hrp0095fc3.1 | Early Life and Multisystem Endocrinology | ESPE2022

HYPO-CHEAT: Personalised Technology Reduces Real-World Hypoglycaemia by 25%

Worth Chris , Nutter Paul , Salomon-Estebanez Maria , Auckburally Sameera , Banerjee Indraneel , Harper Simon

Background and Aims: Hypoglycaemia is a life-threatening risk for many patients and prevention is individualised and complex. Continuous Glucose Monitoring (CGM) shows promise but current accuracy is insufficient for acute hypoglycaemia detection and data review services are complex and generic. Machine Learning is increasingly used but ignores weekly hypoglycaemia patterns and behaviour change and thus has demonstrated no real-world reduction in hypoglycaemia...

hrp0095fc3.2 | Early Life and Multisystem Endocrinology | ESPE2022

Results from a Global, Multi-Center, Phase 2b Study (RIZE) in Congenital Hyperinsulinism: Characterization of a High Unmet Treatment Need and Glycemic Response to RZ358

Demirbilek Huseyin , Melikyan Maria , Galcheva Sonya , Dastamani Antonia , Thornton Paul , De Leon Diva , Raskin Julie , Roberts Brian , Hood Davelyn , O'Boyle Erin , Christesen Henrik

Background: Congenital Hyperinsulinism (CHI) is the most frequent cause of severe, persistent hypoglycemia in children. Persistent hypoglycemia places patients at risk for adverse clinical outcomes, and current guidelines recommend maintaining plasma glucose >3.9mmol/l. CHI patients often have substantial, residual hypoglycemia and fail to meet treatment goals with currently available standard of care (SOC) therapies. In this study, we aimed to characterize...

hrp0095fc3.3 | Early Life and Multisystem Endocrinology | ESPE2022

Targeting androgen production by post-translational regulation of CYP17A1 lyase activity

Sharma Katyayani , Pandey Amit V

Introduction: Over-production of androgens is linked to prostate cancer (PCa) in men and polycystic ovary syndrome (PCOS) in women. CYP17A1 produces dehydroepiandrosterone (DHEA), the precursor for androgens, via its 17,20 lyase activity. CYP17A1 lyase activity is regulated by the amount of P450 reductase for electron transfer; the presence of cytochrome b5; and protein phosphorylation. High androgen levels were linked to the phosphorylation of CYP17A1 protein...

hrp0095fc3.4 | Early Life and Multisystem Endocrinology | ESPE2022

A common polymorphism in the human P450 reductase gene (POR) causes defective steroid and drug metabolism due to protein instability

Rojas Velazquez Maria Natalia , Noebauer Mathias , Pandey Amit V

Cytochrome P450 oxidoreductase (POR) is the obligatory redox partner of steroid and drug-metabolizing cytochrome P450s located in the endoplasmic reticulum. Mutations in POR cause a broad range of disorders like congenital adrenal hyperplasia that may resemble bone malformations resembling Antley-Bixler syndrome. Genome sequencing studies have revealed the existence of a POR missense variant P228. We aimed to determine the detailed functional impact of POR variant P228L for it...

hrp0095fc3.5 | Early Life and Multisystem Endocrinology | ESPE2022

Evaluating the Utility of Bi-functional Degrader Molecules for Selective Inhibition of PDE4 In Acrodysostosis Type2

Baillie George , Kyurkchieva Elka , Yan Sin Yuan , Ahmed Faisal , Rajapakse Navin , Schoolmeesters Angela , Richard Normand , Erdman Paul , Hecht David , Hoskote Chourasia Aparajita , Mercurio Frank , Fung Leah , Chan Kyle , Stirling David

Background: Acrodysostosis Type 2 (ACRDYS2) is a rare autosomal dominant skeletal dysplasia associated with intellectual disability and gain-of-function mutations in the phosphodiesterase type 4D gene (PDE4D) which, in turn, leads to a paucity of intracellular cAMP due to increased PDE4D activity. This increased PDE4 activity may be due to a greater existence of a mutant monomeric form of PDE4D. To date, the clinical use of PDE4 inhibitors in ACRDYS2 has been ...

