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.

Influence of ecoregional and lifestyle factors on growth and body composition of Indian children and adolescents aged 9-18 years-A multicenter study.

OBJECTIVES: Ecoregion comprises all the environmental factors such as climate, vegetation, geomorphology, and soil taken together. The objectives of this study were to (1) assess differences in growth and body composition (BC) in 9-18-year-old children and adolescents (CA), across six ecoregions of India, (2) evaluate and compare the magnitude of the effect of ecoregional and lifestyle factors (LSF) on growth and BC in urban (U) and rural (R) children and adolescents, and (3) reassess the applicability of Bergmann's Rule and Allen's Rule to humans. SUBJECTS AND METHODS: Data on 1845 CA (925 boys; 920 girls) were collected (2016-2017) from urban and rural areas of six ecoregions of India. Anthropometric and BC parameters were measured; Z-scores were computed. Lifestyle Index score (LIS) based on LSF-(socioeconomic status [SES], diet, physical activity) was computed (categorized as low, medium, high-indicates better LSF). Univariate analysis was performed to estimate effect size. RESULTS: Significant differences were observed in growth and BC across urban and rural ecoregions. CA with high LIS were taller and heavier than those with low LIS (p < .05). Ecoregion had greater effect on growth (Partial eta square (η2 ) for R = 0.136 vs. U = 0.057) and BC (η2 for R = 0.094 vs. U = 0.058) of rural CA than urban (p < .01). LSF had more effect on the BC of urban CA (η2  = 0.017) than rural (η2  = 0.002, p < .01). CONCLUSION: Disparities among the six ecoregions were not large enough to fully support Bergmann's Rule and Allen's Rule. Ecoregion had greater effect on growth and BC of rural CA than urban, while lifestyle factors had more effect on the BC of urban CA.

Determinants of muscle power and force as assessed by Jumping Mechanography in rural Indian children.

OBJECTIVES: To: 1. Assess muscle function (MF) of rural Indian children (6-11y, n=232), using Jumping Mechanography (JM) and hand dynamometer, 2. Investigate gender differences, 3. Identify determinants of MF. METHODS: Data on anthropometry, muscle mass%, diet, physical activity, sunlight exposure, MF (maximum relative power Pmax/mass, maximum relative force Fmax/BW by JM; relative grip strength (RGS) by hand dynamometer) were collected. Pearson's correlation and hierarchical linear regression was performed. RESULTS: Pmax/mass, Fmax/BW and RGS of the group were 31.7±5.0W/kg, 3.0±0.3 and 0.4±0.1 (mean±SD), respectively. The Pmax/mass Z-score was -1.1±0.9 and Fmax/BW Z-score was -0.9±1 (mean±SD) which was significantly lower than the machine reference data (p<0.05). Positive association of muscle mass% and protein intake was observed with all MF parameters and moderate+vigorous physical activity with Fmax/BW (p<0.05). Determinants of MF identified through regression for Pmax/mass were age (ß=1.83,95% CI=0.973 - 2.686), muscle mass% (ß=0.244,95% CI=0.131-0.358) and protein intake (ß=3.211,95% CI=1.597-4.825) and for Fmax/BW was protein intake (ß=0.130,95% CI=0.023-0.237) (p<0.05). Male gender was a positive predictor of having higher Pmax/mass (ß=1.707,95% CI=0.040-3.373) (p<0.05). CONCLUSION: MF was lower than in western counterparts. To optimize MF of rural Indian children, focus should be on improving muscle mass, ensuring adequate dietary protein, and increasing physical activity, especially in girls.

A comparison of bone age assessments using automated and manual methods in children of Indian ethnicity.

