Association of serum Cyr61 levels with peripheral arterial disease in patients with type 2 diabetes

Abstract

Background: The prevalence of peripheral artery disease (PAD) is obviously increased in diabetic patients. Existing evidences show that cysteine-rich angiogenic inducer 61 (Cyr61), a 40 kD secreted protein, plays important roles in regulating cellular physiological processes. Recent studies have demonstrated a significant correlation between serum Cyr61 levels and atherosclerosis. However, the relationship between Cyr61 levels and PAD in type 2 diabetic patients remains obscure.Methods:. A total of 306 subjects with type 2 diabetes were recruited. The extent of PAD was determined by using the Fontaine classification, which defines four stages. We analyzed Cyr61 serum levels by ELISA in patients with and without PAD at Fontaine’s stage II, III, or IV. Logistic regression models were used to examine the independent association of Cyr61 with PAD.Results: Out of the 306 patients enrolled in this study, 150 patients were free from PAD, while 156 had clinically significant PAD. In PAD patients, the prevalences of Fontaine classification stage II, III and IV were 48.7%, 32.1%, and 19.2%, respectively. Patients with more advanced PAD had significantly higher Cyr61 (P for trend <0.001). The prevalence of PAD on the basis of severity increased with ascending Cyr61 quartiles (all P for trend <0.001), and the severity of PAD was positively correlated with Cyr61 quartiles (r=0.227, P=0.006). The association of Cyr61 levels with PAD remained after adjusting for major risk factors in a logistic regression analysis.Conclusions: Our results demonstrated that Cyr61 was significantly increased in type 2 diabetic patients with PAD and that Cyr61 levels were positively associated with disease severity. It could be a promising biomarker and further studies are needed to assess its clinical utility.