Relationship between insulin resistance and lipid peroxidation and antioxidant vitamins in hypercholesterolemic patients

Background: Several studies have reported that insulin resistance and compensatory hyperinsulinemia increased lipid peroxidation, suggesting the linking to each other. We investigated the relationships between insulin resistance index HOMA-IR and lipid peroxidation, plasma antioxidant status in non-diabetic, hypercholesterolemic patients. Methods: We measured the urinary excretion of 8-epi-prostaglandin F_2α(PGF _2α) levels as a measure of lipid peroxidation in vivo, total radical trapping antioxidant potential (TRAP) and fat-soluble antioxidant vitamins in 76 non-diabetic subjects with hypercholesterolemia (mean age 59 years, 25 males and 51 females). Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) derived from fasting glucose and insulin concentrations. Results: HOMA-IR was positively correlated with the urinary excretion of PGF_2α (r = 0.222, p < 0.05) and negatively correlated with the TRAP (r = -0.211, p < 0.05) in total subjects. Furthermore, there were significant inverse relationships between HOMA-IR and lipid corrected fat-soluble vitamins such as β-carotene (r = -0.297, p < 0.01) and γ-tocopherol (r = -0.243, p < 0.05) and also significant inverse relation was found between lipid corrected β-carotene and the urinary PGF_2αexcretion (r = -0.205, p < 0.05). When total subjects were divided into three groups according to tertiles of HOMA-IR, significant differences in urinary PGF_{2 α}excretion (p < 0.05) and lipid corrected β-carotene (p < 0.005) among the three groups were observed. The highest HOMA-IR group had the higher levels of urinary PGF_2αexcretion and lower levels of plasma β-carotene compared with the lowest HOMA-IR group. Conclusion: Our data showed that the insulin resistance of hypercholesterolemic patients increased oxidative stress and negatively influenced plasma antioxidant system. These results provide evidence in understanding mechanism linking insulin resistance and oxidative stress accompanied by reduced antioxidant system.