Cargando…

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

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-co...

Descripción completa

Detalles Bibliográficos
Autores principales: Donate-Correa, Javier, Martín-Núñez, Ernesto, Ferri, Carla, Hernández-Carballo, Carolina, Tagua, Víctor G., Delgado-Molinos, Alejandro, López-Castillo, Ángel, Rodríguez-Ramos, Sergio, Cerro-López, Purificación, López-Tarruella, Victoria Castro, Arévalo-González, Miguel Angel, Pérez-Delgado, Nayra, Mora-Fernández, Carmen, Navarro-González, Juan F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518424/
https://www.ncbi.nlm.nih.gov/pubmed/30987161
http://dx.doi.org/10.3390/jcm8040448
_version_ 1783418445991247872
author Donate-Correa, Javier
Martín-Núñez, Ernesto
Ferri, Carla
Hernández-Carballo, Carolina
Tagua, Víctor G.
Delgado-Molinos, Alejandro
López-Castillo, Ángel
Rodríguez-Ramos, Sergio
Cerro-López, Purificación
López-Tarruella, Victoria Castro
Arévalo-González, Miguel Angel
Pérez-Delgado, Nayra
Mora-Fernández, Carmen
Navarro-González, Juan F.
author_facet Donate-Correa, Javier
Martín-Núñez, Ernesto
Ferri, Carla
Hernández-Carballo, Carolina
Tagua, Víctor G.
Delgado-Molinos, Alejandro
López-Castillo, Ángel
Rodríguez-Ramos, Sergio
Cerro-López, Purificación
López-Tarruella, Victoria Castro
Arévalo-González, Miguel Angel
Pérez-Delgado, Nayra
Mora-Fernández, Carmen
Navarro-González, Juan F.
author_sort Donate-Correa, Javier
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6518424
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-65184242019-05-31 FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus Donate-Correa, Javier Martín-Núñez, Ernesto Ferri, Carla Hernández-Carballo, Carolina Tagua, Víctor G. Delgado-Molinos, Alejandro López-Castillo, Ángel Rodríguez-Ramos, Sergio Cerro-López, Purificación López-Tarruella, Victoria Castro Arévalo-González, Miguel Angel Pérez-Delgado, Nayra Mora-Fernández, Carmen Navarro-González, Juan F. J Clin Med Article 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. MDPI 2019-04-03 /pmc/articles/PMC6518424/ /pubmed/30987161 http://dx.doi.org/10.3390/jcm8040448 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Donate-Correa, Javier
Martín-Núñez, Ernesto
Ferri, Carla
Hernández-Carballo, Carolina
Tagua, Víctor G.
Delgado-Molinos, Alejandro
López-Castillo, Ángel
Rodríguez-Ramos, Sergio
Cerro-López, Purificación
López-Tarruella, Victoria Castro
Arévalo-González, Miguel Angel
Pérez-Delgado, Nayra
Mora-Fernández, Carmen
Navarro-González, Juan F.
FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus
title FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus
title_full FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus
title_fullStr FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus
title_full_unstemmed FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus
title_short FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus
title_sort fgf23 and klotho levels are independently associated with diabetic foot syndrome in type 2 diabetes mellitus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518424/
https://www.ncbi.nlm.nih.gov/pubmed/30987161
http://dx.doi.org/10.3390/jcm8040448
work_keys_str_mv AT donatecorreajavier fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT martinnunezernesto fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT ferricarla fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT hernandezcarballocarolina fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT taguavictorg fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT delgadomolinosalejandro fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT lopezcastilloangel fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT rodriguezramossergio fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT cerrolopezpurificacion fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT lopeztarruellavictoriacastro fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT arevalogonzalezmiguelangel fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT perezdelgadonayra fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT morafernandezcarmen fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus
AT navarrogonzalezjuanf fgf23andklotholevelsareindependentlyassociatedwithdiabeticfootsyndromeintype2diabetesmellitus