Skin Advanced Glycation End Products Research Articles

Exploring Cognitive Impairments Associated with Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

This study explored the link between different types of glaucoma and cognitive function in a cohort of 620 Japanese patients. Participants were categorized into primary open-angle glaucoma (PG), exfoliation glaucoma (EG), and non-glaucomatous control groups. The findings revealed a significant decline in cognitive function as indicated by the Mini-Cog test in the EG group (mean ± SD: 4.0 ± 1, 95% CI: 3.9 to 4.2) compared to the PG group (4.4 ± 0.1, 4.3 to 4.5, p < 0.0001). Levels of fingertip measured advanced glycation end-products (AGEs) were significantly higher in the EG group (mean ± SD: 0.45 ± 0.006, 95% CI: 0.44 to 0.46) compared to the PG group (0.43 ± 0.004, 0.42 to 0.44, p = 0.0014). Although the multivariate analysis initially showed no direct association between glaucoma types and Mini-Cog scores, the EG group exhibited higher age and intraocular pressure (IOP) compared to the PG group. Further analysis revealed that high levels of AGEs were associated with cognitive decline and decreased mean visual fields in the EG group. Age was identified as a cofounding factor in these associations. An inverse correlation was observed between the accumulation of AGEs and skin carotenoid levels. Early detection of cognitive decline in glaucoma patients could enable timely intervention to preserve visual fields. Fingertip measurements of skin carotenoids and AGEs offer promising potential as non-invasive, straightforward diagnostic tools that could be widely adopted for monitoring ophthalmic and cognitive health in glaucoma patients.

Association between sex hormones and erectile dysfunction in men without hypoandrogenism

In addition to testosterone, various endocrine hormones, such as dehydroepiandrosterone sulfate (DHEA-S) and estradiol, may be involved in erectile function. However, the role of these sex hormones in the erectile function of men without hypoandrogenism remains unclear. This cross-sectional study included 398 community-dwelling men without hypoandrogenism. The participants were categorized into the non-ED and ED groups. Multivariable logistic regression analyses were performed to investigate the relationship between ED and serum sex hormone levels, including total testosterone, DHEA-S, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Among the 398 men, 66 (17%) and 332 (83%) were categorized into the non-ED and ED groups, respectively. In the multivariable analyses, serum DHEA-S and estradiol levels were significantly associated with ED (odds ratio [OR]: 0.996, P = 0.030; OR: 1.082, P = 0.002; respectively), whereas serum total testosterone, LH, FSH, and prolactin levels did not demonstrate significant association. After adjusting for age, none of neutrophil-to-lymphocyte ratio, serum plasminogen activator inhibitor-1 levels, and skin advanced glycation end-products levels demonstrated significant correlation with serum DHEA-S and estradiol levels. In conclusion, lower testosterone levels did not affect ED in men with normal testosterone levels, whereas serum DHEA-S and estradiol levels were significantly associated with ED.

Association of advanced glycation end products with ear lobe crease: A cross-sectional study.

Several studies have demonstrated a significant association between the presence of the ear lobe crease (ELC) and cardiovascular disease. Advanced glycation end-products (AGEs) can affect the structures and functions of proteins and contribute to the development of diabetic complications. However, few studies have reported the relationship between AGEs and ELC. The purpose of this study was to investigate the correlation of skin autofluorescence (SAF)-AGEage (SAF-AGEs × age/100) with ELC. This cross-sectional study enrolled 6500 eligible participants from two communities in Beijing. Skin autofluorescence (SAF) was used to measure skin AGEs (SAF-AGEs). SAF-AGEage was defined as AGEs × age/100. Binary logistic regression analysis and linear regression analysis nested in logistic models were applied to test outcomes. The overall prevalence of ELC with an average age of 62.7 years participants was 57.1% (n = 3714). Age, fasting blood glucose, systolic blood pressure, and lipoprotein cholesterol were all greater in participants with ELC. ELC-positive participants had higher prevalence of coronary heart disease. Logistic analysis showed a significantly positive relationship between quartiles of SAF-AGEage and ELC (odds ratio [OR] 1.526, 95% CI 1.324-1.759; OR 2.072, CI 1.791-2.396; and OR 2.983, CI 2.551-3.489) for the multivariate-adjusted models, respectively. Stratified research revealed that those with a history of diabetes, hypertension, or coronary heart disease experienced the connection between SAF-AGEage and ELC. ELC is associated with coronary heart disease, and the SAF-AGE has a potential role in ELC development in elder people.

