FGF21, Fasting Plasma Glucose, and Type 2 Diabetes

Adrian Post, Wendy A Dam, Sara Sokooti, Dion Groothof, Jolein Gloerich, Alain J van Gool, Daan Kremer, Ron T Gansevoort, Jacob van den Born, Ido P Kema, Casper FM Franssen, Robin PF Dullaart, Stephan JL Bakker
The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 6, June 2023, Pages 1387–1393
https://doi.org/10.1210/clinem/dgac729

Abstract

Objective

Fibroblast growth factor 21 (FGF21) is a peptide hormone synthesized by several organs and regulates, among others, energy homeostasis. In obesity, insulin resistance and type 2 diabetes (T2D), higher circulating FGF21 concentrations have been found. Temporal analyses in murine studies demonstrate that FGF21 increases before insulin resistance occurs. The current study aims to investigate in time-to-event analyses whether FGF21 may be an early biomarker in the development of T2D.

Research Design and Methods

Circulating FGF21 was measured using an immunoassay of the Mesoscale U-PLEX assay platform. The study outcome was incident T2D. Associations of circulating FGF21 concentration with T2D were quantified using Cox proportional hazards models with adjustments for potential confounders.

Results

We included 5244 participants aged 52 ± 12 years, of whom 50% were male. Median [interquartile range] circulating FGF21 concentration was 860 [525–1329] pg/mL. During 7.3 [6.1–7.7] years of follow-up, 299 (5.7%) participants developed T2D. In fully adjusted analyses, higher circulating FGF21 concentration was associated with an increased risk of incident T2D (hazard ratio per doubling: 1.26 [95% CI, 1.06–1.51]; P = 0.008), with effect modification by fasting plasma glucose, consistent with strengthening of the association at lower fasting glucose (interaction coefficient: −0.12; P = 0.022).

Conclusion

Higher circulating FGF21 concentrations are independently associated with an increased risk of incident T2D in participants with a low fasting plasma glucose, making circulating FGF21 concentration a potential early biomarker for type 2 diabetes.

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