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白细胞介素-5:2型糖尿病患者轻度认知障碍的一个指标——从生物信息学分析到临床研究的全面调查

Interleukin-5: an indicator of mild cognitive impairment in patients with type 2 diabetes mellitus - a comprehensive investigation ranging from bioinformatics analysis to clinical research.

作者信息

Zhang Hui, Zhu Wenwen, Yang Shufang, Niu Tong, Fareeduddin Mohammed Farooqui Huzaifa, Song Bing, Wang Hongxiao, Li Sumei, Wang Jumei, Xu Linlin, Zhang Zhen, Zhang Haoqiang

机构信息

Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, College of Clinical Medicine of Henan, University of Science and Technology, Luoyang, China.

Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.

出版信息

J Endocrinol Invest. 2025 Feb;48(2):401-417. doi: 10.1007/s40618-024-02430-2. Epub 2024 Sep 30.

Abstract

PURPOSE

Neuroinflammation constitutes an underlying mechanism for cognitive impairment. Here, we endeavor to scrutinize the potential contribution of interleukin-5 (IL-5) towards mild cognitive impairment (MCI), and to assess its diagnostic value for MCI in patients with type 2 diabetes mellitus (T2DM).

METHODS

RNA-seq was used to explore the potential neuroinflammation factors in the hippocampus of diabetic mice with cognitive decline. Additionally, the promising risk factor was verified in animals. Finally, the association between IL-5 levels and cognitive function and its diagnostic value for MCI were assessed.

RESULTS

In animals, up-regulated IL-5 mRNA and protein levels were detected by RNA-seq and (or) verified experiments in the hippocampus of diabetic db/db mice with cognitive decline, compared to those of db/m mice without diabetes. In human, compared to diabetic patients without MCI, those with MCI demonstrate elevated levels of IL-5. It is natively associated with Montreal Cognitive Assessment (MoCA) scores, reflecting global cognitive function, and positively correlated with Trail Making Test A (TMTA) scores, reflecting information processing speed. Furthermore, an elevated level of IL-5 is identified as a risk factor for MCI, and a factor that influences TMTA scores. Finally, it is recommended that the cut-off value for IL-5 in the diagnosis of MCI is 22.98 pg/mL, with a sensitivity of 68.6% and specificity of 72.9%.

CONCLUSIONS

IL-5 is considered a risk factor for MCI in T2DM patients and is associated with their performance in information processing speed. Moreover, an elevated level of IL-5 is a plausible biomarker for MCI in T2DM patients.

摘要

目的

神经炎症是认知障碍的潜在机制。在此,我们试图仔细研究白细胞介素-5(IL-5)对轻度认知障碍(MCI)的潜在影响,并评估其对2型糖尿病(T2DM)患者MCI的诊断价值。

方法

采用RNA测序技术探索认知功能下降的糖尿病小鼠海马中潜在的神经炎症因子。此外,在动物模型中验证了这一有前景的风险因素。最后,评估IL-5水平与认知功能之间的关联及其对MCI的诊断价值。

结果

在动物实验中,与无糖尿病的db/m小鼠相比,通过RNA测序和(或)验证实验检测到认知功能下降的糖尿病db/db小鼠海马中IL-5 mRNA和蛋白水平上调。在人类中,与无MCI的糖尿病患者相比,患有MCI的患者IL-5水平升高。它与反映整体认知功能的蒙特利尔认知评估(MoCA)评分天然相关,并与反映信息处理速度的连线测验A(TMTA)评分呈正相关。此外,IL-5水平升高被确定为MCI的一个风险因素,以及一个影响TMTA评分的因素。最后,建议将IL-5用于诊断MCI的临界值设定为22.98 pg/mL,灵敏度为68.6%,特异性为72.9%。

结论

IL-5被认为是T2DM患者发生MCI的一个风险因素,并且与其在信息处理速度方面的表现相关。此外,IL-5水平升高是T2DM患者发生MCI的一个合理生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c144/11785607/389202aef8e8/40618_2024_2430_Fig1_HTML.jpg

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