中国2型糖尿病患者周围神经病变的候选代谢物标志物
Candidate metabolite markers of peripheral neuropathy in Chinese patients with type 2 diabetes.
作者信息
Shao Ming-Mei, Xiang Hong-Jiao, Lu Hao, Yin Pei-Hao, Li Guo-Wen, Wang Yun-Man, Chen Lin, Chen Qing-Guang, Zhao Cheng, Lu Qun, Wu Tao, Ji Guang
机构信息
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine Shanghai 201203, China.
Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200032, China.
出版信息
Am J Transl Res. 2022 Aug 15;14(8):5420-5440. eCollection 2022.
OBJECTIVES
To analyze the serum and urine metabolites present in type 2 diabetes mellitus (T2DM) patients and T2DM patients with diabetic peripheral neuropathy (DPN) and to select differentially expressed biomarkers for early diagnosis of DPN.
METHODS
Serum and urine metabolites from 74 T2DM patients with peripheral neuropathy and 41 without peripheral neuropathy were analyzed using gas chromatograph system with time-of-flight mass spectrometer metabolomics to detect biomarkers of peripheral neuropathy in T2DM.
RESULTS
There were increased serum triglycerides, alanine aminotransferase, and decreased C-peptide, and total cholesterol levels in T2DM patients with DPN compared to those without peripheral neuropathy. Metabolomic analysis revealed visible differences in metabolic characteristics between two groups, and overall 53 serum differential metabolites and 56 urine differential metabolites were identified with variable influence on projection (VIP) >1 and <0.05. To further analyze the correlation between the identified metabolites and DPN, four serum metabolites and six urine metabolites were selected with VIP>2, and fold change (FC) >1, including serum β-alanine, caproic acid, β-alanine/L-aspartic acid, and L-arabinose/L-arabitol, and urine gluconic acid, erythritol, galactonic acid, guanidoacetic acid, cytidine, and aminoadipic acid. Furthermore, five serum biomarkers and six urine biomarkers were found to show significant changes (<0.05, VIP>1, and FC>1) respectively in patients with mild, moderate, and severe DPN. In addition, we found that glyoxylate and dicarboxylate metabolism was a differential metabolic pathway not only between T2DM and DPN, but also among different degrees of DPN. The differential metabolites such as β-alanine and caproic acid are expected to be biomarkers for DPN patients, and the significant changes in glyoxylate and dicarboxylate metabolism may be related to the pathogenesis of DPN.
CONCLUSION
There were serum and urine spectrum metabolomic differences in patients with DPN, which could serve as biomarkers for T2DM and DPN patients.
目的
分析2型糖尿病（T2DM）患者及合并糖尿病周围神经病变（DPN）的T2DM患者的血清和尿液代谢物，筛选出差异表达的生物标志物用于DPN的早期诊断。
方法
采用气相色谱-飞行时间质谱代谢组学技术分析74例伴有周围神经病变的T2DM患者和41例无周围神经病变的T2DM患者的血清和尿液代谢物，以检测T2DM患者周围神经病变的生物标志物。
结果
与无周围神经病变的T2DM患者相比，合并DPN的T2DM患者血清甘油三酯、丙氨酸氨基转移酶升高，C肽、总胆固醇水平降低。代谢组学分析显示两组代谢特征存在明显差异，共鉴定出53种血清差异代谢物和56种尿液差异代谢物，其变量投影重要性（VIP）>1且P<0.05。为进一步分析所鉴定代谢物与DPN的相关性，选取VIP>2且变化倍数（FC）>1的4种血清代谢物和6种尿液代谢物，包括血清β-丙氨酸、己酸、β-丙氨酸/L-天冬氨酸、L-阿拉伯糖/L-阿拉伯糖醇，以及尿液葡萄糖酸、赤藓醇、半乳糖酸、胍基乙酸、胞苷和氨基己二酸。此外，发现5种血清生物标志物和6种尿液生物标志物分别在轻度、中度和重度DPN患者中出现显著变化（P<0.05，VIP>1，FC>1）。另外，发现乙醛酸和二羧酸代谢不仅是T2DM与DPN之间的差异代谢途径，也是不同程度DPN之间的差异代谢途径。β-丙氨酸和己酸等差异代谢物有望成为DPN患者的生物标志物，乙醛酸和二羧酸代谢的显著变化可能与DPN的发病机制有关。
结论
DPN患者存在血清和尿液谱代谢组学差异，可作为T2DM和DPN患者的生物标志物。
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