ESPE Abstracts

Background: Type 2 diabetes in children and adolescents is a rare disease with an estimated incidence (age 0–20 years) of below 5/100 000 in Germany.Objective and Hypotheses: We hypothesize that monogenic alterations might contribute to early-onset insulin secretion defects, if islet function was challenged by obesity-associated insulin resistance.Method: We follow more than 1500 children and adolescents with obesity. Patients...

Background: GRB10 negatively regulates IGF1 signalling, influences growth and promoter polymorphisms are associated with GH response1. GRB10 knockout-mouse models display foetal overgrowth2, however, the mouse model has only partial similarity to human growth3. There is evidence that the zebrafish is an appropriate model to study growth4 and has the advantage of being easily genetically manipulated.<p class="abs...

Background: The phases of human growth are associated with gene expression (GE) changes1, raising the possibility that rhythmic patterns of GE occur throughout childhood.Objective: In this study, we have assessed time-series patterns of GE profiles associated with age to characterise oscillations.Methods: GE analysis was conducted on cells of lymphoid origin from normal individuals through childhood (n=87, 43 ma...

Background: GH response is influenced by genetic polymorphisms, including the rs1024531 polymorphism (A/G) in the promoter region of GRB10, a negative regulator of signaling through the IGF1 receptor. Allele A is associated with borderline lower baseline IGF1 SDS and 1.5-fold higher response to GH compared to allele G in children with GHD (P=0.0006).Objective: To test functional impact of the rs1024531 polymorphism in an in vitro</e...

Background: Congenital thyroid dysgenesis usually occurs sporadically and may even be discordant in monozygotic twins. However, when caused by inactivating mutations in the TSH receptor (TSHR) it can be inherited recessively, typically resulting in thyroid gland hypoplasia. We present a new familial case of thyroid dysgenesis with two siblings of consanguineous parents. The daughter was identified in neonatal screening with severely elevated TSH and thyroid agenesis on ultraso...

Background: Poor temperature regulation in Prader–Willi syndrome (PWS) suggests dysautonomia probably secondary to hypothalamic dysfunction. Autonomic nervous system (ANS) has control over orexigenic ghrelin.Objective and hypotheses: We aim to assess ANS function in PWS and its association with acyl ghrelin.Method: We recruited 16 genetically-confirmed children with PWS and 16 controls. Exclusion criteria were diabetes mellitu...

Introduction: Genetic markers associated with the response to recombinant human GH (r-hGH) have been identified in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) children in the PREDICT long-term follow-up (LTFU) prospective study (NCT00699855).1 A validation (VAL) study (NCT01419249) was conducted to confirm association.Methods/design: Inclusion criteria for GHD and TS children were identical in the LTFU and VAL studies (GHD defined...

Background: Low birth weight, unfavourable intrauterine conditions, and post-natal catch-up growth are associated with a subsequent impact on growth and pubertal development. Start of puberty is genetically determined but might be altered due to environmental influences.Objective and hypotheses: In a longitudinal study we observed genetically identical twins with intra-twin birth-weight (bw) differences from birth until puberty.Met...

Background: Low birth weight, unfavourable intrauterine conditions, and post-natal catch-up growth are associated with a subsequent impact on growth, pubertal development, and metabolic disturbances later in life. Although the start of puberty is genetically determined it might be altered due to environmental influences.Objectives: In a longitudinal study (birth to final height) we observed growth and pubertal development of genetically identical twins b...

Background: Oxidative stress has been implicated in the development and progression of complications in type 1 diabetes (T1DM). Vitamin E (α-tocopherol) undergoes β-oxidation of its chomanol ring and the resulting metabolite α-TLHQ has been proposed as a potential biomarker of oxidative stress. HbA1c relates in T1DM to microvascular complications predominantly although the end-points are late in disease development. The oxidative stress process may act independe...