Skin Autofluorescence as a Novel and Noninvasive Technology for Advanced Glycation End Products in Diabetic Foot Ulcers: A Systematic Review and Meta-analysis

Abstract

OBJECTIVE Skin autofluorescence (SAF) has been suggested as a novel and noninvasive technique for assessing tissue accumulation of advanced glycation end products in diabetes and related complications. The aim of this systematic review and meta-analysis was to evaluate the use of SAF in diabetic foot ulcers (DFUs). DATA SOURCES PubMed/MEDLINE and other digital databases. STUDY SELECTION The authors included studies comparing the SAF levels in patients with DFU with a non-DFU group to determine its association with DFU risk. DATA EXTRACTION Collected data included the SAF method and its values in DFU and non-DFU groups, covariates used in adjustment along with the unadjusted and/or multivariate adjusted odds ratios (ORs) for the association of SAF with DFU risk, and other study characteristics. DATA SYNTHESIS A total of six studies were included in this meta-analysis. Five studies that involved 611 participants were included to compare SAF methods. Compared with the non-DFU group, the DFU group showed a significantly increased level of SAF (standardized mean difference, 0.67; 95% confidence interval [CI], 0.32–1.01; P < .001). The results of meta-analysis of ORs revealed that the increased SAF level was independently associated with increased DFU risk in both unadjusted (OR, 3.16; 95% CI, 2.18–4.57; P < .001) and adjusted models (OR, 3.07; 95% CI, 1.95–4.81; P < .001). CONCLUSIONS These findings suggest that SAF could be useful as a novel and noninvasive technology to help determine DFU risk. However, further studies establishing its diagnostic and prognostic utilities are needed.

Is skin autofluorescence a novel non-invasive marker in diabetes? A systematic review and meta-analysis of case–control studies

“…[ 52 ] The development of AGEs that bind to AGE receptors primes the initiation of the signaling cascade of nuclear factor-κβ, which leads to loss of protein function, followed by cellular dysfunction, and consequently matrix degeneration. [ 6 ] In tissue, increased AGE can impact collagen cross-linking, cause the inability to generate an appropriate mechanical response, lead to mechanical stress, and increase the risk of injury, eventually progressing to a diabetic foot ulcer. [ 6 ] The AGE can lead to cardiovascular morbidity and mortality by several mechanisms, including affecting the calcium hemostasis in cardiac muscles, weakening the extracellular matrix leading to stiffness and fibrosis of the vasculature, extension of oxidative stresses, initiation of inflammation, priming the release of growth factors, and decreasing the nitric oxide levels.…”

“…[ 6 ] In tissue, increased AGE can impact collagen cross-linking, cause the inability to generate an appropriate mechanical response, lead to mechanical stress, and increase the risk of injury, eventually progressing to a diabetic foot ulcer. [ 6 ] The AGE can lead to cardiovascular morbidity and mortality by several mechanisms, including affecting the calcium hemostasis in cardiac muscles, weakening the extracellular matrix leading to stiffness and fibrosis of the vasculature, extension of oxidative stresses, initiation of inflammation, priming the release of growth factors, and decreasing the nitric oxide levels. As a result, endothelial dysfunction, vasoconstriction, fibrosis, atherosclerosis, and thrombosis would develop.…”

“…Accordingly, a strong relationship was found between SAF measurement and AGE accumulation by skin biopsy, glycated hemoglobin (HbA1c), or several diabetic complications. [ 6 ] Increased tissue AGE in body organs causes various pathologies that lead to organ dysfunction and complications. In our previous meta-analysis study, we obtained that higher SAF measurements were significantly associated with several diabetic complications, such as retinopathy, nephropathy, and neuropathy.…”

“…[ 3 ] Similarly, a recent meta-analysis study demonstrated that SAF as a novel technology can successfully evaluate the risk of diabetic foot ulcers. [ 6 ] In addition, in a study, the authors suggested SAF measurement as a noninvasive technology for the detection of DM and individuals with impaired fasting glucose. [ 7 ] There are limited and discrete data comparing SAF levels in DM patients with nondiabetic individuals.…”

Diabetic Foot Care: A Screening on Primary Care Providers’ Attitude and Practice in Riyadh, Saudi Arabia

“…Several publications showed the implication of these end-products in the development of diabetes micro- and macrovascular complications [ 4 ]. Primary care providers can utilize skin autofluorescence which is one of the novel techniques that can be used to detect the accumulation of glycation end-products, thus, can aid in the detection and follow-up of diabetes micro complications [ 5 , 6 ]. A study performed in Saudi Arabia reported that 3.3% of diabetic patients were diagnosed with diabetic foot (DF) complications [ 7 ].…”