Search

Aims: Islet antibody-negative type 1 diabetes mellitus (T1DM) has not been well characterised. We determined the frequency of antibody-negative T1DM and compared it with antibody-positive T1DM in a cohort of north Indian children., Methods: In a multi-centre, prospective, observational study, 176 Indian children (age 1-18 years) were assessed within 2 weeks of diagnosis of T1DM. Antibodies against GAD65 (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A), were estimated using validated ELISA. HLA-DRB1, DQA1 and DQB1 alleles were studied by Luminex-based typing. Monogenic diabetes was determined by targeted next-generation sequencing using the Illumina platform., Results: After excluding 12 children with monogenic diabetes, GADA, IA-2A and ZnT8A were present in 124 (76%), 60 (37%) and 62 (38%) o children, respectively, while 24 (15%) were negative for all antibodies. A single antibody (most frequently GADA) was present in 68 (41%) of children, while all three antibodies were found in 34 (21%). Islet antibody-negative T1DM (n = 24, 15%) did not differ from antibody-positive children in their clinical features, HbA1c or plasma C-peptide, both at onset or after 1 year follow-up (available in 62 children). The frequency of other organ-specific antibodies or high-risk HLA-DR and DQ alleles were also similar. Children with a single islet antibody did not differ from those with multiple antibodies., Conclusions: The frequency of various islet-antibodies, in isolation and combination, differed considerably from studies among children of European descent with T1DM. Children with T1DM who were islet antibody-negative were indistinguishable from those who were antibody-positive., (© 2024 Diabetes UK.)

Context: The long term outcomes for individuals with a difference in sex development (DSD) are influenced by ethnic, socio-cultural and economic factors, besides the medical issues. Data from India on these aspects are sparse., Design and Measurements: We report on gender identity, patients' opinion regarding timing of genitalia surgery, suicidal thoughts, romantic inclination, and quality of life (QOL, SF36 scale), in 31 young adults with a DSD., Results: Median (IQR) age was 23 (19-27) years; 16 raised male, 15 female. Age at first surgery was 6.0 (2.0-16.25) years. Gender identity in 30 patients remained identical with sex of rearing. Majority (27) thought the timing of genital surgery should be in childhood. Six of 31 patients had attempted suicide at least once. Four patients reported sexual abuse in the past. Twelve patients reported romantic relationships, rates similar to reports from India, with seven reporting sexual intercourse. Eleven of 31 patients reported aversion to and fear of sexual activity, due to fear of rejection. Heterosexual orientation was reported by 25 of 29 patients. QOL scores were not different between patients and 46 healthy controls or 43 people with type 1 diabetes. Mental QOL scores were lower for those with history of teasing (37.10 ± 16.01 vs. 47.76 ± 9.4 in those without, p = 0.04) and with suicidal thoughts (33.9 ± 14.51 vs. 45.65 ± 13.2 for those without, p = 0.04)., Conclusions: The absence of prominent gender dysphoria in our young adults was noteworthy, as was their preference for early genital surgery. Lack of adequate mental health support is a high alert for our teams involved in the care of DSD and as well as for policy-makers., (© 2024 John Wiley & Sons Ltd.)

