Effect of recombinant human erythropoietin on insulin, amino acid, and lipid metabolism in uremia.

OBJECTIVE: To determine whether anemia is important in the pathogenesis of metabolic abnormalities in insulin, amino acid, and lipid metabolism in uremia.
METHODS: Twelve adolescents (15 +/- 1 years of age) undergoing long-term dialysis were studied before and after correction of their anemia by human recombinant erythropoietin at a mean interval of 6 months. Six patients received hemodialysis, and six received continuous-cycling peritoneal dialysis. Insulin sensitivity was measured by the euglycemic clamp technique and insulin secretion by the hyperglycemic clamp technique in these patients.
RESULTS: Hematocrit increased from 0.219 +/- 0.006 to 0.344 +/- 0.007 (p <0.01). Ferritin concentration did not change significantly (11,252 +/- 356 mg/dl to 785 +/- 226 mg/dl). Serum iron concentration decreased from 134 +/- 13 mg/dl to 83 +/- 11 mg/dl, and percentage saturation decreased from 56 +/- 4 to 41 +/- 5 (p <0.05 in both cases). There were no significant changes in weight, height, blood pressure, caloric intake, triceps skinfold thickness, or arm muscular area. There were also no significant changes in serum calcium, phosphate, bicarbonate, albumin, creatinine, or blood urea nitrogen concentration. Insulin sensitivity increased by 33% (p <0.01), but insulin secretion did not change significantly. Insulin sensitivity during the euglycemic clamp studies in patients before erythropoietin therapy was lower (145 +/- 10 mg/m2 per minute; p <0.01) than published normal values (201 +/- 12 mg/m2 per minute) and was normal after erythropoietin therapy (193 +/- 11 mg/m2 per minute). Insulin secretion was low in patients before erythropoietin therapy (44 +/- 8 microU/ml) compared with published normal values (68 +/- 6 microU/ml) and did not change after erythropoietin therapy (46 +/- 4 microU/ml). Plasma concentrations of branched-chain amino acids and lipids in the patients were compared with values from eight healthy adolescents. Plasma concentrations of valine, leucine, and isoleucine were low before treatment and were normal after 6 months of erythropoietin therapy. Plasma concentrations of triglycerides, total cholesterol, and low-density lipoprotein cholesterol were all high before treatment and were normal after treatment of anemia.
CONCLUSIONS: Treatment of anemia by erythropoietin reversed insulin resistance as well as amino acid and lipid abnormalities in adolescents undergoing dialysis.