Endocrine Abstracts

Background: Bardet-Biedl Syndrome (BBS) is a rare genetic disease in which impaired melanocortin-4 receptor (MC4R) signaling leads to hyperphagia and obesity. In an index Phase 3 trial, broad clinical benefit was observed in patients with BBS based on improvement or stabilization in ≥1 measure of weight, hunger, or quality of life with 1 year of treatment with the MC4R agonist setmelanotide. Reported here are long-term extension (LTE) weight outcomes after 3 years of set...

Background: Proopiomelanocortin (POMC; including biallelic variants in PCSK1) and leptin receptor (LEPR) deficiency are associated with hyperphagia and early-onset, severe obesity. Treatment with the melanocortin-4 receptor agonist setmelanotide for 1 year results in significant and sustained improvements in weight (POMC, −25.6%; LEPR, −12.5%), hunger, and quality of life. We used the metabolic syndrome Z score based on body mass index (MetS-Z-BMI) to asse...

Background: Rare variants in the melanocortin-4 receptor (MC4R) pathway are associated with early-onset, severe obesity and hyperphagia. Setmelanotide, an MC4R agonist, reduced body mass index (BMI) and decreased hunger in patients with obesity due to biallelic variants in genes encoding proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) in Phase 3 trials. The current analysis assesses the durability of setmelanotide ef...

Objective: Ideally, treatment strategies designed to reduce weight or body mass index in patients with obesity should reduce fat mass while preserving lean mass because reduced lean mass can negatively impact overall health and energy expenditure, thus favoring weight regain. In Phase 3 trials, 1 year of treatment with the melanocortin-4 receptor agonist setmelanotide led to weight reduction in patients with obesity due to biallelic variants in the genes encoding proopiomelano...

Background: Patients with Bardet-Biedl syndrome (BBS), a rare syndrome associated with obesity and hyperphagia, commonly manifest traits of metabolic syndrome, including abdominal obesity, impaired fasting glucose, low high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension. Setmelanotide treatment results in significant improvement in weight, hunger, and quality of life in these patients and may improve measures associated with metabolic syndrome developm...

Objective: We describe two first cousins presenting with neonatal corticotropic deficiency and severe, early-onset obesity. This study aims to identify the molecular etiology of these disorders in both cases and highlights the limits of genetic investigations.Methods: We collected the clinical-biological data of the family and, more particularly, of the two first cousins (A and B). We performed several constitutive Next-generation Sequencing (NGS) protoc...

Background: In patients with Bardet-Biedl syndrome (BBS), signaling impairments in the melanocortin-4 receptor (MC4R) pathway lead to hyperphagia and severe obesity, which negatively impact quality of life (QOL). We evaluated the impact of setmelanotide, an MC4R agonist, on age-appropriate weight-related parameters, hunger, and QOL in a Phase 3 trial of patients with BBS to further characterize clinical benefit in this patient population.Methods: Patient...

The leptin/melanocortin pathway plays a critical role in hypothalamic control of food intake. Variants in the genes involved in this pathway, such as leptin (LEP), its receptor (LEPR), proopiomelanocortin (POMC) or proconvertase 1 (PCSK1) are associated with early-onset severe obesity and endocrine abnormalities especially in case of homozygosity. Heterozygous variants in the melanocortin-4 receptor (MC4R) gene are associated with an increased risk of severe obesity. The aim i...

Background: Patients with proopiomelanocortin (POMC; including variants in POMC or PCSK1) or leptin receptor (LEPR) deficiency due to biallelic gene variants have impaired melanocortin-4 receptor signaling that leads to hyperphagia and early-onset, severe obesity. Setmelanotide treatment in this population improved weight-related measures and hunger severity and was well tolerated. Reported here are long-term extension (LTE) outcomes after 4 years of setmelan...

Introduction: While extensive research on the fecal microbiome (FM) has already underscored the gut microbiome’s role in metabolic diseases, it is imperative to recognize its limitations in depicting the entire gastrointestinal tract. Each segment of the tract harbors unique conditions shaping microbial ecosystems, necessitating exploration beyond the FM. The upper small intestine (USI) significantly impacts nutrient digestion and absorption, hinting at its microbiome&#14...