Single-Center Experience of Using Liraglutide in Adolescents With Obesity +/- Type 2 Diabetes.

Background Childhood obesity is recognized as a chronic illness with limited therapeutic options. Tackling obesity (BMI; the weight in kilograms divided by the square of the height in meters, at the 95th percentile or higher) with lifestyle interventions, especially in adolescents, has proven to be a daunting task, yielding only modest results. Research on the use of liraglutide for weight reduction in pediatric patients has yielded conflicting results. Notably, there is a lack of studies in the Middle East reporting on the outcomes of glucagon-like peptide 1 (GLP-1) receptor agonists in treating obesity in children and adolescents, with or without diabetes. This study, conducted in the Middle East, represents the first investigation into the utilization of liraglutide for weight reduction in this pediatric population. Methods This retrospective study collected data on 22 consecutive participants, aged 12 to 19 years, who were diagnosed with obesity (defined as having a BMI greater than the 95th percentile for their age and sex) and had either type 2 diabetes mellitus (T2DM) or were non-diabetic who attended endocrine clinics in Sidra Medicine, Doha, Qatar, between 2020 and 2022. The study protocol involved a liraglutide treatment period spanning 18 months (72 weeks), with scheduled follow-up appointments at six-month intervals. The primary endpoints were changes in weight and BMI from baseline to the 72-week mark. Secondary endpoints were safety measures and changes in HbA1c.  Results Out of the initial cohort of 22 patients, 12 completed the full 72-week duration of the study, while 10 patients either discontinued treatment or did not adhere to the prescribed medication regimen due to side effects. Among the 12 patients who completed the study, six had a diagnosis of T2DM. At baseline, the weight, standard deviation score (SDS), BMI, and BMI standard deviation (SD) were 113.9 kg, 2.9, 40.9 kg/m2, and 2.6 respectively. At the 18-month follow-up, the weight, SDS, BMI, and BMI SD were 117.8kg, 2.6, 39kg/m2, and 2.5, respectively. Thus, no statistically significant change in the weight parameters was evident at 18 months compared to baseline. Dropout from the study and poor compliance were high (10 out of 22 patients) due to side effects, mainly gastrointestinal (nausea, abdominal pain, diarrhea, and vomiting). No statistically significant differences were observed between obese vs. obese with T2DM. No significant change in HbA1c was found between baseline and treatment follow-up in the diabetes patients. No adverse effects in terms of impairment of liver and kidney function or pancreatitis were observed. Conclusions The administration of liraglutide to adolescents with obesity, regardless of whether they had T2DM or not, in a real-life setting, did not yield statistically significant reductions in BMI/weight parameters, and HbA1c levels at the 72-week mark. Nevertheless, the study findings indicate that liraglutide is deemed safe for utilization within this age group, despite the presence of mild gastrointestinal side effects.

Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar.

CONTEXT: Monogenic obesity is a rare form of obesity due to pathogenic variants in genes implicated in the leptin-melanocortin signaling pathway and accounts for around 5% of severe early-onset obesity. Mutations in the genes encoding the MC4R, leptin, and leptin receptor are commonly reported in various populations to cause monogenic obesity. Determining the genetic cause has important clinical benefits as novel therapeutic interventions are now available for some forms of monogenic obesity. OBJECTIVE: To unravel the genetic causes of early-onset obesity in the population of Qatar. METHODS: In total, 243 patients with early-onset obesity (above the 95% percentile) and age of onset below 10 years were screened for monogenic obesity variants using a targeted gene panel, consisting of 52 obesity-related genes. RESULTS: Thirty rare variants potentially associated with obesity were identified in 36 of 243 (14.8%) probands in 15 candidate genes (LEP, LEPR, POMC, MC3R, MC4R, MRAP2, SH2B1, BDNF, NTRK2, DYRK1B, SIM1, GNAS, ADCY3, RAI1, and BBS2). Twenty-three of the variants identified were novel to this study and the rest, 7 variants, were previously reported in literature. Variants in MC4R were the most common cause of obesity in our cohort (19%) and the c.485C>T p.T162I variant was the most frequent MC4R variant seen in 5 patients. CONCLUSION: We identified likely pathogenic/pathogenic variants that seem to explain the phenotype of around 14.8% of our cases. Variants in the MC4R gene are the commonest cause of early-onset obesity in our population. Our study represents the largest monogenic obesity cohort in the Middle East and revealed novel obesity variants in this understudied population. Functional studies will be required to elucidate the molecular mechanism of their pathogenicity.

