Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence

J Atheroscler Thromb. 2016 Oct 1;23(10):1178-1187. doi: 10.5551/jat.30155. Epub 2016 Mar 10.


Aim: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes.

Methods: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader.

Results: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone.

Conclusion: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism*
  • Calcinosis / blood
  • Calcinosis / diagnosis*
  • Calcinosis / etiology
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / etiology
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Female
  • Fluorescence*
  • Glycated Hemoglobin A / metabolism
  • Glycation End Products, Advanced / blood*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Multidetector Computed Tomography
  • Optical Imaging
  • Pulse Wave Analysis
  • Risk Factors
  • Skin / metabolism
  • Skin / pathology*
  • Young Adult


  • Biomarkers
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced