Association of Plasma DPP4 Activity With Mild Cognitive Impairment in Elderly Patients With Type 2 Diabetes: Results From the GDMD Study in China
Association of Plasma DPP4 Activity With Mild Cognitive Impairment in Elderly Patients With Type 2 Diabetes: Results From the GDMD Study in China
复制标题
血浆 DPP4 活性与老年 2 型糖尿病患者轻度认知障碍的关联：中国 GDMD 研究的结果。
DOI：
10.2337/dc16-0316
复制
发表时间：
2016-09-01
期刊：
影响因子：
16.2
通讯作者：
Li, Qinghua
中科院分区：
文献类型：
--
作者：
Zheng, Tianpeng;Qin, Linyuan;Li, Qinghua
目的：高血糖、炎症和氧化应激被认为与认知能力下降的发病机制有关。二肽基肽酶-4 （DPP4）是一种新发现的与这些危险因素相关的脂肪因子。因此，我们旨在研究老年2型糖尿病患者血浆DPP4活性与轻度认知功能障碍（MCI）之间的关系。研究设计和方法我们对中国1160例60岁及以上2型糖尿病患者的血浆DPP4活性、炎症标志物和氧化应激参数进行了评估。结果DPP4活性最高四分位数的患者与最低四分位数的患者相比，HbA（1c）、白细胞介素6 （IL-6）、CRP、硝基酪氨酸、8-iso-PGF2a得分较高，蒙特利尔认知评估（MoCA）得分较低（P < 0.001）。调整潜在混杂因素后，DPP4最高四分位数的MCI风险高于最低四分位数（优势比3.49;95% CI 1.97-4.57）。DPP4活性、IL-6、CRP、硝基酪氨酸和8-iso-PGF2a水平越高，MCI的风险越高（P < 0.05），但HbA（1c）水平越高，MCI的风险越高（P < 0.05）。结论老年2型糖尿病患者DPP4活性升高与MCI独立相关。其机制可能部分解释为DPP4对炎症和氧化应激的作用。这些观察结果进一步引起了人们对DPP4活性的兴趣，因为它对这些MCI相关危险因素的潜在影响是一种生物学标记物，甚至可能是MCI的治疗靶点。
OBJECTIVEHyperglycemia, inflammation, and oxidative stress are thought to be involved in the pathogenesis of cognitive decline. Dipeptidyl peptidase-4 (DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes.RESEARCH DESIGN AND METHODSWe evaluated plasma DPP4 activity, inflammatory markers, and oxidative stress parameters in a cross-sectional sample of 1,160 patients with type 2 diabetes aged 60 years or older in China. MCI was diagnosed based on criteria established by the National Institute on Aging-Alzheimer's Association workgroupsRESULTSPatients in the highest quartile of DPP4 activity had higher HbA(1c), interleukin 6 (IL-6), CRP, nitrotyrosine, 8-iso-PGF2a, and lower Montreal Cognitive Assessment (MoCA) scores compared with subjects in the lowest quartile (P < 0.001). In the highest DPP4 quartile, MCI risk was higher (odds ratio 3.49; 95% CI 1.97-4.57) than in the lowest quartile after adjustment for potential confounders. The risk for MCI increased more with higher levels of DPP4 activity, IL-6, CRP, nitrotyrosine, and 8-iso-PGF2a (P < 0.05), but not with higher levels of HbA(1c).CONCLUSIONSThis study shows that increased DPP4 activities are independently associated with MCI in elderly patients with type 2 diabetes. The mechanisms might be partly explained by the effect of DPP4 on inflammation and oxidative stress. These observations raise further interest in DPP4 activity for its potential effect on these MCI-related risk factors as a biological marker or even a possible therapeutic target for MCI.