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. 2024 Sep 9;23(1):332.
doi: 10.1186/s12933-024-02428-3.

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults

Juanita J Fewkes  1   2 , Aimee L Dordevic  1   2 , Margaret Murray  1   3 , Gary Williamson  1   2 , Nicole J Kellow  4   5
Affiliations

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults

Juanita J Fewkes et al. Cardiovasc Diabetol. .

Abstract

Background: In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium.

Methods: A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4-36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates.

Results: FMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001.

Conclusions: Higher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers.

Trial registration: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.

Keywords: AGEs; Advanced glycation end products; Cardiovascular risk; Endothelial function; Endothelium-dependent vasodilation; Flow-mediated dilation; Skin autofluorescence; Vascular endothelium.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of participant inclusion. AGE, advanced glycation end-products
Fig. 2
Fig. 2
Unadjusted linear regression and Spearman correlation analysis to evaluate the association between SAF and FMD. N = 121. Scatter plot with linear trend line (solid line). Abbreviations: SAF, skin autofluorescence; AU, arbitrary units; FMD, flow-mediated dilation; N, sample size
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