Diabetic ketoacidosis at type 1 diabetes diagnosis in children during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has led to significant public health measures that have resulted in decreased acute pediatric care utilization. We evaluated whether the rate of severe presentations of new onset type 1 diabetes (DM1), such as, diabetic ketoacidosis (DKA) has changed since the COVID-19 public health measures were enacted. RESEARCH DESIGN AND METHODS: A retrospective chart review of children less than 18 years of age presenting with new onset DM1 during the pandemic period of March 17, 2020 to August 31, 2020 was conducted at two tertiary care pediatric hospitals in Alberta, Canada. Rates of DKA and severe DKA were compared to the same time period in the year 2019 (pre-pandemic control). RESULTS: The number of children presenting with newly diagnosed DM1 was similar during the pandemic year of 2020 compared with 2019 (107 children in 2020 vs. 114 in 2019). The frequency of DKA at DM1 onset was significantly higher in the pandemic period (68.2% vs 45.6%; p < 0.001) and incidence of severe DKA was also higher (27.1% in 2020 vs 13.2% in 2019; p = 0.01). CONCLUSIONS: There was a significant increase in DKA and severe DKA in children presenting with new onset DM1 during the COVID-19 pandemic period. This emphasizes the need for educating health care professionals and families to be aware of the symptoms of hyperglycemia and the importance of early diagnosis and treatment even during public health measures for COVID-19.

A novel MC4R mutation associated with childhood-onset obesity: A case report.

The melanocortin-4-receptor gene (MC4R) is a key regulator of energy homeostasis, food intake and body weight. MC4R gene mutations are associated with early-onset severe obesity. Most patients are heterozygotes, with some reports of homozygotes and compound heterozygotes. The authors report a case involving an eight-year-old girl with progressive weight gain from infancy, body mass index 44 kg/m(2) (>97th percentile), hyperphagia, hyperinsulinemia and increased linear growth. There was no phenotype of morbid obesity in the parents or sibling. Coding regions and intron-exon boundaries of the genes encoding leptin, leptin receptor, pro-opiomelanocortin and MC4R were analyzed. Two heterozygous coding mutations in the MCR4 gene (S94N and C293R) were detected, of which the second has not been previously reported. The mutations were on opposite chromosomes, confirming compound heterozygosity. The molecular findings and clinical features associated with this novel MC4R mutation are described. The authors emphasize that rare mutations can be found in some patients with severe childhood-onset obesity.

Le gène récepteur de la mélanocortine 4 (MC4R) joue un rôle clé dans le maintien de l'homéostasie énergétique, de la prise alimentaire et du poids corporel. Les mutations du gène MC4R s'associent à une grave obésité à apparition précoce. La plupart des patients sont hétérozygotes, mais il y a certaines descriptions de patients homozygotes et d'hétérozygotes composés. Les auteurs présentent le cas d'une fillette de huit ans ayant une prise de poids progressive depuis la première enfance, un indice de masse corporel de 44 kg/m2 (>97e percentile), une hyperphagie, une hyperinsulinémie et une augmentation de la croissance linéaire. Les parents et la fratrie ne possédaient pas de phénotype d'obésité morbide. Les auteurs ont analysé les régions codantes et les limites intron-exon des gènes codant la leptine, son récepteur, la pro-opiomélanocortine et le MC4R. Ils ont décelé deux mutations en région codante du gène MCR4 (S94N et C293R), la deuxième n'ayant jamais été déclarée auparavant. Les mutations se situaient sur des chromosomes opposés, ce qui confirme leur hétérozygotie composée. Les auteurs décrivent les observations moléculaires et les caractéristiques cliniques associées à cette nouvelle mutation MC4R. Ils soulignent que certains patients ayant une importante obésité qui se manifeste pendant l'enfance peuvent présenter des mutations rares.

Leuprolide Acetate and QTc Interval in Gender-Diverse Youth.

