Standardization of Weightage Assigned to Different Segments of the Hand X-ray for Assessment of Bone Age by the Greulich-Pyle Method.

Introduction: Bone age (BA) assessment is important in evaluating disorders of growth and puberty; the Greulich and Pyle atlas method (GP) is most used. We aimed to determine the weightage to be attributed by raters to various segments of the hand x-ray, namely, distal end of radius-ulna (RU), carpals, and short bones for rating bone age using the GP atlas method. Methods: 692 deidentified x-rays from a previous study (PUNE-dataset) and 400 from the Radiological Society of North America (RSNA-dataset) were included in the study. Mean of BA assessed by experienced raters was termed reference rating. Linear regression was used to model reference age as function of age ratings of the three segments. The root-mean-square-error (RMSE) of segmental arithmetic mean and weighted mean with respect to reference rating were computed for both datasets. Results: Short bones were assigned the highest weightage. Carpals were assigned higher weightage in pre-pubertal PUNE participants as compared to RSNA, vice-versa in RU segment of post-pubertal participants. The RMSE of weighted mean ratings was significantly lower than for the arithmetic mean in the PUNE dataset. Conclusion: We thus determined weightage to be attributed by raters to segments of the hand x-ray for assessment of bone age by the GP method.

Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Longitudinal assessment of auxological parameters, adult height outcome and its determinants in leuprolide-treated Indian girls with idiopathic central precocious puberty.

OBJECTIVES: To assess auxological parameters, adult height outcome and its determinants in Indian girls with idiopathic central precocious puberty (iCPP) treated with gonadotropin-releasing hormone analogues (GnRHa). METHODS: Retrospective study. Inclusion: data on girls with iCPP from initiation to stopping GnRHa (n=179). Exclusion: boys, peripheral, organic central precocity. RESULTS: Mean age of starting GnRHa: 8.2± 1.1 years, duration: 2.8± 1.2 years. 11.7 % had attained menarche at first presentation. The difference between bone (BA) and chronological (CA) ages reduced significantly from 2.6± 0.9 years (onset) to 1.6± 0.8 years (cessation). Weight, BMI Z-scores increased (p<0.01), height Z-scores decreased (0.8 vs. 0.6; p<0.01), predicted adult height (PAH) and Z-scores improved by 3.5 cm, 0.5 SDS following treatment (p<0.01). Overweight/obese girls (vs. normal BMI) were taller, with more advanced BA at starting (height Z-score: 0.7 vs. 1.0, BA-CA: 2.2 vs. 2.9 years), stopping (height Z-score: 0.5 vs. 0.9, BA-CA: 1.4 vs. 1.9 years) treatment, but showed no difference in PAH at starting, stopping treatment. Adult height data (n=58) revealed 1.9 cm gain above target height. Adult height Z-scores significantly exceeded target height Z-scores (p<0.01). Mean adult height (157.1± 5.8 cm) crossed PAH at starting treatment (155.9± 6.4 cm) but remained 1.6 cm lesser than PAH at cessation. Adult weight, BMI Z-scores (-0.2± 1.3, -0.1± 1.2) were significantly lower (p<0.01) than those at stopping GnRHa. Height gain adjusted for age at starting GnRHa correlated negatively with height, weight, BMI, Tanner-staging, BA, FSH, Estradiol at treatment onset, BA at cessation, and correlated positively with treatment duration. CONCLUSIONS: GnRHa treatment in Indian girls with iCPP resulted in improved PAH, decelerated bone age advancement and growth velocity. Most girls achieved adult height within target range, surpassing PAH at treatment initiation. Lesser anthropometric, sexual, skeletal maturity, lower baseline FSH, estradiol, longer treatment duration, less advanced BA at stopping GnRHa may translate into better adult height outcomes.

Comparison of Nutritional Status of Healthy Under-Five Indian Children Using Composite Index of Anthropometric Failure on WHO 2006 versus 2019 Indian Synthetic Growth Charts.

OBJECTIVES: To assess nutritional status of apparently-healthy under-five Indian children using Composite Index of Anthropometric Failure (CIAF) and to compare anthropometric failure prevalence using conventional indices and CIAF on World Health Organization (WHO) vs. synthetic Indian growth charts. METHODS: This observational study was conducted over 2 y. The inclusion criteria was apparently-healthy children (0-60 mo) and the exclusion criteria were acute/chronic illness and small for gestational age. RESULTS: A total of 1557 children (762 girls) were included in the study. The mean age of the subjects was 21 mo. The Z-scores for height, weight, body mass index (BMI) for age and weight for height in children were lower on WHO vs. synthetic charts (p = 0.0001). Significantly higher proportion of children were moderately and severely underweight, stunted and wasted on WHO charts. Synthetic charts identified significantly higher proportion as normal for weight, height, BMI for age, weight for height, overweight (overall), and a higher prevalence of severe stunting, and severe acute malnutrition (SAM) was noted among girls compared to boys. Using CIAF, 54.1% children were normal on WHO charts vs. 78.0% on synthetic (p = 0.0001). Larger proportion of girls (8.8%) were stunted+underweight (category-E) vs. boys (4.3%) on synthetic charts (p = 0.0003). Significantly higher proportion of children demonstrated failure (single/dual/multiple) on WHO charts except category-Y (higher proportion of underweight on synthetic charts). Maximum difference in CIAF (WHO vs. synthetic) was observed between 0-24 mo age. Of 1215 children normal on synthetic charts, 837 (68.9%) were normal on WHO charts. Of 116 underweight children (category-Y) on synthetic charts, 20 (17.2%) were underweight on WHO charts; remaining had compound failure (wasting+underweight = 49.1%, wasting+stunting+underweight = 14.7%, stunting+underweight = 12.1%) on WHO charts. Among those stunted+underweight (category-E) on synthetic charts, WHO charts classified 1/4th as wasted+stunted+underweight (category-D). CONCLUSIONS: Synthetic references are more representative of Indian growth patterns, and seem more appropriate for monitoring growth of Indian children to avoid mislabelling as malnourished.

