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Polymorphonuclear Leukocytes in Non-Insulin-dependent Diabetes Mellitus: Abnormalities in Metabolism and Function

Jadwiga M. Alexiewicz, MD; Dinesh Kumar, MD; Miroslaw Smogorzewski, MD; Mariusz Klin, MD; and Shaul G. Massry, MD
[+] Article and Author Information

From the University of Southern California School of Medicine, Los Angeles, California. Grant Support: By National Institute of Diabetes and Digestive and Kidney Diseases grant DK 29955. Dr. Klin was supported by the Fogarty International Fellowship. Request for Reprints: Shaul G. Massry, MD, Chief, Division of Nephrology, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033. Current Author Addresses: Drs. Alexiewicz, Smogorzewski, Klin, and Massry: Division of Nephrology, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033. Dr. Kumar: Division of Endocrinology, Diabetes and Hypertension, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1995;123(12):919-924. doi:10.7326/0003-4819-123-12-199512150-00004
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Objective: To determine basal levels of cytosolic calcium ([Ca2+]i) and phagocytic activity in polymorphonuclear leukocytes (PMNLs) from patients with non–insulin-dependent diabetes (NIDDM).

Design: Prospective cohort study.

Setting: A university-county hospital.

Measurements: Cytosolic calcium levels, adenosine triphosphate (ATP) content, and phagocytosis of PMNLs from patients with NIDDM and from controls.

Intervention: In patients with NIDDM, we evaluated the effect of treatment with an oral hypoglycemic agent (glyburide) on [Ca2+]i levels, ATP content, and the phagocytosis of PMNLs.

Patients: 22 controls and 34 patients with NIDDM were examined. Fifteen patients were studied before and after 3 months of treatment with glyburide.

Results: Polymorphonuclear leukocytes from patients with NIDDM showed significantly elevated basal 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 nmol/106PMNLs; P < 0.01); and impaired phagocytosis (117 ± 21.0 compared with 145 ± 17.4 µg oil/107PMNLs per minute; P < 0.01) compared 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 significant 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 the impaired phagocytosis seen in these patients.

Figures

Grahic Jump Location
Figure 1.
Basal levels of cytosolic calcium, phagocytosis, and adenosine triphosphate (ATP) content in polymorphonuclear leukocytes (PMNLs) from controls and patients with non–insulin-dependent diabetes mellitus.

Each datum point represents one person. Brackets denote ± SE.

Grahic Jump Location
Grahic Jump Location
Figure 2.
The relation between cystolic calcium ([Ca2+]i) levels in polymorphonuclear leukocytes (PMNLs) and serum glucose levels (top), between phagocytosis and serum glucose levels (middle), and between phagocytosis and [Ca2+]i levels (bottom) in PMNLs in patients with non–insulin-dependent diabetes mellitus.
Grahic Jump Location
Grahic Jump Location
Figure 3.
In patients with non–insulin-dependent diabetes mellitus, the effect of 3 months of treatment with glyburide on cytosolic calcium levels, adenosine triphosphate (ATP) content, and the phagocytic activity of PMNLs.

Open circles represent data before treatment, and closed circles represent data after therapy. Each line represents one patient. Brackets denote ± SE.

Grahic Jump Location

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