Glycated peptides are associated with proximal tubule dysfunction in type 2 diabetes mellitus

International Journal of Clinical and Experimental Medicine

Adrian Vlad¹  Silvia Velciov¹  Cristina Popescu¹  Daliborca Vlad¹  Roxana Popescu¹  Ligia Petrica¹  Cristina Gluhovschi¹  Alina Zamfir¹  Flaviu Bob¹  Sorin Ursoniu¹  Victor Dumitrascu¹  Oana Milas¹  Florica Gadalean¹  Gheorghe Gluhovschi¹ 

关键词: Glycated peptides;    proximal tubule;    normoalbuminuria;    Type 2 diabetes mellitus;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Background: Advanced glycation end-products have been involved in the pathogenesis of proximal tubule dysfunction which characterizes diabetic tubulopathy. Methods: A total of 76 Type 2 diabetes mellitus patients and 28 healthy controls were evaluated concerning a potential association of glycated peptides with proximal tubule dysfunction by assessing urine albumin:creatinine ratio, urinary alpha₁-microglobulin, urinary neutrophil gelatinase-associated lipocalin, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C. Fully automated chip-nanoelectrospray ionization and high-capacity ion trap multistage mass spectrometry characterized the urinary proteomic profile. Results: The urinary glycated proteins displayed a molecular weight of 15,121.4 Da in normoalbuminuric patients and of 30,180.4 Da in microalbuminuric patients. Urinary alpha₁-microglobulin and neutrophil gelatinase-associated lipocalin correlated with urinary advanced glycation end-products (R²=0.586; R²=0.415), urine albumin: creatinine ratio (R²=0.292; R²=0.116), estimated glomerular filtration rate (R²=0.172; R²=0.135), serum cystatin C (R²=0.146; R²=0.129), but not with asymmetric dimethyl-arginine. In multivariable regression analysis models, the correlations for urinary alpha₁-microglobulin and neutrophil gelatinase-associated lipocalin remained significant with urine albumin: creatinine ratio, urinary advanced glycation end-products, estimated glomerular filtration rate (P<0.0001, R²=0.674; P<0.0001, R²=0.551; P<0.0001, R²=0.482). Conclusions: In patients with Type 2 diabetes mellitus urinary glycated peptides are associated with proximal tubule dysfunction. The proteomic patterns of urinary glycated peptides could differentiate normo- from microalbuminuric patients and may explain a potential relation between the size and the glycation status of glycated peptides, and the extent of proximal tubule dysfunction. The lack of correlation between parameters of endothelial dysfunction and proximal tubule dysfunction cannot exclude glomerular involvement in early diabetic nephropathy.

【 授权许可】

Unknown