Skin Autofluorescence Research Articles

Evaluation of the Impact of Advanced Glycation End-Products on Peripheral Neuropathy Outcomes in Type 2 Diabetes

Background: Type 2 diabetes (T2DM) affects over 500 million people worldwide, and over 50% of this group experience the most common complication, diabetic peripheral neuropathy (DPN). The presence of advanced glycation end-products (AGEs) has been linked with the development of DPN. The present study assessed AGE levels in participants with type 2 diabetes and explored the hypothesis that there may be increased AGE levels in more severe DPN. Methods: A total of 124 participants with T2DM were consecutively recruited, and they underwent skin autofluorescence, clinical assessment for peripheral neuropathy, peripheral nerve ultrasound, nerve conduction studies, and axonal excitability assessment. Results: AGE accumulation showed weak but significant correlations with neuropathy severity and reduced nerve conduction function. However, after adjusting for confounding variables, a linear regression analysis did not reveal significant associations between the AGE levels and neuropathy outcomes. Conclusions: The present study suggests that the accumulation of AGE is not associated with the clinical, electrophysiological, and morphological measures of neuropathy in T2DM.

The Role of Advanced Glycation End Products in Saphenous Vein Graft Failure

Objective: We aimed to investigate the relationship between advanced glycation end product (AGE) levels in patients with saphenous vein graft (SVG) failure and in patients without SVG failure. Subjects and Methods: In our study, 55 patients with a history of previous coronary artery bypass grafting (CABG) surgery, who subsequently underwent coronary angiography for any reason and were found to have either SVG occlusion or significant lesions, were included as study patients. Additionally, 55 patients who have had CABG surgery without SVG failure for at least 1 year served as the control group. AGE values of the patients were measured using the skin autofluorescence method. Results: In our study results, we observed a significant difference in AGE levels between the two groups of patients with similar demographic characteristics (SVG failure groups AGE 3.2 [2.8–3.6] vs. control groups AGE 2.4 [2.1–2.7] p < 0.001). In the receiver operating characteristic curve analysis, we determined the ability of AGE levels to detect SVG failure with an area under the curve of 0.869. We found that in patients with AGE >3, it could detect SVG failure with a sensitivity of 70.9% and a specificity of 87.3%. Conclusions: Our results demonstrate that AGE levels can predict SVG failure risk inexpensively, easily, and quickly.

The Effects of the AGE Inhibitor Pyridoxamine on Bone in Older Women with Type 2 Diabetes: a Randomized Clinical Trial.

Type 2 diabetes (T2D) patients have reduced bone turnover and increased fractures. Advanced glycation endproducts (AGEs) impair osteoblasts and are implicated in diabetic fractures. Pyridoxamine (PM) is a vitamin B6 metabolite which inhibits formation of AGEs. We hypothesized that PM treatment in older T2D patients, by inhibiting AGEs, would increase bone formation. Double-blind RCT. Academic center. Older T2D women (n=55). Oral PM 200 mg twice daily for one year. The primary outcome was the change in the bone formation marker P1NP. Other outcomes were changes in bone resorption, bone mineral density (BMD), HbA1c and skin autofluorescence (SAF), and in a bone biopsy sub-group, the correlation between bone fluorescent AGEs (fAGEs) and SAF. P1NP increased 23.0% with PM (95% CI: 9, 37; within-group p=0.028) vs. 4.1% with placebo (-9, 17; within-group p=0.576; between-groups p=0.056). BMD increased at the femoral neck (PM: 2.6±5% vs. placebo: -0.9±4%; between-groups p=0.007). Bone resorption markers and SAF did not change. HbA1c decreased (PM: -0.38 ± 0.7% vs. placebo: 0.05 ± 1.7%; between-groups p =0.04). Within the PM group, the HbA1c change correlated inversely with the % P1NP change (r =-0.50, p=0.034). Cortical bone biopsy fAGEs correlated with SAF (r=0.86, p=0.001). Adverse events were similar between groups. PM tended to increase P1NP in older T2D women, as well as increasing bone density and reducing HbA1c. Further studies are needed to investigate the potential of PM as a disease mechanism-directed approach to reduce fractures in T2D.

