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

Abstract

AimsAdvanced 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. MethodsIn 670 type 1 diabetic individuals we determined serum levels of protein-bound AGEs Nε-(carboxymethyl)lysine (CML), Nε-(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. ResultsAfter 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. ConclusionsWe 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.