【摘要】 目的：通过检测2型糖尿病（Type 2 Diabetes Mellitus,T2DM）患者外周血中hsa＿circ＿0104358、hsa＿circ＿0117890、hsa＿circ＿0008139的表达水平，分析比较其与各临床指标的相关性，从而初步探讨hsa＿circ＿0104358、hsa＿circ＿0117890、hsa＿circ＿0008139与T2DM可能存在的关系。方法：选取2023年3月—2023年9月就诊于石河子大学第一附属医院内分泌代谢科的T2DM患者71例及体检科的健康体检者54例，收集一般资料及临床指标，应用RT-q PCR检测2组候选circ RNA的表达水平；采用Spearman相关分析探讨候选circ RNA与各临床指标的关系；ROC曲线评估候选circ RNA在T2DM中的诊断价值；Logistic回归模型分析T2DM的影响因素；生物信息学分析预测候选circ RNAs的靶mi RNAs和可能参与的信号通路。结果：hsa＿circ＿0104358在T2DM组中相对表达水平低于NC组（P<0.05）,hsa＿circ＿0117890、hsa＿circ＿0008139相对表达水平在NC组与T2DM组间差异无统计学意义（P>0.05）;hsa＿circ＿0104358表达水平与BMI、FPG、2H-PG、Hb A1C、FLNS、TG、HOMA-IR呈负相关，与HDL-C呈正相关（P<0.05）;hsa＿circ＿0104358诊断T2DM的AUC为0.824(95%CI:0.651～0.868,P<0.001，灵敏度=78.9%，特异度=77.8%),hsa＿circ＿0104358+危险因素诊断T2DM的AUC为0.928(95%CI:0.849～0.985,P<0.001，灵敏度=76.1%，特异度=94.4%)；多元线性回归显示hsa＿circ＿0104358水平降低可增加胰岛素抵抗性；多元Logistic回归显示hsa＿circ＿0104358水平降低可增加糖尿病患病风险；生物信息学分析结果显示，与hsa＿circ＿0104358相结合的5个mi RNA为hsa-mi R-139-3p、hsa-mi R-578、hsa-mi R-622、hsa-mi R-1827、hsa-mi R-584;GO功能分析发现hsa＿circ＿0104358可能参与GTP酶介导的信号转导或调节基因转录等生物过程；KEGG通路分析显示hsa＿circ＿0104358可能参与了MAPK信号通路。结论：hsa＿circ＿0104358在T2DM患者外周血中表达水平显著降低，与糖脂代谢密切相关，对T2DM具有较高的诊断价值，可作为T2DM诊断潜在的生物标志物。更多还原

【Abstract】 Objective: To investigate the possible relationship between hsa＿circ＿104358, hsa＿circ＿1117890, and hsa＿circ＿0008139 in peripheral blood of T2DM patients by detecting their expression levels and analyzing their correlation with various clinical indicators. Methods: 71 T2DM patients who visited the endocrine metabolism department of the First Affiliated Hospital of Shihezi University from March 2023 to September 2023 and 54 healthy individuals who underwent physical examinations were selected. General information and clinical indicators were collected, and the expression levels of candidate circ RNAs in both groups were detected using RT-q PCR. Using Spearman correlation analysis to explore the relationship between candidate circ RNAs and various clinical indicators. ROC curve evaluation of candidate circ RNAs for diagnostic value in T2DM. Logistic regression model is used to analyze the influencing factors of T2DM.Bioinformatics analysis predicts the target mi RNAs and potential signaling pathways involved in candidate circ RNAs.Results: The relative expression level of hsa＿circ＿0104358 in the T2DM group was lower than that in the NC group(P<0.05). There was no statistically significant difference in the relative expression levels of hsa＿circ＿0117890 and hsa＿circ＿0008139 between the NC group and T2DM group(P>0.05). The expression level of hsa＿circ＿0104358 is negatively correlated with BMI, FPG, 2H-PG, Hb A1C, FLNS, TG, HOMA-IR, and positively correlated with HDL-C(P<0.05); The AUC for diagnosing T2DM with hsa＿circ:0104358 was 0.824(95% CI: 0.651～0.868,P<0.001,sensitivity=78.9%, specificity=77.8%), while the AUC for diagnosing T2DM with hsa＿circ:0104358+ risk factors was 0.928(95%CI:0.849～0.985,P<0.001, sensitivity=76.1%, specificity=94.4%). Multiple linear regression showed that a decrease in the level of hsa＿circ＿0104358 can increase insulin resistance. Multivariate logistic regression showed that the lower level of hsa＿circ＿0104358 could increase the risk of diabetes. The bioinformatics analysis results showed that the five mi RNAs bound to hsa＿circ＿0104358 were hsa-mi R-139-3p, hsa-mi R-578, hsa-mi R-622,hsa-mi R-1827, and hsa-mi R-584. GO functional analysis revealed that hsa＿circ＿0104358 may be involved in biological processes such as GTP enzyme mediated signal transduction or regulation of gene transcription;KEGG pathway analysis shows that hsa＿circ＿0104358 may be involved in the MAPK signaling pathway.Conclusion: The expression level of hsa＿circ＿0104358 in peripheral blood of T2DM patients is significantly reduced, closely related to glucose and lipid metabolism, and has high diagnostic value for T2DM. It can be used as a potential biomarker for T2DM diagnosis.更多还原