Exosomal miR-let-7c-5p is involved in the cognitive function of type 2 diabetes mellitus patients by interleukin 10: A cross-sectional study

J Diabetes. 2023 Nov;15(11):978-986. doi: 10.1111/1753-0407.13450. Epub 2023 Aug 2.

Abstract

Background: Interleukin (IL)-10 plays a notable role in the inflammatory-associated mild cognitive impairment (MCI). We aimed to investigate whether IL-10 and its upstream factors exert an impact on MCI in type 2 diabetes mellitus (T2DM) patients.

Methods: A total of 117 T2DM patients were recruited and divided into Control group and MCI group based on the presence or absence of MCI. Clinical parameters were collected. The Montreal Cognitive Assessment (MoCA) was conducted for global cognitive function. Digit Span Test (DST), Verbal Fluency Test (VFT), and Trail Making Test-B (TMTB) were used to evaluate the executive functions of the diabetic patients. Trail Making Test-A (TMTA) was performed to examine the information processing speed function. Patients' scene memory was examined by Logical Memory Test (LMT). After the baseline data were compared, correlation and regression analyses were performed to explore the relationship among IL-10, miR-let-7c-5p and cognitive function.

Results: Compared to 80 patients in the control group, 37 patients in the MCI group exhibited lower IL-10 in plasma and higher miR-let-7c-5p levels in exosomes from plasma. The IL-10 level was negatively associated with MoCA. Likewise, miR-let-7c-5p levels were negatively correlated with IL-10 levels and MoCA. Elevated miR-let-7c-5p levels and decreased IL-10 levels are risk factors for MCI in T2DM patients. Increased miR-let-7c-5p and downregulated IL-10 may influence VFT and TMTB, respectively, associated with executive function.

Conclusions: We demonstrated that IL-10 is correlated to the executive function of T2DM patients. Decreased IL-10 may result from the regulation of miR-let-7c-5p in exosomes.

目的:白细胞介素(IL)-10在与炎症相关的轻度认知障碍(MCI)中起着显著作用。我们旨在研究IL-10及其上游因素是否对2型糖尿病(T2DM)患者的MCI产生影响。 方法:共招募117名T2DM患者, 根据是否存在MCI将其分为对照组和MCI组。收集临床参数。进行蒙特利尔认知评估(MoCA)以评估整体认知功能。使用数字跨度测试(DST)、言语流畅性测试(VFT)和连线测验B(TMTB)评估糖尿病患者的执行功能。进行连线测验A(TMTA)以检查信息处理速度功能。通过逻辑记忆测试(LMT)检查患者的场景记忆。比较基线数据后, 进行相关性和回归分析, 探讨IL-10(miR-let-7c-5p)与认知功能之间的关系。 结果:与80名对照组患者相比, 37名MCI组患者表现出较低的血浆IL-10水平和较高的血浆外泌体中miR-let-7c-5p水平。IL-10水平与MoCA呈负相关。同样, miR-let-7c-5p水平与IL-10水平和MoCA呈负相关。升高的miR-let-7c-5p水平和降低的IL-10水平是T2DM患者MCI的危险因素。增加的miR-let-7c-5p和下调的IL-10可能分别影响与执行功能相关的VFT和TMTB。 结论:我们表明IL-10与T2DM患者执行功能相关。降低的IL-10可能是由于外泌体中miR-let-7c-5p的调控所致。.

Keywords: 2型糖尿病; exosome; interleukin 10; miR-let-7c-5p; mild cognitve impairment; type 2 diabetes mellitus; 外泌体; 炎症; 白细胞介素10.

MeSH terms

  • Cognition*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / psychology
  • Humans
  • Interleukin-10
  • MicroRNAs* / genetics

Substances

  • Interleukin-10
  • MicroRNAs