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

  1. Tagua, Víctor
  2. Cerro-López, Purificación
  3. López-Castillo, Ángel
  4. Donate-Correa, Javier
  5. Delgado-Molinos, Alejandro
  6. Arévalo-González, Miguel
  7. Hernández-Carballo, Carolina
  8. Martín-Núñez, Ernesto
  9. López-Tarruella, Victoria
  10. Rodríguez-Ramos, Sergio
  11. Ferri, Carla
  12. Pérez-Delgado, Nayra
  13. Mora-Fernández, Carmen
  14. Navarro-González, Juan
  1. 1 Hospital Universitario Nuestra Señora de Candelaria
    info

    Hospital Universitario Nuestra Señora de Candelaria

    Santa Cruz de Tenerife, España

    ROR https://ror.org/005a3p084

Revista:
Journal of Clinical Medicine

ISSN: 2077-0383

Año de publicación: 2019

Volumen: 8

Número: 4

Páginas: 448

Tipo: Artículo

DOI: 10.3390/JCM8040448 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Journal of Clinical Medicine

Resumen

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.

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