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults

BackgroundIn populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium.MethodsA cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4–36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates.ResultsFMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001.ConclusionsHigher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers.Trial registrationThe study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.

Skin autofluorescence and cause-specific mortality in a population-based cohort

We aimed to assess the association of SAF with cardiovascular mortality in the general population and the possible association between SAF with other disease-specific mortality rates. We evaluated 77,143 participants without known diabetes or cardiovascular disease. The cause of death was ascertained by the municipality database. The associations between SAF and all-cause mortality, cardiovascular mortality and cancer mortality were assessed with Cox proportional hazard analysis.After a median follow-up of 115 months, 1447 participants were deceased (1.9%). SAF and age-adjusted SAF-z score were higher in all mortality groups. Cox regression analysis revealed that the highest quartile of SAF was associated with increased odds of cardiovascular mortality, (HR) 12.6 (7.3–21.7) and after adjusting for age (HR 1.8 (1.0–3.2)). Significance was lost after additional adjustments for sex, smoking status, and BMI (HR 1.4 (0.8–2.5). For cancer-related mortality the highest quartile of SAF was associated with higher probability of mortality in all models (unadjusted HR 8.6 (6.6–11.3), adjusted for age HR 2.1 (1.6–2.8)), adjusted for age, sex, smoking status, and BMI HR 1.7 (1.3–2.4)). SAF is associated with all-cause mortality as well as cardiovascular and cancer-related mortality in the general population.

Association between skin autofluorescence and coronary calcification in the general population.

To address the relationship between tissue accumulation of advanced glycation end-products, assessed by skin autofluorescence (SAF), and subclinical atherosclerosis quantified with coronary artery calcium score (CACS) in the general Dutch population. A total of 3,839 participants of the LifeLines Cohort Study without diabetes or cardiovascular disease were included in this cross-sectional evaluation. They underwent SAF measurement and cardiac computed tomography to measure CACS. Associations between SAF and CACS was assessed using regression models. Participants at elevated risk for cardiovascular disease were selected by either CACS≥100, or SAF value in the top 15%; overlap and cardiovascular risk profile of these participants were compared. In univariate analysis, every 1 arbitrary unit (AU) increase in SAF resulted in an odds ratio of 2.91 (95% confidence interval 2.44-3.48, p<0.001) for coronary calcification. After adjustment for cardiovascular risk factors, there was still 20% higher odds of coronary calcification with 1 AU increase in SAF, but significance was lost. In total, 1025 (27%) participants either had high SAF and/or high CACS, of these 441 (12%) had only high SAF, 450 (12%) had only high CACS and 134 (3%) participants had high SAF and high CACS. In a population-based Dutch cohort, SAF was associated with the degree of coronary calcification. This association was largely explained by classical cardiovascular risk factors. Limited overlap was found in subgroups with high SAF or high CACS, indicating that SAF and CACS may have complementary role in identifying individuals at elevated cardiovascular risk.

Different Measures of Hyperglycemia Are Negatively Associated With Skin Microvascular Flowmotion: TheMaastricht Study.

