Oxidative stress-mediated influence of plasma DPP4 activity to BDNF ratio on mild cognitive impairment in elderly type 2 diabetic patients: results from the GDMD study in China
Oxidative stress-mediated influence of plasma DPP4 activity to BDNF ratio on mild cognitive impairment in elderly type 2 diabetic patients: results from the GDMD study in China
复制标题
氧化应激介导的血浆DPP4活性与BDNF比值对老年2型糖尿病患者轻度认知障碍的影响：中国GDMD研究结果
DOI：
10.1016/j.metabol.2018.03.014
复制
发表时间：
2018-10-01
影响因子：
9.8
通讯作者：
Qin, Shenghua
中科院分区：
文献类型：
--
作者：
Zheng, Tianpeng;Liu, Hongbo;Qin, Shenghua
目的：外周循环中二肽基肽酶-4（DPP 4）活性增加和脑源性神经营养因子（BDNF）减少均与老年人轻度认知功能障碍（MCI）的高风险相关。因此，我们的目的是探讨血浆DPP 4活性与BDNF比值（DBR）和MCI在老年2型糖尿病患者之间的关联。设计和方法：我们测量血浆DPP 4活性，BDNF水平，氧化应激参数，炎症标志物和计算DBR在1833年老年2型糖尿病患者年龄在60岁或以上。MCI根据国家老年痴呆症协会工作组的标准进行诊断。结果：DPP 4活性与BDNF呈负相关（r =-0.408，P < 0.001），DPP 4活性与BDNF呈负相关（r =-0.408，P < 0.001）。氧化应激，特别是在男性参与者中，在DPP 4活性和BDNF之间的关系中充当了部分介导者。与最低四分位数的参与者相比，DBR最高四分位数的参与者具有较高的硝基酪氨酸，8-isoPGF 2a，白细胞介素-6，C-反应蛋白和较低的蒙特利尔认知评估评分。最高DBR四分位数中MCI的比值比（5.15，95% CI 3.64-7.30）显著高于最低四分位数。结论：氧化应激部分介导了DPP 4和BDNF之间的负相关关系。我们的数据为DBR和MCI之间的密切联系提供了证据，表明DBR是2型糖尿病患者MCI的新生物标志物。(C)2018由Elsevier Inc.出版
Objective: Increased dipeptidyl peptidase-4 (DPP4) activity and reduced brain-derived neurotrophic factor (BDNF) in peripheral circulation are both associated with a high risk of mild cognitive impairment (MCI) in the elderly. Hence, we aimed to investigate the association between plasma DPP4 activity to BDNF ratio (DBR) and MCI in elderly patients with type 2 diabetes.Design and Methods: We measured plasma DPP4 activity, BDNF levels, oxidative stress parameters, inflammatory markers and calculated DBR in 1833 elderly type 2 diabetic patients aged 60 years or older. MCI was diagnosed according to the National Institute on Aging-Alzheimer's Association workgroups criteria. Further, mediation analysis was performed to estimate the mediator role of oxidative stress on the relationship between DPP4 activity and BDNF.Results: DPP4 activity was negatively associated with BDNF (r = -0.408, P < 0.001). Oxidative stress, particularly in male participants, acted as a partial mediator in the relationship between DPP4 activity and BDNF. Participants in the highest quartile of DBR had higher nitrotyrosine, 8-isoPGF2a, interleukin-6, C-reactive protein and lower Montreal Cognitive Assessment score compared with those in the lowest quartile. The odds ratio (5.15, 95% CI 3.64-7.30) for MCI in the highest DBR quartile was significantly higher than in the lowest quartile. The risk for MCI increased with higher levels of DPP4 activity and lower levels of BDNF.Conclusions: Oxidative stress partially mediates the inverse relationship between DPP4 and BDNF. Our data provide evidence for a strong link between DBR and MCI, suggesting DBR to be a new biomarker for MCI in type 2 diabetic patients. (C) 2018 Published by Elsevier Inc.