Rasic-Milutinovic Z, Perunicic-Pekovic G, Cavala A, Gluvic Z, Bokan L, Stankovic S
Department of Endocrinology, University Hospital Zemun/Belgrade, Serbia.
Hippokratia. 2008 Jul;12(3):157-61.
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.
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-alpha, 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.
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 g/L vs. 116.40+/-21.03 g/L, p: 0.01; Hct 0.28 (0.24-0.31) vs. 0.33% (0.31-0.37), p: 0.01] as well as a trend toward iron stores decrease [ferritin 466.45 (174.40-886.90) vs. 279 microg/L (137.00-648.50), p: 0.06]. A significant decrease of TNF-alpha [2.30 pg/ml (1.48-2.95) vs. 1.65 pg/ml (0.11-1.96), p: 0.01] and IL6 levels [8.32 pg/ml (2.31-9.83) vs. 2.60 pg/ml (2.00-3.05), p: 0.01] was presented. After adjustment for confounding variables (age, sex, and Kt/v), a model consisting of BMI, ferittin, and TNF alpha accounted for 96% of the variance in HOMA-IR in Epo treated patients.
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.
铁过载和炎症可能参与社区胰岛素抵抗的发病机制。血液透析（HD）患者贫血纠正后，胰岛素抵抗常有所改善。本研究旨在探讨重组人促红细胞生成素（Epo）治疗对非糖尿病HD患者胰岛素抵抗的影响。
我们研究了16例（6例男性/10例女性）维持性HD且伴有肾性贫血（血红蛋白浓度≤105g/l）患者接受Epo治疗6个月对胰岛素抵抗和炎症参数的影响。对照组由15例患有肾性贫血且未接受Epo治疗的HD患者组成。进一步观察了临床和实验室变量：空腹血糖（FBG）、胰岛素、白蛋白、铁、总铁结合力（TIBC）、转铁蛋白饱和度（TSAT）、铁蛋白、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。通过多元线性回归分析确定了采用稳态模型评估（HOMA-IR）计算的胰岛素抵抗指数变化的独立预测因素。
Epo治疗组胰岛素水平显著降低，因此HOMA-IR也显著降低。观察到贫血有所改善[血红蛋白93.90±17.34g/L对116.40±21.03g/L，p：0.01；血细胞比容0.28（0.24 - 0.31）对0.33%（0.31 - 0.37），p：0.01]，同时铁储存有下降趋势[铁蛋白466.45（174.40 - 886.90）对279μg/L（137.00 - 648.50），p：0.06]。TNF-α[2.30pg/ml（1.48 - 2.95）对1.65pg/ml（0.11 - 1.96），p：0.01]和IL-6水平[8.32pg/ml（2.31 - 9.83）对2.60pg/ml（2.00 - 3.05），p：0.01]显著降低。在对混杂变量（年龄、性别和Kt/v）进行校正后，由体重指数、铁蛋白和TNF-α组成的模型解释了Epo治疗患者HOMA-IR变异的96%。
本研究表明，Epo治疗可通过减少铁储存和改善维持性HD患者的慢性炎症来参与降低胰岛素抵抗。