Diabetes can lead to microvascular complications such as diabetic neuropathy, nephropathy, and retinopathy. Hyperglycemia may initiate microvascular function impairment early in the course of diabetes, even prior to its clinical establishment during the pre-diabetes stage. Microvascular vasomotion, that is, the rhythmic arteriolar constriction and dilation, is an important function that regulates oxygen and nutrient delivery within the tissue and regulates peripheral resistance. Using laser Doppler flowmetry (LDF), vasomotion in skin microcirculation can be measured as flowmotion. Changes in flowmotion have been shown in individuals with obesity, and type 1 or type 2 diabetes mellitus. However, no data are available on associations between hyperglycemia and flowmotion in the general population. Our aim was to study whether measures of hyperglycemia were associated with different components of skin microvascular flowmotion (SMF) in a population-based cohort (The Maastricht Study). Data from 7293 participants of The Maastricht Study were used. SMF was measured using LDF. Endothelial, neurogenic and myogenic component SMF power were used as dependent variables. We investigated the associations of glucose metabolism status (normal glucose metabolism, prediabetes, and type 2 diabetes mellitus), measures of hyperglycemia (fasting plasma glucose [FPG], 2-h post-load glucose [2 h-PG], HbA1c, advanced glycation end-products [AGEs] assessed as skin autofluorescence [SAF]), and indices of glucose variability (incremental glucose peak [IGP] and continuous glucose monitoring [CGM] -assessed as standard deviation [SD]) with each component of SMF power. We used linear regression analyses with adjustments for confounders, and trend analyses. We observed consistent negative associations between HbA1c levels and all three (endothelial, neurogenic, and myogenic) skin microvascular flowmotion (SMF) powers in the additionally adjusted model. Similarly, in the conservative model, we found that multiple hyperglycemia metrics such as GMS trend, PreD, T2DM, FPG, 2 h-PG, and HbA1c were consistently negatively associated with all three SMF powers. We showed that skin microvascular flowmotion is reduced in individuals with (pre)diabetes. In addition, different measures of hyperglycemia are negatively associated with skin microvascular flowmotion.

Advancing the Diagnosis of Diabetic Neuropathies: Electrodiagnostic and Skin Autofluorescence Methods.

Diabetic neuropathy (DN) is a generic term for various neuropathies coexisting in a single patient. Clinical diagnosis alone can be misleading, yet routine electrodiagnostic studies in diabetes care are rare. Skin autofluorescence (SAF) is a recognized DN risk factor with potential screening value. This article highlights the diagnostic challenges and raises awareness of the often underdiagnosed neuropathic conditions in diabetes patients. We present common entrapment neuropathy cases from our diabetes clinic's electrodiagnosis laboratory in Iași, Romania. We selected seven type 2 diabetes patients with sensory or sensory-motor distal polyneuropathy and atypical DN presentations investigated through electroneurography (ENG) and electromyography (EMG) with the Neurosoft® EMG instrument and SAF measured by standard procedures. Subsequently, a narrative literature review was conducted. Entrapment neuropathies were diagnosed in all the patients: three carpal tunnel syndromes, two ulnar neuropathies (one proximal, one distal), one peroneal neuropathy, and one case of meralgia paresthetica. The lower-limb cases showed radiculoplexopathy, and there was one case of superficial radial nerve neuropathy. The SAF values ranged from 2.5 AU to 3.4 AU. Electrodiagnosis is essential for detecting focal neuropathies in patients with sensory-motor distal polyneuropathy. Elevated SAF levels may correlate with symptom severity, although further research, including large cohorts, is needed.

Frailty and aging are associated with cognitive decline and dermal advanced glycation end-product accumulation in older Japanese men

BackgroundDermal advanced glycation end-product (AGE) accumulation is associated with various diseases, as well as frailty and aging. Frailty and aging are well known to be associated with a decline in cognitive function. We placed middle-aged and older Japanese people into four groups according to their physical frailty status and age, and then evaluated the relationship their dermal AGE accumulation and cognitive function. Materials and methodsWe performed a cross-sectional study of 559 participants (236 men, mean age 67.3 years). Dermal AGE accumulation in the forearms of the participants was assessed using skin autofluorescence (SAF), and cognitive function was assessed using the touch panel-type dementia assessment scale (TDAS). Parameters relating to anthropometry, atherosclerosis, and frailty were evaluated at medical check-ups. The factors independently associated with TDAS score were identified by multivariate analysis. ResultsMultivariate analysis showed that age and frailty were inversely associated with TDAS. We then allocated risk scores (0–3) to reflect the combination of these parameters (age, 0 or 1; SAF score, 0, 1, or 2). The SAF corresponding to a score of 2-3 points on the receiver operating characteristic curve was 2.18 units in men (sensitivity 67.2 %, specificity 70.0 %, area under the curve (AUC) 0.695, p < 0.001) and 2.03 units in women (sensitivity 65.8 %, specificity 52.3 %, and AUC 0.600, p = 0.009), implying a closer relationship in men than women. ConclusionsWe have identified a relationship between dermal AGE accumulation and a high risk of cognitive decline in middle-aged and older Japanese people, especially in men.

