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Open Access Original investigation

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*

Author Affiliations

1 Department of Internal Medicine, Maastricht University Medical Centre (MUMC) and Cardiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, Maastricht 6200, MD, the Netherlands

2 Biomedical Research Institute, University of Dundee, Dundee, Scotland

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Cardiovascular Diabetology 2013, 12:149  doi:10.1186/1475-2840-12-149

Published: 17 October 2013

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