The effect of erythropoietin treatment on insulin resistance and inflammatory markers in patients on maintenance hemodialysis
Zorica Rasic-Milutinovic1, Marina Vujovic1, Gordana Perunicic-Pekovic2, Vesna Popovic1, Jelena Tica1, Zoran Gluvic1, Milena Lackovic1 & Ljiljana Bokan3
Background and aim: Iron overload and inflammation might participate in the pathogenesis of insulin resistance in community. The improvement of insulin resistance in hemodialysis (HD) patients is frequently seen after correction of anemia. The aim of this study was to investigate the influence of recobinant humam erythropoietin (Epo) treatment on insulin resistance in non-diabetic HD patients.
Patients and methods: We investigated the effects of 6 months-duration treatment with Epo on insulin resistance and inflammatory parameters in 16 (6 male/10 female) patients on maintenance HD with renal anemia (hemoglobin concentration ≤105 g/l). The control group consisted of 15 patients on HD with renal anemia, without Epo treatment. Further clinical and laboratory variables were observed: fasting blood glucose (FBG), insulin, albumin, iron, total iron binding capacity (TIBC), transferrin saturation (TSAT), ferritin, TNF-α, and IL-6. Independent predictors for changes of calculated insulin resistance index by homeostasis model assessment (HOMA-IR) were identified by multivariate linear regression analysis.
Results: A significant reduction of insulin levels and therefore significant lowering of HOMA-IR was registered in Epo treated group. It was observed improvement of anemia (Hb 93.90±17.34 vs 116.40±21.03 g/L, P=0.01; Hct 0.28 (0.240.31) vs. 0.33% (0.310.37), P=0.01) as well as a trend toward iron stores decrease (ferritin 466.45 (174.40886.90) vs 279 μg/l (137.00648.50), P=0.06). A significant decrease of TNF-α (2.30 pg/ml (1.482.95) vs 1.65 pg/ml (0.111.96), P=0.01) and IL6 levels (8.32 pg/ml (2.319.83) vs. 2.60 pg/ml (2.003.05), P=0.01) was presented. After adjustment for confounding variables (age, sex, and Kt/v), a model consisting of BMI, ferittin, and TNF-α accounted for 96% of the variance in HOMA-IR in Epo treated patients.
Conclusions: The present study demonstrated that Epo treatment could participate in reducing insulin resistance through iron stores reduction and improvement of chronic inflammation in patients on maintenance HD.