·1 (28·4, 54·4) and 53·5 (33·7, 71·2) ng/ml, respectively; P = 0·045. Radiological scores were comparable at endline among daily and weekly vitamin D groups with greater change from baseline in daily supplemented group.

Predictive Performance of Different Diagnostic Criteria for Overweight and Obesity Between 2008-2015 in Adolescents.

BACKGROUND: The reference cut-offs for overweight and obesity have evolved from the use of International obesity task force (IOTF) to extended IOTF and revised Indian Academy of Pediatrics (IAP) growth charts. METHODS: Secondary analysis of anthropometric data of school-going children from Delhi in the year 2008, 2013 and 2015 was performed. The proportions of children with overweight, obesity, and undernutrition were checked for agreement using different diagnostic cutoffs, and compared at three-time points. RESULTS: Among 8417 adolescents, weighted Kappa statistics showed good agreement between extended IOTF and IAP cutoffs (k=0.933; 95% CI 0.93-0.94), between eIOTF and IOTF (k=0.624; 95% CI 0.619 - 0.629) and between IAP and IOTF (k=0.654; 95% CI 0.645-0.662). A higher proportion of adolescents were diagnosed with obesity with extended IOTF and IAP charts than IOTF charts (P<0.001 for both genders). The mean (SD) BMI showed a rising trend for adolescents overall from 19.61 (3.89) kg/m2 in 2008, 20.44 (4.37) kg/m2 in 2013 and 20.88 (4.60) kg/m2 in 2015 (P<0.001). 158 adolescent (97 girls) were undernourished using combined IAP and extended IOTF criteria. CONCLUSION: Both extended IOTF and IAP charts showed good agreement for diagnosing overweight and obesity in adolescents. A secular trend in malnutrition was observed in adolescent girls.

Efficacy of Daily Supplementation of Milk Fortified With Vitamin D2 for Three Months in Healthy School Children: A Randomized Placebo Controlled Trial.

OBJECTIVE: To evaluate the efficacy of daily supplementation of 200 mL milk fortified with 240 IU of vitamin D2 (ergocalciferol). DESIGN: Double-blind randomized controlled trial. SETTINGS: School-based study in Delhi between October and December, 2019. PARTICIPANTS: 235 healthy children aged 10-14 years. INTERVENTION: Daily supplementation of 200 mL milk fortified with 240 IU of ergocalciferol in intervention group (n=119) and 200 mL of plain milk in control group (n =116) for 3 months. OUTCOME MEASURES: Change in serum 25 hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), bone formation and resorption markers, and urinary calcium creatinine ratio (U-Ca/CrR). RESULTS: The mean (SD) baseline serum 25(OH) D level in control and fortification groups was 11.9 (3.8) and 11.4 (3.6) ng/mL (P=0.23), respectively. The serum 25(OH)D levels did not increase post-intervention with the dose used for fortification, but were significantly higher in intervention group as compared to control group [10.8 (3.4) vs 6.7 (3.5) ng/mL; P<0.001]. A higher proportion of secondary hyperparathyroidism was observed post-intervention in control (39%) than in intervention group (13.3%); P<0.001. Serum carboxy-terminal telopeptide levels were similar in both groups but the serum procollagen type1 N-terminal propeptide levels were higher in the control than intervention group (P<0.007), following supplementation. CONCLUSIONS: Supplementation of milk fortified with approximately 240 IU vitamin D2 for three months did not achieve sufficient serum 25(OH)D levels in Indian children with vitamin D deficiency during winter.

Comparison of plasma adipocytokines & C-reactive protein levels in healthy schoolgoing adolescents from private & government-funded schools of Delhi, India.

Background & objectives: Obesity-mediated chronic inflammatory state is primarily governed by lifestyle and food habits in adolescents and marked by alterations in the level of various inflammatory markers. This cross-sectional study was aimed to compare the inflammatory status of healthy Indian adolescents vis-à-vis their obesity profile. The inflammatory state of urban adolescents attending private and government-funded schools, and the relationship between inflammatory marker levels and anthropometric indices in the study participants from both groups were examined. Methods: A total of 4438 study participants (10-17 yr) were chosen from various schools of Delhi, India, and their anthropometric parameters were measured. Plasma adipocytokines (adiponectin, leptin and resistin) of the study participants were measured by enzyme-linked immunosorbent assay, and plasma C-reactive protein (CRP) levels were assayed by a biochemical analyzer. Metabolic syndrome-related risk factors such as waist circumference, hip circumference (HC), fasting glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and triglycerides of normal-weight adolescents were also evaluated. Results: The level of leptin and CRP increased with increasing adiposity, whereas adiponectin levels were found to be negatively related to obesity. All plasma cytokine levels (adiponectin, leptin and resistin) were significantly elevated in female than male adolescents. Age-based classification revealed a distinct trend of variability in the levels of all the inflammatory markers among adolescents of varying age groups. Significant differences were observed between private and government schoolgoing adolescents in terms of anthropometric and inflammatory parameters, with higher adiposity indices in the former group. The relationship of plasma adipokine and CRP levels with various adiposity indices was found to be distinctly different between private and government schoolgoing students. Interpretation & conclusions: Inflammatory markers were significantly elevated in overweight/obese adolescents. The socio-economic condition of urban Indian schoolgoing adolescents reflecting lifestyle transition has profound effects on their adiposity indices and inflammatory states. Longitudinal studies in different regions of the country need to be done to further confirm the findings.

