Determinants of Course of Type 2 Diabetes in Indian Adolescents.

OBJECTIVES: To identify determinants of the course of Type 2 diabetes in Indian adolescents. METHODS: Records of 37 adolescents (24 boys; 29 post pubertal and eight pubertal) with Type 2 diabetes (initial HbA1C 10.1 ± 1.9% and BMI SDS 2.0 ± 0.8; family history of diabetes in 33, 89.2%) diagnosed at 15.2 ± 2.5 y and followed up for 3.8 ± 2.2 y till 19.1 ± 3.3 y of age, were reviewed. RESULTS: Initial treatment included insulin in 11 (29.7%), metformin alone in 22 (59.5%), and a combination of anti-diabetic medication in four (10.8%). Eleven subjects (29.7%) achieved remission at a median period of 5.3 mo (IQR- 17.13) after diagnosis; six of these relapsed within 0.9 ± 0.3 (range 0.4-1.3) y. The proportion of subjects requiring multiple anti-diabetic agents increased over follow-up (19% at six months, 32.5% at one year, 50% at two years, 59.1% at three, and 64.8% at four years), with the need for combination therapy after 0.9 ± 1.4 y. At the last follow-up, five were off treatment (13.5%), 10 (27%) were on metformin alone, and 22 (59.5%) were on multiple medications. The need for combination therapy at the last follow-up was lower in subjects with remission (27% against 73.1%, p = 0.02). CONCLUSIONS: The findings of this study suggest delayed presentation and rapid progression of Type 2 diabetes in Indian adolescents. Diagnosis on screening and achievement of remission were predictors of good outcome.

Precocious Puberty.

Precocious puberty is a common presentation to pediatricians with a significant overlap between physiology and pathology. While most girls with precocious puberty have no identifiable cause, boys are more likely to have a pathological cause. The trend of earlier onset of thelarche with slow pubertal tempo has led to a significant increase in the number of girls presenting with precocious puberty. Advanced growth, bone age, uterine maturation, and elevated LH suggest rapidly progressive puberty. The critical issues in evaluating a child presenting with precocious puberty include its confirmation, exclusion of physiological variants, identification of the cause, and determining the need for treatment. Step-wise evaluation with emphasis on clinical parameters provides cost-effective assessment. Gonadotropin-releasing hormone (GnRH) analogs remain the mainstay of treatment for central precocious puberty but should be restricted to individuals with rapidly progressive puberty and compromised final height. The management of rarer forms of peripheral precocious puberty (McCune Albright syndrome, congenital adrenal hyperplasia, and testotoxicosis) involves using experimental drugs under the guidance of specialists.

Gastrointestinal polyps in McCune Albright syndrome.

BACKGROUND: McCune Albright syndrome (MAS), a disorder caused by somatic activating mutations in the GNAS gene, usually presents with cutaneous, skeletal, and endocrine manifestations. While focal lesions involving multiple tissues have been identified in MAS, almost nothing is known about gastrointestinal lesions in this disease. METHODS: Two MAS patients with perioral freckling, resembling Peutz-Jeghers syndrome (PJS), and two MAS patients without similar pigmentation underwent gastrointestinal endoscopy to establish if they had coexisting hamartomatous polyposis. Three of 4 subjects had documented GNAS mutations in peripheral blood. Genetic testing for STK11 and PRKAR1A genes was performed to exclude presence of coexistent PJS and Carney complex. Genetic testing of biopsy material was also performed. RESULTS: Hamartomatous gastrointestinal polyps with histological features similar to those in PJS were observed in all 4 subjects, only in the stomach and/or upper duodenum. Activating GNAS mutations were found in the polyps or adjacent mucosa in 3 of 4 subjects. One patient each had mutation only in the blood or tissue, while 2 patients had both. No subject harboured any detectable PRKARIA or STK11 mutation as determined by direct DNA sequencing and copy number variation analysis. CONCLUSIONS: These findings confirm that gastrointestinal polyps are a common manifestation of MAS, indicate an overlap between MAS and PJS, and point towards a putative interaction between the GNAS and STK11 genes in the pathogenesis of these two disorders. The findings suggest a need for routine gastrointestinal endoscopy in patients with MAS, to establish the true incidence of polyps in these patients.

The Development and Validation of a Mobile Application for Guidance for Management of Severe Diabetic Ketoacidosis.

