Department of Medical, Technological and Translational Sciences, Division of Internal Medicine, University of Trieste, Italy.
Clin Exp Med. 2011 Sep;11(3):181-7. doi: 10.1007/s10238-010-0119-0. Epub 2010 Nov 16.
Insulin resistance and anemia secondary to erythropoietin deficiency characterize patients with end-stage kidney disease. In a cross-sectional analysis, we examined the relationship between erythropoietin-mediated correction of anemia and insulin sensitivity in nondiabetic hemodialysis patients. Insulin sensitivity (euglycemic-hyperinsulinemic clamp) and endogenous glucose production (primed-continuous infusion of [6,6-(2)H(2)]glucose) were determined in two groups of patients with normal hemoglobin (n:8; mean hemoglobin: 14.0 ± 0.3 g/dl) or with mild anemia (n:10; mean hemoglobin: 12.1 ± 0.9 g/dl). The patients with normal hemoglobin were receiving higher (P < 0.05) erythropoietin doses than those with mild anemia (171 ± 73 and 91 ± 39 U kg(-1) wk(-1), respectively). The two groups were matched for all other potential determinants of insulin resistance. Endogenous glucose production was similar in the two groups of patients in the postabsorptive state and was completely suppressed by insulin infusion. During the hyperinsulinemic clamp, the rate of glucose infusion to maintain euglycemia was significantly lower (P < 0.01) in the patients with normal hemoglobin levels [166 ± 31 mg (m(2))(-1) min(-1)] than in those with mild anemia [251 ± 49 mg (m(2))(-1) min(-1)] and in a group of matched controls [275 ± 68 mg (m(2))(-1) min(-1)]. In pooled patients, individual values of hemoglobin concentrations inversely correlated with the rates of insulin-mediated glucose infusion, both as absolute values (r = -0.58; P < 0.05) and as values normalized by steady-state plasma insulin concentration (r = -0.74; P < 0.001). In conclusion, this exploratory study indicates that complete correction of anemia by erythropoietin treatment in patients with end-stage kidney disease on hemodialysis is associated with impaired insulin sensitivity.
胰岛素抵抗和促红细胞生成素缺乏引起的贫血是终末期肾病患者的特征。在一项横断面分析中，我们研究了非糖尿病血液透析患者中促红细胞生成素纠正贫血与胰岛素敏感性之间的关系。胰岛素敏感性（正葡萄糖高胰岛素钳夹）和内源性葡萄糖生成（[6,6-(2)H2]葡萄糖持续输注）在两组血红蛋白正常（n=8；平均血红蛋白 14.0±0.3g/dl）或轻度贫血（n=10；平均血红蛋白 12.1±0.9g/dl）的患者中进行了测定。血红蛋白正常的患者接受的促红细胞生成素剂量高于轻度贫血的患者（分别为 171±73 和 91±39Ukg-1wk-1）（P<0.05）。两组患者的所有其他潜在胰岛素抵抗决定因素均匹配。两组患者在吸收后状态下的内源性葡萄糖生成相似，且均被胰岛素输注完全抑制。在高胰岛素钳夹期间，维持正常血糖所需的葡萄糖输注率在血红蛋白水平正常的患者[166±31mg(m2)-1min-1]中明显低于轻度贫血的患者[251±49mg(m2)-1min-1]和一组匹配的对照组[275±68mg(m2)-1min-1]（P<0.01）。在汇总患者中，血红蛋白浓度的个体值与胰岛素介导的葡萄糖输注率呈负相关，无论是绝对值（r=-0.58；P<0.05）还是通过稳态血浆胰岛素浓度校正的值（r=-0.74；P<0.001）。总之，这项探索性研究表明，终末期肾病血液透析患者经促红细胞生成素治疗完全纠正贫血与胰岛素敏感性受损有关。
