髓过氧化物酶、超氧化物歧化酶-3、心脏代谢危险因素与远段感觉运动性多发性神经病：KORA F4/FF4 研究。

Myeloperoxidase, superoxide dismutase-3, cardiometabolic risk factors, and distal sensorimotor polyneuropathy: The KORA F4/FF4 study.

机构信息

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.

出版信息

Diabetes Metab Res Rev. 2018 Jul;34(5):e3000. doi: 10.1002/dmrr.3000. Epub 2018 Apr 6.

DOI:10.1002/dmrr.3000

PMID:29577557

Abstract

BACKGROUND

Oxidative stress has been proposed as important pathomechanism of cardiometabolic diseases and distal sensorimotor polyneuropathy (DSPN). However, the relevance of biomarkers of oxidative stress has not been investigated in this context. Therefore, this study aimed to assess the association of the prooxidant myeloperoxidase (MPO) and the antioxidant extracellular superoxide dismutase (SOD3) with cardiometabolic risk factors and with prevalence and incidence of DSPN.

METHODS

Cross-sectional analyses comprised 1069 participants (40.3% with prediabetes and 20.5% with type 2 diabetes) of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006-2008), 181 of whom had DSPN at baseline. Prospective analyses included 524 individuals without DSPN at baseline who also participated in the KORA FF4 study (2013-2014), 132 of whom developed DSPN during the 6.5-year follow-up. Serum MPO and SOD3 were measured by ELISA, and their association with cardiometabolic risk factors and DSPN were estimated by using linear and logistic regression analyses.

RESULTS

Higher MPO and SOD levels showed multiple positive associations with cardiometabolic risk factors including age, indices of obesity, insulin resistance, serum lipids, renal dysfunction, and biomarkers of inflammation. Higher MPO levels were associated with prevalent DSPN (fully adjusted OR 1.38 [95% CI 1.10; 1.72] per doubling of MPO). Higher baseline SOD3 levels were related to incident DSPN (age and sex-adjusted OR 2.14 [1.02; 4.48] per doubling of SOD3), which was partially explained by cardiometabolic risk factors.

CONCLUSIONS

Systemic levels of both pro- and antioxidant enzymes appear involved in cardiometabolic risk and development of DSPN.

摘要

背景

氧化应激被认为是心脏代谢疾病和远端感觉运动多发性神经病（DSPN）的重要发病机制。然而，氧化应激生物标志物在这方面的相关性尚未得到研究。因此，本研究旨在评估促氧化剂髓过氧化物酶（MPO）和抗氧化剂细胞外超氧化物歧化酶（SOD3）与心脏代谢危险因素以及 DSPN 的患病率和发病率的相关性。

方法

横断面分析包括基于人群的奥格斯堡合作健康研究（KORA）F4 研究（2006-2008 年）的 1069 名参与者（40.3%患有前驱糖尿病，20.5%患有 2 型糖尿病），其中 181 名参与者在基线时患有 DSPN。前瞻性分析包括在基线时没有 DSPN 的 524 名参与者，他们也参加了 KORA FF4 研究（2013-2014 年），其中 132 名参与者在 6.5 年的随访期间发展为 DSPN。通过 ELISA 测量血清 MPO 和 SOD3，并用线性和逻辑回归分析估计它们与心脏代谢危险因素和 DSPN 的关系。

结果

较高的 MPO 和 SOD 水平与心脏代谢危险因素呈多种正相关，包括年龄、肥胖指数、胰岛素抵抗、血脂、肾功能障碍和炎症生物标志物。较高的 MPO 水平与普遍存在的 DSPN 相关（MPO 每加倍的完全调整后的 OR 为 1.38[95%CI 1.10;1.72]）。较高的基线 SOD3 水平与 DSPN 的发病相关（年龄和性别调整后的 OR 为 2.14[1.02;4.48]，每加倍 SOD3），这部分被心脏代谢危险因素所解释。