Correction of anemia by erythropoietin reverses insulin resistance and hyperinsulinemia in uremia.

Ten patients (18 +/- 1 yr) on chronic hemodialysis (HD) with anemia were studied before and after treatment with erythropoietin (EPO) for 9 mo. Six patients had evidence of iron overload (serum ferritin over 300 ng/ml; group I) and the other four patients (serum ferritin below 300 ng/ml; group II) did not. Before treatment, both groups of patients were glucose tolerant but insulin resistant and hyperinsulinemic. There was equal correction of anemia but no significant changes in serum biochemistry (apart from iron studies) or anthropometric measurements in both groups. With amelioration of anemia and iron overload in group I, insulin sensitivity increased by 53% to within normal values. Insulin secretion also normalized. With amelioration of anemia but no change in iron status in group II, insulin sensitivity (increased by 60%) and insulin secretion also normalized. Thus correction of anemia by EPO reversed insulin resistance and hyperinsulinemia in HD patients with or without iron overload. The effects of correction of anemia rather than iron overload may be more important in the pathogenesis of insulin abnormalities in end-stage renal disease.