Monogenic forms of rickets are being increasingly recognized. However, vitamin D-dependent rickets 1b (VDDR1b) due to CYP2R1 gene mutation is exceedingly rare. We report a 4.5-year-old girl and her younger sibling who presented with clinical, radiological, and biochemical features suggestive of nutritional rickets that did not resolve despite repeated therapeutic doses of vitamin D3. This led to evaluation for resistant rickets, which revealed a novel homozygous CYP2R1 c.50_51insTCGGCGGCGC; p.Leu18ArgfsTer79 variant in the affected siblings. The children were treated with oral calcium and cholecalciferol, dose titrated to maintain serum alkaline phosphatase, 25 hydroxy vitamin D, and parathyroid hormone levels in the normal range, with good clinical and radiological response. This case highlights the importance of genetic evaluation in patients with suspected nutritional rickets who have a family history of similar illness and require higher than usual doses of vitamin D for healing or relapse on stopping treatment. To the best of our knowledge this is the first case of VDDR1b reported from Asia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Pediatric endocrine disorders requiring surgical intervention are rare and so are experienced surgeons dealing with these. The aim of the current study was to investigate disease profile and perioperative outcome of pediatric patients with surgical endocrine disorders in an endocrine surgery unit., Methods: This retrospective study (Sep 1989-Aug 2019) consisted of pediatric endocrine surgery patients (<18 years) who were managed by a team of pediatric endocrinologists and endocrine surgeons at our center. Patients were divided into three cohorts consisting of a decade each. Clinico-pathologic variables, perioperative events operative and follow-up details were recorded., Results: A total of 332 children were included and their mean age was 14.6 ± 3.9 years (M:F = 1:1.6). Thyroid disorders were most prevalent (59.8%), followed by adrenal (28.2%), parathyroid (10.4%), and pancreas (1.5%). Incidence of benign, malignant, and congenital/developmental disorders were 65.4, 28.1 and 8.3, respectively. Familial association was observed in 8.9% children, which is highest among pheochromocytoma patients. Overall, 201 thyroidectomies + associated procedures, 35 parathyroidectomies, 96 adrenal and paraganglioma resections, and 5 pancreatic procedures were performed. Median hospital stay was 5.6 ± 4.1 days. The number of cases increased significantly over 3 decades. Clinical profile and outcome did not vary except for significant decrease in incidence of malignant pathology (p = 0.04) and increase in VHL cases (p = 0.04) in the last decade though overall increase in familial cases was nonsignificant (p = 0.11). No perioperative mortality was observed except for 3% after adrenalectomy., Conclusion: A team of dedicated endocrine surgeons and pediatric endocrinologists is effective in management of pediatric endocrine surgery., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Objectives: The aim of this study was to evaluate the effect on glycemic control and acceptability of basic carbohydrate counting (BCC) in children and young adults with type 1 diabetes (T1DM)., Methods: Ninety-two children and young adults (6-25 y of age) with T1DM were randomized to receive either routine nutrition education (RNE), which addressed food groups, glycemic index, and effects of food and exercise on glycemia, or learn BCC with personalized portion size education. A continuous glucose monitoring study and glycosylated hemoglobin (HbA1c) were performed at baseline and after 12 wk. The primary outcome was a change in time-in-range from baseline through 12 wk. A questionnaire on the acceptability of BCC was administered., Results: At 12 wk, there was no significant difference in change in time-in-range between the two groups (BCC group: 1.2 ± 12.2; RNE group: 1.9 ± 12.3; P = 0.786). No significant changes were observed in the percentage of time that blood glucose was >180 or >250 mg/dL; <70 or <54 mg/dL; glycemic variability, percentage of nights with hypoglycemia and HbA1c. In subgroup analysis, there was a significant decrease in HbA1c in the BCC group among participants with higher maternal education (-0.5 versus 0.2, P = 0.042). The total score on the acceptability questionnaire was higher in the BCC group (P = 0.022)., Conclusion: Among children and young adults in our region with T1DM, BCC provided flexibility in food choices and perception of greater ease of insulin adjustment. Although BCC was equivalent to RNE in terms of glycemic control, larger studies may reveal benefit in outcomes in certain subgroups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM., Methods: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing., Results: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected., Conclusion: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Since the 2018 ISPAD guidelines on this topic, follow-up of large cohorts from around the globe have continued informing the current incidence and prevalence of co-morbidities and complications in young adults with youth-onset type 2 diabetes (T2D). This chapter focuses on the risk factors, diagnosis and presentation of youth-onset T2D, the initial and subsequent management of youth-onset T2D, and management of co-morbidities and complications. We include key updates from the observational phase of the multi-center Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial, the SEARCH for Diabetes in Youth (SEARCH) study and new data from the Restoring Insulin Secretion (RISE) study, a head-to-head comparison of youth onset vs adult-onset T2D. We also include an expanded section on risk factors associated with T2D, algorithms and tables for treatment, management, and assessment of co-morbidities and complications, and sections on recently approved pharmacologic therapies for the treatment of youth-onset T2D, social determinants of health, and settings of care given COVID-19 pandemic., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bronchial carcinoid is the most common primary malignant lung tumor in children; however, it remains a very rare diagnosis due to the overall low incidence of childhood lung malignancies. We report a case of a 17-year-old girl with respiratory symptoms who was initially misdiagnosed as a case of COVID pneumonia. She was later detected to have a right mainstem bronchial carcinoid which was managed successfully by a multi-disciplinary team., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Indian Association of Pediatric Surgeons.)

