Journal
JOURNAL OF PROTEOME RESEARCH
Volume 17, Issue 11, Pages 3997-4007Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.8b00644
Keywords
liquid chromatography; mass spectrometry; diabetic nephropathy; metabolomics; urine; biomarker
Categories
Funding
- China Medical University Hospital [DMR-106-126]
- Ministry of Science and Technology [MOST 105-2113-M-039-001]
- Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence [MOHW107-TDU-B-212-123004]
- Academia Sinica's Diabetes Biosignature Project [BM 10601010027]
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Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). To discover early stage biomarkers of DN, untargeted liquid chromatography-mass spectrometry-based metabolomic analysis was performed in urine samples from healthy subjects and patients with micro- or macroalbuminuria due to nondiabetic disease (macro), type 2 DM without microalbuminuria (T2DM), and type 2 DM with microalbuminuria (T2DM+micro). Levels of four metabolites were significantly different among groups, and they were quantified in a larger group of 267 urine samples. Two metabolites were also discovered and validated in targeted metabolic study of amino acids. For diagnosis of nephropathy, N1-methylguanosine had the highest area-under-the-curve (AUC) value of 0.75 when compared to those of valine (0.68), xanthosine (0.67), and 7-methyluric acid (0.69). After combining fasting blood glucose and diastolic blood pressure (DBP) with N1-methylguanosine, the AUC increased to 0.987. To distinguish between T2DM and T2DM+micro conditions, xanthosine and N1-methylguanosine have AUC value of 0.612 and 0.624, respectively. After adjustment of HbA1c and DBP, AUC values of xanthosine and N1-methylguanosine increased to 0.716 and 0.723, respectively, and could be used to predict the development of nephropathy in T2DM patients.
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