Impairment of Polymorphonuclear Leukocyte Function and Metabolic Control of Diabetes

Abstract

Objective: In this study, ingestion of Staphylococcus aureus and “bacteria killing” (BK) were measured to evaluate polymorphonuclear leukocyte (PMN) phagocytic functions and chemiluminescence response (CL) to phorbolmyristic acetate (PMA) as respiratory burst activity with regard to metabolic control parameters in diabetic patients. Research Design and Methods: PMN phagocytic functions were assessed in 40 diabetic patients, all receiving insulin and in poor metabolic control, with 3H-thymidine-labeled Staphylococcus aureus in a modified radiometric assay. Bacteria killing was determined by pure-plate counting of surviving bacteria (colony-forming units [cm]) and luminol-enhanced CL in response to PMA as a measure of respiratory burst. PMN function data were correlated to HbA1 as parameter of recent metabolic control. Results: PMN of diabetic patients showed a significant reduction in Staphylococcus aureus (50.7 ± 4.1%) and BK (29.4 ± 4.2%) compared with healthy nondiabetic control subjects (76.6 ± 4.6% and 16.3 ± 3.1%, respectively, P < 0.001), and PMN CL response was markedly reduced in diabetic patients also. Linear regression analysis showed a highly significant negative correlation of HbAi versus Staphylococcus aureus (r = -0.67, P = 0.001) and a positive correlation for BK (r = 0.73, P < 0.001). This was also true for CL, although this did not reach statistical significance (P = 0.06). Conclusions: The data obtained demonstrate impaired PMN phagocytic functions and CL response in diabetic patients. These findings suggest inhibitory effects of elevated glucose concentrations on PMNs, a possible role of protein glycosylation for impairing PMN function, thus contributing in part to altered host defense.