Format

Send to

Choose Destination
J Clin Med. 2019 Apr 3;8(4). pii: E448. doi: 10.3390/jcm8040448.

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

Author information

1
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), 38010 Santa Cruz de Tenerife, Spain. jdonate@ull.es.
2
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), 38010 Santa Cruz de Tenerife, Spain. emarnu87@gmail.com.
3
Doctoral and Graduate School, University of La Laguna, 38200 San Cristóbal de La Laguna, Spain. emarnu87@gmail.com.
4
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), 38010 Santa Cruz de Tenerife, Spain. carlamferri@gmail.com.
5
Doctoral and Graduate School, University of La Laguna, 38200 San Cristóbal de La Laguna, Spain. carlamferri@gmail.com.
6
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), 38010 Santa Cruz de Tenerife, Spain. carolinahdezcarballo@gmail.com.
7
Doctoral and Graduate School, University of La Laguna, 38200 San Cristóbal de La Laguna, Spain. carolinahdezcarballo@gmail.com.
8
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), 38010 Santa Cruz de Tenerife, Spain. vtagua@funcanis.es.
9
Vascular Surgery Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain. adelgadomolinos@gmail.com.
10
Vascular Surgery Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain. angellopezcastillo24@gmail.com.
11
Transplant Coordination, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain. sergiotomasr@hotmail.com.
12
Transplant Coordination, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain. pcerlop@gobiernodecanarias.org.
13
Pathology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain. vcaslop@gmail.com.
14
Human Anatomy and Histology Department, University of Salamanca, 37008 Salamanca, Spain. marevalo@usal.es.
15
Clinical Analysis Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain. nperdel@gobiernodecanarias.org.
16
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), 38010 Santa Cruz de Tenerife, Spain. carmenmora.fdez@gmail.com.
17
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), 38010 Santa Cruz de Tenerife, Spain. jnavgon@gobiernodecanarias.org.
18
Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain. jnavgon@gobiernodecanarias.org.
19
Institute of Biomedical Technologies, University of La Laguna, 38200 San Cristóbal de La Laguna, Spain. jnavgon@gobiernodecanarias.org.

Abstract

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.

KEYWORDS:

Klotho; diabetic foot syndrome; fibroblast growth factor 23; inflammation; vascular disease

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center