Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence

Abstract

Aim: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes.Methods: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader.Results: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone.Conclusion: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects.

Autofluorescence of Skin Advanced Glycation End Products as a Risk Factor for Open Angle Glaucoma: The ALIENOR Study

“…27,30,52 In nondiabetic patients, increased sAF was also associated with increased arterial stiffness, peripheral arterial disease, and coronary artery calcifications. 23,25,37 sAF was also associated with brain atrophy using magnetic resonance imaging, impaired cognitive functions, or some neurologic diseases. 26,29,32 Finally and more interestingly, sAF was proposed as a long-term metabolic marker and a predictive factor of diseases or complications.…”

“…[22][23][24][25][26][27][28][29][30][31][32] In diabetic patients, sAF was described as a marker of chronic hyperglycemia for a longer lifetime period than HbA1c and was also independently associated with micro-and macrovascular complications. 27,30,52 In nondiabetic patients, increased sAF was also associated with increased arterial stiffness, peripheral arterial disease, and coronary artery calcifications.…”

“…However, by showing an association with chronic age-related disease or its complications, the measurement provided by the AGE-reader has demonstrated its clinical value in numerous studies. [22][23][24][25][26][27][28][29][30][31][33][34][35][36][37] Thus, we assume that our results are clinically relevant in glaucoma, but would also probably need further exploration, including longitudinal sAF measurements and an independent assessment of skin content of AGEs and lipofuscin or melanin on skin biopsy, in an attempt to cross-validate these findings in our population sample composed of elderly people. These explorations could confirm these results and determine which AGEs are particularly involved or how they could influence the pathogenesis of the disease.…”

“…73 Our population sample of elderly people has a higher mean age than that observed in other published studies with a cumulative exposure to metabolic activity over a longer period. [22][23][24][25][26][27][28][29][30][31][32]38 Thus, it could have led to a higher accumulation of AGEs in skin collagen and also other fluorophores and chromophores that progressively accumulates with increasing age. Hence, we cannot exclude a higher confounding influence of these non-AGEs components on sAF measurements in our population of elderly people than that observed in younger population sample.…”

“…10,21 Several studies have also demonstrated an association between higher level of sAF and some chronic diseases as diabetes mellitus and associated complications, chronic kidney disease, some cardiovascular diseases, arterial stiffness, and peripheral arterial disease or some neurologic diseases. [22][23][24][25][26][27][28][29][30][31][32] Furthermore, as sAF reflects tissue accumulation of AGEs in long-lived proteins, sAF has also been described as a marker of metabolic memory, defined as the cumulative effect of metabolic activity over a long period, and a strong predictive factor of cardiovascular or end-stage renal disease complications. [33][34][35][36][37] Many structures of the eye, including conventional and uveoscleral aqueous outflow pathways or some structures of the optic nerve head, are mainly composed of collagen or other extracellular matrix molecules with a slow turnover time.…”