OBJECTIVE: To develop and validate a mobile application-based tool for the management guidance of children and adolescents with diabetic ketoacidosis (DKA). METHODS: The study involved the development of a mobile application-based tool for DKA management in accordance with the International Society of Pediatric and Adolescent Diabetes (ISAPD) guidelines, 2018. The impact of the mobile application in preventing protocol deviation and resultant complications was assessed. Case records of 70 children and adolescents [39 boys, 8.9 (4.1) y of age] with severe DKA managed in the authors' intensive care unit were examined. The application guidance and real-time management were compared to the standard protocol. RESULTS: Protocol deviations were observed in 58 (82.9%), with two or more errors in 28 (40%). These included lack of initial fluid bolus (4, 5.7%), excessive fluid supplementation (8, 11.4%), inadequate initial fluid (25, 35.7%) and potassium supplementation (13, 18.6%), delayed response to fall in potassium (15, 21.4%) and glucose levels (24, 34.3%), and erroneous insulin administration (19, 27.1%). These errors contributed to 42.1% of severe hypokalemia and 56% of significant hypoglycemia episodes. The mobile application guidance was in accordance with the protocol in all the case scenario. CONCLUSION: Deviation from the management protocol is common in DKA and associated with adverse outcomes. Mobile application guidance is expected to reduce the protocol deviation with a potential of improving outcomes.

Comparison of the Predictive Value of IAP 2015 and WHO Body Mass Index Criteria for Hypertension in Indian Children and Adolescents.

OBJECTIVE: To compare the predictive value of the IAP and WHO criteria in identifying obesity complications in Indian children and adolescents. METHODS: Blood pressure and body mass index was measured in 4434 children and adolescents [2539 boys; mean age 11.9 (3.0), 5.1-18 y] from affluent schools. The predictive accuracy of IAP 2015 and WHO BMI criteria in identifying hypertension was assessed. RESULTS: IAP 2015 BMI criteria labelled 203 more children obese than the WHO reference (649 as against 446). Hypertension was present in 75 (37%) of these. The difference in the prevalence of hypertension in subjects obese as per IAP 2015 criteria and their nonobese counterparts (50.2% as against 10.8%, p < 0.0001) was greater than that between subjects obese only by IAP 2015 or by both the criteria (36.9% as against 56.3%, p < 0.0001). The difference in the proportion of subjects with hypertension between two consecutive IAP 2015 BMI SDS category was highest for + 1.5 in boys (32.3% as against 49.8%, p < 0.0001) and + 2 in girls (25.9% as against 59.3%, p < 0.00012). CONCLUSION: IAP BMI criteria better predict hypertension in Indian children than WHO cutoffs and should be used in clinical practice to predict obesity complications.

Determinants and Predictors of Body Fat in Indian Children and Adolescents.

OBJECTIVE: To study determinants and predictors of body fat in Indian children and adolescents. METHODS: In this cross-sectional study, 5175 children and adolescents [3014 boys, age 12.8 (3) y, 5-18 y] participated. Determinants and predictors of body fat were assessed using partial correlation (corrected for age, and gender) and linear regression. RESULTS: Fat percentage correlated negatively with the duration of physical activity (r = -0.091, p < 0.01) and sleep (r = -0.044, p = 0.01) and positively with parental body mass index (BMI) (r = 0.202, p < 0.01 for father and r = 0.235, p < 0.01 for mother), and birth weight (r = 0.050, p < 0.01). On linear regression, fat percentage was positively associated with parental BMI and birth weight, and negatively with physical activity and sleep duration. All adiposity markers [BMI standard deviation score (SDS) (r = 0.863, p < 0.01), weight SDS (r = 0.827, p < 0.01) waist to height ratio (r = 0.819, p < 0.01), waist circumference SDS (r = 0.765, p < 0.01) wrist circumference (r = 0.21, p < 0.01), and neck circumference (r = 0.19, p < 0.01)] correlated significantly with fat percentage, showing highest correlation with BMI SDS. CONCLUSION: Reduced sleep and physical activity are the key modifiable risk factors for adiposity. BMI SDS is the best clinical surrogate of body fat in Indian children and adolescents. There is a need to explore the impact of lifestyle interventions targeting sleep and physical activity on adiposity.

Development and validation of a mobile application for point of care evaluation of growth failure.

