The association between various smoking behaviors, cotinine biomarkers and skin autofluorescence, a marker for advanced glycation end product accumulation

PLoS One. 2017 Jun 20;12(6):e0179330. doi: 10.1371/journal.pone.0179330. eCollection 2017.


Background: Skin autofluorescence, a biomarker for advanced glycation end products (AGEs) accumulation, has been shown to predict diabetes-related cardiovascular complications and is associated with several environmental and lifestyle factors. In the present study, we examined the association between various smoking behaviors and skin autofluorescence, as well as the association between several cotinine biomarkers and skin autofluorescence, using both epidemiological and metabolomics data.

Methods: In a cross-sectional study, we evaluated participants from the LifeLines Cohort Study and the Qatar Metabolomics Study on Diabetes (QMDiab). In the LifeLines Cohort Study smoking behavior and secondhand smoking were assessed in 8,905 individuals including 309 individuals (3.5%) with type 2 diabetes. In QMDiab, cotinine biomarkers were measured in saliva, plasma and urine in 364 individuals of whom 188 (51%) had type 2 diabetes. Skin autofluorescence was measured non-invasively in all participants using the AGE Reader.

Results: Skin autofluorescence levels increased with a higher number of hours being exposed to secondhand smoking. Skin autofluorescence levels of former smokers approached levels of never smokers after around 15 years of smoking cessation. Urinary cotinine N-oxide, a biomarker of nicotine exposure, was found to be positively associated with skin autofluorescence in the QMDiab study (p = 0.03).

Conclusions: In the present study, we have demonstrated that secondhand smoking is associated with higher skin autofluorescence levels whereas smoking cessation has a beneficial effect on skin autofluorescence. Finally, urinary cotinine N-oxide might be used as an alternative way for questionnaires to examine the effect of (environmental) tobacco smoking on skin autofluorescence.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / urine
  • Cohort Studies
  • Cotinine / analogs & derivatives
  • Cotinine / analysis*
  • Cotinine / blood
  • Cotinine / urine
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Glycation End Products, Advanced / analysis*
  • Humans
  • Male
  • Middle Aged
  • Saliva / chemistry
  • Saliva / metabolism
  • Skin / chemistry
  • Skin / metabolism*
  • Smoking Cessation
  • Smoking*
  • Spectrometry, Fluorescence
  • Time Factors
  • Tobacco Smoke Pollution*


  • Biomarkers
  • Glycation End Products, Advanced
  • Tobacco Smoke Pollution
  • cotinine-N-oxide
  • Cotinine

Grant support

The manuscript is based on data from the LifeLines cohort study. LifeLines adheres to standards for open data availability. The data catalogue of LifeLines is publicly accessible on All international researchers can apply for data at the LifeLines research office ( The LifeLines system allows access for reproducibility of the study results. The QMDiab study was supported by ‘Biomedical Research Program’ funds at Weill Cornell Medical College in Qatar, a program funded by the Qatar Foundation. Support for some of the experiments was provided by the Weill Cornell Medical College in Qatar (WCMC-Q) bioinformatics and virtual metabolomics core which is funded by the Qatar Foundation. Dennis Mook-Kanamori is supported by Dutch Science Organization (ZonMW-VENI Grant 916.14.023). This work was supported by Netherlands Consortium for Healthy Ageing (NCHA), Bio-SHaRE-EU, Biobank Standardisation and Harmonisation for research excellence in the European Union. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.