ESPE Abstracts

Background: Autoimmune thyroid diseases are multifactorial diseases with a genetic susceptibility and environmental factors. A potential role of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, the interferon induced helicase domain 1 (IFIH1) gene, the TSH receptor (TSH-R) gene polymorphisms on autoimmune thyroid diseases (AITDs) in children has not been established equivocally yet.Objective and hypotheses: To estimate the association...

Objectives: Data on the role of gluten in type 1 diabetes (T1D) pathogenesis are scarce. We aimed to test whether gluten-free diet (GFD) can decelerate the decline in beta-cell capacity in newly diagnosed non-coeliac T1D children.Methods: Forty six children (aged 10.2±3.3 years) were recruited into this non-randomized self-selected intervention trial: 26 started with GFD, whereas 20 remained on standard diet. Main o...

Background: The majority of drug developments in type 1 diabetes (T1D) are aimed at preventing decline of beta cell function (BCF), as this has been associated with better glycaemic control and fewer long-term complications. Traditionally, BCF is evaluated by the C-peptide response to the labour-intensive mixed-meal-tolerance-test (MMTT), but there’s a need for a more practical alternative. We developed a new method to measure C-peptide in ‘dried blood spots’ (D...

Background: The post-authorisation registry, European Increlex® Growth Forum Database (EU-IGFD), initiated in December 2008, collects data in children receiving Increlex (mecasermin (rDNA origin) injection) for growth failure, including Laron syndrome (LS) (severe primary IGF1 deficiency with confirmed GH-receptor mutation).Objective and hypotheses: Report safety and effectiveness data in children with LS.Method: Multicentre, ...

Background: Hypoglycaemia in patients with a high concentration of insulin and low concentration of C-peptide can be secondary to administration of exogenous insulin. This often results in safeguarding measures, with significant consequences for the patient and family. We report a novel case of a patient with symptomatic hypoglycaemia. Initial results suggested high insulin and low C-peptide levels, but subsequent testing revealed a pro-insulin processing diso...

Background: Our first report of this randomized controlled trial (RCT) demonstrated improved treatment satisfaction but no difference in HbA1c between the CSII and MDI treated groups, and added to the controversy as to whether CSII improves HbA1c or not. Therefore, we thought it would be valuable to assess if CSII had other potential advantages and if our finding of lower insulin dose requirements could be explained.Objective and Hypotheses: To study how...

Introduction: The melanocortin 4 receptor (MC4R) is a G protein coupled receptor (GPCR) and plays a pivotal role in the central regulation of body weight in the hypothalamus. In the context of the leptin-melanocortin signaling pathway, the MC4R is activated by the endogenous ligands a- and b-MSH (melanocyte-stimulating hormone). This leads to the feeling of satiety and to a reduction in food intake. Mutations within the genes leptin, leptin receptor (LEPR), pr...

Background: Patients with rare monogenic obesity caused by biallelic variants of genes such as proopiomelanocortin (POMC; including variants in PCSK1) or leptin receptor (LEPR) deficiency, experience hyperphagia (a pathologic, insatiable hunger) and early-onset, severe obesity. This suggests potential increased risk over time of obesity-related comorbidities, including metabolic syndrome, a cluster of conditions associated with increased risk of cardiovascular...

Background: Response to GH treatment has been associated with single nucleotide polymorphisms (SNPs) within the promoter region of growth-related genes including GRB10 (rs1024531 (A/G, allele A increased response)), IGFBP3 (rs3110697 (G/A, G increased response)), CYP19A1 (rs10459592 (T/C, T increased response)) and SOS1 (rs2888586 (G/C, C increased response)). SOS1 is a positive regulator of GH signalling (MAPK pathway); the aromatase CYP19A1 promotes oestrogen synthesis to im...

The leptin melanocortin signaling pathway plays a pivotal role in body weight regulation within the hypothalamus. Gene mutations within this cascade are leading to early onset obesity and severe hyperphagia in rodents and humans. For the affected patients it is extremely difficult to stabilize body weight based on the persisting hunger feeling. Traditional treatment options (increased exercise, reduced caloric intake) are not effective in most cases. Therefore, there is a need...