Zheng Hangping, Sun Wanwan, Zhang Qi, Zhang Yuanpin, Ji Lijin, Liu Xiaoxia, Zhu Xiaoming, Ye Hongying, Xiong Qian, Li Yiming, Lu Bin, Zhang Shuo
Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai 200040, China.
Department of Endocrinology, Shanghai Gonghui Hospital, Shanghai 200041, China.
EClinicalMedicine. 2020 Dec 23;31:100649. doi: 10.1016/j.eclinm.2020.100649. eCollection 2021 Jan.
Inflammation has been implicated in the pathogenesis of diabetic peripheral neuropathy (DPN) as suggested in various cross-sectional studies. However, more convincing prospective studies in diabetes patients are scarce. Therefore, we aimed to evaluate whether proinflammatory cytokines could predict the incidence of DPN through a prospective study with a five-year follow-up.
We followed up 315 patients with diabetes who did not have DPN, recruited from five community health centers in Shanghai in 2014, for an average of 5.06 years. Based on the integrity of blood samples, 106 patients were selected to obtain the proinflammatory cytokines. Plasma markers of proinflammatory cytokines at baseline included interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1). Neuropathy was assessed by MSNI at baseline and during follow-up.
Among the 106 chosen patients, 63 developed DPN after 5.06±1.14 years of follow-up. The baseline plasma levels of TNF-α, IL-6, and ICAM-1 were higher in the neuropathic group (p<0.05). In multivariate models, increased plasma levels of TNF-α (hazard ratio, HR: 8.74 [95% confidence interval, CI: 1.05-72.68]; <0.05) and ICAM-1 (HR 23.74 [95% CI:1.47-383.81]; <0.05) were both associated with incident DPN, after adjusting for known DPN risk factors.
Increased plasma levels of proinflammatory factors, especially TNF-α and ICAM-1, predicted the incidence of DPN over 5 years in Chinese diabetes patients, but larger longitudinal studies are required for confirmation.
National Natural Science Foundation of China, Shanghai Talent Development Fund Program, Shanghai Shenkang Hospital Developing Center Clinical Scientific and Technological Innovation Program, Shanghai Science and Technology Committee Program, Shanghai General Hospital Program of Chinese traditional and Western medicine combination and Shanghai Municipal Commission of Health and Family Planning Clinical Research Project.
正如各项横断面研究所示，炎症与糖尿病周围神经病变（DPN）的发病机制有关。然而，针对糖尿病患者的更具说服力的前瞻性研究却很匮乏。因此，我们旨在通过一项为期五年随访的前瞻性研究，评估促炎细胞因子是否能够预测DPN的发病率。
我们对2014年从上海五个社区卫生中心招募的315例无DPN的糖尿病患者进行了平均5.06年的随访。基于血样的完整性，选择106例患者获取促炎细胞因子。基线时促炎细胞因子的血浆标志物包括白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、血管内皮生长因子（VEGF）和细胞间黏附分子1（ICAM-1）。在基线和随访期间通过MSNI评估神经病变。
在106例入选患者中，63例在5.06±1.14年的随访后发生了DPN。神经病变组的TNF-α、IL-6和ICAM-1基线血浆水平较高（p<0.05）。在多变量模型中，在调整已知的DPN危险因素后，TNF-α血浆水平升高（风险比，HR：8.74 [95%置信区间，CI：1.05 - 72.68]；<0.05）和ICAM-1（HR 23.74 [95% CI：1.47 - 383.81]；<0.05）均与新发DPN相关。
促炎因子血浆水平升高，尤其是TNF-α和ICAM-1，可预测中国糖尿病患者5年内DPN的发病率，但需要更大规模的纵向研究来证实。
中国国家自然科学基金、上海人才发展基金项目、上海申康医院发展中心临床科技创新项目、上海市科委项目、上海交通大学医学院附属瑞金医院中西医结合项目以及上海市卫生和计划生育委员会临床研究项目。