BACKGROUND: Bone age is useful for pediatric endocrinologists in evaluating various disorders related to growth and puberty. Traditional methods of bone age assessment, namely Greulich and Pyle (GP) and Tanner-Whitehouse (TW), have intra- and interobserver variations. Use of computer-automated methods like BoneXpert might overcome these subjective variations. OBJECTIVE: The aim of our study was to assess the validity of BoneXpert in comparison to manual GP and TW methods for assessing bone age in children of Asian Indian ethnicity. MATERIALS AND METHODS: We extracted from a previous study the deidentified left hand radiographs of 920 healthy children aged 2-19 years. We compared bone age as determined by four well-trained manual raters using GP and TW methods with the BoneXpert ratings. We computed accuracy using root mean square error (RMSE) to assess how close the bone age estimated by BoneXpert was to the reference rating. RESULTS: The standard deviations (SDs) of rating among the four manual raters were 0.52 years, 0.52 years and 0.47 years for GP, TW2 and TW3 methods, respectively. The RMSEs between the automated bone age estimates and the true ratings were 0.39 years, 0.41 years and 0.36 years, respectively, for the same methods. The RMSE values were significantly lower in girls than in boys (0.53, 0.5 and 0.47 vs. 0.39, 0.47 and 0.4) by all the methods; however, no such difference was noted in classification by body mass index. The best agreement between BoneXpert and manual rating was obtained by using 50% weight on carpals (GP50). The carpal bone age was retarded in Indian children, more so in boys. CONCLUSION: BoneXpert was accurate and performed well in estimating bone age by both GP and TW methods in healthy Asian Indian children; the error was larger in boys. The GP50 establishes "backward compatibility" with manual rating.

Prevalence of dyslipidemia in Indian children with poorly controlled type 1 diabetes mellitus.

BACKGROUND: Children with type 1 diabetes having dyslipidemia are at increased risk of developing premature atherosclerosis and cardiovascular disease. The present study aims to determine the prevalence of dyslipidemia and its predictors in poorly controlled Indian children with type 1 diabetes. METHODS: The cross-sectional study included 235 children and youth (3-18 years) with type 1 diabetes having disease duration of at least 1 year. Demographic data and laboratory findings were obtained from patients' records. RESULTS: The prevalence of dyslipidemia in our study was 47.2% with abnormal low-density lipoprotein cholesterol being the most common lipid abnormality. Poor glycemic control and higher thyroid stimulating hormone values were important predictors of likelihood of dyslipidemia and hypertriglyceridemia. Despite a low percentage of overweight and obese children in our study, body fat percentage was a significant predictor of likelihood of high total cholesterol and abnormal high-density lipoprootein. Interestingly, 28 children under the age of 10 years were found to have dyslipidemia, which constitutes 11.9% of the total study group. CONCLUSIONS: We found a high prevalence of dyslipidemia in children with type 1 diabetes including children under age of 10 years, which emphasize the need for early screening and regular monitoring of lipid profile in these children.

Effect of Yoga or Physical Exercise on Muscle Function in Rural Indian Children: A Randomized Controlled Trial.

BACKGROUND: Synergistic effects of yoga or physical exercise (PE) along with protein supplementation on children's muscle function in rural India have not been studied. Hence, we aimed to study the effect of yoga and PE along with protein supplementation on muscle function in healthy 6- to 11-year-old rural Indian children post 6 months of intervention. METHODS: A randomized controlled trial on 232 children, recruited into 3 groups, each receiving 1 protein-rich ladoo (148 kcal, 7 g protein/40 g ladoo-an Indian sweet snack) daily and performing (1) yoga (n = 78) for 30 minutes 5 times per week, (2) PE (n = 76) for 30 minutes 5 times per week, or (3) control group (n = 78) no additional exercise. Maximum power, maximum voluntary force (Fmax), and grip strength (GS) were measured. Data were analyzed using paired t tests and a 2-way mixed analysis of variance with post hoc Bonferroni adjustment. RESULTS: GS, maximum power, and Fmax within yoga group increased significantly (P < .05) from baseline to endline. GS and Fmax increased significantly within PE group postintervention (P < .001). In controls, GS increased (P < .05) at endline. No significant effect of the intervention was observed on the change in maximum power (P > .05) postintervention. The 2 exercise groups showed significant increase in Fmax compared with the control group (P < .05). Similarly, increase in GS was significantly higher in both the exercise groups compared with the control group (P < .05). No significant difference was observed in change in muscle function between the 2 exercise groups (P > .05). CONCLUSIONS: Structured physical activity along with protein supplementation resulted in improved muscle function in children. Yoga and PE showed a comparable impact on muscle force.

Role of Dietary Macronutrient Composition and Fibre Intake in Development of Double Diabetes in Indian Youth.

