Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Sci Rep. 2017 Sep 12;7(1):11272. doi: 10.1038/s41598-017-11820-x.
Critical Limb Ischemia (CLI) is common but uncommonly diagnosed. Improved recognition and early diagnostic markers for CLI are needed. Therefore, the aim of our study was to identify plasma biomarkers of CLI in patients with type 2 diabetes mellitus (T2DM). In this study, antibody-coated glass slide arrays were used to determine the plasma levels of 274 human cytokines in four matched cases of diabetes with and without CLI. Potential biomarkers were confirmed in an independent cohort by ELISA. After adjusting for confounding risk factors, only plasma level of Siglec-5 remained significantly associated with an increased odds ratio (OR) for diabetes with CLI by binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off points for Siglec-5 was 153.1 ng/ml. After entering Siglec-5, the AUC was 0.99, which was higher than that of confounding risk factors only (AUC = 0.97, P < 0.05). Siglec-5 was expressed in plaques, but not in healthy artery wall in T2DM patients. Elevated plasma Siglec-5 was independently associated with CLI in T2DM. Plasma Siglec-5 levels are implicated as an early diagnostic marker of CLI in T2DM patients and it may become a target for the prevention or treatment of CLI in diabetes.
严重肢体缺血(CLI)较为常见但诊断率低。需要提高对 CLI 的认识并寻找早期诊断标志物。因此,我们的研究目的是确定 2 型糖尿病(T2DM)患者 CLI 的血浆生物标志物。在本研究中,采用抗体包被的玻片阵列来检测四对匹配的糖尿病合并和不合并 CLI 患者的 274 个人类细胞因子的血浆水平。采用 ELISA 在独立队列中验证潜在的生物标志物。在调整混杂危险因素后,二项逻辑回归分析仅发现 Siglec-5 的血浆水平与糖尿病合并 CLI 的比值比(OR)显著相关。受试者工作特征(ROC)曲线分析显示 Siglec-5 的最佳截断值为 153.1ng/ml。在纳入 Siglec-5 后,AUC 为 0.99,高于仅纳入混杂危险因素时的 AUC(AUC=0.97,P<0.05)。Siglec-5 在斑块中表达,但在 T2DM 患者的健康动脉壁中不表达。血浆 Siglec-5 升高与 T2DM 患者的 CLI 独立相关。血浆 Siglec-5 水平可能是 T2DM 患者 CLI 的早期诊断标志物,有望成为糖尿病 CLI 预防或治疗的靶点。