Skin advanced glycation end-products as indicators of the metabolic profile in diabetes mellitus: correlations with glycemic control, liver phenotypes and metabolic biomarkers

IntroductionThe production of advanced glycation end-products (AGEs) is a key pathomechanism related to the complications of diabetes mellitus. The measurement of HbA1c as one of the AGEs is widely used in the clinic, but also other proteins undergo glycation in the course of diabetes. Here, we measure skin AGEs (SAGEs) in patients with diabetes type 1 (DM1) and type 2 (DM2) and correlate them with metabolic markers as well as non-invasively measured liver fibrosis and steatosis.Patients and methodsIn this cross-sectional study, a total of 64 patients with either DM1 or DM2 and 28 healthy controls were recruited. SAGEs were measured using autofluorescence (AGE Reader). Liver fibrosis and steatosis were quantified using transient elastography, which determines liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). FGF19, FGF21 and GDF-15 were measured in blood samples using ELISA.ResultsSAGEs were elevated in both groups of patients with diabetes as compared to healthy controls (both p < 0.001) and were higher in patients with DM2 in comparison to DM1 (p = 0.006). SAGEs correlated positively with HbA1c (r = 0.404, p < 0.001), CAP (r = 0.260, p = 0.016) and LSM (r = 0.356, p < 0.001), and negatively with insulin growth factor binding protein 3 (p < 0.001). We also detected a positive correlation between GDF15 and SAGEs (r = 0.469, p < 0.001).ConclusionsSAGEs are significantly elevated in patients with both DM types 1 and 2 and correlate with metabolic markers, including HbA1c and GDF15. They might also help to detect patients with advanced liver injury in the setting of diabetes.

Research Progress of Skin Advanced Glycation End Products in Predicting Vascular Complications in Patients with Type 2 Diabetes Mellitus

Research Progress of Skin Advanced Glycation End Products in Predicting Vascular Complications in Patients with Type 2 Diabetes Mellitus

Accumulation of advanced glycation end products in skin and increased vascular ageing in the general population: the Malmö Offspring Study.

Advanced glycation end product (AGE) is an established risk marker for diabetic vascular disease, and associated with the degree of diabetes complications, renal failure, and atherosclerosis in middle-aged and older individuals. The relationship between AGEs and aortic stiffness has not been thoroughly examined in the younger general population. We aimed to evaluate the association between AGEs and aortic stiffness in the general population of young and middle-aged adults. We analysed cross-sectionally 2518 participants from a Swedish population-based cohort, the Malmö Offspring Study (mean age 41.8 ± 14.5 years, 52.2%). Advanced glycation end-products (AGEs) were measured by a well validated, noninvasive method using skin autofluorescence with AGE-Reader. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) was calibrated to a standard heart rate of 75 bpm at the arteria radialis using SphygmoCor. Multivariable linear regression was performed stratified by age to analyse the association between skin AGE and aortic stiffness. Increased levels of AGEs were significantly associated with higher direct measurements of aortic stiffness (vascular ageing) in younger individuals (PWV β 0.55 m/s, P < 0.001) after adjustment for traditional cardiometabolic risk factors, however, not in older individuals (PWV β 0.23 m/s, P = 0.10). Indirect vascular ageing was also significantly associated with higher levels of AGEs in both younger (Aix β 7.78, P < 0.001) and older individuals (Aix β 3.69, P < 0.001). Higher levels of skin autofluorescence-AGEs are positively associated with increased vascular ageing in younger adults from the general population, independent of cardiometabolic risk factors.

