Effect of Cilostazol Treatment on Adiponectin and Soluble CD40 Ligand Levels in Diabetic Patients With Peripheral Arterial Occlusion Disease

Abstract

Circ J 2009; 73: 948 -954 eripheral arterial occlusion disease (PAOD) is a common manifestation of atherosclerosis in patients with type 2 diabetes mellitus (DM). 1,2 In Taiwan, approximately 33-50% of patients undergoing lower extremity amputation have DM, and more than 50% of them have PAOD. 3,4 The risk factors associated with PAOD are similar to those for coronary artery disease and cerebrovascular disease.It has been proved that atherosclerosis-related macroangiopathy is a result of chronic inflammation and endothelium dysfunction. Levels of high-sensitivity C-reactive protein (hs-CRP) and adiponectin have been found to be markers of chronic inflammation in many human studies. [5][6][7] Interaction of the multipotent immunomodulator CD40 ligand with its receptor is also as an important contributor to chronic inflammation and endothelium dysfunction. The soluble form of the CD40 ligand (sCD40L), a marker of proinflammatory and platelet activation, is high in the sera of DM patients with coronary artery disease. 8 However, few studies have investigated the relationships between PAOD and adiponectin and sCD40L levels.Cilostazol, a vasodilator and inhibitor of platelet aggregation, has been used in the treatment of chronic PAOD since 1988. Because little is known regarding its effects on PAOD and the aforementioned atherogenic cytokines in DM patients, we performed a randomized, placebo-controlled, single-blinded trial to examine the effect of cilostazol treatment on the serum levels of sCD-40L, adiponectin and hs-CRP in patients with type 2 DM. Methods SubjectsWe enrolled 92 PAOD patients (53 women, 39 men; mean age 63.3±18.8 years) and 100 non-PAOD patients as controls (58 women, 42 men; mean age 63.0±14.7 years) at our outpatient clinic from 2006 to 2008. Sex ratio and ranges of age and body mass index (BMI) were considered while selecting the controls. All patients were confirmed to have type 2 DM based on the 2005 American Diabetes Association diagnostic criteria and had received oral antidiabetic drugs (OADs) for more than 6 months. Because some antiplatelet, antihypertension and antihyperlipidemia drugs have an antiinflammatory effect, the dosages of all medications, including OADs, aspirin, antihypertension drugs and antihyperlipidemia drugs, were not changed for 6 months prior to the study or during the study period. We excluded any patient who had received insulin injections for more than 1 month or had been found to have had cardiogenic shock, unstable angina, old stroke, or myocardial infarction during the preceding 6 months, had an ankle systolic blood pressure (SBP) ≥200 mmHg, had been treated with insulin, and had impaired renal function (creatinine level >1.4 mg/dl), cancer, systemic inflammatory disease or (Received September 24, 2008; revised manuscript received November 26, 2008; accepted December 15, 2008; released online March 12, 2009 Effect of Cilostazol Treatment on Adiponectin and Soluble CD40 Ligand Levels in Diabetic Patients With Peripheral Arterial Occlusion DiseaseChing-Jung...

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