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微小RNA-375:它可能是1型糖尿病患者及其兄弟姐妹代谢变化和炎症的一种通用生物标志物。

MiR-375: it could be a general biomarker of metabolic changes and inflammation in type 1 diabetes patients and their siblings.

作者信息

Mostafa Eman A, Ismail Nagwa Abdallah, El Din Abd El Baky Abeer M Nour, ElShaer Tarek F, Ashmawy Ingy, Wahby Aliaa Ahmed, Wahed Mai Magdy Abdel, Hamdy Abd El Aziz Shereen

机构信息

National Research Center, Department of Pediatrics, El Buhouth St., P. O. 12622, Dokki, Cairo, Egypt.

National Research Center, Department of Clinical and Chemical Pathology, Cairo, Egypt.

出版信息

J Endocrinol Invest. 2025 Mar;48(3):757-764. doi: 10.1007/s40618-024-02474-4. Epub 2024 Oct 25.

Abstract

PURPOSE

Type 1 diabetes (T1D) is a chronic autoimmune illness that results in loss of pancreatic beta cells and insulin insufficiency. MicroRNAs (miRNAs) are linked to immune system functions contributing to the pathophysiology of T1D, miRNA-375 is significantly expressed in the human pancreas and its circulatory levels might correspond to beta cell alterations. Pancreatic islet cell antibodies (ICA) and Glutamic acid decarboxylase antibodies (GADA) have roles in autoimmune pathogenesis and are predictive markers of T1D. The aim of this work was to detect serum level changes of miRNA-375, ICA, and GADA in T1D patients, and their siblings compared to healthy controls and correlate them with T1D biochemical parameters.

METHODS

The study included 66 T1D patients (32 males and 34 females; age range 3-18 years), 22 patients' siblings (13 males and 9 females; age range 4-17 years), and 23 healthy controls (7 males and 16 females; age range 4-17 years). MiRNA-375 levels were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR), while ICA and GADA levels were measured using enzyme-linked immunosorbent assay (ELISA). Data analysis was done utilizing SPSS-17 software.

RESULTS

MiR-375 levels were downregulated in T1D patients and further decreased in their siblings when compared to healthy controls. Furthermore, miR-375 exhibited inverse correlations with HbA1c levels but no correlations with Total Insulin Dose, disease duration, or autoantibodies (GADA & ICA).

CONCLUSION

Our study indicates that miR-375 is significantly downregulated in children with T1D and their siblings, suggesting its potential role as a biomarker for beta-cell function and glycemic control.

摘要

目的

1型糖尿病(T1D)是一种慢性自身免疫性疾病,会导致胰腺β细胞丧失和胰岛素分泌不足。微小RNA(miRNA)与免疫系统功能相关,参与T1D的病理生理过程,miRNA - 375在人类胰腺中显著表达,其循环水平可能与β细胞改变相对应。胰岛细胞抗体(ICA)和谷氨酸脱羧酶抗体(GADA)在自身免疫发病机制中起作用,是T1D的预测标志物。本研究的目的是检测T1D患者及其兄弟姐妹血清中miRNA - 375、ICA和GADA水平的变化,并将它们与T1D生化参数相关联,同时与健康对照进行比较。

方法

该研究纳入了66例T1D患者(32例男性和34例女性;年龄范围3 - 18岁)、22例患者的兄弟姐妹(13例男性和9例女性;年龄范围4 - 17岁)以及23名健康对照(7例男性和16例女性;年龄范围4 - 17岁)。使用定量逆转录聚合酶链反应(RT - qPCR)测量miRNA - 375水平,而使用酶联免疫吸附测定(ELISA)测量ICA和GADA水平。利用SPSS - 17软件进行数据分析。

结果

与健康对照相比,T1D患者的MiR - 375水平下调,其兄弟姐妹中的MiR - 375水平进一步降低。此外,miR - 375与糖化血红蛋白(HbA1c)水平呈负相关,但与总胰岛素剂量、病程或自身抗体(GADA和ICA)无相关性。

结论

我们的研究表明,miR - 375在T1D儿童及其兄弟姐妹中显著下调,提示其作为β细胞功能和血糖控制生物标志物的潜在作用。

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