How dietary advanced glycation end products could facilitate the occurrence of food allergy

BackgroundFood allergy (FA) is one of the most common chronic conditions in the pediatric age with an increasing prevalence under the pressure of environmental factors in predisposed individuals. It has been hypothesized that the increased consumption of ultra-processed foods, containing high levels of dietary advanced glycation end-products (AGEs), could facilitate the occurrence of food allergy. ObjectiveHere we provide preclinical and clinical evidence on the potential role of AGEs in facilitating the occurrence of FA. MethodsHuman enterocytes, human small intestine organ culture, and peripheral mononuclear blood cells (PBMCs) from children at risk for allergy were used to investigate the direct effect of AGEs on gut barrier, inflammation, Th2 cytokines response and mitochondrial function.The intake of the three most commonly glycation products in Western diet-foods Nε -(carboxymethyl) lysine (CML), Nε -(1-carboxyethyl) lysine (CEL), and Nδ -(5-hydro-5- methyl-4-imidazolon-2-yl)-ornithine (MG-H1), and the skin AGEs accumulation were comparatively investigated in children with FA and in age-matched healthy controls. ResultsHuman enterocytes exposed to AGEs showed alteration in gut barrier, AGEs receptor expression, reactive oxygen species production and autophagy, with increased transepithelial passage of food antigens. Small intestine organ culture exposed to AGEs showed an increase of CD25+ cells and proliferating crypt enterocytes. PBMCs exposed to AGEs showed alteration in proliferation rate, AGEs receptor activation, release of inflammatory and Th2 cytokines, and mitochondrial metabolism.Significant higher dietary AGEs intake and skin accumulation were observed in FA children (n=42) compared with age-matched healthy controls (n=66). ConclusionsThese data, supporting a potential role for dietary AGEs in facilitating the occurrence of FA, suggest the importance of limiting the AGEs exposure in the pediatric age as potential preventive strategy against this common condition.

Diabetes Risk Factors and Bone Microarchitecture as Assessed by High-Resolution Peripheral Quantitative Computed Tomography in Adults With Long-standing Type 1 Diabetes.

To determine whether type 1 diabetes and its complications are associated with bone geometry and microarchitecture. This cross-sectional study was embedded in a long-term observational study. High-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal and diaphyseal tibia were performed in a subset of 183 participants with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study and 94 control participants without diabetes. HbA1c, skin advanced glycation end products (AGEs), and diabetes-related complications were assessed in EDIC participants with >30 years of follow-up. Compared with control participants (aged 60 ± 8 years, 65% female), EDIC participants (aged 60 ± 7 years, diabetes duration 38 ± 5 years, 51% female) had lower total bone mineral density (BMD) at the distal radius (-7.9% [95% CI -15.2%, -0.6%]; P = 0.030) and distal tibia (-11.3% [95% CI -18.5%, -4.2%]; P = 0.001); larger total area at all sites (distal radius 4.7% [95% CI 0.5%, 8.8%; P = 0.030]; distal tibia 5.9% [95% CI 2.1%, 9.8%; P = 0.003]; diaphyseal tibia 3.4% [95% CI 0.8%, 6.1%; P = 0.011]); and poorer radius trabecular and cortical microarchitecture. Estimated failure load was similar between the two groups. Among EDIC participants, higher HbA1c, AGE levels, and macroalbuminuria were associated with lower total BMD. Macroalbuminuria was associated with larger total area and lower cortical thickness at the distal radius. Higher HbA1c and AGE levels and lower glomerular filtration rate, peripheral neuropathy, and retinopathy were associated with deficits in trabecular microarchitecture. Type 1 diabetes is associated with lower BMD, larger bone area, and poorer trabecular microarchitecture. Among participants with type 1 diabetes, suboptimal glycemic control, AGE accumulation, and microvascular complications are associated with deficits in bone microarchitecture and lower BMD.

