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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 52, Issue 1


Total plasma Nε-(carboxymethyl)lysine and sRAGE levels are inversely associated with a number of metabolic syndrome risk factors in non-diabetic young-to-middle-aged medication-free subjects

Katarína Šebeková
  • Corresponding author
  • Medical Faculty, Institute of Molecular BioMedicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
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/ Zora Krivošíková
  • Medical Faculty, Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovakia
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/ Martin Gajdoš
  • Medical Faculty, Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovakia
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Published Online: 2013-03-18 | DOI: https://doi.org/10.1515/cclm-2012-0879


Background: Interaction of advanced glycation end products (AGEs) with their specific cell-surface receptor for AGEs (RAGE) induces production of reactive oxygen species, pro-diabetic, pro-inflammatory, and pro-atherogenic responses. The metabolic syndrome (Metsy) imposes a high risk of development of cardiovascular disease and unequivocally predisposes the non-diabetics to type 2 diabetes mellitus. The aim of the study was to investigate the association between circulating soluble RAGE (sRAGE), Nε-(carboxymethyl)lysine (CML) or AGE-associated fluorescence of plasma (AGE-Fl) with the number of manifested Metsy risk factors in young-to-middle-aged medication-free non-diabetic subjects.

Methods: Metsy was classified according to NCEP/ATP III criteria; plasma sRAGE and total CML were determined by ELISA methods and AGE-Fl fluorimetrically.

Results: From among 437 participants aged 33±11 years, 58% were females. In total 174 subjects were Metsy risk factors-free, 142 presented one, 59 presented two risk factors, and 62 suffered from Metsy. Plasma sRAGE and CML/albumin levels decreased with increasing number of Metsy risk factors (p<0.01, both), while AGE-Fl/albumin levels remained similar. Multivariate analysis selected waist circumference as a main determinant of plasma sRAGE as well as CML/albumin levels.

Conclusions: In young-to-middle-aged non-diabetic medication-free subjects plasma total CML/albumin and sRAGE levels decrease prior to the manifestation of Metsy. With regards to RAGE-mediated CML trapping into adipose tissue inducing dysregulation of pro-inflammatory cytokines, adipokines, and the development of obesity-related insulin resistance, and the potential involvement of sRAGE in feedback regulation of the toxic effects of AGE/RAGE-mediated signaling, this early decline might be of clinical impact in development of type 2 diabetes and its complications.

This article offers supplementary material which is provided at the end of the article.

Keywords: central obesity; healthy subjects; metabolic syndrome; Nε-(carboxymethyl)lysine (CML); sRAGE


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About the article

Corresponding author: Assoc. Prof. Katarína Šebeková, MD, DSc, Medical Faculty, Institute of Molecular BioMedicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia, Phone: +421 2 59357429, Fax: +421 2 59357631, E-mail:

Received: 2012-12-14

Accepted: 2013-02-04

Published Online: 2013-03-18

Published in Print: 2014-01-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 52, Issue 1, Pages 139–149, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2012-0879.

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