Advanced Glycation End Products, Measured as Skin Autofluorescence and Diabetes Complications: A Systematic Review

BACKGROUND: Advanced glycation end products (AGEs) are long-lived tissue proteins that accumulate in diabetes. Skin AGEs measured in biopsy specimens strongly correlated with complications of diabetes. AGEs can also be measured noninvasively by the AGE Reader™ (DiagnOptics B.V., Groningen, The Netherlands). The aim of this review was to systematically review all articles on the association between skin autofluorescence (SAF), measured by the AGE Reader, and complications of diabetes. METHODS: We screened PubMed for studies on SAF and complications in diabetes mellitus type 1 and type 2. Seven articles met the inclusion criteria. RESULTS: All studies showed positive associations of SAF with one or more complications (all-cause mortality, cardiovascular mortality, micro- and macrovascular complications, neuropathy, and nephropathy), except retinopathy. Only three studies were of prospective design, with a follow-up of 3-5 years; the other four studies were cross-sectional. Studies were of large clinical heterogeneity. CONCLUSIONS: This systematic review of literature showed an association of SAF with end-organ complications in diabetes, except retinopathy, in all seven studies. However, studies were of large clinical heterogeneity, only three studies had a prospective design, and five studies were from the same research group. More prospective studies, with a longer period of follow-up, larger group size, and strict definitions of complications and end points, are needed to demonstrate the potential role and benefit in clinical management before the widespread use of the AGE Reader can be recommended.