Increased erythrocyte 3-DG and AGEs in diabetic hemodialysis patients: Role of the polyol pathway

Background 3-Deoxyglucosone (3-DG) accumulating in uremic serum plays an im portant role in the formation of advanced glycation end products (AGEs). To determine if 3-DG is involved in the formation of intracellular AGEs, we m easured the erythrocyte levels of 3-DG and AGEs such as imidazolone and N-e psilon-carboxymethyllysine (CML) in hemodialysis (HD) patients with diabete s. Further, to determine if the polyol pathway is involved in the formation of erythrocyte 3-DG and AGEs, an aldose reductase inhibitor (ARI) was admi nistered to these patients. Methods. The erythrocyte levels of sorbitol, 3-DG, imidazolone, and CML wer e measured in ten diabetic HD patients before and after treatment with ARI (epalrestat) for eight weeks, and were compared with those in eleven health y subjects. 3-DG was incubated in vitro with hemoglobin for two weeks to de termine if imidazolone and CML are formed by reacting 3-DG with hemoglobin. Results. The erythrocyte levels of sorbitol, 3-DG, imidazolone, and CML wer e significantly elevated in diabetic HE patients as compared with healthy s ubjects. The erythrocyte levels of 3-DG significantly decreased after HD, b ut sorbitol, imidazolone or CML did not. The administration of ARI signific antly decreased the erythrocyte levels of sorbitol, 3-DG and imidazolone, a nd tended to decrease the CML level. Imidazolone was rapidly produced in vi tro by incubating 3-DG with hemoglobin, and CML was also produced, but less markedly as compared with imidazolone. Conclusion. The erythrocyte levels of 3-DG and AGEs are elevated in diabeti c KD patients. The administration of ARI reduces the erythrocyte levels of 3-DG and AGEs, especially imidazolone, as well as sorbitol. Thus, 3-DG and AGEs, especially imidazolone, in the erythrocytes are produced mainly via t he polyol pathway. ARI may prevent diabetic and uremic complications associ ated with AGEs.