Assessment of Skin Autofluorescence in Children with Diabetes Mellitus Type 1

Assessment of Skin Autofluorescence in Children with Diabetes Mellitus Type 1

Usefulness of Serum Testosterone Concentration and Skin Autofluorescence as Coronary Risk Markers in Male Patients With Type 2 Diabetes Mellitus.

No studies have reported simultaneous evaluation of the two coronary risk markers of testosterone and skin autofluorescence (SAF) as a marker of advanced glycation end products in patients with type 2 diabetes mellitus (T2DM) at present. This study aimed to clarify the clinical significance of both indicators as risk markers of coronary artery disease (CAD), including the association and background factors between testosterone and SAF in male patients with T2DM. This study enrolled 162 male patients with T2DM (CAD: n = 35). Testosterone was evaluated by serum total testosterone concentration (T-T). Various analyses related to T-T and SAF as coronary risk markers were performed. T-T was significantly lower, and SAF was significantly higher in patients with CAD than in patients with non-CAD. A significant negative correlation was found between T-T and SAF (r = -0.45, P < 0.001), and the correlation was stronger in patients with CAD than in patients with non-CAD (non-CAD, r = -0.27, P = 0.003; CAD, r = -0.51, P < 0.001). However, both T-T and SAF had significant associations with triglyceride-glucose index as an insulin resistance marker and cardio-ankle vascular index as an arterial function marker. Multiple regression analysis revealed that both T-T and SAF were selected as independent variables to the presence of CAD as a dependent variable. However, the odds ratio increased due to the merger of two coronary risk markers, low T-T and high SAF (odds ratio: one risk marker: 3.24, 95% confidence interval: 1.01 - 10.50, P = 0.045; two risk markers: 13.22, 95% confidence interval: 3.41 - 39.92, P < 0.001). The results of this cross-sectional study indicate that T-T and SAF are closely related in CAD patients with T2DM. It also shows that insulin resistance and arterial dysfunction are in the background of both indicators. Additionally, not only are both indicators independent coronary risk markers, but the overlap of both indicators increases their weight as coronary risk markers.

Relationship Between Oxidative Stress in the Rotator Cuff and Transcutaneous Advanced Glycation End-Products Measurement in Diabetic Rats.

Diabetes mellitus increases oxidative stress due to hyperglycemia, resulting in the degeneration of rotator cuff tissue. Currently, there is no established method to non-invasively assess the extent of this oxidative stress. To address this, we aimed to investigate the relationship between the accumulation of advanced glycation end-products (AGEs), a marker of oxidative stress, and transcutaneous autofluorescence intensity in rotator cuff tissue harvested from diabetic rats. Ten control Sprague-Dawley (SD) rats and streptozotocin-induced diabetic rats (n = 10 per group) were used. The rats were euthanized eight and 16 weeks after the induction of diabetes, and rotator cuff attachment sites were collected and histologically analyzed. Prior to euthanasia, autofluorescence intensity was measured transcutaneously in the rotator cuff area. The expressions of AGEs and type I collagen were evaluated immunohistochemically with specific antibodies and the stained areas were quantified. All data were statistically analyzed using the Mann-Whitney U test. Correlation analysis was performed for skin autofluorescence intensity and the percentage of AGEs staining area using Spearman's rank correlation coefficient. The immunohistochemical expression of AGEs at the rotator cuff attachment sites and transcutaneous AGEs measurements were significantly higher in diabetic rats than in the control group at 16 weeks. There was no significant difference in the level of type 1 collagen between the two groups. This study reveals that the accumulation of AGEs in rotator cuff tissue increases due to prolonged hyperglycemia in diabetes. In addition, transcutaneous skin fluorescence intensity may be related to histological oxidative stress at the rotator cuff.

