UNASSIGNED: Elevated skin autofluorescence (SAF), a measure of tissue accumulation of advanced glycation end products (AGEs), is a strong predictor of all-cause and cardiovascular mortality in the hemodialysis population. However, prospective studies investigating the association between changes in SAF over time and mortality are scarce. We therefore aimed to investigate the prognostic value of SAF trend for predicting mortality in a hemodialysis population.
UNASSIGNED: We enrolled 120 patients on hemodialysis in a 5-year observational, prospective study. SAF was measured at baseline, 3, 6, 9, 12, and 24 months. Rate of change in SAF (i.e., SAF trend) was calculated using linear regression. Time to event was the number of days from baseline to death, kidney transplantation, or March 31, 2022.
UNASSIGNED: Mean age, mean baseline SAF, and median SAF trend were 65 ± 14 years, 3.4 ± 0.9 arbitrary units (AU), and an increase of 0.1 (-0.1 to 0.4) AU/yr, respectively. Median observation time was 42 months, during which 59 participants (49%) died. Univariable analysis identified age, history of smoking, lower serum albumin, higher baseline SAF, and increase in SAF as significant predictors of higher mortality. In multivariable analysis, higher baseline SAF (hazard ratio: 1.45; 95% confidence interval: 1.08-1.94; P = 0.01) and increasing SAF trend (2.37 [1.43-3.93]; P < 0.001) were independent predictors of increased mortality.
UNASSIGNED: An increasing SAF trend and higher baseline SAF were independent predictors of all-cause mortality in this hemodialysis population, suggesting that monitoring of SAF may have clinical utility. Strategies to improve outcomes by reducing or preventing the increase in SAF should now be investigated in prospective studies.

Advanced glycation end products (AGEs) have been reported to be associated with osteoporosis, aging, sarcopenia, and frailty. This study aimed to investigate the association AGEs with locomotive syndrome (LS). Participants were Japanese individuals aged 39 years or older who participated in the Yakumo Study (n=230). AGEs were measured by skin autofluorescence (SAF) using an AGE reader. We investigated SAF values for each locomotive stage. Multivariate logistic regression models were used to calculate the odds ratios of LS-associated factors. The relationships between SAF and physical performance and bone mineral density (BMD) were investigated. A receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value of SAF for predicting LS. SAF values tended to increase correspondingly with LS severity. SAF was an independently explanatory factor for LS (odds ratio 2.70; 95% confidence interval [CI] 1.040-6.990). SAF was positively correlated with the 10-m walking speed, The Timed Up and Go test results, and was negatively correlated with BMD. ROC curve represented by SAF for the presence or absence of LS risk had an area under the curve of 0.648 (95% CI: 0.571-0.726). High SAF values were identified as an independent risk factor for LS. AGEs could be a potential screening tool for people for LS.

Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF\'s association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D).
METHODS: A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation.
RESULTS: We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; p = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all p < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; p = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, p < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], p = 0.001).
CONCLUSIONS: Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.

OBJECTIVE: Previous studies have shown that skin autofluorescence (SAF), measured with an advanced glycation end product (AGE) reader, estimates the accumulation of AGEs in tissues. SAF is predictive of incident type 2 diabetes, cardiovascular disease (CVD), and CV mortality in the general population. Studies in diabetic mice have shown that activation of the receptor for AGEs in hematopoietic progenitor cells increases blood neutrophils and monocytes, impairing atherosclerosis regression. We asked whether SAF is associated with blood neutrophil and monocyte counts in the general population, and whether this was moderated by prediabetes, diabetes, and sex.
METHODS: We examined the associations between SAF and blood neutrophil/monocyte counts in participants of the Lifelines cohort (n = 58,923: n = 24,382 men, and n = 34,541 women), a prospective population-based cohort from the North of the Netherlands, employing multivariable regression analyses.
RESULTS: SAF positively associated with blood neutrophil and monocyte counts in the whole cohort. The positive association between SAF and monocyte, but not neutrophil, counts was moderated by prediabetes and diabetes. Positive associations between SAF and blood neutrophil and monocyte counts were moderated by male sex. Moreover, three-way interaction analyses revealed that the positive associations between SAF and neutrophil and monocyte counts were moderated by prediabetes, but not diabetes, in male sex.
CONCLUSIONS: SAF is positively associated with blood neutrophil and monocyte counts in the general population, especially in men with prediabetes. This may contribute to the increased CV risk in men with prediabetes.

