基于代谢组学的苯乙酰谷氨酰胺作为伴有远端对称性多发性神经病的 2 型糖尿病的新型生物标志物。
Phenylacetylglutamine as a novel biomarker of type 2 diabetes with distal symmetric polyneuropathy by metabolomics.
机构信息
Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Department of Emergency, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
出版信息
J Endocrinol Invest. 2023 May;46(5):869-882. doi: 10.1007/s40618-022-01929-w. Epub 2022 Oct 25.
PURPOSE
Type 2 diabetes mellitus (T2DM) with distal symmetric polyneuropathy (DSPN) is a disease involving the nervous system caused by metabolic disorder, while the metabolic spectrum and key metabolites remain poorly defined.
METHODS
Plasma samples of 30 healthy controls, 30 T2DM patients, and 60 DSPN patients were subjected to nontargeted metabolomics. Potential biomarkers of DSPN were screened based on univariate and multivariate statistical analyses, ROC curve analysis, and logistic regression. Finally, another 22 patients with T2DM who developed DSPN after follow-up were selected for validation of the new biomarker based on target metabolomics.
RESULTS
Compared with the control group and the T2DM group, 6 metabolites showed differences in the DSPN group (P < 0.05; FDR < 0.1; VIP > 1) and a rising step trend was observed. Among them, phenylacetylglutamine (PAG) and sorbitol displayed an excellent discriminatory ability and associated with disease severity. The verification results demonstrated that when T2DM progressed to DSPN, the phenylacetylglutamine content increased significantly (P = 0.004).
CONCLUSION
The discovered and verified endogenous metabolite PAG may be a novel potential biomarker of DSPN and involved in the disease pathogenesis.
目的
2 型糖尿病伴远端对称性多发性神经病（DSPN）是一种由代谢紊乱引起的涉及神经系统的疾病，而代谢谱和关键代谢物仍未得到明确界定。
方法
对 30 名健康对照者、30 名 2 型糖尿病患者和 60 名 DSPN 患者的血浆样本进行非靶向代谢组学分析。基于单变量和多变量统计分析、ROC 曲线分析和逻辑回归筛选 DSPN 的潜在生物标志物。最后，对另外 22 例随访后发生 DSPN 的 2 型糖尿病患者进行靶向代谢组学验证新生物标志物。
结果
与对照组和 2 型糖尿病组相比，DSPN 组有 6 种代谢物存在差异（P<0.05；FDR<0.1；VIP>1），呈上升趋势。其中，苯乙酰谷氨酰胺（PAG）和山梨醇显示出良好的鉴别能力，并与疾病严重程度相关。验证结果表明，当 2 型糖尿病进展为 DSPN 时，苯乙酰谷氨酰胺含量显著增加（P=0.004）。
结论
所发现和验证的内源性代谢物 PAG 可能是 DSPN 的一种新的潜在生物标志物，参与疾病的发病机制。
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