Complete correction of anemia by erythropoiesis-stimulating agents is associated with insulin resistance in hemodialysis patients

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 [6,6-²H₂]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 (m²)⁻¹ min⁻¹] than in those with mild anemia [251 ± 49 mg (m²)⁻¹ min⁻¹] and in a group of matched controls [275 ± 68 mg (m²)⁻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.