OBJECTIVE: Patients with diabetes commonly have a greater degree of anemia for their level of renal impairment than those presenting with other causes of renal failure. To clarify the contribution and differing roles of diabetes and nephropathy in the development of anemia in diabetic patients, we examined the hematologic and hematinic parameters of diabetic patients without nephropathy. RESEARCH DESIGN AND METHODS: The study group was comprised of 62 patients with type 2 diabetes who had been followed for a median of 7 years. For the study, these patients had additional samples taken during their annual routine blood testing for the measurement of extra parameters, including serum ferritin, serum erythropoietin (Epo) levels, and the percentage of reticulocytes. These measurements were combined with the routine parameters Hb, hematocrit, HbA(1c), and glomerular filtration rate. RESULTS: In all, 8 of the 45 male patients (17.8%) and 2 of the 17 female patients (11.8%) were classified as anemic (Hb <13g/dl and <11.5g/dl, respectively). Although only a small number of the patients had anemia as defined by normal values, a retrospective analysis of individual patients over time revealed a sustained though small decrease in Hb from initial presentation. A statistically significant difference in Epo levels (P = 0.016 by Kruskal-Wallis test) was observed from the group with the lowest (Hb < or =11.5) to that with the highest (Hb > or =14.5) Hb values, with a median Epo value of 37 (interquartile range 24-42) vs. 13 (9-15) IU/l, respectively. In contrast, there was no evidence of an increased reticulocyte response to higher levels of Epo (r = 0.134 [Pearsons], P = 0.36). Reticulocyte counts ranged from 44 (38-57) to 76.5 (56-83) in the lowest and highest Hb groups, respectively. CONCLUSIONS: Although only a small number of subjects in the group were overtly anemic, all subjects had an ongoing, small but significant decrease in Hb since presentation. This study of diabetic patients without nephropathy shows an expected increase in Epo production in response to lowering levels of Hb but without the expected reticulocyte response.