Introduction: Insulin resistance (IR) and obesity are common presentations of double diabetes (DD) in subjects with type-1 diabetes (T1D). There is evidence that dietary composition has an impact on developing IR. Objectives were to assess the impact of macronutrient and fibre intake on glycaemic control and the role of macronutrient composition of diet in the development of DD in subjects with T1D. Methods: This cross-sectional study included 77 young adults (10-25 years) with T1D. Data related to demography, anthropometry, biochemistry and body composition were collected. Dietary data was collected by fourteen-day food diary. IR was calculated using eGDR, SEARCH and CACTI equations, and metabolic syndrome (MS) was diagnosed using the International Diabetes Federation Consensus Definition. Results: Subjects at risk of DD had higher age, leptin levels, percentage carbohydrate consumption in diet and IR. A positive association of insulin sensitivity with fibre intake and %protein intake was noted. Poor glycaemic control, adiponectin/leptin ratio, fibre intake and insulin/carbohydrate ratio were significant negative predictors of IR. Addition of dietary factors to the regression model improved the R square and percentage of subjects identified correctly. Inclusion of dietary parameters significantly improves the prediction of the risk of development of DD in subjects with T1D. Conclusion: Good glycaemic control and increased intake of dietary fibre may prevent the development of IR in subjects with T1D and reduce the burden of DD.

Dynamic Muscle Function Parameters in Indian Children and Adolescents with Type 1 Diabetes Mellitus: A Case-Control Study.

Introduction: Recent evidence reveals that type 1 diabetes mellitus (T1DM) impairs muscle function (MF) in adolescents. However, despite its importance in physical well-being, data on dynamic MF in Indian children and adolescents (C and Y) with T1DM are scarce. We assessed MF using Jumping Mechanography (JM, a measurement method for motion analysis and assessment of muscle power and force). (1) To assess dynamic MF by JM in C and Y with T1DM as compared to healthy controls (2) To determine predictors of MF in children with T1DM. Methods: A cross-sectional observational study on 266 children (133 - T1DM duration >1 year with no known comorbidities + 133 age and gender-matched healthy controls) aged 6-19 years. Anthropometry, body composition, and MF (maximum relative power Pmax/mass, maximum relative force Fmax/BW by JM) were recorded. The lean mass index (LMI) was calculated as lean mass (kg)/height (m2). HbA1c was assessed in T1DM. Independent sample t-test and linear regression were performed. Results: MF parameters (Pmax/mass 33.5 ± 7.2 vs 38.0 ± 8.6 W/kg and Fmax/BW 10.5 ± 2.9 vs 11.4 ± 4.1 N/kg, P < 0.05) were significantly lower in T1DM group vs controls. Positive association of body mass index and LMI with both MF parameters and negative association of insulin requirement and HbA1c with Fmax was observed in T1DM. Predictors of MF identified were MMI (Pmax/mass:b = 1.6,95%CI = 0.6-2.6; Fmax/BW:b =2.0,95%CI = 1.6-2.4) and HbA1c (Pmax/mass:b = -2.1,95%CI = -4.5--0.5; Fmax/BW:b = -1.1,95%CI = -2.0--0.2) (P < 0.05). Conclusion: C and Y with T1DM exhibits compromised muscle function. Poor glycaemic control increases the risk of having decreased MF, irrespective of diabetes duration and may contribute to sarcopenia in adulthood.

Comparison of WHO 2006 Growth Standards and Synthetic Indian References in Assessing Growth in Normal Children and Children with Growth-Related Disorders.

Introduction: A good screening tool, such as a growth chart, should distinguish between children with normal growth and those with perturbed growth. Suitability of synthetic Indian growth references for diagnosing growth-related disorders for under-five children has not been evaluated. To assess the validity of World Health Organization (WHO) 2006 standards vs synthetic Indian references (2019) (by comparing weight, height, body mass index (BMI), standard deviation scores (SDS) and the composite index of anthropometric failure (CIAF)) in differentiating normal children and children with growth-related disorders. Methods: Records of 2188 children (0-60 months) attending a tertiary centre paediatric outpatient department (OPD) were retrospectively studied; 1854 children were healthy and 334 were diagnosed with growth-related disorders as per the European Society for Paediatric Endocrinology (ESPE) classification. The anthropometric parameters converted to Z-scores for weight-for-age (WAZ), height-for-age (HAZ), BMI-for-age (BAZ) and a CIAF were computed using WHO and synthetic charts; Student's t-test was used for assessing differences and Youden's index for validity. Results: Disease status of children and anthropometric failure on WAZ, HAZ, BAZ and CIAF on both WHO and synthetic charts had a significant association (P-value <0.05). WAZ, HAZ on both charts and CIAF on synthetic chart had a fair to moderate agreement (Kappa statistics) with disease status as per diagnosis (P-value <0.05). The sensitivity and negative predictive value for all anthropometric parameters were higher for synthetic charts. Conclusion: Indian charts were more sensitive for diagnosing growth-related disorders from birth to 60 months of age when compared to WHO growth standards.