OBJECTIVES: Lack of systematic evaluation of short stature results in unnecessary work-up on one hand while missing pathology on the other. We have developed a mobile application that guides work-up based on age, auxology (height, BMI, and corrected standard deviation score), and skeletal maturation with an aim of reducing the diagnostic errors. Aim of this study is to develop and validate a mobile application for point of care evaluation of short stature. METHODS: The application was developed (n=400) and validated (n=412) on children and adolescents (2-18 years of age) presenting to our Pediatric Endocrinology Clinic with short stature. Height standard deviation score thresholds determining the need for workup were derived from Receiver Operating Characteristics (ROC) curve. Student's t-test and ROC curves were used to identify the most appropriate parameter differentiating constitutional delay of growth and puberty (CDGP) from pathological and nutritional from endocrine causes. The validation of the application involved comparing the application predicted and clinical diagnosis at each step of the algorithm. RESULTS: The mobile application diagnosis was concordant with clinical diagnosis in 408 (99.0%) with discordance in four (two with CDGP labeled as growth hormone deficiency [GHD] and two with GHD labeled as CDGP). CONCLUSIONS: Mobile application guided short stature assessment has a high concordance with the clinical diagnosis and is expected to help point of care short stature evaluation.

Evaluation of Short Stature in Children and Adolescents.

Short stature is a common presentation to pediatricians with a significant overlap between physiology and pathology. Thus, while most short children have a physiological cause, growth failure may be the only manifestation of severe underlying disease. Growth failure evaluation aims to avoid unnecessary investigations in children with a physiological cause without missing pathology. Guidelines for the evaluation of short stature allow stepwise evaluation but are limited by their resource-intense nature. An objective application of anthropometric indices and careful clinical evaluation allows rational growth failure workup. The use of height standard deviation score (SDS) for determining the need for evaluation (no evaluation above -2, follow-up between -2 to -3, and immediate workup with height below -3), corrected height SDS to identify familial short stature (above -1.5), height SDS for bone age for constitutional delay of puberty and growth (above -2), and BMI SDS for nutritional pattern growth failure (below -1) helps reduce the burden of investigations. The present review provides a framework for comprehensive growth evaluation across resource levels and settings.

Mindfulness Meditation as Adjunctive Therapy to Improve the Glycemic Care and Quality of Life in Patients with Type 1 Diabetes.

BACKGROUND: Mindfulness Meditation (MM) is known to improve glycemic control and enhance the quality of life (QoL) in type 2 diabetes (T2D) patients. Unfortunately, the role of meditation in type 1 diabetes (T1D) has not been studied extensively. Therefore, we conducted this study to determine the effect of MM on the glycemic control and QoL in people living with T1D. METHODOLOGY: Thirty-two adults living with T1D were equally randomized into intervention (meditation) and control groups. The glycemic control and QoL were assessed at the baseline and after six months of intervention. RESULTS: A total of thirty-two adults (15 males, 46.9%; mean age 23.8 ± 6.6 years) with type 1 diabetes (mean diabetes duration 12.7 ± 6.2 years) participated in the study. At the end of six months, a statistically significant improvement was seen in the mean blood glucose level in the control group (222.4 ± 77.8 versus 182.6 ± 52.0; p = 0.007) and the intervention group (215.3 ± 50.1 versus 193.2 ± 31.8; p = 0.008). Additionally, there was a significant reduction in the total diabetes distress score in the intervention group (1.6 ± 0.3 versus 1.3 ± 0.3; p = 0.003), while no change was observed in the control group (1.6 ± 0.7 versus 1.7 ± 0.4; p = 0.762). A statistically significant improvement was noticed in the health and functioning domain in the intervention group (p = 0.023). CONCLUSIONS: An improvement in the glycemic control and quality of life of the patients was observed in our study. MM certainly plays an important role in attaining peace of mind and helps patients to channel their energy in a positive direction.

Predictors of Metabolic Complications in Obese Indian Children and Adolescents.

OBJECTIVE: To identify predictors of metabolic complications in obese Indian children and adolescents. METHODS: This cross-sectional study included 282 obese children and adolescents [188 boys, mean (SD) age of 11.7 (3.1) y, body mass index standard deviation score (BMI SDS) 2.4 (0.6)] who underwent metabolic work-up (oral glucose tolerance test, SGPT, lipid profile) and adiposity assessment (waist circumference and Dual energy X-ray absorptiometry). RESULTS: One hundred and fifteen subjects (40.8%) had no metabolic complication (metabolic healthy obesity) with similar prevalence across BMI SDS categories (38.8% for BMI SDS below 2, 42.1% for 2-3 and 40.4% for those above 3). Normal birth weight (odds ratio 3.2, 95% confidence interval 1.0-10.1, p = 0.04), negative family history of type 2 diabetes (odds ratio 1.81, 95% confidence interval 1.0-3.3, p = 0.04) and younger age [11.3 (3.1) y as against 12.1 (3.1) y, p = 0.03] were associated with metabolically healthy obesity. No difference in BMI SDS [2.4 (0.6) as against 2.4 (0.6), p = 0.7], waist circumference SDS [2.0 (0.7) as against 2.2 (0.9), p = 0.07], waist to height ratio [0.6 (0.05) as against 0.6 (0.05), p = 0.1], DXA derived fat percentage [48.6 (5.4)% as against 47.8% (5.2), p = 0.2], android to gynoid ratio [1.05 (0.1) as against 1.06 (0.1), p = 0.08] and fat mass index [13.8 (3.5) as against 13.8 (3.3), p = 0.9] was observed in the two groups. CONCLUSIONS: A substantial proportion of obese children and adolescents do not develop metabolic complications. Birth weight and family history of type 2 diabetes are the only predictors of complications. Further exploration is needed to identify interventional targets.

