Association of α-klotho with subclinical carotid atherosclerosis in subjects with type 1 diabetes mellitus
Castelblanco, Esmeralda (Institut Universitari d'Investigació en Atenció Primària Jordi Gol)
Hernández, Marta (Hospital Universitari Arnau de Vilanova & Institut d'Investigació Biomédica de Lleida (IRB Lleida))
Alonso Pedrol, Núria (Universitat Autònoma de Barcelona. Departament de Medicina)
Ribes-Betriu, Aina (Institut d'Investigació Biomèdica Sant Pau)
Real, Jordi (CIBER de Diabetes y Enfermedades Metabólicas Asociadas. Instituto de Salud Carlos III)
Granado-Casas, Minerva (Institut d'Investigació Biomèdica Sant Pau)
Rossell, Joana (Institut d'Investigació Biomèdica Sant Pau)
Rojo López, Marina Idalia (Institut d'Investigació Biomèdica Sant Pau)
Dusso, Adriana Silvia (Endocrinology. Metabolism and Lipid Research Division. Department of Medicine. Washington University School of Medicine)
Julve i Gil, Josep (Institut d'Investigació Biomèdica Sant Pau)
Mauricio Puente, Dídac (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	Background: Compelling evidence suggests that the fibroblast growth factor 23 (FGF23) / α-klotho axis is impaired in subjects with diabetes mellitus. We examined the relationship between parameters related to calcium/phosphate homeostasis, including FGF23 and α-klotho, and subclinical carotid atherosclerosis burden in type 1 diabetes mellitus (T1D) subjects. Methods: This cross-sectional study involved 226 subjects with T1D and 147 age-, sex- and plaque-matched, non-diabetic (non-T1D) subjects, both with normal renal function. Carotid ultrasound was performed to determine the presence and burden of atheromatous plaques. Concentrations of the intact form of FGF23 and α-klotho were assessed by ELISA. Calcium, phosphate, parathyroid hormone, and vitamin D levels were also determined. Negative binomial regression models were used to examine relationship between parameters studied and subclinical carotid atherosclerosis. Results: Only FGF23 was increased in T1D compared with non-diabetic subjects (> 2-fold; p < 0. 05). α-klotho was higher in subjects with subclinical carotid atherosclerosis (1. 4-fold, p < 0. 05). Regression analysis revealed that the log α-klotho concentration was positively associated with the presence of subclinical carotid atherosclerosis both in T1D subjects (incidence rate ratio [IRR]: 1. 41; 95% confidence interval [CI], 1. 06-1. 89; p < 0. 05) and in non-T1D subjects (IRR: 1. 65; 95% CI, 1. 02-2. 75; p < 0. 05). The models also showed that age, smoking and albuminuria-to-creatinine ratio were positively associated with subclinical carotid atherosclerosis in T1D subjects. Interestingly, sex-related protection against plaque was also revealed in T1D women. Conclusion: Higher α-klotho was associated with subclinical carotid atherosclerotic in the absence of kidney dysfunction. This finding also points to a new pathophysiological pathway involved in the development and progression of this complication.
Grants:	Instituto de Salud Carlos III PI15/0625 Instituto de Salud Carlos III CB15/00071 Instituto de Salud Carlos III CPII18/00004
Note:	Altrea ajuts: Ministerio de Sanidad y Consumo; European Regional Development Fund (FEDER); CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Type 1 diabetes mellitus ; Mineral metabolism ; Fibroblast growth factor 23 ; α-klotho
Published in:	Cardiovascular diabetology, Vol. 21 Núm. 1 (december 2022) , p. 207, ISSN 1475-2840

DOI: 10.1186/s12933-022-01640-3
PMID: 36221075

9 p, 994.7 KB

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