关键词: 糖尿病肾病 , 代谢组学 , 糖代谢 , 支链氨基酸 , 磷脂酰胆碱

Abstract:

ABSTRACT  Objective: To investigate the metabolomic profile in serum and urine of patients with DN at different stages, and find out biomarkers for early diagnosis and prognosis of DN. Methodology: Ninety male patients diagnosed as type 2 diabetic mellitus (T2DM) were enrolled this study. They were divided into 3 groups (normoalbuminuria, n=30, microalbuminuria, n=30, and proteinuria, n=30). Twenty-five health controls were included. Serum and urine metabolites were analyzed using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS).  Results: Distinct metabolomic differences were observed between different stages of DN. All the three groups of patients showed clear dysfunction of glycolysis and tricarboxylic acid cycle. Activation of protein kinase C pathway and hexosamine biosythesis pathway were also demonstrated. The levels of serum branched-chain amino acids were increased in the diseased group. The levels of serum non-essential fatty acid were elevated, while L-cartinine and acyl CoA were decreased, which indicated the dysfunction of β-oxidation of fatty acids. The palmitic acid in the serum, as well as PC (P-19:1(12Z)/0:1) and dodecanedioic acid in the urine might be candidate biomarker for early diagnosis of DN. Decanoyl-L-carnitine, PC (9:0/0:0) and Dg (17:2(9Z,12Z)/20:3 (8Z,11Z,14Z)/0:0) in the serum, as well as uridine diphosphate and lysoPC (16:0) might be candidate biomarkers for prognosis of DN. Conclusion: Our study demonstrated the changes of metabolic profile in different stages of DN, and provided candidate biomarkers for early diagnosis and prognosis.

Key words: diabetic nephropathy , metabolomics , glucose metabolism , branched-chain amino acids , phosphatidyl choline