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尿 N6-甲基腺苷水平降低与 2 型糖尿病中糖尿病肾病的发生密切相关。

Decreased Urine N6-methyladenosine level is closely associated with the presence of diabetic nephropathy in type 2 diabetes mellitus.

机构信息

Central Laboratory, The first affiliated hospital of Wannan Medical College, Wuhu, China.

Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes (Wannan Medical College), Wuhu, China.

出版信息

Front Endocrinol (Lausanne). 2022 Sep 27;13:986419. doi: 10.3389/fendo.2022.986419. eCollection 2022.

DOI:10.3389/fendo.2022.986419
PMID:36237191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9553099/
Abstract

BACKGROUND

To investigate the dynamic changes of urine N6-methyladenosine (m6A) levels in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) and evaluate the clinical significance.

METHODS

First, the levels of urine m6A were examined and compared among 62 patients with T2DM, 70 patients with DN, and 52 age- and gender-matched normal glucose tolerant subjects (NGT) by using a MethyIFIashTM Urine m6A Quantification Kit. Subsequently, we compared the concentrations of urine m6A between different stages of DN. Moreover, statistical analysis was performed to evaluate the association of urine m6A with DN.

RESULTS

The levels of m6A were significantly decreased in patients with DN [(16.10 ± 6.48) ng/ml], compared with NGT [(23.12 ± 7.52) ng/ml, < 0.0001] and patients with T2DM [(20.39 ± 7.16) ng/ml, < 0.0001]. Moreover, the concentrations of urine m6A were obviously reduced with the deterioration of DN. Pearson rank correlation and regression analyses revealed that m6A was significantly associated with DN ( < 0.05). The areas under the receiver operator characteristics curve (AUC) were 0.783 (95% CI, 0.699 - 0.867, < 0.0001) for the DN and NGT groups, and 0.737 (95% CI, 0.639 - 0.835, < 0.0001) for the macroalbuminuria and normoalbuminuria groups, and the optimal cutoff value for m6A to distinguish the DN from NGT and the macroalbuminuria from normoalbuminuria cases was 0.4687 (diagnostic sensitivity, 71%; diagnostic specificity, 76%) and 0.4494 (diagnostic sensitivity, 79%; diagnostic specificity, 66%), respectively.

CONCLUSIONS

The levels of urine m6A are significantly decreased in patients with DN and change with the deterioration of DN, which could serve as a prospective biomarker for the diagnosis of DN.

摘要

背景

探讨 2 型糖尿病(T2DM)及糖尿病肾病(DN)患者尿 N6-甲基腺苷(m6A)水平的动态变化,并评估其临床意义。

方法

首先,采用 MethyIFIashTM 尿 m6A 定量试剂盒检测 62 例 T2DM 患者、70 例 DN 患者和 52 例年龄和性别匹配的正常糖耐量受试者(NGT)的尿 m6A 水平,并比较不同 DN 分期患者的尿 m6A 浓度。此外,进行统计学分析以评估尿 m6A 与 DN 的相关性。

结果

与 NGT[(23.12±7.52)ng/ml, < 0.0001]和 T2DM[(20.39±7.16)ng/ml, < 0.0001]患者相比,DN 患者的 m6A 水平明显降低[(16.10±6.48)ng/ml, < 0.0001]。此外,随着 DN 的恶化,尿 m6A 浓度明显降低。Pearson 秩相关和回归分析显示,m6A 与 DN 显著相关( < 0.05)。DN 和 NGT 组受试者工作特征曲线(ROC)下面积(AUC)为 0.783(95%可信区间,0.699-0.867, < 0.0001),大量白蛋白尿和正常白蛋白尿组 AUC 为 0.737(95%可信区间,0.639-0.835, < 0.0001),m6A 区分 DN 与 NGT 以及大量白蛋白尿与正常白蛋白尿的最佳截断值分别为 0.4687(诊断敏感度,71%;诊断特异性,76%)和 0.4494(诊断敏感度,79%;诊断特异性,66%)。

结论

DN 患者的尿 m6A 水平明显降低,且随 DN 的恶化而变化,可作为诊断 DN 的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f120/9553099/f6844d825558/fendo-13-986419-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f120/9553099/491834748d0d/fendo-13-986419-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f120/9553099/550192e341a9/fendo-13-986419-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f120/9553099/f6844d825558/fendo-13-986419-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f120/9553099/491834748d0d/fendo-13-986419-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f120/9553099/550192e341a9/fendo-13-986419-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f120/9553099/f6844d825558/fendo-13-986419-g003.jpg

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