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We studied the in vitro rate of fluorescent advanced glycation end products (fAGEs) formation with multiphoton microscopy in different porcine tissues (aorta, cornea, kidney, dermis, and tendon). These tissues were treated with d‐glucose, d‐galactose, and d‐fructose, three primary monosaccharides found in human diets. We found that the use of d‐fructose resulted in the highest glycation rate, followed by d‐galactose and then d‐glucose. Moreover, compared to non‐collagen tissue constituents such as elastic fibers and cells, the rate of tissue glycation was consistently higher in collagen, suggesting that collagen is a more sensitive target for fAGE formation. However, we also found that collagen in different tissues exhibits different rates of fAGE formation, with slower rates observed in tightly packed tissues such as cornea and tendon. Our study suggests that for fAGE to be developed into a long‐term glycemic biomarker, loosely organized collagen tissues located in the proximity of vasculature may be the best targets. [ABSTRACT FROM AUTHOR]

Diabetes is a serious disease whose patients often require long‐term care. Blood glucose and intermediate glycation product of glycated hemoglobin (HbA1c) are, at best, surrogate biomarkers of disease progression. There is indication that advanced glycation end products (AGEs) better reflect diabetic risks. In this study, we explored the use of red blood cells (RBCs) and lysed hemoglobin (Hb) autofluorescence (AF) as potential biomarkers of diabetic complication. AF spectra measured under 370 nm excitation reveals that both RBC and Hb fluorescence in the 420 to 600 nm region. At early time points following diabetic induction in rats, AF increase in lysed Hb is more dramatic compared to that of RBCs. Moreover, we found significance variance of Hb autofluorescence despite relatively constant HbA1c levels. Furthermore, we found that although a correlation exists between AGE autofluorescence and HbA1c levels, the lack of complete correspondence suggests that the rate of AGE production differs significantly among different rats. Our results suggest that with additional development, both RBC and Hb autofluorescence from lysed RBCs may be used act long‐term glycemic markers for diabetic complications in patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tissue glycation, the main cause of many diabetes-related complications, results in the accumulation of advanced glycation endproducts (AGE). Objectives: These AGEs are endogenous fluorophores that can serve as a viable pathological indicator for disease diagnostics. Here we explore the capabilities of multiphoton microscopy to non-invasively localize and quantify the skin glycation. Methods: In our study, multiphoton microscopy and spectroscopy were used to investigate glycation events-induced changes in the intensities of autofluorescence and second harmonic generation on ex vivo human skin. Results: Temporal and spatial dependence of degrees of glycation of the epidermis, collagen and elastin fibers of dermis were evaluated for their relevance to the changes in amplitudes of autofluorescence signals. We found that glycation drastically and linearly increases multiphoton autofluorescence intensity of epidermis and dermal collagen whereas changes in dermal elastin are moderate. We also found decrease in the level of second harmonic generation signal. Conclusion: Our study suggests that due to intrinsically weak autofluorescence the dermal collagen is the most sensitive skin tissue to be used for detecting changes in tissue glycation. [Copyright &y& Elsevier]

The maillard reaction on proteins is a nonenzymatic glycosylation that is now termed glycation and produces a ketoamine linkage on the protein. The extent of this glycation was estimated by determining furosine (ε-N-(2-furoylmethyl)-L-lysine), which is derived from glycated lysine residues. Glycation of rat sciatic nerve and aorta increased with advancing age for up to 50 weeks and the high degree of glycation was maintained thereafter. The level of hemoglobin did not change significantly after 14 weeks. These results suggest that tissue glycation may increase with aging and may be involved in the mechanism of aging. [ABSTRACT FROM PUBLISHER]

Background: Skin autofluorescence has been used to assess longer term glycemic control and risk of complications. There is however no agreed site at which autofluorescence should be measured. This study evaluated the within- and between-site agreement in measurement of skin autofluorescence using a noninvasive advanced glycation end product (AGE) reader., Methods: Overall, 132 participants were included: 16 with diabetes-related foot ulcers (DFU), 63 with diabetes but without foot ulcers (DMC), 53 without diabetes or foot ulcers (HC). Skin autofluorescence was measured using the AGE Reader (DiagnOptics technologies BV, the Netherlands). Three consecutive skin autofluorescence measurements were each performed at six different body sites: the volar surfaces of both forearms (arms), dorsal surfaces of both calves (legs), and plantar surfaces of both feet (feet). Within- and between-site agreements were analyzed with concordance correlation coefficients (CCC) and 95% confidence intervals (95% CI), absolute mean differences (±standard deviation), and Bland-Altman limits of agreement., Results: The agreement between repeat assessments at the same site was almost perfect (CCC [95% CI] ranging from 0.94 [0.91-0.96] for assessments in the right foot to 0.99 [0.99-0.99] for assessments in the left arm). The limits of agreement were narrow within ±0.5 arbitrary units for all sites. The between-site agreement in measurements was poor (CCC < 0.65) with large maximum absolute mean differences (±SD) in arbitrary units (DFU = 3.40 [±2.04]; DMC = 3.15 [±2.45]; HC = 2.72 [±1.83]) and wide limits of agreement., Conclusions: Skin autofluorescence measurements can be repeated at the same site with adequate repeatability but measurements at different sites in the same patient have marked differences. The reason for this variation across sites and whether this has any role in diabetes-related complications needs further investigation.