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Increased Monocytic Activity and Biomarkers of Inflammation in Patients With Type 1 Diabetes

¹ Department of Pathology, Laboratory for Atherosclerosis and Metabolic Research, General Clinical Research Center, University of California at Davis Medical Center, Sacramento, California
² Department of Internal Medicine, Laboratory for Atherosclerosis and Metabolic Research, University of California at Davis Medical Center, Sacramento, California

Address correspondence and reprint requests to Ishwarlal Jialal, MD, PhD, Director, Laboratory for Atherosclerosis and Metabolic Research, Departments of Pathology and Internal Medicine, UC Davis Medical Center, Sacramento, CA 95817. E-mail: ijialal{at}ucdavis.edu

Abbreviations: CAM, cell adhesion molecule; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; HAEC, human aortic endothelial cell; hsCRP, high-sensitivity CRP; IL, interleukin; LPS, lipopolysaccharide; MCP-1, monocyte chemoattractant protein 1; sCD40L, soluble CD40 ligand; sICAM, soluble intracellular adhesion molecule; sVCAM, soluble vascular cell adhesion molecule; TNF-, tumor necrosis factor-

Type 1 diabetes is associated with increased vascular complications, and monocytes are pivotal cells in atherogenesis. However, there are few data on monocyte function and inflammation in type 1 diabetes. The aim of this study was to compare monocyte function and biomarkers of inflammation in type 1 diabetic subjects without macrovascular disease with that in matched control subjects (n = 52 per group). Fasting blood was obtained for biomarkers of inflammation (C-reactive protein [CRP], plasma-soluble cell adhesion molecules [CAMs], monocyte chemoattractant protein 1, nitrotyrosine, CD40 ligand [CD40L], and monocyte function). High-sensitive CRP, soluble intracellular adhesion molecule (sICAM), sCD40L, and nitrotyrosine levels were significantly elevated in type 1 diabetic subjects compared with in control subjects (P < 0.05). Monocyte superoxide anion release was significantly increased in the resting (37%; P < 0.05) and activated state (26%; P < 0.005) in type 1 diabetic compared with in control subjects. Monocyte interleukin (IL)-6 levels were significantly elevated in type 1 diabetic subjects compared with in control subjects in the resting state (51%; P < 0.05) and after lipopolysaccharide activation (31%; P < 0.01). Monocyte IL-1ß levels were increased in the activated monocytes in type 1 diabetic compared with in control subjects. There were no significant differences in monocyte tumor necrosis factor levels or adhesion between the two groups. Thus type 1 diabetes is a proinflammatory state, as evidenced by increased levels of monocyte IL-6, superoxide anion, and plasma CRP, sICAM, sCD40L, and nitrotyrosine levels. These results have a major implication on our understanding of the role of inflammation in vasculopathies in type 1 diabetes.

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