A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness

Abstract

Background: We compared skin and plasma measurements of advanced glycation end products (AGEs), with particular focus on their levels in the presence of hypertension or diabetes and prediabetes and their associations with arterial stiffness in outpatients with suspected or diagnosed hypertension. Methods: Skin AGE accumulation was measured as autofluorescence on the left forearm using the skin autofluorescence Reader and expressed in arbitrary units in the range from 0 to 25. Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) using the SphygmoCor system (Sydney, Australia). Results: The 218 participants (96 [44.0%] men, mean age 51.9 years) had a mean skin autofluorescence of 1.89 arbitrary units, plasma AGE concentration of 4.47 μg/ml, and cfPWV of 8.0 m/s. Skin autofluorescence was significantly correlated with plasma AGEs in diabetic or prediabetic patients (n = 31, r = 0.37, p = 0.04) but not in subjects with normoglycemia (n = 187, r = -0.05, p = 0.48). Nonetheless, both measurements were significantly (p ≤ 0.001) higher in men (2.00 arbitrary units and 6.73 μg/ml, respectively) than women (1.81 arbitrary units and 3.60 μg/ml, respectively) and in diabetic or prediabetic (2.03 arbitrary units and 6.61 μg/ml, respectively) than normoglycemia subjects (1.87 arbitrary units and 4.17 μg/ml, respectively), but similar in hypertensive (n = 105) and normotensive subjects (n = 113, p ≥ 0.35). In adjusted multiple regression analyses, plasma AGE concentration, but not skin autofluorescence (p ≥ 0.37), was significantly associated with cfPWV in all subjects (β 0.44 m/s for each 10-fold increase; p = 0.04) and in subgroups of men and diabetes and prediabetes (β 0.12-0.55 m/s for each 10-fold increase; p ≤ 0.02). Conclusions: Although skin and plasma AGEs were similarly associated with gender and diabetes or prediabetes, they might measure something different and have different clinical relevance, such as for arterial stiffness.

Consumption of Cuban Policosanol Improves Blood Pressure and Lipid Profile via Enhancement of HDL Functionality in Healthy Women Subjects: Randomized, Double‐Blinded, and Placebo‐Controlled Study

“…The antiglycation effect is known to be associated with vasorelaxation via improvement of atrial stiffness since AGEs are a proven marker of CVD, diabetes, and hypertension [ 50 ]. From a study with Chinese subjects, plasma AGE concentration was found to be positively correlated with pulse wave velocity from the carotid to femoral arteries [ 51 ]. More interestingly, the serum TG level was elevated under conditions of high plasma AGE content.…”

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

“…To address this, AGEs' assays are mostly based on the use of specific antibodies or spectrofluorimetric measurements based on the fluorescent properties of AGEs [212, 213]. Although promising results came from studies on skin autofluorescence in diabetic patients [214, 215], the serum fluorescence AGE (F-AGE) method did not distinguish women with gestational diabetes from the healthy controls [216]. …”

Skin autofluorescence predicts incident type 2 diabetes, cardiovascular disease and mortality in the general population

“…In addition to the classic Maillard reaction, AGEs are formed through the reaction of amino groups with α-dicarbonyls, such as 3-deoxyglucosone, methylglyoxal and glyoxal [ 8 – 10 ]. AGEs may form cross-links between tissue proteins in the vascular wall, causing increased vascular stiffness and elevated BP [ 11 , 12 ]. Moreover, binding of circulating AGE to its receptor (receptor for AGE [RAGE]) and uptake into the vessel wall may accelerate the progression of atherosclerosis [ 13 , 14 ].…”