Correlation Between Advanced Glycation End Products and Ultrasonographic Measurements of Cervico-Facial Skin Tissue

Background/Objectives: Advanced Glycation End Products (AGEs) are the end products of the Maillard reaction, derived from reduced sugars and proteins, lipids or DNA. AGEs accumulate in dermal collagen and elastin, causing several changes: skin stiffening and loss of elasticity, stimulation of inflammation and the result of accelerated photo- and chronological aging, manifested by skin yellowing, wrinkles, and dryness. High Fre-quency Ultrasound (HFU) offers precise and non-invasive assessments of structural and inflammatory changes in the skin: it measures the thickness of the epidermis and dermis, echogenicity and the hypoechoic band under the epidermis. The aim of the study is to correlate AGEs levels in biological fluids with ultrasonographic measurements of sun-exposed skin and non-sun-exposed tissue. Methods: Patients (N=113) were enrolled and demographic, clinical, and anthropometric measurements were recorded: age, gender, body mass index (BMI), waist circumference, and Fitzpatrick skin type. Venous blood, urine and salivary samples were harvested. The following AGEs were assessed in biological fluids (plasma, saliva, urine): Fruc-tose-Lysine, Pyridine, Methyl-Glyoxal-H1, Carboxyethyl-lysine, Carboxymethyllysine, Arginine, Lysine. The tissue glycation process of collagen fibers was indirectly evaluated with a 22 MHz HFU ultrasound device (DUB cutis, Taberna Pro Medicum, Lüneburg, Germany). The assessment was performed on sun-exposed skin (left zygomatic area) and on non-sun-exposed tissue (non-keratinized mucosa of the lower lip). For the sun-exposed skin of the zygomatic area, including the epidermis, dermis, and subcuta-neous tissue (hypodermis), tissue depth (thickness), pixel count (px), and density (au-tomatic) were recorded. The non-sun-exposed tissue examined was the oral mucosa on the inner surface of the lower lip including the non-keratinized epithelium, lamina propria, and submucosa. Results: The study evidences a weak positive correlation between UV exposed dermis collagen and serum Pyr, salivary MG-H1, salivary Arg and salivary Lys. Between bio-fluid AGEs and the degree of pixelation of dermal collagen exposed to UV rays, we determined weak direct correlations with salivary MG-H1 and salivary CML. Significant indirect weak and medium correlations were found between dermal collagen density affected by UV exposure with serum CEL, Arg, Lys, weak direct correlation with sali-vary MG-H1 and salivary CML. Regarding the density of the dermis affected by UV exposure, we found a weak indirect correlation with salivary FruLys, MG-H1, CML and Lys . Conclusions: HFU ultrasound assessment revealed structural changes in the cervi-co-facial dermis, which were associated with increased AGEs, suggesting that gly-cation-induced tissue remodeling can be detected non-invasively. This data obtained might be the based for future studies on the clinical utility of the combined assessment of AGEs and skin changes by HFU as modern, rapid and non-invasive tools to identify patients at increased cardiovascular risk.