ESPE Abstracts

Background: Congenital hyperinsulinism (CHI) is a rare disease affecting neonates, infants, and children. CHI is characterized by dysregulated insulin secretion resulting in severe recurrent hypoglycemia. Early treatment is necessary to limit the risk of neurologic and developmental sequelae. Current treatment options are limited and inadequate. Dasiglucagon (DASI) is a glucagon analog suitable for continuous subcutaneous infusion which has been shown to raise...

Background and Objective: Continuous Glucose Monitoring (CGM) is gaining in popularity for patients with paediatric hypoglycaemia disorders such as Congenital Hyperinsulinism (CHI), but no standard measures of accuracy or associated clinical risk are available. A small number of studies have shown suboptimal accuracy of CGM in CHI but assessments have been inconsistent, incomplete and offer no measure of clinical application. Error grids that categorise clinic...

Background & Aims: Hypoglycaemia is a constant threat for all patients with congenital hyperinsulinism (CHI) and, left untreated, can lead to neurological damage and impaired development. To improve glycaemic monitoring, self-monitoring-blood-glucose (SMBG) is increasingly being replaced by Continuous Glucose Monitoring (CGM) with potential to identify illness patterns and treatment responses although with unproven benefit for patients and families. Explor...

Background: Congenital Hyperinsulinism in Infancy (CHI) is characterised by inappropriate insulin release. We currently attribute hypoglycaemia to β-cell dysfunction because of defects in the ion channel genes ABCC8 or KCNJ11. However, the CHI pancreas is also associated with inappropriate expression of foetal-like transcription factors and enhanced cell proliferation.Hypothesis: As the CHI pancreas bears similarities to the foetal pancreas, we hypo...

Background: Congenital hyperinsulinism in infancy (CHI) is associated with inappropriate insulin release from β-cells. This is causally linked to defects in the ion channel genes ABCC8 and KCNJ11 regulating insulin, but little is known about the metabolic support for sustained insulin exocytosis.Objective and hypotheses: We hypothesised that inappropriate insulin release in CHI would require sustained ATP generation by enhanced mit...

Background: Congenital hyperinsulinism of infancy (CHI) is the most common cause of severe hypoglycaemia in children. Although CHI arises from mutations in KATP channels which lead to inappropriate insulin secretion, CHI it also is associated with marked changes in islet organization.Aims and objectives: Our aim was to investigate the structure and composition of the islet capsule in CHI and age-matched control tissue.Me...

Background: Atypical forms of congenital hyperinsulinism in infancy (CHI-A) represent a novel subgroup of patients who present later in the neonatal period; have poor responses to medical intervention; an unremarkable histopathology and no known genetic cause of disease.Objective and hypotheses: To compare the expression profiles of insulin and somatostatin in islets from patients with CHI-A, diffuse CHI (CHI-D) and age-matched control tissue.<p clas...

Background: Congenital hyperinsulinism in infancy (CHI) is a neonatal disorder of uncontrolled insulin release leading to profound hypoglycaemia. In addition to defects in pancreatic β-cell function, we have recently demonstrated that the CHI pancreas is highly proliferative, with rates of proliferation up to 14-fold higher than in age-matched controls.Objective and hypotheses: As patients require pancreatectomy to alleviate hypoglycaemia, our aim w...

Background: Diffuse congenital hyperinsulinism in infancy (CHI-D) mainly arises from mutations in KATP channel genes. In addition, there are also several reports of increased cell proliferation in CHI-D. We hypothesised that the higher rates of proliferation in CHI-D are as a consequence of failure to terminate proliferation in the neonatal period.Objective and hypotheses: To test this we examined the proliferative index (PI) of CHI-D tissue a...

Background: Adrenal Insufficiency (AI) is a heterogeneous diagnosis comprising multiple central and peripheral causes. The unifying feature is the requirement for glucocorticoid replacement and subsequent risk of life-threatening Adrenal Crisis (AC) and Adrenal Death (AD). Very few studies have investigated rates of AD in children. Multiple studies have reported symptoms of children with AC as interpreted by medical staff but no studies have looked at parental...