Role of leukocytes in diabetic microcirculatory disturbances.

Various rheological abnormalities of the blood have been widely reported in diabetes. However, it remains unclear which one affects blood flow at the level of microcirculation, an important site in the pathogenesis of diabetic microangiopathy. To differentiate which blood component leads to microcirculatory disturbances in diabetes, we studied the hemorheological properties of diabetic patients using an array flow analyzer that has microchannels simulating capillaries. Venous blood was collected from 19 diabetic patients and 24 control subjects. Three blood samples were prepared: plasma alone, erythrocyte suspension (ES) at 10% hematocrit (Ht), and erythrocyte and leukocyte suspension (ELS) having leukocyte counts of 1000/microl at 10% Ht. These samples were forced to flow through microchannels (equivalent diameter 6 micron, equivalent length 30 micron, 2600 in parallel) by applying a pressure difference of 20 cm H2O. Transit times for 100 microl of samples were measured, and the flow behavior of cells through the microchannels was recorded with a video-microscope. The transit time of ELS was 52.5 +/- 6.2 sec (mean +/- SD) in the diabetic group and 47.7 +/- 3.3 sec in the control group; there was significant prolongation in the transit time of diabetic ELS (P = 0.005), whereas the transit times of plasma alone and ES showed no significant differences between control and diabetic groups. Leukocytes were occasionally observed to plug the microchannels during the measurements of ELS from some diabetic patients. Our results imply that reduced deformability of leukocytes in diabetes may contribute to flow disturbances in the microcirculation. Leukocytes could play a potential role in the pathogenesis of diabetic microangiopathy.