FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus
AbstractBackground: 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
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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.
Donate-Correa J, Martín-Núñez E, Ferri C, Hernández-Carballo C, Tagua VG, Delgado-Molinos A, López-Castillo Á, Rodríguez-Ramos S, Cerro-López P, López-Tarruella VC, Arévalo-González MA, Pérez-Delgado N, Mora-Fernández C, Navarro-González JF. FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus. Journal of Clinical Medicine. 2019; 8(4):448.Chicago/Turabian Style
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 C.; Arévalo-González, Miguel A.; Pérez-Delgado, Nayra; Mora-Fernández, Carmen; Navarro-González, Juan F. 2019. "FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus." J. Clin. Med. 8, no. 4: 448.
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