Relationship between insulin resistance and erythropoietin responsiveness in hemodialysis patients

Background: Insulin resistance is an independent predictor of cardiovascular mortality in hemodialysis (HD) patients. Inflammation plays an important role in insulin resistance, and adipocytokines, including tumor necrosis factor-alpha and leptin, can induce insulin resistance. However, data on insulin resistance and erythropoietin responsiveness in HD patients are lacking. Methods: We conducted a prospective, observational cohort study to clarify the relationship between insulin resistance and erythropoietin responsiveness in HD patients. Insulin resistance as assessed by the homeostasis model assessment for insulin resistance (HOMA-IR), levels of adiponectin and inflammatory cytokines, required erythropoietin (EPO) dose, and other metabolic parameters were measured in patients with (n = 52) and without diabetes (n = 55) over the course of 12 months. Results: The diabetes group had significantly higher serum leptin, high-sensitivity C-reactive protein, and interleukin-6 concentrations but lower serum adiponectin concentration. Average hemoglobin (Hb) levels during the 12-month study period were significantly lower in the diabetes group than in the non-diabetes group, and a higher dose of EPO was required in the diabetes group. There was a significant negative correlation between adiponectin and HOMA-IR, a significant positive correlation between EPO dose and HOMA-IR, and a significant negative correlation between EPO dose and adiponectin in the two groups. Insulin resistance as established by HOMA-IR and adiponectin was associated with EPO responsiveness in HD patients. HOMA-IR, Hb, and adiponectin levels were found to be independent predictors of EPO dose in HD patients with diabetes. Conclusion: Insulin resistance is associated with EPO responsiveness in HD patients. Patients in the diabetes group had a lower response to EPO than those in the non-diabetes group. For improvement in EPO response, insulin resistance maybe a new target for treating HD patients.