Associations between advanced glycation endproducts and matrix metalloproteinases and its inhibitor in individuals with type 1 diabetes

S. A. Peeters*, L. Engelen, J. Buijs, S. Theilade, P. Rossing, C. G. Schalkwijk, C. D. A. Stehouwer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Web of Science)

Abstract

Aims: Advanced glycation endproducts (AGEs) and altered extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) are associated with vascular complications in type 1 diabetes. Experimental studies have shown that AGEs regulate the production of MMPs and/or TIMP-1. Therefore, we investigated associations between specific AGEs and MMP-1, -2, -3, -9, and -10, and TIMP-1 in individuals with type 1 diabetes. Methods: In 670 type 1 diabetic individuals we determined serum levels of protein-bound AGEs N-epsilon-(carboxymethyl)lysine (CML), N-epsilon-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1) and pentosidine, and MMP-1, -2, -3, -9, and -10, and TIMP-1. We performed linear regression analyses to investigate associations between AGEs and markers of the MMP-TIMP system. Analyses were adjusted for age, sex, HbA1c and duration of diabetes, and additionally for other potential confounders and presence of vascular complication. Results: After full adjustment, levels of CML were positively associated with levels of MMP-2 and inversely with MMP-9. CEL was positively associated with MMP-3 and TIMP-1. MG-H1 was only associated with TIMP-1, whereas pentosidine was not associated with MMPs or TIMP-1. Conclusions: We showed independent associations between several AGEs and markers of the MMP-TIMP system, which indicate specific AGE-MMP/TIMP-1 interactions potentially contributing to vascular complications in patients with type 1 diabetes. (C) 2017 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)325-329
Number of pages5
JournalJournal of Diabetes and Its Complications
Volume32
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Type 1 diabetes
  • AGES
  • MMPs
  • TIMP-1
  • Cardiovascular disease (CVD)
  • INCIDENT CARDIOVASCULAR-DISEASE
  • BLOOD-RETINAL BARRIER
  • ALL-CAUSE MORTALITY
  • END-PRODUCTS
  • ENDOTHELIAL-CELLS
  • SOLUBLE RECEPTOR
  • GENE-EXPRESSION
  • PLASMA-LEVELS
  • NEPHROPATHY
  • COMPLICATIONS

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