Increased dietary intake of ultraprocessed foods and mitochondrial metabolism alterations in pediatric obesity

The increased intake of ultraprocessed foods (UPFs) in the pediatric age paralleled with the risen prevalence of childhood obesity. The Ultraprocessed Foods in Obesity (UFO) Project aimed at investigating the potential mechanisms for the effects of UPFs in facilitating pediatric obesity, focusing on the direct role of advanced glycation end-products (AGEs) on mitochondrial function, the key regulator of obesity pathophysiology. We comparatively investigated the daily dietary intake of UPFs, energy, nutrients, dietary AGEs [Nε -(carboxymethyl)lysine (CML), Nε -(1-carboxyethyl)lysine (CEL), and Nδ -(5-hydro-5- methyl-4-imidazolon-2-yl)-ornithine (MG-H1)] in 53 obese patients and in 100 healthy controls visiting the Tertiary Center for Pediatric Nutrition of the Department of Translational Medical Science at the University of Naples “Federico II”. AGEs skin accumulation and mitochondrial function in peripheral blood mononuclear cells (PBMCs) were also assessed. A higher intake of UPFs and AGEs, energy, protein, fat, and saturated fatty acids was observed in obese patients. Obese children presented significantly higher skin AGEs accumulation and alterations in mitochondrial metabolism. PBMCs from healthy controls exposed to AGEs showed the same mitochondrial alterations observed in patients. These findings support the UPFs role in pediatric obesity, and the need for dietary strategies limiting UPFs exposure for obesity prevention and treatment.

Dysmetabolism-related early sensory Deficits and their Relationship with peripheral Neuropathy Development.

To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. 196 were followed-up over a mean of 2.64 years for PN occurrence. Among those without T2DM, apart from male gender, height, higher fat and lower lean mass, only higher insulin resistance (IR, HOMA-R: OR 1.70, p=0.009, McAuley index OR: 0.62, p=0.008), was independently associated with EPSD. In T2DM, metabolic syndrome (MetS, OR 18.32, p<0.001) and skin advanced glycation end-products (AGEs, OR 5.66, p=0.003) were independent predictors of EPSD. In longitudinal analysis, T2DM (HR 3.32 vs. no DM, p<0.001), EPSD (aHR 1.88 vs. healthy, p=0.049 adjusted for DM and gender), higher IR and AGEs predicted PN development. Among the three EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (aHR 4.35, p=0.011). We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, MetS and higher AGEs which in turn are shown to influence PN development.

Association of skin autofluorescence with depressive symptoms and the severity of depressive symptoms: The prospective REACTION study

AimMillions of people are afflicted by depression, a highly prevalent mental illness with increased morbidity and mortality. Advanced glycation end-products (AGEs) are potential risk factors for depression. We aimed to investigate the correlation of AGEs with depressive symptoms and the severity of depressive symptoms. MethodsThis study was nested in the prospective REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study and included 4420 eligible participants. skin autofluorescence (SAF) was used to measure skin AGEs. Depressive symptoms were evaluated by the Self-Rating Depression Scale (SDS). Multiple logistic regression analysis was used to assess the association of AGEs with depressive symptoms and the severity of depressive symptoms. ResultsLogistic analysis showed a significantly positive relationship between quartiles of SAF-AGEs and the risk of depressive symptoms with the OR [95% confidence interval (CI), p value] of 1.24 (95% CI: 1.03–1.50, p = 0.022), 1.39 (95% CI: 1.15–1.68, p = 0.001) and 1.57 (95% CI: 1.28–1.91, p < 0.001) for multivariable-adjusted model respectively. And SAF-AGEs were associated with the severity of depressive symptoms with the multivariable-adjusted OR (95% CI, p value) of 1.06 (95% CI:0.79–1.43, p = 0.681), 1.47 (95% CI: 1.08–1.99, p = 0.014), and 1.54 (95% CI: 1.12–2.11, p = 0.008) respectively. Stratified analyses showed that SAF-AGEs were significantly associated with the severity of depressive symptoms only in females, overweight people, individuals with hypertension, and those without diabetes and insomnia. ConclusionsThe present study showed that a higher SAF-AGEs level was associated with depressive symptoms and the severity of depressive symptoms.

Skin Autofluorescence Mirrors Surrogate Parameters of Vascular Aging: An Enable Study

Advanced glycation end-products (AGEs) are implicated in vascular aging due to their pro-inflammatory properties. Skin autofluorescence (SAF) is a measure to estimate their deposition. It is an easily quantifiable marker that has been shown to correlate with cardiovascular risk and parameters of metabolic diseases. Herein, we compared skin autofluorescence with other techniques indicating increased cardiovascular diseases, namely, pulse wave velocity (PWVao) and intima-media thickness (IMT). We also studied the impacts of other parameters in deeply phenotyped cohorts of young, middle-aged, and older individuals. SAF, aortic PWVao, and IMT proved to be significantly correlated with each other and with age. However, based on a moderator analysis, we could not show that these associations were affected by age. Some specific parameters such as creatinine and CRP were found to be significantly associated with skin AGE values after adjusting for confounding variables. In conclusion, SAF is a simple screening tool for vascular health with comparable power to more elaborated technical tests.

