Kumar, Seema

ABSTRACT Melanocortin‐4 receptor (MC4R) deficiency is the most common cause of monogenic obesity; yet treatment options for children with MC4R mutations are limited. We describe significant improvement in weight in three patients with pathogenic or likely pathogenic MC4R mutations; two adolescents treated with semaglutide, and a younger child treated with metformin and topiramate. These findings indicate GLP‐1 receptor agonists, topiramate and metformin can be helpful in managing obesity associated with MC4R deficiency.

Background: Pharmacological options for severe obesity in early childhood are limited. While lisdexamfetamine is approved for attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder, its role in managing obesity in children without these conditions has not been well studied. This case series assessed the effect of lisdexamfetamine on weight in young children with severe obesity but without ADHD or binge eating disorder. Methods: We conducted a retrospective chart review of six children with severe obesity treated with lisdexamfetamine for weight management. Demographic, anthropometric, and metabolic data were collected. One patient had Prader–Willi syndrome (PWS); the others had no known syndromic obesity. Results: Median age at treatment initiation was 6.5 years (range: 4.5–14), with equal male and female distribution. Median treatment duration was 12 months (range: 12–24), and mean maximum tolerated lisdexamfetamine dose was 35 mg (range: 10–60). In patients without syndromic obesity (n = 5) including one child with hypothalamic obesity, lisdexamfetamine significantly reduced body mass index (BMI) percent of the 95th percentile at 12 months (median change –24%, range: −18 to −28, p = 0.031), equating to a 13.8% reduction in BMI. Height percentile remained unchanged ( p = 0.59). The patient with PWS did not achieve lasting weight loss. Three children reported decreased appetite. Conclusions: Lisdexamfetamine was associated with weight loss in young children with severe obesity without genetic syndromes. Further studies are warranted to assess the long-term efficacy and safety of lisdexamfetamine in the management of pediatric obesity.

AbstractPediatric obesity, characterized by a body mass index (BMI) at or above the 95th percentile for age, affects a substantial number of children and adolescents worldwide. Metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, represents a prominent hepatic manifestation of obesity and metabolic syndrome, emerging as the most prevalent hepatic disorder among pediatric patients and a significant contributor to liver transplantation in adults. The escalating prevalence of pediatric MASLD mirrors the alarming rise in childhood obesity rates over recent decades. While lifestyle modifications focusing on dietary changes and increased physical activity constitute the cornerstone of MASLD management, achieving and maintaining significant weight reduction remains challenging. Moreover, disease progression often persists despite standard‐of‐care interventions, warranting exploration into alternative therapeutic strategies. Pharmacological interventions, particularly, glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), have shown promise in addressing pediatric obesity and its associated comorbidities, including MASLD. Recent studies have demonstrated the efficacy of GLP‐1RA in inducing weight loss and improving liver enzyme levels, suggesting a potential role in halting disease progression, and reducing the risk of major adverse liver outcomes. This review provides a comprehensive overview of the current pharmacotherapy landscape for pediatric MASLD, with a focus on novel agents such as GLP‐1RA. Furthermore, the manuscript proposes a practical algorithm to assist in integrating GLP‐1RA into the clinical management of pediatric patients with obesity and MASLD. Despite promising results, further research is warranted to elucidate the long‐term efficacy and safety of GLP‐1RA in pediatric populations.

Adverse childhood experiences (ACE) have been associated with a greater prevalence of risky behaviors and chronic health conditions, such as diabetes in adulthood. While adolescents with risk taking behaviors experience worsening of diabetic metabolic control, it is yet to be determined whether glycemic management in children and adolescents is negatively and independently influenced by ACEs. This study examines the relationship between ACEs in children and adolescents with type 1 diabetes (T1DM) and glycemic control, BMI and lipids. For such children, we hypothesized that hemoglobin A1c (HbA1c) is positively correlated with ACE scores. Parents of children (age 2–18 years) with T1DM completed a validated ACE questionnaire. The associations between parent and child ACE score and HbA1c, lipids and BMI z-scores were assessed using linear regression. The prevalence of any ACE was 27.9% among children and 49.0% among parents. HbA1c was significantly higher in children who had exposure to three or more ACEs (β:0.63 (4.5 mmol/mol); p = 0.02), in those who had a parent exposed to four or more ACEs (β:0.87 (7.2 mmol/mol); p = 0.03), in children who had exposure to household incarceration (β:0.62 (4.4 mmol/mol); p = 0.05) and children who witnessed or had been victim of violence in the neighborhood (β:0.71 (5.4 mmol/mol); p = 0.02). ACEs were highly prevalent among children with T1DM and had a positive association with glycemic control.