Effect of metformin adjunct therapy on cardiometabolic parameters in Indian adolescents with type 1 diabetes: a randomized controlled trial.

Introduction: Insulin resistance is being increasingly reported in type-1 Diabetes (T1D) and is known to accelerate microvascular complications. The Asian Indian population has a higher risk of double diabetes development compared to Caucasians. Hence, we studied the effect of adding Metformin to standard insulin therapy on glycemic control, insulin sensitivity (IS), cardiometabolic parameters and body composition in Indian adolescents with T1D. Methods: A Randomized controlled trial was conducted spanning 9 months (Registration number:CTRI/2019/11/022126). Inclusion: Age 10-19 years, T1D duration>1year, HbA1c>8% Exclusion: Uncontrolled vascular complications/comorbidities, Metformin intolerance, concomitant drugs affecting insulin sensitivity. Participants were randomized to Metformin/Placebo (n=41 each) groups and age, sex, duration-matched. Assessments were performed at baseline, 3 and 9 months. Results: 82 participants aged 14.7 ± 3years (40 females) were enrolled, with a mean diabetes duration of 5.2 ± 2.3 years. Over 9 months, HbA1c decreased significantly by 0.8 (95% confidence interval: -1.2 to -0.3) from 9.8 ± 1.8% to 9.1 ± 1.7% on Metformin but remained largely unchanged (difference of 0.2, 95% confidence interval: -0.7 to 0.2) i.e. 9.9 ± 1.6% and 9.7 ± 2.2% on placebo. HbA1c improvement correlated negatively with baseline IS (EGDR:r= -0.3;SEARCH:r = -0.24, p<0.05) implying better HbA1c-lowering in those with decreased initial IS. CGM-based glycemic variability (standard deviation) reduced by 6.3 mg/dL (95% confidence interval: -12.9 to 0.2) from 100.2 ± 19.1 mg/dL to 93.7 ± 19.9 mg/dL in those on Metformin (p=0.05) but not placebo (94.0 ± 20.5; 90.0 ± 22.6 mg/dL). Insulin sensitivity: CACTIexa & SEARCH scores demonstrated no change with Metformin but significant worsening on placebo. Significant increase in LDL-C(42%), total cholesterol(133.6 to 151.1 mg/dL), triglyceride (60.0 to 88.0 mg/dL) and carotid intima-media thickness was noted on placebo but not Metformin. Weight, BMI, fat Z-scores increased significantly on placebo but not Metformin. Adverse events (AE) were minor; AE, compliance and safety parameters were similar between the two groups. Conclusion: Metformin as an adjunct to insulin in Asian Indian adolescents with T1D demonstrated beneficial effect on glycemic control, glycemic variability, IS, lipid profile, vascular function, weight and body fat, with a good safety profile when administered for 9 months.

Longitudinal trends in lipid profile in indian children and youth with type-1 diabetes: a 5-year follow up from a single centre.

