POLYMORPHONUCLEAR LEUKOCYTES IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS - ABNORMALITIES IN METABOLISM AND FUNCTION

Objective: To determine basal levels of cytosolic calcium ([Ca2+]i) an d phagocytic activity in polymorphonuclear leukocytes (PMNLs) from pat ients with non-insulin-dependent diabetes (NIDDM). Design: Prospective cohort study. Setting: A university-county hospital. Measurements: Cy tosolic calcium levels, adenosine triphosphate (ATP) content, and phag ocytosis of PMNLs from patients with NIDDM and from controls. Interven tion: In patients with NIDDM, we evaluated the effect of treatment wit h an oral hypoglycemic agent (glyburide) on [Ca2+]i levels, ATP conten t, and the phagocytosis of PMNLs. Patients: 22 controls and 34 patient s with NIDDM were examined. Fifteen patients were studied before and a fter 3 months of treatment with glyburide. Results: Polymorphonuclear leukocytes from patients with NIDDM showed significantly elevated basa l levels of [Ca2+]i (68 +/- 9.6 compared with 43 +/- 4.9 nmol/L; P < 0 .01); reduced ATP content (1.30 +/- 0.58 compared with 2.35 +/- 0.45 n mol/10(6) PMNLs; P < 0.01); and impaired phagocytosis (117 +/- 21.0 co mpared with 145 +/- 17.4 mu g oil/10(7) PMNLs per minute; P < 0.01) co mpared with controls. There was a direct and significant correlation ( P < 0.01, r = 0.80) between [Ca2+]i levels in PMNLs and serum glucose levels and an inverse correlation between phagocytic ability and [Ca2]i levels (P < 0.01; r = 0.62) as well as between phagocytic activity and fasting serum glucose levels (P < 0.01, r = 0.54) in patients with NIDDM. Glyburide therapy resulted in significant reduction in fasting serum glucose levels; in PMNLs, this treatment resulted in a signific ant reduction in [Ca2+]i levels, a significant increase in ATP content , and a significant improvement of phagocytosis. Conclusions: Patients with NIDDM have elevated [Ca2+]i levels in PMNLs. This abnormality is probably induced by hyperglycemia and is primarily responsible for th e impaired phagocytosis seen in these patients.