Glycated peptides are associated with proximal tubule dysfunction in type 2 diabetes mellitus.
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 (R(2)=0.586; R(2)=0.415), urine albumin: creatinine ratio (R(2)=0.292; R(2)=0.116), estimated glomerular filtration rate (R(2)=0.172; R(2)=0.135), serum cystatin C (R(2)=0.146; R(2)=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, R(2)=0.674; P<0.0001, R(2)=0.551; P<0.0001, R(2)=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.
Department of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Ligia
L
Petrica
Department of Diabetes and Metabolic Diseases, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Adrian
A
Vlad
Department of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Gheorghe
G
Gluhovschi
National Institute for Research and Development of Electrochemistry and Condensed Matter Timisoara, Romania.
Alina
A
Zamfir
Department of Experimental and Applied Biology, Institute of Life Sciences, "Vasile Goldis" Western University Arad, Romania.
Cristina
C
Popescu
Department of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Florica
F
Gadalean
Department of Pharmacology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Victor
V
Dumitrascu
Department of Pharmacology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Daliborca
D
Vlad
Department of Cellular Biology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Roxana
R
Popescu
Department of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Silvia
S
Velciov
Department of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Cristina
C
Gluhovschi
Department of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Flaviu
F
Bob
Department of Nephrology, County Emergency Hospital Timisoara, Romania.
Oana
O
Milas
Department of Public Health Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Sorin
S
Ursoniu
Glycated peptides; Type 2 diabetes mellitus; normoalbuminuria; proximal tubule