INTRODUCTION: High prevalence of dyslipidaemia in children and adolescents with type-1 diabetes (T1D) places them at increased risk of developing atherosclerosis leading to mortality caused by cardiovascular disease(CVD). Thus, screening for fasting blood lipids when diabetes is stabilized in children aged 11 years and above is routinely recommended with follow-up every 5 years. OBJECTIVES: (1) To characterize the lipid profile of children and adolescents with respect to diabetes duration. (2) To describe longitudinal changes in lipid profile over a 5-year period in patients with T1D. METHODS: This longitudinal 5-year follow-up study included 112 patients with T1D aged 3-18 years. Demographic data, anthropometry and laboratory measurements were performed using standard protocols at baseline and endline. P value < 0.05 was considered significant. RESULTS: The prevalence of dyslipidaemia in our study was 49.5% with abnormal LDL as the most frequently deranged parameter. Duration of illness played a major role in deterioration of lipid profile mediated by triglyceride and VLDL. Duration of illness and fibre intake in diet significantly predicted the change in lipid profile which were driven by triglycerides and VLDL. Glycemic control, insulin sensitivity and serum TSH also significantly altered components of lipid profile with no impact on overall dyslipidaemia. A total of 6.5% subjects had LDL concentrations >130 mg/dl and the same proportion had non-HDL cholesterol concentrations >145 mg/dl at baseline while at endline, 11.9% subjects had LDL concentrations >130 mg/dl and 15.6% subjects had non-HDL cholesterol concentrations >145 mg/dl. 28.6% subjects with LDL > 130 mg/dl and non-HDL cholesterol >145 mg/dl at baseline had persistently elevated concentrations while 10.3% and 14.4% additional subjects developed elevated LDL and non-HDL cholesterol concentrations respectively during the study period. CONCLUSIONS: The deterioration of lipid profile in T1D, due to increase in disease duration was chiefly mediated by increase in serum triglyceride and VLDL concentrations which may be prevented by improving glycaemic control, insulin sensitivity and fibre intake in diet.

Dietary diversity and food variety scores and their association with nutrition and health status of Indian children and adolescents: A multicenter study.

BACKGROUND: The objectives of this study were to 1) evaluate the dietary diversity scores (DDS) and food variety scores (FVS) among Indian children and adolescents aged 9-18 y; 2) compare the DDS and FVS in association with demographic, socioeconomic, and health characteristics (growth and hemoglobin [Hb] concentrations); and 3) determine DDS and FVS cutoffs to identify dietary micronutrient adequacy. METHODS: This study was performed in a subset (n = 1845) of children and adolescents enrolled in a multicenter study (2016-2017) from urban and rural areas of six Indian states. Height, weight, and Hb were measured, and anthropometric Z-scores were computed. Sociodemographic data were collected using a structured questionnaire. Dietary data collected by 24-h dietary recall were used to calculate the DDS and FVS. The mean adequacy ratio (MAR) for 10 micronutrients was computed. Receiver operating characteristic analysis was performed to define cutoffs of DDS and FVS. RESULTS: In comparison with children and adolescents from rural areas, urban children and adolescents consumed more diverse diets (urban, 4.1 ± 1.1; rural, 3.5 ± 1; P < 0.01) and had a higher mean FVS (urban, 19.9 ± 5.7; rural, 15.9 ± 4.5; P < 0.01). Both the DDS and FVS were significantly correlated with each other (r = 0.860; P < 0.01) and were positively correlated with MAR, growth, and Hb (P < 0.001) and mother's educational level (P < 0.01). The cutoffs of ≥6.5 (DDS) and ≥17 (FVS) were determined to predict micronutrient adequacy. CONCLUSIONS: Both the DDS and FVS can be used interchangeably for assessing growth, health status, and nutritional adequacy. Single cutoff values of the DDS and FVS may aid in prompt identification of children and adolescents with micronutrient inadequacy.

Utility of apolipoprotein ratio in predicting metabolic risk and microvascular complications in Indian children and young adults with type 1 diabetes mellitus.

OBJECTIVES: To assess the relationship of apolipoproteins with glycemic control and insulin resistance (IR) in Indian children and youth with type-1 diabetes (T1D) and to assess its utility in predicting metabolic risk (MR) and microvascular complications in these subjects. METHODS: This cross-sectional study included 152 participants aged 6-23 years with T1D. Demographic, anthropometric, clinical, biochemical and body composition data were obtained using standard protocols. IR was calculated using estimated glucose disposal rate (eGDR) and metabolic syndrome (MS) was diagnosed using the international diabetes federation consensus definition 2017. RESULTS: Apolipoprotein ratio in subjects with T1D had negative and positive correlation with eGDR and HbA1c respectively. Positive correlation of Apolipoproten B and apolipoprotein ratio with urinary albumin creatinine ratio is noted. The ratio had area under curve of 0.766 and 0.737 to predict MR and microvascular complications respectively. The ratio cut-off of 0.536 yielded 77.1 % sensitivity and 61 % specificity to predict MR. On adding the apolipoprotein ratio as a predictor to the regression model developed to predict MR, the R2 and accuracy improved. CONCLUSIONS: The apolipoprotein ratio had significant correlation with IR, microalbuminuria and glycaemic control. The ratio also predicts risk of development of microvascular complications and maybe used to predict MR in subjects with T1D.