Association between Advanced Glycation End-Products, Carotenoids, and Severe Erectile Dysfunction.

To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community-dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels.

Time-varying parameters of glycemic control and glycation in relation to arterial stiffness in patients with type 1 diabetes.

A substantial proportion of type 1 diabetes (T1D) patients free from known cardiovascular disease (CVD) show premature arterial stiffening, with age, blood pressure, and HbA1c-as gold standard of glycemic control-as main predictors. However, the relationship of arterial stiffness with other time-varying parameters of glycemic control and glycation has been far less explored. This study investigated the relationship of arterial stiffness with several short- and long-term parameters of glycemic control and glycation in patients with T1D, such as advanced glycation end-products (AGEs) and continuous glucose monitoring (CGM)-derived parameters. Cross-sectional study at a tertiary care centre including 54 patients with T1D free from known CVD. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (cf-PWV). Current level and 10-year history of HbA1c were evaluated, and skin AGEs, urinary AGEs, and serum soluble AGE-receptor (sRAGE) concentrations. CGM for 7days was used to determine time in range, time in hyper- and hypoglycemia, and glycemic variability. Cf-PWV was associated with current HbA1c (rs = + 0.28), mean 10-years HbA1c (rs = + 0.36), skin AGEs (rs = + 0.40) and the skin AGEs-to-sRAGE ratio (rs = + 0.40), but not with urinary AGE or serum sRAGE concentrations; and not with any of the CGM-parameters. Multiple linear regression for cf-PWV showed that the model with the best fit included age, T1D duration, 24-h mean arterial pressure and mean 10-years HbA1c (adjusted R2 = 0.645, p < 0.001). Longer-term glycemic exposure as reflected by current and mean 10-years HbA1c is a key predictor of arterial stiffness in patients with T1D, while no relationship was found with any of the short-term CGM parameters. Our findings stress the importance of early and sustained good glycemic control to prevent premature CVD in patients with T1D and suggest that HbA1c should continue to be used in the risk assessment for diabetic complications. The role of skin glycation, as a biomarker for vascular aging, in the risk assessment for CVD is an interesting avenue for further research.

Skin advanced glycation end products and the risk of dementia

AbstractBackgroundConditions such as hyperglycemia and oxidative stress lead to the formation of advanced glycation end products (AGEs), which have also been implicated in neurodegeneration including dementia. Previous studies have shown a link between these AGEs and the occurrence of Alzheimer’s neuropathology and worse cognitive functioning. However, no study examined the association between AGE levels and the risk of dementia. Therefore, we used skin AGE levels, reflecting accumulation of AGEs in long‐lived tissues, to determine the association with the risk of dementia and brain MRI measures.MethodWithin the Rotterdam Study, we determined skin AGEs using skin autofluorescence (SAF [arbitrary units]) measured at the forearm, between 2013 and 2016 in 2938 participants without dementia. Of them, 1515 also underwent brain MRI. All participants were followed for the incidence of dementia until 2020. The associations of SAF with incident dementia and with brain MRI measures were assessed, adjusting for potential confounders, namely age, sex, education, APOE ε4 carriership, smoking, estimated glomerular filtration rate, fasting glucose level and use of antidiabetic medication.ResultOf 2938 participants (mean age 72.6 years, 57% women), 124 developed dementia during a median follow‐up of 4.3 years. Higher SAF was associated with an increased risk of dementia (hazard ratio (HR) 1.22 per standard deviation increase of SAF [95% confidence interval 1.03‐1.45]) and of Alzheimer’s disease (HR 1.21 [1.00‐1.48]). Stronger effects were seen in APOE ε4 carriers with HRs of 1.38 [1.03‐1.84] for all‐cause dementia and 1.51 [1.10‐2.09] for Alzheimer’s disease. Participants with higher SAF also had lower total brain volumes on MRI (difference per standard deviation increase: ‐2.71 mL [‐4.54; ‐0.89]), lower grey matter volumes (‐1.77 mL [‐3.45; ‐0.08]) and lower hippocampus volumes (‐0.04 [‐0.07; ‐0.01]). In addition, they tended to more often have lacunar infarcts and microbleeds (odds ratios: 1.22 [0.99‐1.50] and 1.09 [0.96‐1.25]).ConclusionHigher levels of AGEs in the skin are associated with an increased risk of dementia, especially in APOE ε4 carriers, and with lower brain volumes. These results suggest that AGEs are involved in dementia pathophysiology and may provide potential for prevention.

