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

Abstract

Background The prevalence of peripheral artery disease (PAD) is obviously increased in patients with diabetes. Existing evidence shows 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 and atherosclerosis. However, the relationship between Cyr61 levels and PAD in patients with type 2 diabetes (T2DM) remains obscure. Methods Data from a total of 306 subjects with T2DM were cross-sectionally analysed. The extent of PAD was determined by using the Fontaine classification, which defines four stages. We measured serum Cyr61 concentrations by ELISA in subjects 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 subjects enrolled, 150 were free from PAD, while 156 had clinically significant PAD. In subjects with PAD, the prevalences of Fontaine classification stages 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 increasing Cyr61 quartiles (all P values for trends < 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 PAD patients with T2DM and that Cyr61 levels were positively associated with disease severity. Cyr61 could be a promising biomarker and further studies are needed to assess its clinical utility.