Background: Puberty suppression is a standard of care for gender-affirming therapy in gender-diverse youth. Leuprolide acetate is a gonadotropin-releasing hormone agonist (GnRHa) commonly used for pubertal suppression. There are concerns that GnRHa agents prolong the rate-corrected QT interval (QTc) when used as androgen deprivation therapy in management of prostate cancer; however, there is a paucity of literature regarding the effect of leuprolide acetate on QTc intervals in gender-diverse youth. Aim: To determine the proportion of gender-diverse youth with QTc prolongation on leuprolide acetate therapy. Methods: A retrospective chart review of gender-diverse youth initiated on leuprolide acetate between July 1, 2018 and December 31, 2019 was conducted at a tertiary care pediatric hospital in Alberta, Canada. Youth aged 9-18 years were included if a 12-lead electrocardiogram was completed after initiating leuprolide acetate. The proportion of adolescents with clinically significant QTc prolongation was assessed, defined as QTc >460 milliseconds (ms). Results: Thirty-three pubertal youth were included. The cohort had a mean age of 13.7 years (standard deviation [SD] 2.1) and 69.7% identified as male (assigned female at birth). The mean post-leuprolide acetate QTc was 415 ms (SD 27, range 372-455). Twenty-two (66.7%) of youth were prescribed concomitant medications, including QTc-prolonging medications in 15.2%. None of the 33 youth on leuprolide acetate had QTc prolongation. Only 24.2% patients had a borderline QTc (QTc 440-460 ms). Conclusion: No gender-diverse youth on leuprolide acetate demonstrated clinically significant QTc prolongation.

Impact of the Balanced School Day on Glycemic Control in Children with Type 1 Diabetes.

OBJECTIVE: The balanced school day (BSD) is an alternative elementary school schedule whereby children have 2 20-minute eating periods instead of 1 20-minute lunch, as is found in the traditional schedule (TS). We assessed the glycated hemoglobin (A1C) levels of children with type 1 diabetes in the TS vs. the BSD because 2 eating periods have the potential to impact blood glucose control. METHODS: A1C levels representative of the summer months (SumA1C) and A1C levels occurring at least 3 months after the start of the school year (SchA1C) were obtained retrospectively. A parental survey of perceptions of lunch planning, activity levels and diabetes management at school was also completed. RESULTS: Our sample included 97 students (TS=42, BSD=55). The mean age ± SD was 10.9±2.6 and 10.1±2.8 years in the TS and BSD, respectively (p=0.12). Sex distribution was not statistically different; 54% were female in TS vs. 36% in BSD; p=0.08. SumA1C was similar in the 2 groups (TS: 8.3±1.1% vs. BSD: 8.0±0.8%; p=0.08). There was a significant within-group increase from SumA1C to SchA1C in the BSD group only (p=0.001), with mean A1C values increasing from 8.0%±0.8% to 8.5%±1.0% in the BSD group compared to no significant increase in the TS group. Parental perceptions of lunch planning, physical activity and diabetes management were similar, regardless of school schedule. CONCLUSIONS: Children with type 1 diabetes in the BSD appear to have worse diabetes control during the school year compared to the summer, which is not evident in children in the TS. Additional school supports may assist students in the BSD.

Effect of prebiotic intake on gut microbiota, intestinal permeability and glycemic control in children with type 1 diabetes: study protocol for a randomized controlled trial.

BACKGROUND: The gut microbiome is increasingly recognized as a contributor to disease states. Patients with type 1 diabetes (DM1) have distinct gut microbiota in comparison to non-diabetic individuals, and it has been linked to changes in intestinal permeability, inflammation and insulin resistance. Prebiotics are non-digestible carbohydrates that alter gut microbiota and could potentially improve glycemic control in children with DM1. This pilot study aims to determine the feasibility of a 12-week dietary intervention with prebiotics in children with DM1. METHODS/DESIGN: This pilot study is a single-centre, randomized, double-blind, placebo-controlled trial in children aged 8 to 17 years with DM1 for at least one year. Participants will be randomized to receive either placebo (maltodextrin 3.3 g orally/day) or prebiotics (oligofructose-enriched inulin 8 g orally/day; Synergy1, Beneo, Mannheim, Germany). Measures to be assessed at baseline, 3 months and 6 months include: anthropometric measures, insulin doses/regimens, frequency of diabetic ketoacidosis, frequency of severe hypoglycemia, average number of episodes of hypoglycemia per week, serum C-peptide, HbA1c, serum inflammatory markers (IL-6, IFN-gamma, TNF-alpha, and IL-10), GLP-1 and GLP-2, intestinal permeability using urine assessment after ingestion of lactulose, mannitol and 3-O-methylglucose, and stool sample collection for gut microbiota profiling. DISCUSSION: This is a novel pilot study designed to test feasibility for a fully powered study. We hypothesize that consumption of prebiotics will alter gut microbiota and intestinal permeability, leading to improved glycemic control. Prebiotics are a potentially novel, inexpensive, low-risk treatment addition for DM1 that may improve glycemic control by changes in gut microbiota, gut permeability and inflammation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02442544 . Registered on 10 March 2015.