Background & Objectives: The association between hyperglycaemia at admission, diabetes mellitus (DM) status and mortality in hospitalized SARS-CoV-2 infected patients is not clear. The purpose of this study was to determine the relationship between DM, at-admission hyperglycaemia and 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection requiring intensive care., Methods: All consecutive moderate-to-severe patients with SARS-CoV-2 infection admitted to the intensive care units (ICUs) over six months were enrolled in this single-centre, retrospective study. The predicators for 28 day mortality were analysed from the independent variables including DM status and hyperglycaemia at-admission., Results: Four hundred and fifty two patients with SARS-CoV-2 were admitted to the ICU, with a mean age of 58.5±13.4 yr, 78.5 per cent being male, HbA 1c of 7.2 per cent (6.3-8.8) and 63.7 per cent having DM. Overall, 28 day mortality was 48.9 per cent. In univariate analysis, mortality in diabetes patients was comparable with non-diabetes (47.9 vs. 50.6%, P=0.58), while it was significantly higher in hyperglycaemic group (60.4 vs. 35.8%, P<0.001). In multivariate Cox regression analysis, after adjusting for age, sex and comorbidities, hyperglycaemia at-admission was an independent risk factor of mortality [hazard ratio (HR) 1.45, 95% confidence interval (CI) (1.06-1.99), P<0.05]., Interpretation & Conclusions: This study showed that the presence of hyperglycaemia at-admission in critically ill SARS-CoV-2 patients was an independent predictor of 28 day mortality. However, the findings may be susceptible to unmeasured confounding, and more research from prospective studies is required.

Background: Craniopharyngiomas are associated with long-term morbidity in the form of hormone deficiencies, visual deficits, and hypothalamic obesity., Objective: To study the long-term outcomes, including cure rates, endocrine dysfunction, visual dysfunction, hypothalamic obesity, and mortality in pediatric-onset craniopharyngiomas., Methods: A retrospective data analysis of pediatric (onset <18 years) craniopharyngioma diagnosed between 2003 and 2018. Data were collected from electronic hospital records, case files, and direct patient interviews., Results: The mean age at presentation was 10.4 ± 4.5 years (n = 62). The median duration of symptoms at diagnosis was 6 months (3-13 months). At presentation, central diabetes insipidus was present in four (6.5%), central hypothyroidism in 27 (43.5%), secondary adrenal insufficiency in 20 (32%) and delayed puberty in 15 (24%) patients. Hypothalamus was involved in 59/60 patients (98%). At last visit, 22.6% were obese in comparison to 4.6% at presentation, and anterior pituitary deficiency was present in 90% of the patients. Sixty-one percent patients (n = 62) had delayed puberty and 67% (n = 53) had short-stature. Out of 35 short children, nine (14%) children who received growth hormone had significant increase in height SD score (-3.8 (1.4) at start vs. -2.9 (1.2) at last follow-up; P = 0.008). Tumor progression was significantly less in the group that received RT compared to those who did not (8% vs. 39%; P = 0.002)., Conclusion: Childhood-onset craniopharyngioma results in significant morbidity. The prevalence of pituitary hormones deficiency, visual deficits, and obesity are high at long-term follow-up. Incomplete tumor removal is also frequent. Thus, long-term monitoring is necessary for the timely management of the morbidities associated with craniopharyngioma., Competing Interests: None

Background: The HLA associations of celiac disease (CD) in north Indians differ from that in Europeans. Our dietary gluten is among the highest in the world. Data on CD in people with diabetes (PWD) in north India is scant., Objective: To estimate the prevalence and clinical profile of CD in children with type 1 diabetes (T1D)., Research Design and Methods: Retrospective review of case records of PWD with onset ≤18 years of age, registered between 2009 and 2020, having at least one anti tissue-transglutaminase (anti-tTG) serology report., Results: Of 583 registered PWD, 398 (68.2%) had celiac serology screening. A positive report was obtained in 66 (16.6%). Of 51 biopsied people, 22 (5.5%) were diagnosed to have CD, 12 in the first 2 years of diabetes onset. Symptomatic CD at diagnosis was seen in 63% (14/22). Age at diabetes onset (median [IQR] age 5.5 years, [2-12]) was lower in PWD and CD compared to PWD alone (10 years, [7-14], p < 0.016). Of 36 biopsied children with anti-tTG >100 au/ml, 20 (55.5%) had CD, while 2 out of 15 (13.3%) of those with lower anti-tTG titer had histopathology suggestive of CD. Of 23 seropositive children not diagnosed with CD, 5 of 8 with anti tTG >100 au/ml, and all 15 with lower anti-tTG, had normalization of titers over the 24 (10-41) months., Conclusions: Our prevalence of CD is comparable to international data. Celiac disease was common with younger age at onset of T1D and higher titer of celiac serology. A high proportion was symptomatic of CD at diagnosis., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)