Abstract 6262: Obesity in Childhood is Associated With an Impaired Regenerative Capacity of Circulating Progenitor Cells and Vascular Dysfunction

Abstract

The raising prevalence of obesity in childhood appears to preceed the development of atherosclerosis and the increased incidence of cardiovascular diseases in adulthood. This might be related to the fact that already in children, obesity is associated with classical risk factors for coronary disease, like hypertension, hyperlipidemia, or diabetes. Therefore, aim of the present study was to evaluate, whether obese children (compared to lean controls) are characterized by vascular damages and altered regenerative capacity of circulating endothelial progenitor cells (CPCs) as an early indicator of developing atherosclerosis. Methods: In 30 obese (11±3 years of age, BMI 28.1±1.3) and 30 lean control children (12±3 years of age, BMI 17.5±0.4) insulin sensitivity was evaluated by oral glucose tolerance testing (OGT). Peripheral flow-mediated dilatation (FMD) and intima media thickness (IMT) of the carotid artery were assessed as measures of vascular integrity. The number of CD34/KDR+ CPCs was quantified using FACS analysis and the functional capacity of CPCs was determined by migration assay. Results: Obesity in early childhood is associated with peripheral insulin resistance as an early manifestation of diabetes (serum insulin in OGT after 120 min: 543±102 pmol/L in obese vs. 275±39 pmol/L in lean, p<0.05). FMD was significantly impaired in obese compared to lean children (reactive hyperemia index 1.25±0.05 vs. 1.55±0.08, p<0.05). Already in childhood, obesity was accompanied by a gain in IMT (0.40±0.01 mm vs. 0.30±0.01 mm in lean, p<0.05). Obese children had significantly reduced numbers of circulating CPCs compared to lean children (70±7 vs. 119±13 cells/mL blood, p<0.05). There was an inverse correlation between the number of CPCs and the extent of obesity as determined by BMI-SDS (r=−0.27, p<0.05). Additionally, functional capacity of CPCs was significantly reduced in obese children (migration following a SDF-1 gradient: 170±31 CPCs/1000 plated CPCs in obese vs. 258±37 CPCs/1000 plated CPCs in lean, p<0.05). Conclusion: Already in childhood, obesity is associated with an impaired endogenous regenerative capacity, which might result in generalized vascular damage as an early stage of atherosclerosis.