Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus

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Abstract

Increased monocyte recruitment into subendothelial space in atherosclerotic lesions is one of the hallmarks of diabetic angiopathy. The aim of this study was to determine the state of peripheral blood monocytes in diabetes associated with atherosclerosis. Diabetic patients treated with/without an oral hypoglycemic agent and/or insulin for at least 1 year were recruited (n = 106). We also included 24 non-diabetic control subjects. We measured serum levels of monocyte chemoattractant protein (MCP)-1, fasting plasma glucose (FPG), HbA1c, total cholesterol, triglyceride, body mass index (BMI), high sensitivity CRP (hs-CRP) and evaluated CCR2, CD36, CD68 expression on the surface of monocytes. Serum MCP-1 levels were significantly (p < 0.05) higher in diabetic patients than in normal subjects. In diabetic patients, serum MCP-1 levels correlated significantly with FPG, HbA1c, triglyceride, BMI, and hs-CRP. The expression levels of CCR2, CD36, and CD68 on monocytes were significantly increased in diabetic patients and were more upregulated by MCP-1 stimulation. Our data suggest that elevated serum MCP-1 levels and increased monocyte CCR2, CD36, CD68 expression correlate with poor blood glucose control and potentially contribute to increased recruitment of monocytes to the vessel wall in diabetes mellitus.

Section snippets

Materials and methods

Study participants. We studied patients who visited our hospital between April 2002 and July 2002. The inclusion criteria were the presence of type 2 diabetes mellitus, treated with/without an oral hypoglycemic agent and/or insulin for at least one year. We excluded patients with the above criteria but had a history of alcohol abuse, evidence of liver disease, or severe cardiac problems. We also included a control group consisting of 24 individuals referred to our department for admission who

Patients characteristics

A total of 106 diabetic patients and 7 patients with hyperlipidemia were enrolled in this study (Table 1). Peripheral blood MCP-1 levels were significantly (p < 0.05) higher in diabetic patients than in the normal control or in hyperlipidemic patients (Fig. 1). There was no significant difference in serum MCP-1 level based on the type of medications and there were no significant differences in body mass index (BMI), FPG, HbA1c, total cholesterol, triglyceride, hs-CRP between patients with

Discussion

Although a great deal has been reported on vessel wall stiffness and the prevalence of inflammatory markers in association with endothelial dysfunction, very little attention has been paid to the state of peripheral blood monocytes in diabetes associated with atherosclerosis [20]. In this study, we measured peripheral blood MCP-1 concentrations and CCR2 expression on silent monocytes isolated by counterflow centrifugal elutriation in diabetic patients with the aim of determining the relevance

Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research by the Ministry of Health, Labor, and Welfare of Japan, the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and a Grant from the University of Occupational and Environmental Health, Japan.

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