Association between Mediterranean Diet and Advanced Glycation End Products in University Students: A Cross-Sectional Study.

The aim of this study was to evaluate the association between the Mediterranean diet (MD) and the accumulation of advanced glycation end products (AGEs) measured by skin autofluorescence. This cross-sectional study included 1016 healthy students from the University of Split, Croatia. Participants completed a self-administered questionnaire. Adherence to the MD was assessed using the Mediterranean Diet Serving Score (MDSS), and tissue AGEs accumulation was measured using the AGE Reader mu (DiagnOptics). Multivariate linear regression was used in the analysis. Students' age and female gender were associated with higher levels of AGEs, which was likewise found for greater coffee intake, adequate olive oil consumption, smoking, and lower levels of physical activity. Higher consummation of vegetables and eating breakfast regularly were associated with lower AGEs levels. The overall MD adherence was not associated with AGEs, possibly due to very low overall compliance to the MD principles among students (8.3% in women and 3.8% in men). Health perception was positively associated with the MD and nonsmoking and negatively with the perceived stress level, while AGEs did not show significant association with self-rated students' health. These results indicate that various lifestyle habits are associated with AGEs accumulation even in young and generally healthy people. Hence, health promotion and preventive measures are necessary from an early age.

Possibilities of Skin Autofluorescence Reflecting the Characteristics of Diabetes Mellitus in Childhood

Objective: To measure skin autofluorescence in children and adolescents suffering from type 1 diabetes mellitus and evaluate its relationship with gender, age, experience and chronic complications of the disease. Materials and Methods: The study group included 47 children and adolescents with type 1 diabetes. Autofluorescence of the skin from the inner surface of the shoulder and nail of patients was measured using an original compact spectrofluorimeter based on the STS-VIS OCEAN OPTICS © USA microspectrometer with UVA excitation. Statistical analysis was carried out using StatsoftStatistica 12.0 software. The data is presented as a two-dimensional array. The UV LED signal was averaged and smoothed using the moving average method with a 10 nm window. Then the spectra were renormalized taking into account the found coefficients. The result of applying additional normalization is a decrease in the standard deviation. Results and Discussion: Significant differences were revealed in the skin fluorescence spectra of children of different ages. between age groups (5-7) and (8-12) is most significant in the region of the alpha band of oxyhemoglobin (540 nm) (p &lt;0.005). When using I-normalization, the NADH peak region (p &lt; 0.02) is significant with increasing disease duration. When studying the influence of gender factors on the level of skin autofluorescence, the most significant differences are found in the area of only the isosbestic points of deoxy and oxyhemoglobin 442 nm (p&lt;10-7) and 491 nm (p&lt;10-8). Significant differences in skin autofluorescence at the reference length were also obtained waves in the autofluorescence spectrum of 500 nm correspond to p&lt;10-14, depending on the presence of complications. Conclusion: In Russia, as well as throughout the world, there is an increase in the incidence of type 1 diabetes mellitus. For early diagnosis of changes in carbohydrate metabolism and complications of the disease, a simple, accessible, non-invasive research method is needed. Taking into account the results of our study, when creating non-invasive methods for monitoring the state of carbohydrate metabolism, it is necessary to take into account gender and age characteristics, experience and the presence of complications of type 1 diabetes mellitus.

Assessment of Skin Autofluorescence and Its Association with Glycated Hemoglobin, Cardiovascular Risk Markers, and Concomitant Chronic Diseases in Children with Type 1 Diabetes.

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. 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). 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.

