Association between Subclinical Atherosclerosis Markers and the Level of Accumulated Advanced Glycation End-Products in the Skin of Patients with Diabetes

J Atheroscler Thromb. 2018 Dec 1;25(12):1274-1284. doi: 10.5551/jat.44859. Epub 2018 Jun 30.


Aim: The level of accumulated advanced glycation end-products (AGEs) in the skin has been shown to predict the risk of complications in patients with diabetes mellitus (DM). Recently, the level of accumulated fluorescent AGEs in the skin has become measurable as skin autofluorescence (skin AF) using a non-invasive apparatus, autofluorescence reader. The purpose of this study was to evaluate the association between skin AF and the subclinical atherosclerosis markers, especially endothelial dysfunction, in patients with DM.

Methods: We enrolled 140 Japanese subjects with DM who attended Osaka University Hospital, and measured the skin level of AGEs by skin AF and three subclinical atherosclerosis markers: endothelial function by flow-mediated vasodilation, FMD; carotid intima-media thickness, IMT; and brachial-ankle pulse wave velocity, baPWV.

Results: FMD was significantly associated with skin AF (r=-0.259, p=0.002). Furthermore, a stepwise multivariate regression analysis revealed that skin AF was an independent determinant of FMD (β=-0.180, p=0.038). Although there were significant associations between skin AF and maximum carotid intima-media thickness (max-IMT)(r=0.298, p<0.001) as well as baPWV (r=0.284, p= 0.001) in univariate analysis, skin AF was not an independent determinant of either carotid max-IMT or baPWV after adjustment for conventional cardiovascular risk factors. Receiver-operating characteristic curve analysis revealed that skin AF can identify the subjects whose FMD, max-IMT, and baPWV were completely within the normal range (C-statistics, 0.73; 95% confidence interval, 0.61-0.84; p<0.001).

Conclusions: Skin AF was independently associated with FMD as an indicator of endothelial dysfunction, and can be utilized as a screening marker of atherosclerosis in Japanese patients with DM.

Keywords: Advanced glycation end products; Atherosclerosis; Diabetes; Endothelial dysfunction; Skin autofluorescence.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atherosclerosis / blood
  • Atherosclerosis / diagnosis*
  • Atherosclerosis / etiology
  • Biomarkers / blood*
  • Carotid Intima-Media Thickness
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / diagnosis*
  • Diabetic Angiopathies / etiology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Female
  • Follow-Up Studies
  • Glycation End Products, Advanced / blood*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Skin / metabolism
  • Skin / pathology*
  • Young Adult


  • Biomarkers
  • Glycation End Products, Advanced