Bioavailability of nanoemulsion formulations vs conventional fat soluble preparations of cholecalciferol (D3) - An overview.

Vitamin D deficiency is recognized as a pandemic affecting all ages and strata of population. The endogenous cutaneous synthesis of vitamin D is insufficient to maintain normal body requirement which necessitates the need for vitamin D supplementation or food-fortification. Conventional fat-soluble preparations of vitamin D have been traditionally used for prevention and therapeutic purposes. Recent advances in technology have enabled delivery of vitamin D through nanoemulsion formulations which ensure higher absorption and drug delivery. The following review briefly discusses the issues of bioavailability of nanoemulsion preparation of vitamin D vis-a-vis conventional fat soluble preparations.

Reference range of random urinary calcium creatinine ratio in North Indian children and adolescents.

PURPOSE: Urinary calcium creatinine ratio (UCaCrR) is a reliable indicator for monitoring hypercalciuria following vitamin D supplementation. However, the reference range varies from region to region. Previous studies did not take vitamin D and parathyroid hormone status into account while evaluating UCaCrR. Hence, we undertook this study to establish the 95th percentile of UCaCrR as an indicator of hypercalciuria in North Indian children and adolescents. METHODS: Four hundred seventy-three participants (boys 62.2%, girls 37.8%) with adequate dietary calcium intake, normal serum levels of 25-hydroxy-vitamin D (>20 ng/mL), and without secondary hyperparathyroidism following supplementation were selected for evaluation of UCaCrR. RESULTS: The mean age and body mass index of subjects were 11.2±2.6 years and 18.0±3.6 kg/m2, respectively. The 95th percentile of UCaCrR in the study population was 0.126. The mean, median, and 95th percentile of UCaCrR was significantly higher in prepubertal children (age ≤10 years) (0.0586±0.0374, median=0.0548, 95th percentile=0.136) compared to those >10 years old (0.0503±0.0363, median=0.0407, 95th percentile=0.123, P=0.02). No significant difference in UCaCrR was observed between genders and different weight categories. CONCLUSION: UCaCrR of 0.13 defines the cutoff value for hypercalciuria in North Indian children and adolescents with adequate dietary intake of calcium and sufficient serum vitamin D levels.

Interventions for Prevention and Control of Epidemic of Vitamin D Deficiency.

Vitamin D deficiency (VDD) remains a significant health challenge globally with its overwhelming effects on skeletal growth and varied associations with extra-skeletal diseases. The last decade has reported a high prevalence of VDD in all age-groups across all zones of India. Children and adolescents are most vulnerable to ill-effects of VDD as peak linear growth and bone mass accrual occurs during these years. Vitamin D deficiency in mothers predisposes their infants to have low serum vitamin D levels. Indians have increased susceptibility to develop VDD due to predominant vegetarian dietary habits, high melanin skin content, atmospheric pollution, modest tradition of clothing and limited availability of fortified foods. Vitamin D supplementation during infancy and childhood has emerged as an effective strategy to combat VDD. However, effects of vitamin D supplementation are transient and are not cost-effective as a maintenance strategy. Fortification of foodstuffs has been adopted by many developed countries globally which has emerged as a safe, efficacious and cost-effective strategy to control VDD. A strong political will and support is required to sustain food fortification in India. The current review focuses on strategies to prevent and control the epidemic of VDD in children.

Supplementation with Three Different Daily Doses of Vitamin D3 in Healthy Pre-pubertal School Girls: A Cluster Randomized Trial.

