Ghosh Shatabdi, Mukhopadhyay Pradip, Banerjee Mainak, Ghosh Debakreeta, Bhattacharya Tuhin, Chatterjee Raghunath, Ghosh Sujoy, Dey Sanjit
Department of Physiology, University of Calcutta, Kolkata, West Bengal, India.
Department of Endocrinology, Institute of Post Graduate Medical Education and Research, Kolkata, India.
Endocrine. 2025 Jun 7. doi: 10.1007/s12020-025-04285-w.
BACKGROUND: Unattended diabetic neuropathy (DN) significantly contributes to lower limb amputations and diminished quality of life, making diabetes mellitus (DM) management a global public health concern. Altered expression levels of long noncoding RNA (lncRNA) may play a pivotal role in neuropathy in diabetic conditions potentially linking hyperglycaemia-induced inflammation and oxidative stress. The current study investigated whether the expression levels of long non-coding RNAs (lncRNAs) can serve as potential biomarkers for the early identification of subclinical diabetic neuropathy (DN) in type 1 diabetes (T1DM) patients. METHODS: Cellular, physiological, and systemic parameters alongside differential lncRNA expression in the blood of T1DM patients with and without subclinical neuropathy, confirmed via Quantitative Sensory Testing (QST) and In Vivo Corneal Confocal Microscopy (IVCCM) compared to age-matched healthy siblings were analysed from a government hospital. Healthy siblings (n = 20) served as controls with no diabetes or neuropathy. Diabetes participants were categorised into groups with neuropathy T1DN (n = 21) and without neuropathy T1DM (n = 22). LncRNA expression from peripheral blood mononuclear cells (PBMCs) was determined by Quantitative Real-Time PCR (qRT-PCR). Intracellular and mitochondrial reactive oxygen species (ROS), inflammatory protein markers, and endogenous oxidative stress parameters were evaluated from PBMCs and serum. Statistical analyses were performed using SPSS statistics version 20 and GraphPad Prism version 8.0.1. RESULTS: Significant upregulation of lncRNAs XIST, NEAT1, MALAT1, and DLX6AS, along with distinct expression profiles of PVT1, TUG1, IGF2AS, and MEG3, were observed between T1DM and T1DN groups. Notably, MALAT1, NEAT1, XIST, and DLX6AS exhibited marked upregulation (p < 0.001), while MEG3 was significantly downregulated (p < 0.001), with high specificity demonstrated by Receiver Operating Characteristics (ROC) curve analysis. Diabetic neuropathy (DN) patients exhibited significant levels of elevated intracellular and mitochondrial ROS. The inflammatory milieu was also noted to be significantly perturbed. CONCLUSION: LncRNAs are novel and more reliable genomic imprints, as per expensive IVCCM, used to study the functional and structural changes in small nerve fibres. The identified lncRNA expression patterns may serve as predictive markers for early detection and monitoring of the risk of diabetic neuropathy in DM.
背景:无症状性糖尿病神经病变(DN)是导致下肢截肢和生活质量下降的重要原因,这使得糖尿病(DM)的管理成为一个全球公共卫生问题。长链非编码RNA(lncRNA)表达水平的改变可能在糖尿病性神经病变中起关键作用,可能与高血糖诱导的炎症和氧化应激有关。本研究调查了长链非编码RNA(lncRNAs)的表达水平是否可作为1型糖尿病(T1DM)患者亚临床糖尿病神经病变(DN)早期识别的潜在生物标志物。 方法:从一家政府医院分析了1型糖尿病患者(无论有无亚临床神经病变,通过定量感觉测试(QST)和体内角膜共聚焦显微镜检查(IVCCM)确诊)与年龄匹配的健康同胞相比的细胞、生理和全身参数以及血液中lncRNA的差异表达。健康同胞(n = 20)作为无糖尿病或神经病变的对照。糖尿病参与者被分为有神经病变的T1DN组(n = 21)和无神经病变的T1DM组(n = 22)。通过定量实时聚合酶链反应(qRT-PCR)测定外周血单核细胞(PBMCs)中的lncRNA表达。评估PBMCs和血清中的细胞内和线粒体活性氧(ROS)、炎症蛋白标志物和内源性氧化应激参数。使用SPSS统计软件20版和GraphPad Prism 8.0.1版进行统计分析。 结果:在T1DM组和T1DN组之间观察到lncRNAs XIST、NEAT1、MALAT1和DLX6AS的显著上调,以及PVT1、TUG1、IGF2AS和MEG3的不同表达谱。值得注意的是,MALAT1、NEAT1、XIST和DLX6AS表现出明显上调(p < 0.001),而MEG3显著下调(p < 0.001),通过受试者工作特征(ROC)曲线分析显示出高特异性。糖尿病神经病变(DN)患者的细胞内和线粒体ROS水平显著升高。炎症环境也被注意到受到显著干扰。 结论:根据昂贵的IVCCM,lncRNAs是用于研究小神经纤维功能和结构变化的新型且更可靠的基因组印记。所确定的lncRNA表达模式可作为糖尿病患者糖尿病神经病变风险早期检测和监测的预测标志物。
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