Advanced Glycation End Products (AGEs) contribute to the pathophysiology of type 2 diabetes mellitus (T2DM) and cardiovascular (CV) diseases (CVDs), making their non-invasive assessment through skin autofluorescence (SAF) increasingly important. This study aims to investigate the relationship between SAF levels, cardiovascular risk, and diabetic complications in T2DM patients. We conducted a single-center, cross-sectional study at Consultmed Hospital in Iasi, Romania, including 885 T2DM patients. The assessment of SAF levels was performed with the AGE Reader™, (Diagnoptics, Groningen, The Netherlands). CVD prevalence was 13.9%, and according to CV risk category distribution, 6.1% fell into the moderate-risk, 1.13% into the high-risk, and 92.77% into the very-high-risk category. The duration of DM averaged 9.0 ± 4.4 years and the mean HbA1c was 7.1% ± 1.3. After adjusting for age and eGFR, HbA1c values showed a correlation with SAF levels in the multivariate regression model, where a 1 SD increase in HbA1c was associated with a 0.105 SD increase in SAF levels (Nagelkerke R2 = 0.110; p < 0.001). For predicting very high risk with an SAF cut-off of 2.35, sensitivity was 67.7% and specificity was 56.2%, with an AUC of 0.634 (95% CI 0.560-0.709, p = 0.001). In T2DM, elevated SAF levels were associated with higher CV risk and HbA1c values, with 2.35 identified as the optimal SAF cut-off for very high CV risk.

This article examines the importance of advanced glycation endproducts (AGEs) and summarizes the structure of AGEs, pathological changes associated with AGEs, the contribution of AGEs to metabolic memory, and the value of AGEs as a predictor of diabetic complications and cardiovascular disease in people with and without diabetes. As a practical focus, skin autofluorescence (SAF) is examined as an attractive approach for estimating AGE burden. The measurement of AGEs may be of significant value to specific individuals and groups, including Black and Hispanic/Latino Americans, as they appear to have higher concentrations of hemoglobin A1c (HbA1c) than would be predicted by other metrics of mean glycemia. We hypothesize that if the amount of glycation of HbA1c is greater than expected from measured glucose levels, and if AGEs are accumulating, then this accumulation of AGEs might account for the increased rate of complications of diabetes in populations with high rates of vascular disease and other complications. Thus, identifying and modifying the burden of AGEs based on measurement of AGEs by SAF may turn out to be a worthwhile metric to determine individuals who are at high risk for the complications of diabetes as well as others without diabetes at risk of vascular disease. We conclude that available evidence supports SAF as both a clinical measurement and as a means of evaluating interventions aimed at reducing the risks of vascular disease and diabetic complications.

BACKGROUND: Cardiovascular disease is frequent in type 2 diabetes mellitus (T2DM). We investigated the relationship between skin autofluorescence (SAF) of advanced glycation end-products and later cardiovascular events (CVEs) in patients with T2DM.
METHODS: We conducted a retrospective analysis of 504 patients hospitalized for uncontrolled and/or complicated T2DM between 2009 and 2017. SAF was measured using an AGE-Reader. Participants were followed up from admission to December 2020, for the onset of a CVE (myocardial infarction, stroke, revascularization procedures or cardiovascular death). The relationship between SAF and CVE was analyzed by multivariable Cox regression. Log-rank curves were used to compare CVE-free survival in patients whose SAF at admission was above versus below the whole-population median. The analysis was repeated in subjects without/with macroangiopathy (defined as myocardial infarction, stroke, peripheral revascularization) at baseline.
RESULTS: During 54 months of follow-up, 69 (13.7%) patients had a CVE. Baseline SAF was significantly higher in patients with T2DM who later experienced a CVE (2.89 ± 0.70 arbitrary units versus 2.64 ± 0.62 in others, P = 0.002). This relationship was significant after adjusting for age, sex, conventional risk factors (diabetes duration, HbA1c, arterial hypertension, dyslipidemia, smoking, body mass index), vascular complications, C-reactive protein, and treatments for diabetes. The CVE-free survival curves differed between subjects whose SAF was above the whole-population median (log-rank: P = 0.002) and those whose SAF was above the macroangiopathy-free sub-population median (log-rank: P = 0.016).
CONCLUSIONS: SAF of advanced glycation end-products was related to a higher incidence of later CVE in patients with T2DM.

