Normalization of plasma lipid peroxides, monocyte adhesion, and tumor necrosis factor-alpha production in NIDDM patients after gliclazide treatment

• Published in: Diabetes care Vol. 21; no. 4; pp. 487 - 493
• Main Authors: Desfaits, Anne-Cécile, Serri, Omar, Renier, Geneviève
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.1998
• Subjects: Animals; Aorta; Arteriosclerosis - prevention & control; Biological and medical sciences; Cattle; Cell Adhesion - drug effects; Cell Adhesion Molecules - blood; Cells, Cultured; Cytokines - blood; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - immunology; E-Selectin - blood; Endothelium, Vascular - physiology; Gliclazide - therapeutic use; Glyburide - therapeutic use; Hormones. Endocrine system; Humans; Hypoglycemic Agents - therapeutic use; Intercellular Adhesion Molecule-1 - blood; Interleukin-1 - blood; Interleukin-6 - biosynthesis; Interleukin-6 - blood; Lipid Peroxides - blood; Lipopolysaccharides - pharmacology; Medical sciences; Monocytes - drug effects; Monocytes - immunology; Monocytes - physiology; Pharmacology. Drug treatments; Reference Values; Treatment Failure; Tumor Necrosis Factor-alpha - biosynthesis; Vascular Cell Adhesion Molecule-1 - blood; Canada; North America; America; Endocrinopathy; Human; Monocyte; Treatment efficiency; Cytokine; Lipids; Adhesion; Non insulin dependent diabetes; Blood plasma; Endocrine secretion; Assay; Hypoglycemic agent; Chemotherapy; Treatment; Sulfonylureas; Gliclazide; Adult; Peroxides; Elderly; Comparative study
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.21.4.487

Normalization of plasma lipid peroxides, monocyte adhesion, and tumor necrosis factor-alpha production in NIDDM patients after gliclazide treatment. A C Desfaits , O Serri and G Renier Metabolic Unit, CHUM Research Center, Montreal, Quebec, Canada. Abstract OBJECTIVE: To evaluate the effect of gliclazide administration to NIDDM patients on 1) monocyte adhesion to cultured endothelial cells, 2) plasma cytokine and lipid peroxide levels, and 3) monocyte cytokine production. RESEARCH DESIGN AND METHODS: Poorly controlled glyburide-treated diabetic patients (n = 8) and healthy control subjects (n = 8) were recruited. At the beginning of the study, glyburide was replaced by an equivalent hypoglycemic dose of gliclazide. Serum and monocytes were isolated from blood obtained from control and diabetic subjects before and after 3 months of treatment with gliclazide. RESULTS: Plasma lipid peroxide levels and monocyte adhesion to endothelial cells are enhanced in NIDDM patients, and gliclazide administration totally reverses these abnormalities. Before gliclazide treatment, serum levels of cytokines did not differ in the control and the diabetic groups, with the exception of an enhancement of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL)-6 in NIDDM subjects. Basal and lipopolysaccharide (LPS)-stimulated monocyte production of interleukin-1 beta, IL-6, and IL-8 did not differ between the two groups. Furthermore, basal monocyte production of TNF-alpha was similar in the control and the diabetic groups, whereas a marked increase in the LPS-stimulated monocyte production of TNF-alpha was observed in the NIDDM group. Gliclazide treatment lowered LPS-stimulated TNF-alpha production by diabetic monocytes to levels similar to those observed in control subjects. CONCLUSIONS: Gliclazide administration to NIDDM patients inhibits the increased adhesiveness of diabetic monocytes to endothelial cells and reduces the production of TNF-alpha by these cells. These results suggest that treatment of NIDDM subjects with gliclazide may be beneficial in the prevention of atherosclerosis associated with NIDDM.