Factors Determining Risk Categories in Differentiated Thyroid Carcinoma: Study of an Indian Cohort.

Introduction: Differentiated thyroid carcinoma/cancer (DTC) burden in developing countries could be different from that of the developed nations. Aims and Objectives: To describe the clinicopathological characteristics in a cohort of DTC patients in a south Indian state of Kerala and to compare with the data from other centres. Materials and Methods: A retrospective analysis of the data collected on DTC patients, from January 2010 to August 2018, attending thyroid cancer clinic at a tertiary care centre. Results: mong the 944 patients (male 262; female 682; mean age 43.8 years; standard deviation, SD 13.8), types of tumour were as follows: classical papillary thyroid carcinoma (cPTC) 48.3%, follicular variants of PTC (FVPTC) 28.8%, follicular and hurthle cell carcinoma (FTC&HCC) 10.1%. Mean size of the tumour was 2.7 cm (SD 1.8) papillary thyroid micro carcinomas (PTMC) were seen in 113 patients (12%), which were detected incidentally. Metastases were present at diagnosis in 40.2% cases, most common site being cervical lymph nodes. Distant metastases were seen in 113 patients (14.5%) and commonest site was bone. The American Thyroid Association (ATA) risk stratification was possible only in 684 subjects and showed 31.3% low risk, 41.8% intermediate risk and 26.9% at high-risk category. Lymph node metastasis and distant metastasis were the commonest determining factors for intermediate and high-risk category, respectively. High-risk category was significantly higher in patients >55 years, tumour size >4 cm, FTC/HCC tumour type and extranodal extension (ENE) of lymph node metastasis. Radio active iodine ablation was given to 85.2% subjects. Conclusion: In our DTC population, FVPTC formed the second most common type and PTMC were all incidentalomas. Metastasis at diagnosis was higher suggesting delayed presentation. Old age, FTC/HCC, large size of the tumour, ENE were significantly higher in high-risk patients. Rest of the features of these cohort was comparable with the United States cohort of DTC patients.

Prospective Study of Bethesda Categories III and IV Thyroid Nodules: Outcomes and Predictive Value of BRAFV600E Mutation.

INTRODUCTION: Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has emerged as the most controversial category because of its heterogeneity and inconsistent reporting. There is a definite paucity in data available from the Indian subcontinent about the outcome of nodules carrying Bethesda category III or Bethesda category IV diagnoses. AIMS AND OBJECTIVES: The primary objective of our study was to determine the malignancy rate in Bethesda categories III and IV nodules. The secondary objectives were to determine predictive value of BRAFV600E mutation analysis on indeterminate thyroid nodules, predictive value of Thyroid image reporting and data system (TI-RADS) in malignancy prediction and to study the common histological variants in indeterminate nodules. MATERIALS AND METHODS: This prospective study included 176 consecutive nodules of Bethesda categories III and IV, diagnosed over a period of 2 years from August 2015 to August 2017. A part of the fine needle aspirate was used to perform the BRAFV600E mutation analysis. The malignancy risk associated with these Fine needle aspiration Cytology categories were discussed with the patients. Those with Bethesda category IV diagnosis was advised surgery, whereas those with Bethesda category III were given the options of close follow-up with repeat FNA in 3 months or immediate surgery. RESULTS: In our prospective study, there were 176 consecutive samples of categories III (140/79.5%) and IV (36/20.5%). Seventy-five (53.6%) category III nodules and 29 (80.6%) category IV nodules underwent immediate surgical excision. Fifty-five consecutive indeterminate cytology nodules were subjected for BRAFV600E. One of the samples was found to be positive for BRAF T1799A (V600E) mutation. The second sample harboured a missense mutation at position 1819 (TCC--GCC), wherein the codon 607 (TCC) coding for serine was substituted by alanine (GCC) which is a variant of unknown significance. In our study, the malignancy rate of Bethesda categories III and IV, which were triaged for immediate surgery were 54.6% and 72.4%, respectively. CONCLUSION: Malignancy rate in Category III at our center was much higher than that described by ATA and by other studies published from centers around the world, including the only two studies from India. In view of the strikingly high malignancy rate in these indeterminate nodules, strong consideration to surgery should be given to patients with FNA results suggesting these two categories. BRAFV600E mutation analysis in FNA specimen has limited utility in improving the preoperative diagnostic rate for malignancy.