Chen et al. recently related the skin autofluorescence (SAF) of Advanced Glycation End-products to subclinical cardiovascular disease in the 3001 participants from the general population (Rotterdam study), with a particularly close relationship for the 413 subjects with diabetes. Because conventional vascular risk factors do not capture the risk in diabetes very well, this relationship may help to select high-risk individuals for the screening of silent myocardial ischemia, which has yet to prove its benefit in randomized controlled trials. Among 477 patients with uncontrolled and/or complicated Type 2 Diabetes, we measured the SAF ten years ago, and we registered new revascularizations during a 54-months follow-up. The patients with SAF > 2.6 Arbitrary units (AUs), the median population value, experienced more revascularizations of the coronary (17/24) and lower-limb arteries (13/17) than patients with a lower SAF, adjusted for age, sex, diabetes duration, vascular complications, and smoking habits: HR 2.17 (95% CI: 1.05-4.48), p = 0.035. The SAF has already been reported to predict cardiovascular events in three cohorts of people with diabetes. We suggest that its measurement may help to improve the performance of the screening before vascular explorations and revascularizations.

It has previously been unclear whether the accumulation of advanced glycation end products, which can be measured using skin autofluorescence (SAF), has a significant role in diabetic kidney disease (DKD), including glomerular injury and tubular injury. This study was therefore carried out to determine whether SAF correlates with the progression of DKD in people with type 2 diabetes (T2D). In 350 Japanese people with T2D, SAF values were measured using an AGE Reader®, and both urine albumin-to-creatinine ratio (uACR), as a biomarker of glomerular injury, and urine liver-type fatty acid-binding protein (uLFABP)-to-creatinine ratio (uL-FABPCR), as a biomarker of tubular injury, were estimated as indices of the severity of DKD. Significant associations of SAF with uACR (p < 0.01), log-transformed uACR (p < 0.001), uL-FABPCR (p < 0.001), and log-transformed uL-FABPCR (p < 0.001) were found through a simple linear regression analysis. Although SAF was positively associated with increasing uL-FABPCR (p < 0.05) and increasing log-transformed uL-FABPCR (p < 0.05), SAF had no association with increasing uACR or log-transformed uACR after adjusting for clinical confounding factors. In addition, the annual change in SAF showed a significant positive correlation with annual change in uL-FABPCR regardless of confounding factors (p = 0.026). In conclusion, SAF is positively correlated with uL-FABP but not with uACR in people with T2D. Thus, there is a possibility that SAF can serve as a novel predictor for the development of diabetic tubular injury.

OBJECTIVE: Advanced glycation end products (AGEs) accumulate in the body with increasing age. However, their excessive accumulation may lead to various inflammatory and chronic diseases. While it is common for older adults to experience various comorbidities, there is a scarcity of published literature documenting the specific impact of ageing and comorbidities on AGEs in this population. The present study aimed to retrospectively evaluate the correlation among AGEs in the skin, calendar age, and comorbidities in older adults.
METHODS: Accumulated AGEs in the skin were assessed by non-invasive measurement of skin autofluorescence (SAF) inside the forearm. This retrospective study included individuals who underwent SAF measurements at Shujitsu University Community Pharmacy with or without a prescription from October 2019 to October 2021. Subsequently, the associations between SAF, calendar age, comorbidities, and blood test parameters were investigated.
RESULTS: SAF showed a positive correlation with calendar age for all enrolled participants; the correlation weakened for participants aged ≥50 years and plateaued for those aged ≥60 years. Furthermore, we observed a significant increase in SAF among all participants with comorbidities compared to those without comorbidities. By contrast, among participants aged ≥50 years, SAF did not show a significant association with comorbidities. However, SAF was significantly positively correlated with white blood cell (WBC) counts in these aged populations.
CONCLUSIONS: The non-invasive assessment of SAF holds promise in evaluating changes in the physical condition associated with WBC counts among older adults.