The advanced glycation end product methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in childhood diabetes

Diab Vasc Dis Res. 2015 Mar;12(2):139-45. doi: 10.1177/1479164114560910. Epub 2015 Jan 23.

Abstract

Background: Advanced protein glycation is an important mechanism for the development of late diabetic complications including atherosclerosis. Methylglyoxal-derived hydroimidazolone-1 is the most abundant advanced glycation end product in human plasma.

Aim: To investigate the relationship between methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in children and adolescents with type 1 diabetes and healthy controls.

Methods: A total of 314 diabetes patients aged 8-18 years were compared with 120 healthy controls. Serum methylglyoxal-derived hydroimidazolone-1 was measured by immunoassay. Atherosclerosis was evaluated by assessing carotid intima-media thickness by ultrasound, arterial stiffness by Young's modulus and inflammation by C-reactive protein.

Results: Methylglyoxal-derived hydroimidazolone-1 was significantly increased in the diabetes group compared with controls, 155.3 (standard deviation (SD) = 41.0) versus 143.0 (SD = 35.1) U/mL, p = 0.003, as was C-reactive protein, median 0.51 (0.27, 1.83) versus 0.31 (0.19, 0.67) mg/L, p < 0.001. There was no significant difference between the groups regarding carotid intima-media thickness or Young's modulus. Multiple regression analysis showed a significant positive association between methylglyoxal-derived hydroimidazolone-1 and C-reactive protein in the diabetes group.

Conclusion: Serum levels of methylglyoxal-derived hydroimidazolone-1 in diabetes patients are increased and associated with low-grade inflammation, but not yet arterial stiffness or wall thickness. This indicates that methylglyoxal-derived hydroimidazolone-1 may be important in the early phase of the accelerated atherosclerotic process in diabetes.

Keywords: C-reactive protein; Diabetes mellitus type 1; advanced glycation end products; atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Carotid Artery Diseases / blood*
  • Carotid Artery Diseases / diagnosis
  • Carotid Artery Diseases / physiopathology
  • Carotid Intima-Media Thickness
  • Case-Control Studies
  • Child
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetic Angiopathies / blood*
  • Diabetic Angiopathies / diagnosis
  • Diabetic Angiopathies / physiopathology
  • Early Diagnosis
  • Elastic Modulus
  • Female
  • Humans
  • Imidazoles / blood*
  • Immunoassay
  • Inflammation Mediators / blood
  • Male
  • Predictive Value of Tests
  • Prognosis
  • Risk Factors
  • Up-Regulation
  • Vascular Stiffness

Substances

  • Biomarkers
  • Imidazoles
  • Inflammation Mediators
  • imidazolone
  • C-Reactive Protein