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

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.