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J. Clin. Med. 2019, 8(4), 448; https://doi.org/10.3390/jcm8040448

FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus

1
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), 38010 Santa Cruz de Tenerife, Spain
2
Doctoral and Graduate School, University of La Laguna, 38200 San Cristóbal de La Laguna, Spain
3
Vascular Surgery Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
4
Transplant Coordination, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
5
Pathology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
6
Human Anatomy and Histology Department, University of Salamanca, 37008 Salamanca, Spain
7
Clinical Analysis Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
8
Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
9
Institute of Biomedical Technologies, University of La Laguna, 38200 San Cristóbal de La Laguna, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors share senior authorship.
Received: 26 February 2019 / Revised: 30 March 2019 / Accepted: 1 April 2019 / Published: 3 April 2019
(This article belongs to the Special Issue Clinical Research on Diabetic Complications)
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Abstract

Background: Diabetic foot syndrome (DFS) is a prevalent complication in the diabetic population and a major cause of hospitalizations. Diverse clinical studies have related alterations in the system formed by fibroblast growth factor (FGF)-23 and Klotho (KL) with vascular damage. In this proof-of-concept study, we hypothesize that the levels of FGF23 and Klotho are altered in DFS patients. Methods: Twenty patients with limb amputation due to DFS, 37 diabetic patients without DFS, and 12 non-diabetic cadaveric organ donors were included in the study. Serum FGF23/Klotho and inflammatory markers were measured by enzyme-linked immunosorbent assay (ELISA). Protein and gene expression levels in the vascular samples were determined by immunohistochemistry and quantitative real-time PCR, respectively. Results: Serum Klotho is significantly reduced and FGF23 is significantly increased in patients with DFS (p < 0.01). Vascular immunoreactivity and gene expression levels for Klotho were decreased in patients with DFS (p < 0.01). Soluble Klotho was inversely related to serum C-reactive protein (r = −0.30, p < 0.05). Vascular immunoreactivities for Klotho and IL6 showed an inverse association (r = −0.29, p < 0.04). Similarly, vascular gene expression of KL and IL6 were inversely associated (r = −0.31, p < 0.05). Logistic regression analysis showed that higher Klotho serum concentrations and vascular gene expression levels were related to a lower risk of DFS, while higher serum FGF23 was associated with a higher risk for this complication. Conclusion: FGF23/Klotho system is associated with DFS, pointing to a new pathophysiological pathway involved in the development and progression of this complication. View Full-Text
Keywords: diabetic foot syndrome; vascular disease; fibroblast growth factor 23; Klotho; inflammation diabetic foot syndrome; vascular disease; fibroblast growth factor 23; Klotho; inflammation
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Donate-Correa, J.; Martín-Núñez, E.; Ferri, C.; Hernández-Carballo, C.; Tagua, V.G.; Delgado-Molinos, A.; López-Castillo, Á.; Rodríguez-Ramos, S.; Cerro-López, P.; López-Tarruella, V.C.; Arévalo-González, M.A.; Pérez-Delgado, N.; Mora-Fernández, C.; Navarro-González, J.F. FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus. J. Clin. Med. 2019, 8, 448.

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