Reference values and biological factors influencing skin autofluorescence

Introduction
Tissue glycation, measured as skin autofluorescence (SAF) with an AGE reader, has been associated with incident type 2 diabetes (T2D) and cardiovascular disease (CVD), as well as CVD and cancer mortality. Validated reference intervals in a healthy population are needed to make useful and precise risk estimations.
Methodology
This study utilises data obtained from participants of the Lifelines Cohort Study, an extensive population-based study in the northern region of the Netherlands. For the current study, we used the data of 82,870 participants who had a valid SAF measurement at the baseline Lifelines screening. Reference values for SAF were established in healthy participants who had never smoked. Decade-specific mean SAF values were evaluated for former and current smokers, type 2 diabetes, clinical cardiovascular disease, and impaired renal function. We also assessed the association of regular physical activity (PA) with SAF scores.
Results
Reference values for healthy individuals were established in 8179 men and 7930 women between 18 and 70 years, who had never smoked, had a BMI below 35 kg/m2, and did not meet the metabolic syndrome criteria. Linear regression analyses yielded the following prediction for SAF, separately by sex: in males, SAF predicted = (0.0191 x age) + 1.038, and in females, SAF predicted = (0.0188 x age) + 0.994. Current smokers had consistently higher SAF scores. There was a progressively higher SAF with a higher number of pack-years of smoking in each age decade, in both sexes. For each decade, both people with type 2 diabetes and those with CVD had significantly higher SAF values compared to healthy individuals. The same applied to participants with impaired renal function. There was a complex curvilinear relationship between PA and age-adjusted SAF score, both in never and current smokers: mean SAF was the highest in sedentary participants, e.g. 0 min/week moderate-to-vigorous physical activity, lowest in those with 150-299 min/week PA, and gradually increasing in participants with higher than 600 min/week PA.
Conclusions
SAF increases linearly with age in healthy individuals. We provided robust reference values for SAF, established in healthy individuals of Western European descent, separately by sex, who have never smoked. Higher levels of SAF are observed in former and current smokers, and in people with type 2 diabetes, CVD, and impaired renal function. The relationship between physical activity and SAF scores is complex, with higher SAF scores demonstrated in sedentary people and those performing a large amount of moderate-to-vigorous physical exercise.