The skin autofluorescence of advanced glycation end-products relates to the development of foot ulcers in type 2 diabetes: A longitudinal observational study.

Objectives: The long-term glycemic memory contributes to vascular complications in type 2 diabetes, including those patients with Diabetic Foot Ulcers (DFU). We investigated whether the skin autofluorescence (SAF) of Advanced Glycation End-products related to later DFUs.

Research Design & Methods: SAF was measured with an AGE-Reader in a retrospective cohort of patients hospitalized from 2009 to 2017 for Type 2 Diabetes. New DFUs were registered until the year 2020 and survival analyses were performed.

Results: The 517 patients (men: 58.0 %), were 62 ± 9 years old at baseline, with a duration of diabetes of 14 ± 10 years, HbA1c: 8.7 ± 1.8 %, complications included 33.8 % macroangiopathies, 44.9 % diabetic kidney diseases and 26.7 % retinopathies. According to the IWGDF classification, the grades of risk for DFU were 0 for 43.2 %, 1 for 23.9 %, 2 for 7.2 %, and 3 for 25.7 %. During the 53 months of follow-up, 58 new DFUs occurred, mostly in patients with SAF higher than its median value (2.65 AU). Adjusted for age and sex, conventional risk factors (duration and control of diabetes, arterial hypertension, dyslipidemia, smoking), and other complications (macroangiopathy, diabetic kidney disease, retinopathy), SAF related to later DFUs. Adjusted for the IWGDF classification, SAF related to new DFUs (HR: 1.81, 95%CI:1.25-2.62). This relationship was significant for the 403 subjects without previous history of DFU (HR: 2.32, 95%CI: 1.36-3.95). SAF did not predict recurrence for patients with a previous history of DFUs.

Conclusion: SAF, a simple non-invasive marker of glycemic memory, independently predicts the occurrence of a first foot ulcer in patients with Type 2 Diabetes.