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Review
. 2021 Jul 30;135(14):1669-1687.
doi: 10.1042/CS20201290.

Phosphate and fibroblast growth factor 23 in diabetes

Amarens van der Vaart  1   2 , Stanley M H Yeung  1 , Peter R van Dijk  2 , Stephan J L Bakker  1 , Martin H de Borst  1
Affiliations
Review

Phosphate and fibroblast growth factor 23 in diabetes

Amarens van der Vaart et al. Clin Sci (Lond). .

Abstract

Diabetes is associated with a strongly elevated risk of cardiovascular disease, which is even more pronounced in patients with diabetic nephropathy. Currently available guideline-based efforts to correct traditional risk factors are only partly able to attenuate this risk, underlining the urge to identify novel treatment targets. Emerging data point towards a role for disturbances in phosphate metabolism in diabetes. In this review, we discuss the role of phosphate and the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) in diabetes. We address deregulations of phosphate metabolism in patients with diabetes, including diabetic ketoacidosis. Moreover, we discuss potential adverse consequences of these deregulations, including the role of deregulated phosphate and glucose as drivers of vascular calcification propensity. Finally, we highlight potential treatment options to correct abnormalities in phosphate and FGF23. While further studies are needed to more precisely assess their clinical impact, deregulations in phosphate and FGF23 are promising potential target in diabetes and diabetic nephropathy.

Keywords: Phosphate; diabetes; fibroblast growth factors; vascular calcification.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Schematic overview illustrating the hypothesized role of diabetes-induced and CKD-induced deregulations in phosphate and FGF23 metabolism, and how these factors coincide in diabetic nephropathy
Details are provided in the text (sections on phosphate/FGF23 in diabetes and diabetic nephropathy).
Figure 2
Figure 2. Schematic overview illustrating the hypothesized course of plasma inorganic phosphate in DKA, and potential factors driving changes in plasma phosphate during DKA
The x-axis represents time since DKA onset, the y-axis depicts the hypothesized course of plasma phosphate.
Figure 3
Figure 3. Hyperphosphatemia drives key processes that promote vascular calcification in diabetes
On one hand, high phosphate levels induce VSMC remodeling, mediated by PiT-1 and PiT-2 phosphate transporters. This triggers VSMC osteochondric differentiation as well as matrix mineralization, leading to vascular wall stiffening. On the other hand, high phosphate levels promote the conversion of primary into secondary calcicprotein particles (CPPs), which in turn promote oxidative stress and inflammation.
See this image and copyright information in PMC

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