Assessment of skin autofluorescence in children with diabetes mellitus type

Objective: To measure skin autofluorescence in children and adolescents suffering from type 1 diabetes mellitus and evaluate its relationship with gender, age, experience, and chronic complications of the disease. Materials and methods: The study group included 47 children and adolescents with type 1 diabetes. Autofluorescence of the skin from the inner surface of the shoulder and nail of patients was measured using an original compact spectrofluorimeter based on the STS-VIS OCEAN OPTICS © USA microspectrometer with UVA excitation. Statistical analysis was carried out using StatsoftStatistica 12.0 software. The data is presented as a two-dimensional array. The UV LED signal was averaged and smoothed using the moving average method with a 10 nm window. Then the spectra were renormalized taking into account the found coefficients. The result of applying additional normalization is a decrease in the standard deviation. Results and discussion: Significant differences were revealed in the skin fluorescence spectra of children of different ages. Between age groups (5-7) and (8-12) is most significant in the region of the alpha band of oxyhemoglobin (540 nm) (p &lt; 0.005). When using I-normalization, the NADH peak region (p &lt; 0.02) is significant with increasing disease duration. When studying the influence of gender factors on the level of skin autofluorescence, the most significant differences are found in the area of only the isosbestic points of deoxy and oxyhemoglobin 442 nm (p &lt; 10-7) and 491 nm (p &lt; 10-8). Significant differences in skin autofluorescence at the reference length were also obtained waves in the autofluorescence spectrum of 500 nm correspond to p &lt; 10-14, depending on the presence of complications. Conclusion: In Russia, as well as throughout the world, there is an increase in the incidence of type 1 diabetes mellitus. For early diagnosis of changes in carbohydrate metabolism and complications of the disease, a simple, accessible, non-invasive research method is needed. Taking into account the results of our study, when creating non-invasive methods for monitoring the state of carbohydrate metabolism, it is necessary to take into account gender and age characteristics, experience, and the presence of complications of type 1 diabetes mellitus.

#3001 MtDNA copy number correlates to coronary artery calcium score and biological age in kidney failure patients

Abstract Background and Aims Chronic kidney disease (CKD) and kidney failure are connected to increased oxidative stress and vascular calcification, which are indicators for development of comorbidities and mortality outcome. Mitochondrial (mt)DNA copy number has been reported as independent predictor for frailty and mortality outcome of various cardiovascular diseases (CVD) and cancer. We aimed that mtDNA copy number in whole blood of kidney failure patients can be correlated to coronary artery media calcification score and coronary artery calcium (CAC) score and be used as an independent predictor for comorbidities and mortality outcome. Method Quantitative PCR (qPCR) with TaqMan® probes for three mtDNA genes (mtND1, mtND4 and mtCOX1) and two single locus genes on nuclear DNA (hemoglobin subunit beta and 18S), for normalization, is performed on DNA samples isolated from collected blood of 196 kidney transplant donors and 211 recipients at basal timepoint and 32 at 1-year-follow-up timepoint, included in the KaroKidney biobank. Resulting mtDNA copy number is investigated for correlation to CAC score, patient mortality outcome, biological age determined by skin autofluorescence and other clinical parameters. Results In our Swedish kidney transplant cohort we can see statistically significant difference in mtDNA copy number between kidney failure patients (recipients) and healthy controls (donors). No obvious difference between females and males was observed. mtDNA copy number correlates to biological age determined by skin autofluorescence, CAC score and Framingham CVD risk score. In the 32 1-year-follow-up samples we could see significant increase/recovery of mtDNA copy number for male patients compared to their baseline before receiving a transplant. Conclusion In this study we show that mtDNA copy number in kidney failure patients correlates to biological age and CAC score, affirming mtDNA copy number as an independent predictor of frailty in this Swedish cohort of CKD patients. Additionally, we can see that a kidney transplant can lead to a significant increase of mtDNA copy number in blood one year later, suggesting a general increase in health quality.

#1277 Comparing advanced glycation end products removal in super high-flux hemodialysis versus high-volume hemodiafiltration: a randomized, crossover study