Skin advanced glycation end products as a screening tool of neuropathy in type 2 diabetes mellitus

Aim of the studyTo examine the diagnostic utility of skin advanced glycation end products (AGEs) as screening tool of neuropathy in type 2 diabetes mellitus (T2DM). Patients and methodsWe included 132 participants (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm and were interpreted as normal vs. elevated. Distal sensorimotor polyneuropathy (DSPN) was diagnosed by the Neuropathy Disability Score. Cardiovascular autonomic neuropathy (CAN), sympathetic and parasympathetic nervous system impairment were diagnosed by cardiovascular autonomic reflex tests. ResultsFor DSPN, AGEs yielded high sensitivity (82.8%) and NPV (80.4 %) with moderate specificity (55.4 %). For CAN, they yielded relatively high sensitivity (75.0 %) and NPV (74.5 %) with low specificity (48.7 %). For sympathetic nervous system impairment, AGEs yielded relatively high sensitivity (75.0 %) and high NPV (84.3 %) with low specificity (43.9 %). For parasympathetic nervous system impairment, they yielded high PPV (81.0 %) with moderately high sensitivity (66.7 %) and moderate specificity (55.9 %). ConclusionsIn a simplified approach, skin AGEs may be used as a screening tool of DSPN and CAN (including sympathetic and parasympathetic nervous system impairment) in T2DM.

Correlation Between Skin Advanced Glycation End Products and Cardiac Autonomic Neuropathy Among Subjects with Type 2 Diabetes Mellitus.

Advanced glycation end products (AGEs) are frequently increased in the skin of subjects with type 2 diabetes mellitus (T2DM). This study aimed to examine the correlation of AGEs with cardiac autonomic neuropathy (CAN) in T2DM. To this aim, 132 participants (88 men) with a mean age of 64.57 years and a median T2DM duration of 14.5 years were included. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm (both single and automated triplicate measurements). Diagnosis of CAN, sympathetic and parasympathetic nervous system impairment was based on the four standardised cardiovascular reflex tests (CARTs). On a single measurement, AGEs were increased in subjects with vs. those without CAN (3.20±0.74 vs. 2.66±0.66, p<0.001). As compared with normal results, AGEs were increased for each one of the 4 abnormal CARTs: Valsalva Ratio (3.36±0.67 vs. 2.66±0.72, p=0.004), E/I ratio (3.01±0.72 vs. 2.53±0.68, p=0.001), 30:15 ratio (3.08±0.76 vs. 2.75±0.69, p=0.011), postural hypotension (3.30±0.72 vs. 2.75±0.66, p<0.001). Similar results were obtained for triplicate measurements. Among T2DM subjects, skin AGEs appear to increase in the presence of CAN. This holds true both for sympathetic and parasympathetic nervous system impairment.

Skin and Serum Advanced Glycation End Products in Adults With Type 1 Diabetes

Skin advanced glycation end products (AGEs) may better correlate with diabetes control, duration and complications than serum AGEs, as they reflect long-term tissue accumulation. We evaluated whether, in individuals with type 1 diabetes (T1D): 1). skin AGEs correlate with serum AGEs; 2). AGEs correlate with HbA1c and diabetes duration; 3). AGEs differ in those with microvascular complications from those without.

The Fast-Glycator Phenotype, Skin Advanced Glycation End Products, and Complication Burden Among People With Type 1 Diabetes.

