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Type: Journal article
Title: Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of metalloproteinase-1 are associated with vascular complications in patients with type 1 diabetes: The EURODIAB Prospective Complications Study
Author: Peeters, S.
Engelen, L.
Buijs, J.
Chaturvedi, N.
Fuller, J.
Schalkwijk, C.
Stehouwer, C.
EURODIAB Prospective Complications Study Group
Citation: Cardiovascular Diabetology, 2015; 14(1):31-1-31-10
Publisher: BioMed Central
Issue Date: 2015
ISSN: 1475-2840
Statement of
Stijn A Peeters, Lian Engelen, Jacqueline Buijs, Nish Chaturvedi, John H Fuller, Casper G Schalkwijk, Coen D Stehouwer, and EURODIAB Prospective Complications Study Group
Abstract: BACKGROUND Impaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, −2, −3, −9, −10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). METHODS 493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, −2, −3, −9, −10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED. RESULTS Patients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED. CONCLUSIONS These data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes.
Keywords: Type 1 diabetes; Matrix metalloproteinase; Tissue inhibitor of metalloproteinase; Cardiovascular disease; Albuminuria; Retinopathy
Description: EURODIAB Prospective Complications Study Group member Dorothy M. Keefe for the University of Adelaide.
Rights: © 2015 Peeters et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
RMID: 0030035053
DOI: 10.1186/s12933-015-0195-2
Appears in Collections:Medicine publications

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