Abstract Background and Aims Expanded hemodialysis using super high-flux membrane, is a promising therapy for effectively clearing middle molecule uremic toxins. However, its impact on advanced glycation end products (AGEs), which is related to an increase in cardiovascular mortality [1], remains inconclusive. Previous studies demonstrated that AGEs increased over time in patients treated with high-flux hemodialysis (HD) [2, 3] while remaining stabilized in online hemodiafiltration (ol-HDF) [3]. This study aims to compare the longitudinal tissue AGEs measured by skin autofluorescence (SAF) between super high-flux hemodialysis (SHF-HD) and high-volume post-dilution ol-HDF. Method In this open-label prospective cross-over 24-week trial, twenty-two prevalent HD patients were randomly assigned to undergone two sequences of 24-week treatment periods: SHF-HD followed by high-volume postdilution ol-HDF or vice versa, with a 4-week wash-out period with high-flux HD between. SAF was measured at baseline and 24 weeks. Midweek pre-HD measurements of beta-2 microglobulin (B2M), serum albumin, normalized protein catabolic rate (NPCR) and Kt/V were obtained every 8 weeks. The amount of dialysate albumin was collected by continuous sampling of spent dialysate method and determined by immunoturbidimetric assay Results Seventeen out of twenty-two patients completed the study. At baseline, SAF levels (3.88 ± 0.14 vs 3.99 ± 0.14 AU, p = 0.463) and pre-HD B2M (22.66 ± 1.41 vs 21.09 ± 1.41 mg/L, p = 0.228) were similar between the SHF-HD and ol-HDF groups. After 24 weeks, SAF levels showed no significant change in SHF-HD (from 3.88 ± 0.14 to 3.91 ± 0.14 AU, p = 0.846) and ol-HDF (from 3.99 ± 0.14 to 3.95 ± 0.14 AU, p = 0.796), with a mean difference of change 0.06 (95% CI −0.34, 0.47, p = 0.75). Similarly, mid-week pre-HD serum B2M at 24 weeks exhibited no significant change in the SHF-HD group (22.66 ± 1.41 to 22.18 ± 1.47 mg/L, p = 0.722) and the ol-HDF group (21.09 ± 1.41 to 21.83 ± 1.45 mg/L, p = 0.577), with a mean difference of change −1.22 (95% CI −4.94, 2.49, p = 0.519). The spKt/V urea did not exhibit any notable differences. Furthermore, pre-HD levels of all small uremic toxins after the 24-week periods did not differ between both groups. Nutritional status measured by serum albumin and NPCR were comparable despite higher dialysate albumin loss in postdilution ol-HDF group (0.82 ± 0.04 vs 1.92 ± 0.12 g, p &amp;lt; 0.001 in SHF-HD and ol-HDF, respectively) Conclusion After 24 weeks of treatment, SHF-HD demonstrated levels of AGEs, pre-HD serum B2M, and serum albumin comparable to high-volume ol-HDF. If high-volume postdilution ol-HDF is not feasible, SHF-HD may serve as a valuable alternative treatment for stabilizing AGEs in chronic hemodialysis patients.

A Mediterranean diet improves glycation markers in healthy people and in those with chronic diseases: a systematic review of clinical trials.

Consumption of the Mediterranean diet (MedDiet) has beneficial effects on cardiometabolic health and aging. This systematic review aimed to critically investigate the effect of the MedDiet on glycation markers in healthy or overweight individuals with type 2 diabetes or cardiovascular disease. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched, using the terms "Mediterranean diet" AND "glycation end products, advanced". Three randomized and 3 nonrandomized clinical trials, containing data on 2935 adult and elderly individuals with normal weight or overweight, were included. All extracted data were compiled, compared, and critically analyzed. The authors of most of the studies demonstrated a reduction in serum concentrations of advanced glycation end products (AGEs), such as εN-carboxymethyllysine and methylglyoxal, and in skin autofluorescence levels after at least 4 weeks of adherence to the MedDiet. The MedDiet also led to positive effects on gene expression of receptors for AGEs, as RAGE and AGER1, and an enzyme involved in detoxification (glyoxalase I). There is no evidence that short-term adherence affects glycation markers. Glycation markers improved in response to the MedDiet. The possible mechanisms involved may be related to the low AGE and refined sugars content of the diet, as well as its high monounsaturated fatty acid, phenolic compound, and dietary fiber contents. PROSPERO registration no. CRD42021284006.

Relationship between locomotive syndrome and advanced glycation end products measured by skin autofluorescence in community-dwelling patients: the Yakumo Study.

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.