Assessment of pubertal onset and disorders of puberty in Indian children and youth with type-1 diabetes.

OBJECTIVES: Disorders of pubertal development are enlisted as associated conditions in children and adolescents with type-1 diabetes (T1D). We conducted this study with objective (1) To estimate the median age at onset of puberty and luteinizing hormone (LH) and sex-steroid concentrations in Indian adolescents with T1D and (2) To assess the impact of puberty on glycemic control and insulin resistance (IR). METHODS: This cross-sectional study included 399 children and youth aged 6-23 years with T1D. Demographic, anthropometric, biochemical and pelvic ultrasound data were collected using standard protocols. IR was calculated using estimated glucose disposal rate and puberty was assessed using Tanner staging. RESULTS: Median age at onset of thelarche, pubarche and menarche were 11.3, 11.4 and 12.8 years in girls and that of gonadarche and pubarche were 10.6 and 12.7 years for boys. The mean LH and sex-steroid concentrations of subjects with T1D were similar to healthy subjects at each stage of puberty. The cut-offs of LH and sex-steroids derived from healthy Indian children yielded high sensitivity and specificity in determining pubertal onset. The prevalence of precocity, delayed puberty, ovarian cysts and polycystic ovaries was 0.9 , 5.1, 5.1 and 8.6 %, respectively. Glycaemic control and insulin sensitivity was poor in pubertal subjects. CONCLUSIONS: The age at onset of puberty, LH, and sex-steroid concentrations in subjects with T1D were like otherwise healthy Indian children with poor glycemic control and IR in pubertal subjects. Although most complications of T1D are associated with poor glycemic control, pubertal disorders were significantly low despite the less-than-optimal glycemic control.

A Pilot Study to Assess Effect of Metformin Therapy on Prevention of Double Diabetes in Indian Adolescents with Type-1 Diabetes.

Introduction: Increased prevalence of metabolic syndrome in Indian adolescents owing to the obesity epidemic leads to double diabetes (DD), which is associated with an increased risk of complications in type-1 diabetes (T1D). Metformin may be a useful intervention for the prevention and treatment of insulin resistance in T1D. We conducted this pilot randomized controlled trial with the objective of investigating the effect of metformin on insulin sensitivity in Indian adolescents with T1D. Method: This pilot randomized controlled trial was performed on 59 participants with T1D aged 10-19 years distributed uniformly by gender and puberty across two groups with a 3-month intervention period. The intervention group received metformin (weight less than 60 kg received 500 mg twice daily and more than 60 kg received 1 gm twice daily) and non-metformin group received standard of care for diabetes. Anthropometric, clinical details, biochemistry and insulin sensitivity indices (ISI) were evaluated using standard protocols at baseline and endline. Result: 22.2% of subjects from non-metformin group and 12.5% from metformin group were at the risk of the development of DD. The odds ratio and relative risk for the development of DD in non-metformin subjects were 2.0 and 1.4, respectively, as compared to participants in metformin group. The mean improvement in ISI ranged from 1.4% to 4.6% in participants on metformin as opposed to deterioration of -2% to -14.1% in non-metformin group. On performing the paired sample t-test, the reduction in ISI in non-metformin group was significant. Conclusion: Metformin may prevent deterioration in insulin sensitivity in Indian adolescents with T1D.

Adiponectin-leptin ratio as a marker of cardio-metabolic risk in Indian children and youth with type 1 diabetes.

OBJECTIVES: Adiponectin/leptin ratio (ALR) is a promising novel marker of cardio-metabolic risk in patients with metabolic syndrome. Our aim was to study the association of adiponectin-leptin ratio with markers of obesity and adiposity and also to assess its usefulness as a marker of increased cardiometabolic risk (CMR) in Indian children and youth with type 1 diabetes mellitus. METHODS: This observational study included 79 children and youth with type 1 diabetes (T1DM) (10-21 years) having disease duration>6 months. Demographic data and laboratory findings were obtained from patients' records. Patients with ALR<1 were categorised as having increased CMR and those with ALR>1 were categorised as having no CMR. RESULTS: ALR showed a significant negative correlation with body mass index (BMI), waist and hip circumference and body fat percentage (p<0.05). Body fat percentage was the single most important predictor of ALR. Children and youth with increased CMR had higher weight, BMI, waist and hip circumferences and body fat percentage as compared to those with no CMR (p<0.05). In T1DM children with dyslipidemia, ALR was significantly lower as compared to those without dyslipidemia (p<0.05). CONCLUSIONS: ALR may be a useful marker for adiposity and increased cardiometabolic risk in Indian children and youth with type 1 diabetes mellitus.