Abstract：
Immune cell-mediated chronic inflammation is one of the causes of type 2 diabetes mellitus (T2DM). Therefore, identifying inflammatory markers in circulating immune cells is highly important for predicting insulin resistance (IR) and the occurrence of T2DM. In this study, we discovered that differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) from T2DM patients were associated with innate immunity and chronic inflammatory responses through bulk transcriptome sequencing (bulk RNA-seq). Gene integration analysis revealed that nine DEGs were upregulated, and receiver operating characteristic (ROC) curve analysis revealed that V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), a candidate biomarker, has a certain predictive value for T2DM. In population-based cohort studies, we found that MAFB expression was significantly upregulated in the PBMCs of T2DM patients and was significantly correlated with homeostasis model assessment of IR (HOMA-IR), tumor necrosis factor-α (TNF-α), adiponectin (Adipoq), etc. We further evaluated the sensitivity and specificity of MAFB and other clinical parameters for predicting and diagnosing T2DM and found that MAFB expression in PBMCs had a positive effect on the prediction and diagnosis of T2DM. Finally, single-cell RNA sequencing (scRNA-seq) analysis revealed that the increase in MAFB expression was mainly in nonclassical monocytes. Our results suggest that increased MAFB expression in circulating monocytes may mediate chronic inflammatory status in patients with T2DM. Therefore, MAFB gene expression in circulating monocytes has certain clinical significance for predicting and assisting in the diagnosis of T2DM.
摘要：
免疫细胞介导的慢性炎症是2型糖尿病（T2DM）的病因之一。因此,确定循环免疫细胞中的炎症标志物对于预测胰岛素抵抗（IR）和T2DM的发生具有重要意义。在这项研究中,我们通过批量转录组测序(bulkRNA-seq)发现,T2DM患者外周血单个核细胞(PBMC)中的差异表达基因(DEGs)与先天免疫和慢性炎症反应相关.基因整合分析显示9个DEGs上调,和受试者工作特征（ROC）曲线分析显示，V-maf肌膜膜纤维肉瘤癌基因同源物B（MAFB），候选生物标志物,对T2DM有一定的预测价值。在基于人群的队列研究中，我们发现，在T2DM患者的PBMC中，MAFB表达显著上调，并且与IR的稳态模型评估（HOMA-IR）显著相关，肿瘤坏死因子-α(TNF-α),脂联素（Adipoq），等。我们进一步评估了MAFB和其他临床参数预测和诊断T2DM的敏感性和特异性，发现PBMC中MAFB的表达对T2DM的预测和诊断具有积极作用。最后,单细胞RNA测序（scRNA-seq）分析显示，MAFB表达的增加主要是在非经典单核细胞中。我们的结果表明，循环单核细胞中MAFB表达的增加可能介导T2DM患者的慢性炎症状态。因此,循环单核细胞MAFB基因的表达对预测和辅助诊断T2DM具有一定的临床意义。
