Identification of Urinary Metabolite Biomarkers of Type 2 Diabetes Nephropathy Using an Untargeted Metabolomic Approach.

Abstract

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.

• Authors: Chao-Jung Chen, Wen-Ling Liao, Chiz-Tzung Chang, Yu-Ning Lin, Fuu-Jen Tsai
• Journal: Journal of proteome research (J Proteome Res) Vol. 17 Issue 11 Pg. 3997-4007 (11 02 2018) ISSN: 1535-3907 [Electronic] United States
• PMID: 30265543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Blood Glucose
• Glycated Hemoglobin A
• Ribonucleosides
• Xanthines
• hemoglobin A1c protein, human
• Guanosine
• 1-methylguanosine
• xanthosine
• Valine

Topics

• Aged
• Albuminuria (diagnosis, physiopathology, urine)
• Area Under Curve
• Biomarkers (urine)
• Blood Glucose (metabolism)
• Chromatography, Liquid
• Cross-Sectional Studies
• Diabetes Mellitus, Type 2 (diagnosis, physiopathology, urine)
• Diabetic Nephropathies (diagnosis, physiopathology, urine)
• Fasting
• Female
• Glycated Hemoglobin (metabolism)
• Guanosine (analogs & derivatives, urine)
• Humans
• Male
• Metabolomics (methods)
• Middle Aged
• Principal Component Analysis
• Ribonucleosides (urine)
• Tandem Mass Spectrometry
• Valine (urine)
• Xanthines