Studies on the Effect of Experimental Nonketotic Diabetes Mellitus on Antibacterial Defense I. I)emonstration of a Defect in Piiagocytosis* By

Diabetes mellitus is often cited as a metabolic disease that depresses the antibacterial defenses of the host (1). Many clinical investigators have reported that patients with uncontrolled diabetes are unusually susceptible to bacterial diseases, particularly of staphylococcal etiology (2). Attempts to confirm this relationship experimentally, however, have been only partially successful. No impairment of immunological competence has been detected in diabetic patients (3), and deficiencies in cellular defense have been demonstrated only in the presence of ketoacidosis (4-6), even though an insulin-correctable depression of glycolysis has been noted in the leukocytes of nonacidotic diabetics (7, 8). Similar results have been reported in animals with diabetes induced by pancreatectomy or treatment with ailoxan; i.e., only when the relatively complicated metabolic and circulatory derangements of ketoacidosis have been present, has increased susceptibility to bacter';al (9) and mycotic (10) infections been consistently demonstrated. Although nonacidotic rats with chronic alloxan diabetes have been reported to be more susceptible to experimental staphylococcal peritonitis than nondiabetic rats (11), no such difference was demonstrable in either mice (12) or rabbits (9). The present studies were undertaken in order to determine experimentally whether chronic hyperglycemia per se impairs antibacterial resistance and to define the mechanism involved, if it does so.