Association of α-klotho with subclinical carotid atherosclerosis in subjects with type 1 diabetes mellitus

Background Compelling evidence suggests that the fbroblast 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 atherosc...

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Detalles Bibliográficos
Autores: Castelblanco Echavarría, Esmeralda, Hernández García, Marta, Alonso, Núria, Ribes Betriu, Aina, Real, Jordi, Granado Casas, Minerva, Rossell, Joana, Rojo López, Marina Idalia, Dusso Rosso, Adriana, Julve, Josep, Mauricio Puente, Dídac
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/84473
Acceso en línea:https://doi.org/10.1186/s12933-022-01640-3
http://hdl.handle.net/10459.1/84473
Access Level:acceso abierto
Palabra clave:Type 1 diabetes mellitus
Mineral metabolism
Fibroblast growth factor 23
α-klotho
Descripción
Sumario:Background Compelling evidence suggests that the fbroblast 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, nondiabetic (non-T1D) subjects, both with normal renal function. Carotid ultrasound was performed to determine thepresence 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% confdence 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 fnding also points to a new pathophysiological pathway involved in the development and progression of this complication.