Non-invasive skin autofluorescence (SAF) is a reliable measurement of advanced glycation end products (AGE) which contribute to diabetic end-organ damage. High SAF levels demonstrate significant associations with diabetic retinopathy, diabetic peripheral neuropathy, diabetic nephropathy, diabetic micro and macrovascular events, and glycated hemoglobin,(HBA1c), according to a study in EClinicalMedicine

The investigators performed a systematic review and meta-analysis, identifying 881 studies published in PubMed and Cochrane databases up until August 10, 2021. They selected 29 of the 881 studies which met the eligibility criteria.

Six studies each determined significant positive relationships between SAF and diabetic retinopathy (OR= 1.05, 95% CI =1.03,1.08), (I2 =63.78%, P <.05), diabetic peripheral neuropathy (OR= 1.11, 95% CI = 1.06,1.16), (I2 =79.17%, P <.05), and diabetic nephropathy (OR= 1.08, 95% CI = 1.05,1.11)., (I2 =65.36%, P <.05). Four articles confirmed a significant positive relationship between SAF and diabetic microvascular complications (OR=1.06, 95%CI=1.01,1.11), (I2 =85.79%, P <.05), and six articles confirmed a positive association between SAF and diabetic macrovascular complications (OR= 1.08, 95% CI = 1.05,1.11),(I2 =67.32%, P <.05).

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The researchers also found that SAF had significant correlation with specific characteristics including age (pooled correlation coefficient = [(0.38 (0.33, 0.43)], [(I2 =64.5%, P <.05)], diabetes duration (pooled correlation coefficient = [0.33(0.25, 0.42), (I2 =84.06%, P <.05)], HbA1c (pooled correlation coefficient = 0.21 (0.13,0.28), (I2 =77.99%, P <.05)], and maximum of carotid Intima Media Thickness (max-IMT) level (pooled correlation coefficient = 0.29 (0.14, 0.44), (I2 =69.01%, P <.05).

The authors acknowledged the variability of the 29 studies were cross-sectional, prospective, or retrospective in nature, limiting the systematic review and meta-analysis. Each of the studies measured different outcomes using different diagnostic tools. Other limitations included the lack of adjusted complication risk factors due to diverse confounding factors in the studies, the heterogeneity of participant ages within the cohort groups of the studies, publication bias of the studies, and lack of validation of the required sample size as well as lack of sufficient blinding of the assessors within the majority of the studies.

“Our study confirms the evidence that SAF measurement could be a non-invasive surrogate marker of DM micro and macrovascular complications,” the researchers concluded. “Skin AGE accumulation estimation may be a useful factor for the prediction and early detection of irreversible diabetic complications. Thus, various anti-AGE therapies might be needed. More studies with larger populations and longer follow-up are required.”


Hosseini MS, Razavi Z, Ehsani AH, Firooz A, Afazeli S. Clinical significance of non-invasive skin autofluorescence measurement in patients with diabetes: a systematic review and meta-analysis. EClinicalMedicine. 2021;42:101194. doi:10.1016/j.eclinm.2021.101194