Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Diabetes Care. 2017 Apr;40(4):569-576. doi: 10.2337/dc16-2259. Epub 2017 Feb 7.
Experimental and epidemiological studies have implicated inflammatory processes in the pathogenesis of distal sensorimotor polyneuropathy (DSPN), but prospective studies are lacking. We hypothesized that biomarkers of inflammation predict the development and progression of DSPN in a population-based cohort.
This study was based on participants aged 62-81 years from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort, with a mean follow-up of 6.5 years. The predictive value of systemic levels of eight biomarkers of inflammation was assessed for incident DSPN in 133 incident case subjects and 397 individuals without incident DSPN, and for DSPN progression in 57 patients with prevalent DSPN at both time points.
Higher hs-CRP, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (IL-1RA), and soluble intercellular adhesion molecule (sICAM-1) and lower adiponectin levels were associated with incident DSPN in age- and sex-adjusted analysis; IL-18 and omentin were not. IL-6 (odds ratio 1.31 [95% CI 1.00-1.71]) and TNF-α (odds ratio 1.31 [95% CI 1.03-1.67]) remained associated with incident DSPN after adjusting for known DSPN risk factors. The addition of both cytokines to a clinical risk model improved model fit and reclassification. sICAM-1 and IL-1RA were positively associated with progression of DSPN.
Systemic subclinical and vascular inflammation predicted both the onset and progression of DSPN over 6.5 years in an older general population. Thus modulation of inflammatory processes may be relevant to prevent and/or treat diabetic neuropathy.
实验和流行病学研究表明，炎症过程与远端感觉运动性多发性神经病（DSPN）的发病机制有关，但缺乏前瞻性研究。我们假设炎症生物标志物可预测基于人群的队列中 DSPN 的发生和进展。
本研究基于年龄在 62-81 岁的 Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 队列参与者，平均随访时间为 6.5 年。在 133 例新发病例患者和 397 例无新发病例的个体中，评估了 8 种炎症系统标志物的水平对 DSPN 发生的预测价值，在这两个时间点上，还评估了 57 例患有常见 DSPN 的患者对 DSPN 进展的预测价值。
hs-CRP、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α、IL-1 受体拮抗剂（IL-1RA）、可溶性细胞间黏附分子（sICAM-1）水平升高和脂联素水平降低与年龄和性别调整后的 DSPN 发生相关；IL-18 和网膜素则没有。在调整已知的 DSPN 风险因素后，IL-6（优势比 1.31 [95%CI 1.00-1.71]）和 TNF-α（优势比 1.31 [95%CI 1.03-1.67]）仍与 DSPN 的发生相关。将这两种细胞因子加入临床风险模型可改善模型拟合和重新分类。sICAM-1 和 IL-1RA 与 DSPN 的进展呈正相关。
全身性亚临床和血管炎症预测了老年人群中 6.5 年内 DSPN 的发生和进展。因此，炎症过程的调节可能与预防和/或治疗糖尿病性神经病有关。
