title: Cilostazol attenuates the severity of peripheral arterial occlusive disease in patients with type 2 diabetes: the role of plasma soluble receptor for advanced glycation end-products.
abstract: Recent studies have demonstrated that the plasma soluble receptor for advanced glycation end-products (sRAGE) play a major role in developing macrovascular complications of type 2 diabetes, including peripheral arterial occlusion disease (PAOD). Cilostazol is an antiplatelet, antithrombotic agent, which has been used for the treatment of PAOD. We hypothesized that cilostazol attenuates the severity of PAOD in patients with type 2 diabetes through the augmentation of plasma sRAGE. Ninety type 2 diabetic patients with PAOD defined as intermittent claudication with ankle-brachial index (ABI) ≦0.9 were recruited for an open-labeled, placebo-controlled study for 52 weeks with oral cilostazol 100 mg twice daily (n = 45) or placebo (n = 45). Fasting plasma sRAGE, endothelial variables of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and inflammatory markers of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α) were determined. After completely the 52-week treatment program, the ABI values were elevated in cilostazol group (P < 0.001). The plasma sRAGE was significantly increased (P = 0.007), and hsCRP, sVCAM, and E-selectin concentrations were significantly decreased (P = 0.028, <0.001 and <0.001, respectively) with cilostazol treatment. In a partial correlation analysis with adjustments for sex and age, the net change of sRAGE significantly correlated with the change of ABI in the cilostazol group (P = 0.043). In a stepwise multiple regression model, only the change with regards to sRAGE was significantly associated with the change of ABI (P = 0.046). Our results suggest that cilostazol may effectively attenuate the severity of PAOD in patients with type 2 diabetes. Plasma sRAGE plays a role as an independent predictor for improving the index of PAOD.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, #325, Sec. 2, Chen-Kung Rd., Nei-Hu, Taipei, Taiwan.
authors: Jhih-Syuan
authors: JS
authors: Liu
authors: Tsung-Ju
authors: TJ
authors: Chuang
authors: Jui-Hung
authors: JH
authors: Chen
authors: Chien-Hsing
authors: CH
authors: Lee
authors: Chang-Hsun
authors: CH
authors: Hsieh
authors: Tsung-Kun
authors: TK
authors: Lin
authors: Fone-Ching
authors: FC
authors: Hsiao
authors: Yi-Jen
authors: YJ
authors: Hung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000209:etiology*; D002097:C-Reactive Protein / Q000032:analysis; D000077407:Cilostazol; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D019040:E-Selectin / Q000097:blood; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007383:Intermittent Claudication / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood* / Q000235:genetics; D013777:Tetrazoles / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: C000593871:AGER protein, human; D019040:E-Selectin; D005343:Fibrinolytic Agents; D000067759:Receptor for Advanced Glycation End Products; C546936:SELE protein, human; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; D002097:C-Reactive Protein; D000077407:Cilostazol