Glucosepane and oxidative markers in skin collagen correlate with intima media thickness and arterial stiffness in long-term type 1 diabetes

J Diabetes Complications. 2015 Apr;29(3):407-12. doi: 10.1016/j.jdiacomp.2014.12.011. Epub 2014 Dec 29.

Abstract

Aims: To study intima media thickness (cIMT) and arterial stiffness in type 1 diabetes of long duration, and their associations with the collagen cross-linker glucosepane and inflammatory and oxidative markers.

Methods: Twenty-seven individuals with type 1 diabetes mellitus of 40 years duration from the Oslo Study cohort and 24 age-matched controls were included. cIMT measurements of the carotid artery were performed longitudinally. Pulse wave velocity (PWV), augmentation index (AIx) and augmentation pressure (AP) were assessed cross-sectionally. Glucosepane and the oxidative product methionine sulfoxide (MetSO) were determined in skin collagen by liquid chromatography-mass spectrometry. Circulating inflammatory markers were determined by ELISAs.

Results: The diabetes patients had significantly increased cIMT and arterial stiffness compared to controls. Significant correlations were noted for skin glucosepane with cIMT (r=0.41) and PWV (r=0.44). Skin MetSO and monocyte chemoattractant protein-1 (MCP-1) correlated significantly with AIx and AP. After correcting for age and mean arterial pressure in multiple linear regression analysis, MetSO and MCP-1 were both independently associated with AIx and AP.

Conclusions: These results suggest more premature atherosclerosis and arterial pathology in individuals with diabetes compared to age-matched controls. They also suggest an association between the arterial pathology and markers of collagen crosslinking, oxidative damage and inflammation in type 1 diabetes patients of forty years disease duration.

Keywords: Arterial stiffness; Diabetes mellitus; Glucosepane; Methionine sulfoxide; Type 1.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Biomarkers / metabolism*
  • Carotid Intima-Media Thickness
  • Case-Control Studies
  • Collagen / chemistry
  • Collagen / metabolism*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / diagnostic imaging
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetic Angiopathies / complications
  • Diabetic Angiopathies / diagnostic imaging
  • Diabetic Angiopathies / metabolism
  • Diabetic Angiopathies / physiopathology
  • Female
  • Follow-Up Studies
  • Glycation End Products, Advanced / analysis
  • Glycation End Products, Advanced / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Skin / chemistry
  • Skin / metabolism*
  • Vascular Stiffness
  • Young Adult

Substances

  • Biomarkers
  • Glycation End Products, Advanced
  • glucosepane
  • Collagen