Predictive Value of IAP 2015, IAP 2007 and WHO Growth Charts in Identifying Pathological Short Stature.

OBJECTIVE: To compare the diagnostic accuracy of IAP 2015, WHO and IAP 2007 growth charts in identifying pathological short stature in Indian children. METHODOLOGY: The predictive value of the growth charts for pathological short stature was assessed in 500 (266 boys) short subjects (age 5-17.9 years) presenting to our pediatric endocrine clinic. RESULTS: WHO, IAP 2015, IAP 2007 criteria classified 500, 410 (82%) and 331 (66.2%) subjects short respectively. A total of 218 (43.6%) subjects had a pathological cause. Two out of 90 subjects short by WHO criteria but normal as per IAP 2015 had a pathological cause (2.2%) whereas 38 out of 79 subjects short as per WHO and IAP 2015 criteria but normal by IAP 2007 had pathological short stature. The diagnostic measures of IAP 2015 and IAP 2007 charts in identifying pathological short stature showed a sensitivity 99.1% and 81.7%, negative predictive value 97.8% as against 76.3%, positive predictive value 52.7% and 53.8%, and specificity of 31.2% and 45.7%, respectively. CONCLUSION: IAP 2015 growth charts are superior in identifying pathological growth failure compared to WHO and IAP 2007.

Metabolic Impact of Subclinical Hypothyroidism in Obese Children and Adolescents.

OBJECTIVE: Subclinical hypothyroidism is common in children and adolescents with obesity and has been considered to be its effect with no need for treatment. Its metabolic impact has not been evaluated. Therefore the present study was conducted to determine the metabolic impact of obesity related subclinical hypothyroidism. METHODS: Retrospective record review of obese children and adolescents between 5 and 18 y of age presenting to pediatric endocrine clinic was done. Four hundred four obese children and adolescents [251 boys, 11.8 (3.2); 5.1-18 y, BMI SDS 2.4 (0.7); 1.4-6.6] were assessed regarding thyroid functions, adiposity (clinical and DXA derived) and metabolic complications. RESULTS: Subclinical hypothyroidism was observed in 122 (30.2%) and was associated with higher fat percentage [49.2 (5.8) vs. 47.2 (6.4) p = 0.009], android to gynoid ratio [1.1 (0.1) vs. 1.0 (0.1), p = 0.007] and alanine aminotransferase (ALT) levels [49.3 (31.5) vs. 40.8 (38.1), p = 0.04]. Subjects with subclinical hypothyroidism had 1.9 times greater odds of having non-alcoholic steatohepatitis (47.3% vs. 31.8%, p = 0.005) with no difference in the prevalence of dyslipidemia, dysglycemia or hypertension. Subclinical hypothyroidism was the only determinant of non-alcoholic steatohepatitis on binomial logistic regression (WALD = 11.04, p = 0.001) with no impact of BMI SDS, waist circumference SDS, fat percentage or android to gynoid ratio. Thyroid stimulating hormone (TSH) was the most important determinant of ALT on linear regression (B = 3.027, p < 0.005). CONCLUSIONS: Obesity related subclinical hypothyroidism predisposes to increased ALT and non-alcoholic steatohepatitis independent of severity adiposity. The impact of thyroid supplementation in this setting needs to be explored.

COVID-19 pandemic: a double trouble for Indian adolescents and young adults living with type 1 diabetes.

