Journal of translational medicine · 2025
Cathepsin K: a novel association with glucose intolerance, insulin resistance, and subclinical atherosclerosis in T2DM.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Averta Carolina, Rubino Mariangela, Mancuso Elettra, Massimino Mattia, Coppolino Giuseppe, Bolignano Davide, Cassano Velia, Greco Marta, Palummo Angela, Sciacqua Angela, Perticone Maria, Mannino Gaia Chiara, Sesti Giorgio, Andreozzi Francesco
Аннотация
BACKGROUND: Cathepsin K (CatK) contributes to vessel collagene remodelling and high CatK concentrations have been found in atherosclerotic lesions. CatK ablation in a murine model determined an amelioration of diabetes-induced hyperglycemia and cardiovascular structural/functional abnormalities. To date, it is unknown whether glucose tolerance status affects circulating levels of CatK, and if CatK is involved with the cardiovascular complications associated with type 2 diabetes (T2DM).
METHODS: We assayed the levels of serum CatK in a cohort of 544 well-characterized Caucasian adults. assessing subclinical cardiovascular organ damage defined by carotid artery intima-media thickness (c-IMT) and left ventricular mass index (LVMI) in our T2DM cohort.
RESULTS: CatK levels were significantly higher in individuals with T2DM (2.3 ± 0.8 ng/ml; N = 263) compared to normoglycemia (NGT; 1.2 ± 0.5 ng/ml; N = 146) or predabetes (IFG/IGT; 1.2 ± 0.3 ng/ml; N = 135). Consistent with the literature, CatK levels correlated with age (r = - 0.190, p = 0.001), 2 h-PG (r = - 0.118, p = 0.048) and c-IMT (r = 0.157, p < 0.01) in the subset without T2DM. In the T2DM group, CatK positively correlated with FPI (r = 0.277; p < 0.001), HOMA-IR (r = 0.269; p < 0.001) and c-IMT (r = 0.155; p = 0.013). Multiple logistic regression analysis, adjusted for potential confounders, revealed that a one-quintile increment in CatK levels was associated with a 6.5-fold increased odds of T2DM. Furthermore, multiple linear regression analysis in T2DM patients, including sex, age, BMI, hypotensive therapy, and HOMA-IR (or alternatively HbA1c or FPI) as covariates, identified age and CatK as the strongest determinants of c-IMT. CatK levels did not correlate with LVMI in either the T2DM or non-T2DM cohorts.
CONCLUSIONS: Our data show that the variability of CatK circulating levels is associated with glucose tolerance status, and with early signs of atherosclerosis in a population with T2DM as well as in non-diabetic individuals. These findings, combined with the established role of CatK in vascular remodeling, suggest that CatK may play a role in the early etiopathogenesis of cardiovascular complications in T2DM.
METHODS: We assayed the levels of serum CatK in a cohort of 544 well-characterized Caucasian adults. assessing subclinical cardiovascular organ damage defined by carotid artery intima-media thickness (c-IMT) and left ventricular mass index (LVMI) in our T2DM cohort.
RESULTS: CatK levels were significantly higher in individuals with T2DM (2.3 ± 0.8 ng/ml; N = 263) compared to normoglycemia (NGT; 1.2 ± 0.5 ng/ml; N = 146) or predabetes (IFG/IGT; 1.2 ± 0.3 ng/ml; N = 135). Consistent with the literature, CatK levels correlated with age (r = - 0.190, p = 0.001), 2 h-PG (r = - 0.118, p = 0.048) and c-IMT (r = 0.157, p < 0.01) in the subset without T2DM. In the T2DM group, CatK positively correlated with FPI (r = 0.277; p < 0.001), HOMA-IR (r = 0.269; p < 0.001) and c-IMT (r = 0.155; p = 0.013). Multiple logistic regression analysis, adjusted for potential confounders, revealed that a one-quintile increment in CatK levels was associated with a 6.5-fold increased odds of T2DM. Furthermore, multiple linear regression analysis in T2DM patients, including sex, age, BMI, hypotensive therapy, and HOMA-IR (or alternatively HbA1c or FPI) as covariates, identified age and CatK as the strongest determinants of c-IMT. CatK levels did not correlate with LVMI in either the T2DM or non-T2DM cohorts.
CONCLUSIONS: Our data show that the variability of CatK circulating levels is associated with glucose tolerance status, and with early signs of atherosclerosis in a population with T2DM as well as in non-diabetic individuals. These findings, combined with the established role of CatK in vascular remodeling, suggest that CatK may play a role in the early etiopathogenesis of cardiovascular complications in T2DM.