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

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Castelblanco Echavarría, Esmeralda
Hernández García, MartaHernández García, Marta - ORCID ID
Alonso, Núria
Ribes Betriu, Aina
Real, JordiReal, Jordi - ORCID ID
Granado Casas, MinervaGranado Casas, Minerva - ORCID ID
Rossell, Joana
Rojo López, Marina Idalia
Dusso Rosso, Adriana
Julve, Josep
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cc-by (c) authors, 2022
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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.
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Cardiovascular Diabetology, 2022, vol. 21, núm. 1