Association of alpha-klotho with subclinical carotid atherosclerosis in subjects with type 1 diabetes mellitus
Por:
Castelblanco, E, Hernandez, M, Alonso, N, Ribes-Betriu, A, Real, J, Granado-Casas, M, Rossell, J, Rojo-Lopez, MI, Dusso, AS, Julve, J, Mauricio, D
Publicada:
11 oct 2022
Resumen:
Background Compelling evidence suggests that the fibroblast growth factor 23 (FGF23) / alpha-klotho axis is impaired in subjects with diabetes mellitus. We examined the relationship between parameters related to calcium/phosphate homeostasis, including FGF23 and alpha-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 alpha-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). alpha-klotho was higher in subjects with subclinical carotid atherosclerosis (1.4-fold, p < 0.05). Regression analysis revealed that the log alpha-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 alpha-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.
Filiaciones:
Castelblanco, E:
Washington Univ, Sch Med, Dept Med, Endocrinol Metab & Lipid Res Div, St Louis, MO 63110 USA
Inst Univ Invest Atencio Primaria Jordi Gol & Gur, Unitat Suport Recerca Barcelona, Barcelona 08007, Spain
Hernandez, M:
Hosp Arnau Vilanova, Dept Endocrinol & Nutr, Lleida 25198, Spain
Inst Invest Biomed Lleida IRB Lleida, Lleida 25198, Spain
Alonso, N:
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Asociadas, Madrid 28029, Spain
Hosp Badalona Germans Trias & Pujol, Dept Endocrinol & Nutr, Badalona 08916, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona 08916, Spain
Ribes-Betriu, A:
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08041, Spain
Real, J:
Inst Univ Invest Atencio Primaria Jordi Gol & Gur, Unitat Suport Recerca Barcelona, Barcelona 08007, Spain
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Asociadas, Madrid 28029, Spain
Granado-Casas, M:
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Asociadas, Madrid 28029, Spain
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Dept Endocrinol & Nutr, Barcelona 08041, Spain
Rossell, J:
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Asociadas, Madrid 28029, Spain
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Dept Endocrinol & Nutr, Barcelona 08041, Spain
Rojo-Lopez, MI:
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Dept Endocrinol & Nutr, Barcelona 08041, Spain
Dusso, AS:
Washington Univ, Sch Med, Dept Med, Endocrinol Metab & Lipid Res Div, St Louis, MO 63110 USA
Julve, J:
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Asociadas, Madrid 28029, Spain
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Dept Endocrinol & Nutr, Barcelona 08041, Spain
Mauricio, D:
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Asociadas, Madrid 28029, Spain
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Dept Endocrinol & Nutr, Barcelona 08041, Spain
Univ Vic UVIC UCC, Fac Med, Vic 08500, Spain
Green Published, gold, Gold, Green
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