Adult Height in Indian Girls with Turner Syndrome Treated with Long-Term Growth Hormone Therapy - A Western India Tertiary Centre Experience.

Background and Objectives: Owing to paucity of data on adult height in Indian girls with Turner syndrome treated with growth hormone (GH), this study was conducted to assess improvement in height following GH therapy and adult height achieved with long-term GH therapy in Indian girls with Turner syndrome and to assess relationship between achieved and predicted height. Methodology: Retrospective analysis was performed on 12 girls with karyotype-proven Turner syndrome, who had attained adult height following mean duration of GH therapy of 4.8 years (range: 2.7-7.6). Adult height predictions were performed using index of responsiveness (IOR) and Ranke's prediction model. Results: Mean age at starting GH was 10.2 ± 1.9 years; Pubertal induction was between 11 and 15 years. Mean height gain was 29.3 ± 9.8 cm (range: 14-39.5) from onset of treatment to adult height. Significant improvement in height Z scores (IAP 2015 and Indian Turner reference data) following GH therapy (p = 0.002 and 0.012, respectively) was noted. Using Indian Turner reference data, the height Z score improved from pre-treatment 0.8 ± 0.8 to 2.0 ± 0.9 on stopping GH and adult height Z score of 1.3 ± 0.7. Using Ranke's equation for prediction of near adult height, predicted and achieved adult height showed a strong positive correlation (Spearman correlation coefficient = 0.827, significant at 0.01 level). Conclusion: At a dose in the lower range (40-50 mcg/kg/day) of recommendation and duration of 5 years, Indian girls with Turner syndrome can achieve adult height within the healthy Indian reference range. Dose individualization based on IOR would help in optimizing GH dosage and would turn out to be economically sustainable without compromising on height outcomes.

Establishing a Unique, Single Cutoff Value for Body Frame Size for Screening for Risk of Hypertension in Indian Children and Adolescents-A Multicenter Study.

OBJECTIVES: To evaluate the strength of association of two measures of BFS: frame-size one (FS1; height ÷ wrist circumference) and frame-size two (FS2; elbow breadth), with body-fat indices, body composition, and hypertension in Indian children and adolescents, and to determine age and sex-specific cutoffs of BFS to predict hypertension. METHODS: This was a cross-sectional, multicenter, school-based study in 9- to 18-y-old healthy children (n = 1423) randomly selected from 3 Indian states. Based on tertiles, FS1 and FS2 were categorized as small, medium, and large. RESULTS: Greater BFS (both FS1 and FS2) was associated with higher body-fat indices, BP (r = -0.424 for FS1 and r = 0.282 for FS2, p < 0.01) and lower muscle mass (MM). A significantly greater percentage of children classified as having large BFS according to FS1 were found to be overweight/obese (46% vs. 25%), hypertensive (34% vs. 17%) than FS2 (p < 0.01). FS1 showed strong to very strong association (Cramer's V 0.15 to > 0.25) with body-fat indices, MM, and BP as opposed to FS2 (For BP X2 = 120.9 for FS1 vs. 9.06 for FS2). FS1 better identified obesity and hypertension, and a value of 10.6 was determined to be the optimum cutoff for predicting hypertension in both genders (sensitivity 71%, specificity 75%, AUC 0.795, and NPV 95%). CONCLUSIONS: Height-to-wrist circumference is a novel, simple, and precise BFS measure for predicting hypertension and muscle mass (9-18 y) and a single cutoff value (< 10.6) may contribute to rapid screening and prompt identification of children at risk of hypertension.

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.