hrp0095fc3.6 | Early Life and Multisystem Endocrinology | ESPE2022

The European Registries for Rare Endocrine Conditions (EuRRECa): the Use of a Core Registry for Collecting Common Data Elements and Clinician and Patient Reported Outcomes

Luisa Priego Zurita Ana , Ali Salma R , Bryce Jillian , Cools Martine , Danne Thomas , Dekkers Olaf M. , Hiort Olaf , Katugampola Harshini , Linglart Agnes , Netchine Irene , Nordenström Anna , Patócs Attila , Pereira Alberto M , Persani Luca , Reisch Nicole , Smyth Arlene , Šumnik Zdenek , Taruscio Domenica , Edward Visser W , M Appelman-Dijkstra Natasha , Faisal Ahmed S

Introduction: The European Registries for Rare Endocrine Conditions (EuRRECa) was created in collaboration with the European Reference Network on Rare Endocrine Conditions (Endo-ERN), the European Society for Paediatric Endocrinology and the European Society of Endocrinology to support the needs of the endocrine community.Aim: To describe the patient population and data entered in the EuRRECa Core Registry between June 2...

hrp0095fc4.1 | Fat, Metabolism and Obesity | ESPE2022

Natural History of LEP, LEPR and MC4R Deficiencies – A Population-Based Study

Saeed Sadia , Manzoor Jaida , Khanam Roohia , Janjua Qasim , Ning Lijiao , Ayesha Hina , Khan Waqas , Bonnefond Amélie , Hanook Sharoon , Butt Taeed , Arslan Muhammad , Froguel Philippe

Background: Proteins encoded by LEP, LEPR and MC4R genes are principally involved in driving the leptin-melanocortin pathway. Mutations in these genes induce a rare and severe form of monogenic obesity but the long-term evolution of these afflictions is unknown. Here, we carried out a clinical investigation on 132 children with LEP, LEPR and MC4R deficiency from Pakistan to evaluate progression of the disease and its impact on co-mor...

hrp0095fc4.2 | Fat, Metabolism and Obesity | ESPE2022

Positive effects of a structured pre- and post-bariatric surgery program on follow-up rate and supplement intake in adolescents and youths- Results from the German YES cohort

Brandt Stephanie , Schirmer Melanie , Kleger Pauline , von Schnurbein Julia , Holle Rolf , Holl Reinhard W. , Hebebrand Johannes , Wiegand Susanna , Wabitsch Martin

Introduction: Until recently, bariatric surgery (BS) has been the only option for clinically meaningful weight reduction for adolescents and youth with extreme obesity. Low participation rate in follow-up examinations and low supplement intake after BS in adolescents has been described in literature (PMID: 24048144, 25078533). We developed a structured pre- and post-bariatric surgery program in order to improve follow-up rate and supplement intake in adolescen...

hrp0095fc4.3 | Fat, Metabolism and Obesity | ESPE2022

Impaired Brain Satiety Responses by Functional Neuroimaging After Weight Loss Therapy in Children with Obesity

Roth Christian , Melhorn Susan , DeLeon Mary , Rowland Maya , Elfers Clinton , Huang Alyssa , Saelens Brian , Schur Ellen

Background: Obesity interventions often result in increased motivation to eat after weight loss.Objective: We investigated relationships between obesity outcomes and changes in brain activation by visual food cues and hormone levels in response to obesity intervention by family-based behavioral treatment (FBT).Design, Methods, and Participants: Functional neuroimaging and plasma ho...

hrp0095fc4.4 | Fat, Metabolism and Obesity | ESPE2022

Inhibition of Neuritin 1 induces browning in human white adipocytes and protects from obesity in vivo

Tews Daniel , Roos Julian , Winter Gordon , Beer Ambros , Rasche Volker , Nedivi Elly , Debatin Klaus-Michael , Wabitsch Martin , Fischer-Posovszky Pamela

Recently, we identified Neuritin 1 (NRN1) as preferentially expressed in human white compared to brown adipocyte progenitor cells. In mice, Nrn1 deficiency leads to a reduction in body weight, indicating that it might regulate body weight. In this study, we aim to address the function of NRN1 regarding adipocyte metabolism in vitro and in vivo. We used human SGBS preadipocytes as an in vitro model system. NRN1-deficient cells were generated using len...