The role of advanced glycation end products (AGEs) in bone fragility especially in diabetic bone disease is increasingly recognized and researched. As skeletal frailty in diabetes does not correlate to bone mineral density (BMD) in the same way as in postmenopausal osteoporosis, BMD may not be a suitable measure of bone quality in persons with diabetes. Abundant research exists upon the effect of AGEs on bone, and though full understanding of the mechanisms of actions does not yet exist, there is little doubt of the clinical relevance. Thus, the measurement of AGEs as well as possible treatment effects on AGEs have become issues of interest. The aim of this report is to summarize results of measurements of AGEs. It consists of a systematic review of the existing literature on AGE measurements in clinical research, an evaluation of the precision of skin autofluorescence (SAF) measurement by AGE Reader® (Diagnoptics), and a short commentary on treatment of osteoporosis in patients with and without diabetes with respects to AGEs. We conclude that various AGE measures correlate well, both fluorescent and non-fluorescent and in different tissues, and that more than one target of measure may be used. However, pentosidine has shown good correlation with both bone measures and fracture risk in existing literature and results on SAF as a surrogate measurement is promising as some corresponding associations with fracture risk and bone measures are reported. As SAF measurements performed with the AGE Reader® display high precision and allow for a totally noninvasive procedure, conducting AGE measurements using this method has great potential and further research of its applicability is encouraged.

BACKGROUND: Advanced glycation end products (AGE), one of the main factors causing diabetic end-organ damage, accumulate in long half-life proteins, such as skin and cartilage collagen. AGE measurement may offer additional evidence to predict diabetic vascular complications. Skin autofluorescence (SAF) is suggested as a non-invasive, quick, and reliable method to measure tissue AGE level. The aim of this study was to review and evaluate evidence on the clinical validation of SAF measurement in diabetes mellitus (DM) patients.
METHODS: In this systematic review and meta-analysis, we searched \"PubMed\" (MEDLINE) and \"Cochrane\" databases from their inception to 10 August 2021 for observational studies concerning SAF measurement in diabetic patients. The following key terms were used in advanced searching: \"Diabetes\", \"Diabetes Mellitus\",\" DM\", \"Glycation \", \"Advanced Glycation End product\", \"AGE\", \"skin autofluorescence\", \"SAF\". Published studies that included DM patients and estimated their AGE using SAF were considered eligible for meta-analysis. Articles that were editorials, study proposals, congress posters, or case reports and were not on human subjects were excluded. We used a random-effect models for meta-analyzing the clinical validation of SAF in DM with particular emphasis on chronic diabetes complications.
RESULTS: We identified 881 records and twenty-nine records fulfilled our eligibility criteria and were included in the systematic review and meta-analysis. A statistically significant correlation was found between SAF and diabetes last HbA1c 0.21(0.13,0.28) in studies with substantial heterogeneity (I2=77.99%, p<0.05). Nevertheless, a significant positive association between SAF level and diabetic retinopathy (DR) [(OR= 1.05, 95% CI=1.03,1.08), (I2=63.78%, p<0.05)], diabetic peripheral neuropathy (DPN) [(OR= 1.11, 95%CI= 1.06,1.16), (I2=79.17%, p<0.05)], diabetic nephropathy (DNP) [(OR= 1.08, 95%CI: 1.05,1.11), (I 2 =65.36%, p<0.05)] and diabetic macrovascular events (D-MVE) [(OR=1.08, 95%CI=1.05,1.11) (I2=67.32, p<0.05)] were found.
CONCLUSIONS: Our study confirmed the significance of SAF measurement as a non-invasive surrogate marker of DM micro and macrovascular complications. Skin AGE estimation may be a useful factor for the prediction and early detection of irreversible DM complications. More studies with larger populations and longer follow-up periods are required.

Background Chronic deposits of advanced glycation end products produced by enzymatic glycation have been suggested as predictors of atherosclerotic-related disorders. This study aimed to estimate the relationship between advanced glycation end products indicated by skin autofluorescence levels and the risk of cardiovascular and all-cause mortality based on data from observational studies. Methods and Results We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Web of Science databases from their inceptions until November 2017 for observational studies addressing the association of advanced glycation end products by skin autofluorescence levels with cardiovascular and all-cause mortality. The DerSimonian and Laird random-effects method was used to compute pooled estimates of hazard ratios and their respective 95% confidence intervals for the risk of cardiovascular and all-cause mortality associated with levels of advanced glycation end products by skin autofluorescence. Ten published studies were included in the systematic review and meta-analysis. Higher skin autofluorescence levels were significantly associated with a higher pooled risk estimate for cardiovascular mortality (hazard ratio: 2.06; 95% confidence interval, 1.58-2.67), which might not be important to moderate heterogeneity (I2=34.7%; P=0.163), and for all-cause mortality (hazard ratio: 1.91; 95% confidence interval, 1.42-2.56) with substantial heterogeneity (I2=60.8%; P=0.0.18). Conclusions Our data suggest that skin autofluorescence levels could be considered predictors of all-cause mortality and cardiovascular mortality in patients at high and very high risk.