Circulating FGF21 Concentration, Fasting Plasma Glucose and the Risk of Type 2 Diabetes: Results from the PREVEND study

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OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a peptide hormone that is synthesized by several organs and regulates, amongst 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 type 2 diabetes were quantified using Cox proportional hazards models with adjustments for potential confounders.

RESULTS: We included 5,244 participants aged 52 ± 12 years, of whom 50% were male. Median [interquartile range] circulating FGF21 concentration was 860 [525-1,329] pg/mL. During 7.3 [6.1-7.7] years of follow-up, 299 (5.7%) participants developed type 2 diabetes. In fully adjusted analyses, higher circulating FGF21 concentration was associated with an increased risk of incident type 2 diabetes (HR 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).

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)1387–1393
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
Early online date19-Dec-2022
Publication statusPublished - Jun-2023


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