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. 2023 Dec 1;30(12):1838-1848.
doi: 10.5551/jat.64000. Epub 2023 May 23.

Serum Fibroblast Growth Factor 23 Levels are Associated with Vascular Smooth Muscle Dysfunction in Type 2 Diabetes

Yuka Natsuki  1 , Tomoaki Morioka  1 , Yoshinori Kakutani  1 , Yuko Yamazaki  1 , Akinobu Ochi  1 , Masafumi Kurajoh  1 , Katsuhito Mori  2 , Yasuo Imanishi  1 , Tetsuo Shoji  3   4 , Masaaki Inaba  1 , Masanori Emoto  1   4
Affiliations

Serum Fibroblast Growth Factor 23 Levels are Associated with Vascular Smooth Muscle Dysfunction in Type 2 Diabetes

Yuka Natsuki et al. J Atheroscler Thromb. .

Abstract

Aim: Increased level of serum fibroblast growth factor 23 (FGF23) is a hallmark of abnormal phosphate metabolism in patients with chronic kidney disease (CKD) and is recently shown to be associated with the risk of cardiovascular disease even in those without CKD. This study investigated the association between serum FGF23 levels and vascular function in patients with type 2 diabetes.

Methods: This was a cross-sectional study involving 283 Japanese patients with type 2 diabetes. Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) of the brachial artery were measured via ultrasonography to evaluate vascular endothelial and smooth muscle functions, respectively. Serum intact FGF23 levels were determined via a sandwich enzyme-linked immunosorbent assay.

Results: The median values of FMD, NMD, and serum FGF23 were 6.0%, 14.0%, and 27.3 pg/mL, respectively. The serum FGF23 levels were inversely associated with NMD but not with FMD, and the association was independent of atherosclerotic risk factors, estimated glomerular filtration rate (eGFR), and serum phosphate levels. Furthermore, the relationship between serum FGF23 levels and NMD was modified by kidney function, which was pronounced in subjects with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2).

Conclusion: Serum FGF23 levels are independently and inversely associated with NMD in patients with type 2 diabetes, particularly in those with normal kidney function. Our results indicate that FGF23 is involved in vascular smooth muscle dysfunction and that increased serum levels of FGF23 may serve as a novel biomarker for vascular smooth muscle dysfunction in patients with type 2 diabetes.

Keywords: Fibroblast Growth Factor 23; Flow-Mediated Dilatation; Nitroglycerin-Mediated Dilatation; Type 2 Diabetes.

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Conflict of interest statement

The authors declare no conflict of interest related to this study.

Figures

Fig.1. Correlation between serum FGF23 levels and FMD (a) and NMD (b) in all participants
Fig.1. Correlation between serum FGF23 levels and FMD (a) and NMD (b) in all participants
The upper panel (a) indicates that serum FGF23 levels were not significantly correlated with FMD. The lower panel (b) indicates that serum FGF23 levels were significantly correlated with NMD. Abbreviations: FGF, fibroblast growth factor; FMD, flow-mediated dilatation; NMD, nitroglycerin-mediated dilatation; ρ, Spearman’s rank correlation coefficient
Fig.2. Correlation between serum FGF23 levels and NMD stratified by kidney function
Fig.2. Correlation between serum FGF23 levels and NMD stratified by kidney function
Serum FGF23 levels were significantly and inversely correlated with NMD in both the group with eGFR ≥ 60 mL/min/1.73 m2 (N=172) (a) and the group with eGFR ＜60 mL/min/1.73 m2 (N=111) (b). Abbreviations: FGF, fibroblast growth factor; NMD, nitroglycerin-mediated dilatation; ρ, Spearman’s rank correlation coefficient
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