http://repub.eur.nl/res/aut/34873/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37351/ 2012-10-01T00:00:00Z Aims/hypothesis: In adults, circulating inflammatory mediators and activated CD14++monocytes link obesity to its metabolic and cardiovascular complications. However, it is largely unknown whether these inflammatory changes already occur in childhood obesity. To survey inflammatory changes during the early stages of obesity, we performed a comprehensive analysis of circulating inflammatory mediators, monocyte populations and their function in childhood obesity. Methods: In lean and obese children aged 6 to 16 years (n∈=∈96), 35 circulating inflammatory mediators including adipokines were measured. Hierarchical cluster analysis of the inflammatory mediator profiles was performed to investigate associations between inflammatory mediator clusters and clinical variables. Whole-blood monocyte phenotyping and functional testing with the toll-like receptor 4 ligand, lipopolysaccharide, were also executed. Results: First, next to leptin, the circulating mediators chemerin, tissue inhibitor of metalloproteinase 1, EGF and TNF receptor 2 were identified as novel inflammatory mediators that are increased in childhood obesity. Second, cluster analysis of the circulating mediators distinguished two obesity clusters, two leanness clusters and one mixed cluster. All clusters showed distinct inflammatory mediator profiles, together with differences in insulin sensitivity and other clinical variables. Third, childhood obesity was associated with increased CD14++monocyte numbers and an activated phenotype of the CD14++monocyte subsets. Conclusions/interpretation: Inflammatory mediator clusters were associated with insulin resistance in obese and lean children. The activation of CD14++monocyte subsets, which is associated with increased development of atherosclerosis in obese adults, was also readily detected in obese children. Our results indicate that inflammatory mechanisms linking obesity to its metabolic and cardiovascular complications are already activated in childhood obesity. http://repub.eur.nl/res/pub/25424/ 2009-08-01T00:00:00Z OBJECTIVE - To assess if tooth discoloration is a novel side effect of sulfonylurea therapy in patients with permanent neonatal diabetes due to mutations in KCNJ11. RESEARCH DESIGN AND METHODS - A total of 67 patients with a known KCNJ11 mutation who had been successfully transferred from insulin injections onto oral sulfonylureas were contacted and asked about the development of tooth discoloration after transfer. RESULTS - Altered tooth appearance was identified in 5 of the 67 patients. This was variable in severity, ranging from mild discoloration/staining (n = 4) to loss of enamel (n = 1) and was only seen in patients taking glibenclamide (glyburide). CONCLUSIONS - These previously unreported side effects may relate to the developing tooth and/or to the high local concentrations in the children who frequently chewed glibenclamide tablets or took it as a concentrated solution. Given the multiple benefits of sulfonylurea treatment for patients with activating KCNJ11 mutations, this association warrants further investigation but should not preclude such treatment. http://repub.eur.nl/res/pub/30252/ 2008-08-01T00:00:00Z Objective: Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control. Methods: An open, parallel, randomized controlled prospective comparative study lasting 14months was completed by 38 type 1 children with diabetes (age 4-16yr) following a 3.5-months run-in phase. Standardized quality-of-life Pediatric Quality of life Inventory (PedsQL) and impact of disease scores were obtained every 3.5months as well as regular medical parameters. Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality. Results: Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment. Treatment group comparisons did not show significant improvement. Pump treatment resulted in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22% after run in. Conclusions: Within-patient comparison suggests that metabolic control, frequency of severe hypoglycaemia (a threefold decrease), quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections. © 2008 The Authors Journal compilation