BACKGROUND: Strict isolation measures and interrupted health care services during the COVID 19 pandemic are contemplated to instigate stress universally, particularly in those with chronic illnesses such as type 1 diabetes (T1D). METHODS: A cross-sectional, observational study was done to assess determinants of stress and its impact on glycemic control in adolescents and young adults (aged 12-24 years) living with T1D in India. An online, semi-structured survey including Perceived Stress Scale (PSS-10) was distributed and results were analyzed. RESULTS: A total of 89 participants (46 males, mean age 19.61 ± 3.8 years) with T1D completed the survey. Age (r = 0.325, p = 0.005) and HBA1C level within the preceding 3 months (r = 0.274, p = 0.036) correlated positively with PSS-10 scores. There was a statistically significant difference in PSS-10 score based on gender (t(70) = - 2.147; p = 0.035), education (F (4,67) = 4.34, p = 0.003), and occupation (F(3,68) = 4.50, p = .006). On multiple linear regression, gender, occupation, and HbA1C were the significant determinants of PSS-10 (F(3,55) = 12.01, p < 0.001, R 2 = 0.363). One-way ANOVA showed a significant impact of mean PSS-10 score on the glycemic control (F(2,69) = 3.813, p = 0.027). CONCLUSION: An increased prevalence of stress was seen among Indian adolescents and young adults living with T1D. Female gender, salaried individuals, and pre-existing poorly controlled diabetes contributed to an increased risk of stress. Increased stress resulted in worsened glycemic control.

Goat lung surfactant for treatment of respiratory distress syndrome among preterm neonates: a multi-site randomized non-inferiority trial.

OBJECTIVE: To investigate the safety and efficacy of goat lung surfactant extract (GLSE) compared with bovine surfactant extract (beractant; Survanta®, AbbVie, USA) for the treatment of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: We conducted a double-blind, non-inferiority, randomized trial in seven Indian centers between June 22, 2016 and January 11, 2018. Preterm neonates of 26 to 32 weeks gestation with clinical diagnosis of RDS were randomized to receive either GLSE or beractant. Repeat dose, if required, was open-label beractant in both the groups. The primary outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age (PMA). Interim analyses were done by an independent data and safety monitoring board (DSMB). RESULT: After the first interim analyses on 5% enrolment, the "need for repeat dose(s) of surfactant" was added as an additional primary outcome and enrolment restricted to intramural births at five of the seven participating centers. Following second interim analysis after 98 (10% of 900 planned) neonates were enroled, DSMB recommended closure of study in view of inferior efficacy of GLSE in comparison to beractant. There was no significant difference in the primary outcome of death or BPD between GLSE group (n = 52) and beractant group (n = 46) (50.0 vs. 39.1%; OR 1.5; 95% CI 0.7-3.5; p = 0.28). The need for repeat dose of surfactant was significantly higher in GLSE group (65.4 vs. 17.4%; OR 9.0; 95% CI 3.5-23.3; p < 0.001). CONCLUSIONS: Goat lung surfactant was less efficacious than beractant (Survanta®) for treatment of RDS in preterm infants. Reasons to ascertain inferior efficacy of goat lung surfactant requires investigation and possible mitigating strategies in order to develop a low-cost and effective surfactant.

Platelet dysfunction and increased bleeding tendency in McCune-Albright syndrome.

We observed increased bleeding tendency and platelet function abnormalities in 3 boys with McCune-Albright syndrome (MAS). We speculate that platelet dysfunction contributed to excessive blood loss in our patients. This report of platelet dysfunction in MAS highlights the need for assessment of platelet functions in the condition.

Central diabetes insipidus: clinical profile and factors indicating organic etiology in children.

OBJECTIVE: To evaluate the profile of children with central diabetes insipidus (DI) and identify factors indicating organic etiology. DESIGN: Retrospective chart review. SETTING: Tertiary referral hospital. SUBJECTS: Fifty-nine children with central DI (40 boys, 19 girls). METHODS: Features of organic and idiopathic central DI were compared using students t test and chi square test. Odds ratio was calculated for factors indicating organic etiology. RESULTS: Diagnosis included post-operative central DI (13, 22%), central nervous system (CNS) malformations (5, 8.6% holoprosencephaly 4 and hydrocephalus 1), histiocytosis (11, 18.6%), CNS pathology (11, 18.6%; craniopharyngioma 3, empty sella 2, germinoma 2, neuro-tuberculosis 2, arachnoid cyst 1 and glioma 1) and idiopathic central DI (19, 32.2%). Children with organic central DI were diagnosed later (7.8+/- 3.1 years against 5.3+/-2.4 years, P=0.03) and had lower height standard deviation score (-2.7+/-1.0 versus -1.0+/- 1.0, P<0.001) compared to idiopathic group. A greater proportion of children with organic central DI had short stature (81.8% against 10.5%, P <0.001, odds ratio 38.25), neurological features (45.5% against 0%, p 0.009) and anterior pituitary hormone deficiency (81.8% against 5.3%, P<0.001, odds ratio 81) compared to idiopathic group. A combination of short stature and onset after five years of age led to discrimination of organic central DI from idiopathic group in all cases. CONCLUSION: Organic central DI should be suspected in children presenting after the age of five years with growth retardation and features of anterior pituitary deficiency.