Clinical Significance of Non-invasive Skin Autofluorescence Measurement in Patients with Diabetes: A Systematic Review and Meta-analysis

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. FINDINGS: 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 (I(2)=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), (I(2)=63.78%, p<0.05)], diabetic peripheral neuropathy (DPN) [(OR= 1.11, 95%CI= 1.06,1.16), (I(2)=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) (I(2)=67.32, p<0.05)] were found. INTERPRETATION: 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.