Antioxidants modify the relationship between endothelin-1 level and glucose metabolism-associated parameters

Glucose handling impairment and oxidative stress are implicated in the overexpression of endothelin-1 (ET-1). The objective of the study was to assess possible interplay of the 2 systems in relation to ET-1 in clinical setting. In hypertensive outpatients, on top of typical clinical workup, we assessed ET-1 levels, glucose handling parameters (glycated hemoglobin [HbA1c], homeostasis model assessment [HOMA] index, and insulin level), and antioxidative protection (ferric reducing ability of plasma [FRAP], superoxide dismutase [SOD], and vitamin C). Average age of 68 patients (64% women, 50% diabetic, 40% smokers) was 67.7 (10.6) years. Serum ET-1 level averaged 1.09 (0.48) pg/mL and correlated positively with glucose handling-associated parameters (insulin, r = 0.22; HOMA, r = 0.21; HbA1c, r = 0.23; all Ps < .05) and negatively with constituents of antioxidative protection system (FRAP, r = −0.45; SOD, r = −0.47; both Ps < .0001; vitamin C, r = −0.27; P ≤ .01). In sex-, age-, blood pressure-, and creatinine-adjusted models, with interchangeable introduction of antioxidative parameters on top of interchangeable introduction of glucose handling-associated parameters, ET-1 levels were each time only significantly associated with FRAP in the context of HbA1c; FRAP, SOD, or vitamin C in the context of HOMA; and FRAP or SOD in the context of insulin concentration. In the stepwise regression with the above parameters offered, only FRAP and vitamin C were associated with ET-1 level. In treated hypertensive patients, impaired glucose handling is associated with higher ET-1 levels. This statistical relation is blunted in the context of parameters of antioxidative protection. The hypothesis that poor antioxidation is mediating the effect of impaired glucose handling on ET-1 levels needs further confirmation.