Introduction: Obesity and the metabolic syndrome (MetS) are linked to increased risk for endothelial dysfunction which is considered as the first step in the progression of cardiovascular disease. Fibroblast growth factor 21 (FGF21) is a protein with known effects on various metabolic pathways. In adults, the circulating blood levels of FGF21 have been associated with parameters of lipid/carbohydrate metabolism, and FGF21 is known to be increased in obesity. The prevalence of childhood obesity presents a constant yearly increase. However, there are limited data regarding the potential role of FGF21 in metabolic and cardiovascular disorders in the paediatric population. Our aim was to investigate FGF21 serum levels in metabolic disorders and in relation to endothelial function in children.
Methods: Seventy-eight children (8–16 years old) were classified as obese/overweight (n=41; 53% of total) and normal weight (n=37) defined by body mass index (BMI) percentiles for age and sex. Blood pressure, fasting blood glucose, lipid profile and FGF21 serum levels were assessed. Children with MetS were identified according to the International Diabetes Federation criteria. Endothelial function was assessed by the brachial artery flow-mediated dilation (FMD) technique and normalized to the shear stimulus [i.e. peak%FMD normalized to shear rate (normalized FMD)]. Non-parametric statistics were used to investigate the relationship between FGF21 and FMD (Spearman's rank correlation) and the differences between groups (Mann-Whitney test).
Results: In our entire population, there was a significant negative correlation between FGF21 and normalized FMD (Spearman's rho= 0.239, P=0.035).
In obese/overweight children, FGF21 serum levels were significantly increased [median 73.6 (interquartile range 41.6–127.8) vs. 30.4 (13.9–92.6) pg/ml, P=0.017] and normalized FMD was significantly lower [0.06 (0.04–0.09) vs. 0.09 (0.04–0.12), P=0.044] compared to normal BMI children.
Children with MetS (n=8; 10% of the population) had significantly higher FGF21 serum levels compared to normal BMI ones [127.8 (75.9–261) vs. 30.4 (13.9–92.6) pg/ml, P=0.005]. Normalized FMD was lower in MetS children compared to those with normal BMI without, however, reaching statistical significance [0.07 (0.04–0.08) vs. 0.09 (0.04–0.12), P=0.14].
Conclusions: FGF21 serum levels were negatively correlated to normalized FMD in our paediatric population. FGF21 serum levels were increased in both obese/overweight and MetS children compared to those with normal BMI. Obese/overweight children also showed impaired endothelial response to FMD. Therefore, FGF21 shows promise as a novel biomarker for identifying early in life metabolic disorders and a potential risk for development of cardiovascular disease.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology