Significant gender difference in serum levels of fibroblast growth factor 21 in Danish children and adolescents

Amalie Bisgaard, Kaspar Sørensen, Trine Holm Johannsen, Jørn Wulff Helge, Anna-Maria Andersson, Anders Juul, Amalie Bisgaard, Kaspar Sørensen, Trine Holm Johannsen, Jørn Wulff Helge, Anna-Maria Andersson, Anders Juul

Abstract

Introduction: Fibroblast Growth Factor 21 (FGF21) is a novel metabolic factor with effect on glucose and lipid metabolism, and shown to be elevated in diseases related to metabolic syndrome. Due to the increasing frequency of metabolic syndrome in the pediatric population, and as FGF21 studies in children are limited, we investigated baseline serum levels of FGF21 in healthy children during an oral glucose tolerance test.

Methods: A total of 179 children and adolescents from the COPENHAGEN Puberty Study were included. An OGTT with glucose and insulin measurements, a dual energy X-ray absorptiometry (DXA) scan and a clinical examination including pubertal staging were done on all subjects. Serum levels of FGF21, adiponectin, and leptin were determined by immunoassays at baseline.

Results: The girls had significantly higher levels of FGF21 compared with boys (155 pg/mL vs. 105 pg/mL, P = 0.04). 38 children (21%) had levels below detection limit of assay. Baseline levels of FGF21 showed positive correlation with triglycerides, but no significant correlations were found between FGF21-concentration and body mass index (BMI), DXA-derived fat percentage, LDL- HDL- and non-HDL cholesterol, leptin or adiponectin levels, respectively. Neither was any correlation found between baseline FGF21-levels and the dynamic changes in glucose and insulin levels during the OGTT.

Conclusion: FGF21 is independent of adiposity in children, and the significant metabolic effect seems to be limited to pathological conditions associated with insulin resistance. The higher levels of triglycerides in the girls may explain the significantly higher levels of FGF21 in girls compared with boys.

Systematic review registration: The COPENHAGEN Puberty Study was registered in ClinicalTrials.gov (identifier NCT01411527), and approved by the local ethics committee (reference no. KF 01 282214 and KF 11 2006-2033).

Keywords: Fibroblast growth factor 21; Metabolic syndrome; Oral glucose tolerance test.

Figures

Figure 1
Figure 1
Serum concentration of Fibroblast Growth Factor 21 (FGF21) in a group of 179 healthy, non-obese children (114 girls, 65 boys). Each square represents the FGF21-serum concentration in a child. In 16 boys and 22 girls the FGF21-concentration was below the lowest standard of the assay; these values were set at 15 pg/mL. The solid vertical lines indicate the median values of serum-FGF21 in girls and boys, respectively. The dotted lines indicate the lowest standard of the assay. Note that the Y-axis is logarithmic.

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