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血清和尿液代谢组学揭示2型糖尿病肾病患者的潜在生物标志物。

Serum and urine metabolomics reveal potential biomarkers of T2DM patients with nephropathy.

作者信息

Shao Mingmei, Lu Hao, Yang Ming, Liu Yang, Yin Peihao, Li Guowen, Wang Yunman, Chen Lin, Chen Qingguang, 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

Ann Transl Med. 2020 Mar;8(5):199. doi: 10.21037/atm.2020.01.42.

Abstract

BACKGROUND

Diabetes is a metabolic disease and is often accompanied by severe microvascular and macrovascular complications. A comprehensive understanding of its complex mechanisms can help prevent type 2 diabetes mellitus (T2DM) complications, such as diabetic nephropathy (DN).

METHODS

To reveal the systemic metabolic changes related to renal injury, clinical information of T2DM patients with or without nephropathy was collected, and it was found that serum urea levels of DN patients were significantly higher in T2DM patients without nephropathy. Further along the disease progression, the serum urea levels also gradually increased. We used gas chromatograph coupled with time-of-flight mass spectrometry (GC-TOFMS) metabolomics to analyze the serum and urine metabolites of T2DM patients with or without nephropathy to study the metabolic changes associated with the disease.

RESULTS

Finally, we identified 61 serum metabolites and 46 urine metabolites as potential biomarkers related to DN (P<0.05, VIP >1). In order to determine which metabolic pathways were major altered in DN, we summarized pathway analysis based on P values from their impact values and enrichment. There were 9 serum metabolic pathways and 12 urine metabolic pathways with significant differences in serum and urine metabolism, respectively.

CONCLUSIONS

This study emphasizes that GC-TOFMS-based metabolomics provides insight into the potential pathways in the pathogenesis and progression of DN.

摘要

背景

糖尿病是一种代谢性疾病,常伴有严重的微血管和大血管并发症。全面了解其复杂机制有助于预防2型糖尿病(T2DM)并发症,如糖尿病肾病(DN)。

方法

为揭示与肾损伤相关的全身代谢变化,收集了有或无肾病的T2DM患者的临床信息,发现DN患者的血清尿素水平在无肾病的T2DM患者中显著更高。随着疾病进展,血清尿素水平也逐渐升高。我们使用气相色谱-飞行时间质谱联用(GC-TOFMS)代谢组学分析有或无肾病的T2DM患者的血清和尿液代谢物,以研究与该疾病相关的代谢变化。

结果

最终,我们鉴定出61种血清代谢物和46种尿液代谢物作为与DN相关的潜在生物标志物(P<0.05,VIP>1)。为确定DN中哪些代谢途径发生了主要改变,我们根据其影响值和富集的P值进行了途径分析总结。血清和尿液代谢中分别有9条血清代谢途径和12条尿液代谢途径存在显著差异。

结论

本研究强调基于GC-TOFMS的代谢组学为DN的发病机制和进展中的潜在途径提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d3/7154445/93fadcaf49b6/atm-08-05-199-f1.jpg

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