Plasma levels of advanced glycation endproducts are associated with type 1 diabetes and coronary artery calcification

Cardiovasc Diabetol. 2013 Oct 17;12:149. doi: 10.1186/1475-2840-12-149.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Vessels / diagnostic imaging*
  • Diabetes Mellitus, Type 1 / blood*
  • Female
  • Glycation End Products, Advanced / blood*
  • Humans
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Male
  • Middle Aged
  • Pyrimidines / blood
  • Tomography, X-Ray Computed
  • Vascular Calcification / blood*
  • Vascular Calcification / diagnostic imaging
  • Vascular Cell Adhesion Molecule-1 / blood
  • von Willebrand Factor / metabolism

Substances

  • Biomarkers
  • Glycation End Products, Advanced
  • Pyrimidines
  • Vascular Cell Adhesion Molecule-1
  • von Willebrand Factor
  • N(6)-carboxymethyllysine
  • C-Reactive Protein
  • Arginine
  • pentosidine
  • Lysine