OBJECTIVE: To compare the adequacy and efficacy of different doses of vitamin D3 in pre-pubertal girls. DESIGN: Cluster Randomized controlled trial. SETTING: Public school in Delhi, India, between August 2015 and February 2016. PARTICIPANTS: 216 healthy pre-pubertal girls, aged 6.1-11.8 years. INTERVENTION: Daily supplementation with 600 IU (n=74), 1000 IU (n=67) or 2000 IU (n=75) of vitamin D3 under supervision for 6 months. OUTCOME MEASURES: Primary: Rise in serum 25 hydroxy Vitamin D (25(OH)D); Secondary: Change in bone formation and resorption markers. RESULTS: Following 6 months of supplementation, the mean (SD) rise in serum 25(OH)D was maximum with 2000 IU (24.09 (8.28) ng/mL), followed by with 1000 IU (17.96 (6.55) ng/mL) and 600 IU (15.48 (7.00) ng/mL). Serum 25(OH)D levels of ≥20 ng/mL were seen in 91% in 600 IU group , 97% in 1000 IU group and 100% in 2000 IU group. The overall mean (SD) rise in urinary calcium creatinine ratio (0.05 (0.28) to 0.13 (0.12) mg/mg), and serum procollagen type I N-terminal propeptide (538.9 (199.78) to 655.5 (218.24) ng/mL), and reduction in serum carboxy-terminal telopeptide (0.745 (0.23) to 0.382 (0.23) ng/mL) was significant (P<0.01). The change in the above parameters was comparable among the three groups after adjustment for age. CONCLUSIONS: Daily vitamin D supplementation with 600 IU to 2000 IU for 6 months results in Vitamin D sufficiency in >90% of pre-pubertal girls.

Height Velocity in Apparently Healthy North Indian School Children.

OBJECTIVE: Linear growth is best estimated by serial anthropometric data or height velocity (HV). In the absence of recent data on growth velocity, we undertook to establish normative data in apparently healthy North Indian children. MATERIALS AND METHODS: Prospective longitudinal study in a representative sample of 7710 apparently healthy children, aged 3-17 years from different regions of Delhi. Height was measured at baseline and at 12 months while pubertal examination was performed at baseline in a subset of children. RESULTS: The data on HV and puberty were available in 5635 participants (73.08%; 2341 boys and 3294 girls) and 1553 participants (622 boys; and 931 girls), respectively. The mean peak height velocity (PHV) was 7.82 ± 2.60 cm in boys seen at 12-12.9 years and 6.63 ± 1.81 cm in girls at 10-10.9 years Although late maturing boys had a greater HV than early or normal maturers, it did not vary with the age of pubertal maturation in girls. HV correlated with parental height in prepubertal boys, girls, and pubertal boys (P < 0.01) while no correlation was seen in girls. CONCLUSIONS: The study presents normal height velocities in North Indian children. A secular trend was observed in achieving PHV in both boys and girls.

Pubertal Onset in Apparently Healthy Indian Boys and Impact of Obesity.

OBJECTIVE: Primary - to determine the age of pubertal onset in Indian boys. Secondary - (a) to assess the impact of obesity on pubertal timing, (b) to assess the relationship between gonadotropins and puberty. DESIGN: Cross-sectional. SETTING: General community-seven schools across New Delhi. PARTICIPANTS: Random sample of 1306 school boys, aged 6-17 years. MATERIALS AND METHODS: Anthropometric measurement for weight and height and pubertal staging was performed for all subjects. Body mass index (BMI) was calculated to define overweight/obesity. Serum luteinizing hormone (LH), follicle stimulating hormone, and serum testosterone were measured in every sixth subject. MAIN OUTCOME MEASURE: Age at pubertal onset-testicular volume ≥4 mL (gonadarche) and pubic hair Stage II. RESULTS: Median age of attaining gonadarche and pubarche was 10.41 years (95% confidence interval [CI]: 10.2-10.6 years) and 13.60 (95% CI: 13.3-14.0 years), respectively. No significant difference in the age of attainment of gonadarche was observed in boys with normal or raised BMI, though pubarche occurred 8 months earlier in the latter group. Serum gonadotropins and testosterone increased with increasing stages of puberty but were unaffected by BMI. Serum LH level of 1.02 mIU/mL and testosterone level of >0.14 ng/mL showed the best prediction for pubertal onset. CONCLUSION: The study establishes a secular trend of the age of onset of puberty in Indian boys. Pubarche occurred earlier in overweight/obese boys. The cutoff levels of serum LH and testosterone for prediction of pubertal onset have been established.

Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 ± 5.38 versus 24.77 ± 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 ± 3.39 versus 3.01 ± 2.6; P = 0.006) and QUICKI (0.140 ± 0.013 versus 0.147 ± 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 ± 3.91 versus 10.32 ± 2.22; P = 0.01) and serum total testosterone levels (0.65 ± 0.69 versus 0.86 ± 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.