A comparative study of the gut microbiome in Indian children with type 1 diabetes and healthy controls.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) occurs in genetically susceptible individuals due to certain environmental triggers causing destruction of insulin secreting beta cells. One of the environmental triggers studied recently in the pathogenesis and progression of T1DM is the role of gut microbiome. OBJECTIVES: (1) To compare the gut microbiome profile of T1DM children with healthy age, gender, and body mass index (BMI) matched controls. (2) To assess the relationship of abundance of genera with glycemic control in children with T1DM. METHODS: Cross-sectional, case-control study. Sixty-eight children with T1DM and 61 age-, gender-, and BMI-matched healthy controls were enrolled. QIAamp Fast DNA Stool Mini kit protocol and reagents were used for DNA isolation and Miseq sequencing platform for targeted gene sequencing. RESULTS: Alpha and beta diversity analysis showed no significant differences in the abundance of microbes between the groups. At phylum level, Firmicutes was the dominant phylum followed by Actinobacteria and Bacteroidota in both groups. Analysis of microbiome at the genera level showed that percentage abundance for Parasutterella was higher in children with T1DM as compared to the healthy group (p < .05). A linear regression analysis showed that increase in abundance of Haemophilus (adjusted R2 = -1.481 p < .007) was associated with a significant decrease in glycated hemoglobin (HbA1c) concentrations (p < .05). CONCLUSION: Our comparative study of gut microbiome profile showed significant differences in the taxonomial composition between Indian children with T1DM and healthy controls. Short chain fatty acid producers may play an important role in glycemic control.

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.

Influence of parental anthropometry and gestational weight gain on intrauterine growth and neonatal outcomes: Findings from the MAI cohort study in rural India.

Poor foetal growth and subsequent low birth weight are associated with an increased risk for disease later in life. Identifying parental factors that determine foetal growth are important to curbing intergenerational malnutrition, especially among disadvantaged populations in the global south where undernutrition rates are high. The objective of this study was to assess the relationships between parental biometry, intrauterine growth and neonatal outcomes, while factoring in socioeconomic status of historically disadvantaged households in rural India. Using data from the prospective longitudinal cohort, pregnant women from rural Pune, India (n = 134) were assessed between August 2020 and November 2022. Data on socio-demography, ultrasound measurements, parental and foetal anthropometry were collected. Multiple linear regression models were run to predict determinants of foetal intrauterine and neonatal growth (p value<0.05). The dependent variables were ultrasound measurements and neonatal biometry, and independent variables were gestational weight gain, parental and mid-parental height. Mean(±SD) maternal age, maternal height, paternal height and mid-parental height were 22.8±3.7 years, 153.6±5.5cm, 165.9±6.5cm and 159.1±8.7cm, respectively. Pre-pregnancy body mass index and gestational weight gain was 20.5±4.0 kg/m2 and 9.8±3.7kg respectively. Mid-parental height and gestational weight gain were strongly correlated with neonatal growth and foetal intrauterine growth (p<0.05); however, the correlation peaked at 28 weeks of gestation (p<0.05). Gestational weight gain (B = 28.7, p = 0.001) and mid-parental height (B = 14.3, p = 0.001) were identified as strong determinants of foetal-intrauterine growth and neonatal anthropometry at birth. Maternal height was found to influence length of male neonate (B = 0.18, p = 0.001), whereas, paternal height influenced length of the female neonate (B = 0.11, p = 0.01). Parental socio-economic status, biometry and maternal gestational weight gain influence growth of the child starting from the intrauterine period. Our study underlines the need for interventions during pre-pregnancy, as well as during pregnancy, for optimal weight gain and improved foetal and neonatal outcomes.

Pilot Study on Gut Microbiota Profile in Indian Children with Type 1 Diabetes.

Background: Non-genetic factors like microbial dysbiosis may be contributing to the increasing incidence/progression of type 1 diabetes mellitus (T1DM). Objectives: To analyse the gut microbiota profile in Indian children with T1DM and its effect on glycaemic control. Methodology: Faecal samples of 29 children with T1DM were collected and faecal microbial DNA was extracted and subjected to 16S rRNA (ribosomal RNA) sequencing and further analysis. Results: The dominant phyla in children with T1DM were Firmicutes and Bacteroidetes. Butyrate-producing bacteria Blautia and Ruminococcus showed a significant negative correlation with the glycosylated haemoglobin (HbA1C) levels (p < 0.05). Coprococcus and Propionibacterium were important negative predictors of glycaemic control (p < 0.05). Conclusion: Our study suggests that Indian children with T1DM have a distinct gut microbiome taxonomic composition and that short-chain fatty acid-producing bacteria like Ruminococcus and Blautia (butyrate-producing) may play an important role in the glycaemic control of subjects with T1DM.