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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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 |
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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 |
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