The effect of simvastatin and fenofibrate on the expression of leukocyte adhesion molecules and lipopolysaccharide receptor CD14 in type 2 diabetes mellitus.

BACKGROUND: Mixed hyperlipidemia is often associated with type 2 diabetes mellitus and contributes to atherosclerosis progression in diabetes patients. Leukocyte activation plays an important role in atherogenesis. Both statins and fibrates are used in the treatment of mixed dyslipidemia, but their specific effect on leukocyte function remains to be elucidated. We have therefore compared the effect of simvastatin and fenofibrate on several leukocyte activation markers in diabetes patients.

METHODS: Twenty patients with type 2 diabetes and mixed hyperlipidemia were sequentially treated with simvastatin (20 mg/day) and fenofibrate (200 mg/day) in a randomized cross-over study (12 weeks each treatment). We measured adhesion molecules LFA-1, VLA-4 and CD18; in addition, lipopolysaccharide receptor CD14 on monocytes was analyzed as a marker of innate immunity. Leukocyte expression of these molecules was quantified using flow cytometry. Laboratory examinations were done at baseline and at the end of each treatment. Baseline values were compared to those of 29 healthy controls.

RESULTS: Expression of integrin CD18 (in all leukocyte populations), lipopolysaccharide receptor and VLA-4 (on lymphocytes only) was significantly higher in patients than in controls. Both treatments resulted in significant decrease in CD18 and CD14 expression; LFA-1 and VLA-4 were not influenced.

CONCLUSIONS: Both simvastatin and fenofibrate had similar favorable effect on leukocyte activation markers. This result supports the use of both statins and fibrates for the treatment of mixed hyperlipidemia in patients with type 2 diabetes mellitus.

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