Insulin resistance, adipokines, and oxidative stress in nondiabetic, hypercholesterolemic patients: leptin as an 8-epi-prostaglandin F2α determinant

Abstract

Limited data are available on the association of insulin resistance, adipokines, and in vivo lipid peroxidation. We investigated the relationships between insulin resistance, adipokines (leptin, adiponectin, and resistin), and oxidative stress in nondiabetic, hypercholesterolemic patients. Seventy-six nondiabetic patients with hypercholesterolemia participated in this cross-sectional study. Fasting glucose and insulin concentrations were analyzed. Serum leptin, adiponectin, and resistin concentrations and urinary excretion of 8-epi-prostaglandin F2α (8-epi-PGF2α) were determined using enzyme-linked immunosorbent assay. We divided all subjects into 3 groups, classified by the tertiles of homeostasis model assessment of insulin resistance (HOMA-IR) values, and clinical parameter comparisons were made among the 3 groups. The results showed that serum leptin (P < .001) and adiponectin levels (P < .05) were significantly different among the groups, although serum resistin was not different. Furthermore, the group with the highest HOMA-IR had a significantly higher urinary 8-epi-PGF2α excretion than the group with the lowest HOMA-IR (P = .017). Circulating leptin was positively correlated with urinary 8-epi-PGF2α (r = 0.323, P < .01) and HOMA-IR (r = 0.524, P < .001). Circulating adiponectin was negatively correlated with body mass index (r = −0.252, P < .05) and HOMA-IR (r = −0.228, P < .05). We could not find a relationship between circulating adiponectin or resistin and urinary 8-epi-PGF2α excretion. Stepwise multiple linear regression analysis showed that leptin was associated with the urinary 8-epi-PGF2α excretion after adjusting for age, sex, body mass index, blood lipids, and HOMA-IR (P = .002). In conclusion, our results show that more insulin-resistant state of nondiabetic, hypercholesterolemic patients is associated with decreased adiponectin and increased leptin and urinary 8-epi-PGF2α levels, although no relationship with resistin was observed. Furthermore, serum leptin independently contributed to urinary 8-epi-PGF2α excretion.