ANTITHROMBIN-III, C1-INHIBITOR, METHYLGLYOXAL, AND POLYMORPHONUCLEAR LEUKOCYTES IN THE DEVELOPMENT OF VASCULAR COMPLICATIONS IN DIABETES-MELLITUS

Under conditions closely approximating those in vivo (100 mM sodium carbonate pH 7.3 with 0.9% NaCl, 37-degrees-C),antithrombin III (AT III) and the Cl inhibitor (Cl-INH) are inactivated by methylglyoxal (MG) with pseudofirst-order kinetics and second-order rate constants of 25.2 and 7.8 M-1 min-1, respectively. A study of the functional status of neutrophils from patients with diabetes mellitus (DM)prompts an idea that under hyperglycemia in the diabetic organism the polymorphonuclear leukocytes (PML) endure 'arousal' that is identical or analogous to their activation. Indeed, nonstimulated PML from DM patients display (i) an almost sixfold higher luminol-dependent chemiluminescence and (ii) a double rate of oxygen uptake as compared with those from healthy donors, and (iii) are capable of MG formation in the presence of acetoacetate, which in vivo may be an additional source of this inactivator of AT III and Cl-INH in diabetic patients. Conditions leading to ketosis or lactic acidosis are discussed, and a probable scenario is proposed for the organismic deterioration in DM.