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-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.
['Donate-Correa|Javier|J|0000-0001-7389-7347', 'Martín-Núñez|Ernesto|E|0000-0003-0341-0956', 'Ferri|Carla|C|0000-0002-2711-3836', 'Hernández-Carballo|Carolina|C|', 'Tagua|Víctor G|VG|0000-0003-1494-6895', 'Delgado-Molinos|Alejandro|A|', 'López-Castillo|Ángel|Á|', 'Rodríguez-Ramos|Sergio|S|0000-0003-1635-3604', 'Cerro-López|Purificación|P|', 'López-Tarruella|Victoria Castro|VC|', 'Arévalo-González|Miguel Angel|MA|', 'Pérez-Delgado|Nayra|N|', 'Mora-Fernández|Carmen|C|', 'Navarro-González|Juan F|JF|0000-0002-5015-7474']
Klotho diabetic foot syndrome fibroblast growth factor 23 inflammation vascular disease