Altered red cell turnover in diabetic mice.

In diabetes, a subpopulation of red cells expose phosphatidylserine, and the size of this subpopulation of cells is related to blood glucose levels. Because phosphatidylserine exposure can lead to the recognition and removal of red cells we hypothesized that red cell survival would be altered. In this study, diabetic female mice (db/db) and heterozygous littermate controls were used to explore relationships between red cell characteristics, phosphatidylserine exposure, and red cell survival. Red cell turnover was assessed using random red cell labeling with biotin. To determine if phosphatidylserine exposure was related to age, red cells were double-labeled and analyzed by flow cytometry. Cellular characteristics were measured by flow cytometry and ektacytometry. While red cell removal was linear for the control mice, for the diabetic mice an exponential survival curve was noted with an extended survival of a subpopulation of cells. The subpopulation of red cells exposing phosphatidylserine was significantly increased in the diabetic mice relative to the control mice (0.9% +/- 0.07%, n = 12, and 0.6% +/- 0.05 %, n = 22, respectively; P =.007). This subpopulation increased during the life of the red cell, with a higher rate of increase in the diabetic mice. Red cell hemoglobin content and cell volume were abnormal, but no obvious signs of anemia were found in the diabetic animals. A normal hematocrit, low reticulocyte count, and a much reduced spleen in these animals were consistent with a low red cell turnover. The presence of a population of older phosphatidylserine exposing cells indicates altered red cell removal and suggests a role for older red cells in vascular damage.