Existence of a fast-glycator phenotype among people with type 1 diabetes (T1D) is debated. Routine use of glucose sensors allows the comparison of long-term average glucose levels with laboratory HbA1c values. We herein evaluated whether participants with T1D and HbA1c values higher than their glucose management indicator (GMI) had greater accumulation of advanced glycation end products (AGEs) and chronic complications. We included participants with T1D using the intermittently scanned continuous glucose monitoring system consecutively for at least 90 days and having a laboratory-determined HbA1c at the end of observation. Skin AGEs were estimated using the skin autofluorescence (SAF) method. The complication burden was assessed by a standardized screening. The fast-glycator phenotype was defined as having a GMI to HbA1c ratio <0.9. We included 135 individuals with T1D (58% men; mean age, 44.4 years) with a mean diabetes duration of 21 years and a mean HbA1c value of 7.7%. Thirty (22.2%) were defined as having the fast-glycator phenotype. As expected, fast glycators had higher HbA1c (8.6% vs. 7.5%; P < 0.001) with similar 90-day mean glucose level (172 vs. 168 mg/dL; P = 0.52). Fast glycators had higher SAF than did other participants (2.5 vs. 2.1 arbitrary units; P = 0.005) and had a significantly higher prevalence of dyslipidemia (73% vs. 44%; P = 0.005), macroangiopathy (38% vs. 9%; P = 0.001), albuminuria (25% vs. 7%; P = 0.038), and retinopathy (61% vs. 38%; P = 0.022). After adjusting for age and dyslipidemia, the fast-glycator phenotype remained significantly associated with macroangiopathy (odds ratio 3.72; 95% CI 1.22-11.4). In T1D, a fast-glycator phenotype defined by the GMI to HbA1c ratio is characterized by elevated skin AGEs and is associated with the complication burden.

The Correlation between the Level of Skin Advanced Glycation End Products in Type 2 Diabetes Mellitus and the Stages of Diabetic Retinopathy and the Types of Traditional Chinese Medicine Syndrome.

Objective We aimed to analyze the correlation between the level of skin advanced glycation end products (AGEs) in type 2 diabetes mellitus (T2DM) patients and the diabetic retinopathy (DR) staging in different traditional Chinese medicine (TCM) syndromes. Methods 416 T2DM patients were divided into normal group, nonproliferative diabetic retinopathy (NPDR) group (mild, moderate, and severe), and proliferative diabetic retinopathy (PDR) group according to the DR grade. Patients' height, weight, fasting blood glucose (FBG), hemoglobin A1C (HbA1c), blood lipid, renal function, and skin AGEs were measured. According to TCM syndrome differentiation criteria, 230 patients with T2DM and DR were divided into I. qi and yin deficiency, collateral stasis group; II. liver and kidney deficiency, eye collaterals loss group; and III. yin and yang deficiency, blood stasis, and phlegm coagulation group. Results The skin AGEs levels of different DR staging groups were statistically significant (P < 0.05), and the skin AGEs levels in the mild and moderate NPDR groups were significantly higher (P < 0.05) than those of the normal group. It was significantly higher (P < 0.05) in the severe NPDR group than in the normal group, mild and moderate NPDR groups. The skin AGEs levels of the PDR group were significantly higher (P < 0.05) than the normal group, mild and moderate NPDR groups. It was positively correlated with DR stage, HbA1c, total cholesterol (TC), low-density lipoprotein (LDL), and urine metal analysis (UMA) (r = 0.467, 0.411, 0.413, 0.503, 0.424, P < 0.05). The skin AGEs levels of the qi and yin deficiency and collaterals stasis syndrome group were significantly higher (P < 0.05) than in the liver and kidney deficiency and eye collaterals loss groups. It was also significantly higher (P < 0.05) in yin and yang deficiency, blood stasis, and phlegm coagulation syndrome groups than in qi and yin deficiency and collaterals stasis syndrome groups. Conclusion There is a positive correlation between skin AGEs and DR staging in T2DM patients. Skin AGEs level is predictive for the risk of DR complications in T2DM patients and is vital in assessing DR degree per TCM syndrome type.