Plasma levels of advanced glycation endproducts are associated with type 1 diabetes and coronary artery calcification
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van Eupen et al. Cardiovascular Diabetology 2013, 12:149 http://www.cardiab.com/content/12/1/149
ORIGINAL INVESTIGATION
Open Access
Plasma levels of advanced glycation endproducts are associated with type 1 diabetes and coronary artery calcification Marcelle GA van Eupen1, Miranda T Schram1, Helen M Colhoun2, Jean LJM Scheijen1, Coen DA Stehouwer1 and Casper G Schalkwijk1*
Abstract Background: Advanced glycation endproducts (AGEs) may play a role in the development of coronary artery calcification (CAC) in type 1 diabetes (T1DM). We studied plasma AGEs in association with T1DM and CAC, and whether or not the latter association could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods: We studied 165 individuals with and 169 without T1DM. CAC was quantified in a CAC score based on CT-scanning. Plasma levels of protein-bound pentosidine, Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl) lysine (CEL) were measured with HPLC/UPLC with fluorescence detection or tandem-mass spectrometry. Tetrahydropyrimidine (THP) was measured with ELISA, as were HsCRP, and sVCAM-1 and vWF, as markers for LGI and ED, respectively. Associations were analyzed with ANCOVA and adjusted for age, sex, BMI, waist-to-hip ratio, smoking, blood pressure, lipid profile, eGFR and T1DM. Results: Individuals with T1DM had higher plasma levels of pentosidine, CML and THP compared with controls; means (95% CI) were 0.69 (0.65-0.73) vs. 0.51 (0.48-0.54) nmol/mmol LYS, p < 0.001; 105 (102–107) vs. 93 (90–95) nmol/mmol LYS, p < 0.001; and 126 (118–134) vs. 113 (106–120) U/mL, p = 0.03, respectively. Levels of pentosidine were higher in individuals with T1DM with a moderate to high compared with a low CAC score, means (95% CI) were 0.81 (0.70-0.93) vs. 0.67 (0.63-0.71) nmol/mmol LYS, p = 0.03, respectively. This difference was not attenuated by adjustment for LGI or ED. Conclusions: We found a positive association between pentosidine and CAC in T1DM. These results may indicate that AGEs are possibly involved in the development of CAC in individuals with T1DM. Keywords: Advanced glycation endproducts, Coronary artery calcification, Type 1 diabetes
Background Individuals with type 1 diabetes mellitus (T1DM) have an increased risk of cardiovascular disease (CVD) [1]. Advanced glycation endproducts (AGEs), which are formed by a nonenzymatic reaction between reducing sugars and proteins, are thought to play an important role in the development of CVD in T1DM [2,3]. AGEs are able to affect cell function via intracellular glycation of proteins, altering * Correspondence: [email protected] 1 Department of Internal Medicine, Maastricht University Medical Centre (MUMC) and Cardiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, Maastricht 6200, MD, the Netherlands Full list of author information is available at the end of the article
their function [2], via cross-linking of extracellular matrix proteins in large arteries, resulting in arterial stiffness [4], and by binding to the rece
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