Ann Pediatr Endocrinol Metab.  2021 Dec;26(4):242-251. 10.6065/apem.2040258.129.

Association of fibroblast growth factor 21 with metabolic syndrome and endothelial function in children: a prospective cross-sectional study on novel biomarkers

• Domouzoglou EM
• Vlahos AP
• Cholevas VK
• Papafaklis MI
• Chaliasos N
• Siomou E
• Michalis LK
• Tsatsoulis A
• Naka KK

• KMID: 2523830
• DOI: http://doi.org/10.6065/apem.2040258.129

Abstract

Purpose
Metabolic and cardiovascular disease prevention starting in childhood is critical for reducing morbidity later in life. In the present study, the association of novel biomarkers with metabolic syndrome (MS) and vascular function/structure indices of early atherosclerosis in children was investigated.
Methods
This was a prospective study of 78 children (8–16 years of age) grouped based on the presence or absence of MS. The serum biomarkers investigated included fibroblast growth factor 21 (FGF21), leptin, adiponectin, and insulinlike growth factor binding protein-1 (IGFBP1). Endothelial function and carotid atherosclerosis were assessed based on brachial artery flow-mediated dilation (FMD) and carotid intima-media thickness, respectively.
Results
Children with MS (n=12) had higher levels of FGF21 (median [interquartile range]: 128 [76–189] pg/mL vs. 60 [20–98] pg/mL, P=0.003) and leptin (18.1 [11–34.8] pg/mL vs. 7.5 [1.9–16.5] ng/mL, P=0.003), and lower levels of IGFBP1 (1.5 [1.2–2.1] ng/mL vs. 2.3 [1.5–6] ng/mL, P=0.028) compared with children without MS. FMD inversely correlated with FGF21 (Spearman rho= -0.24, P=0.035) and leptin (rho= -0.24, P=0.002) in all children. The best cutoff value of FGF21 levels for MS diagnosis was above 121.3 pg/mL (sensitivity/specificity, 58/86%). Only FGF21 was significantly associated with the presence of MS after adjustment for body mass index, age, and sex (odds ratio per 10 pg/mL increase: 1.10 [95% confidence interval, 1.01–1.22]; P=0.043).
Conclusion
Increased FGF21 levels were associated with the presence of MS and worse endothelial function in children. Larger studies are needed to evaluate the potential value of FGF21 as a biomarker that could predict future metabolic/cardiovascular disease at an early stage.

Keyword

Metabolism; Obesity; Fibroblast growth factor 21; Metabolic syndrome; Leptin; Flow-mediated dilation

Figure

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  Fig. 1. (A–D) Serum biomarkers in the metabolic syndrome (MS) group compared with the non-MS group. Non-MS children were further categorized into children with normal body mass index (BMI) (non-MS-N) and children with increased BMI (obese/overweight; non-MS-O). Bars indicate the median values and error bars the 75th percentile of the interquartile range. P-values represent the comparison with children with MS. FGF21, fibroblast growth factor 21; IGFBP1, insulin-like growth factor binding protein-1.

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  Fig. 2. Vascular indices in the metabolic syndrome (MS) group compared with the non-MS group and in non-MS children with normal body mass index (BMI) (non-MS-N) compared with non-MS children with increased BMI (obese/overweight; nonMS-O). (A) Brachial flow-mediated dilation (FMD). (B) Carotid intima-media thickness (IMT). Bars indicate the median values and error bars the 75th percentile of the interquartile range. P-values represent the comparison with children with MS.

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  Fig. 3. Negative correlations of normalized flow-mediated dilation (FMD) with fibroblast growth factor 21 (FGF21) (A) and leptin (B). Correlations were tested using Spearman rho (ρ) correlation coefficient. Best fit curves are shown for visualization purposes.

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  Fig. 4. Receiver operating characteristic (ROC) curves for the diagnosis of metabolic syndrome. Both fibroblast growth factor 21 (FGF21) (A) and leptin (B) showed good discrimination capability (area under the curve [AUC] > 0.75).

Reference

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