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Serum 25-hydroxyvitamin D₃ is associated with advanced glycation end products (AGEs) measured as skin autofluorescence: The Rotterdam Study.

ABSTRACT: Advanced glycation end products (AGEs) accumulate in tissues with aging and may influence age-related diseases. They can be estimated non-invasively by skin autofluorescence (SAF) using the AGE Reader™. Serum 25-hydroxyvitamin D₃ (25(OH)D₃) may inhibit AGEs accumulation through anti-oxidative and anti-inflammatory properties but evidence in humans is scarce. The objective was to investigate the association between serum 25(OH)D₃ and SAF in the population-based cohort study. Serum 25(OH)D₃ and other covariates were measured at baseline. SAF was measured on average 11.5 years later. Known risk factors for AGE accumulation such as higher age, BMI, and coffee intake, male sex, smoking, diabetes, and decreased renal function were measured at baseline. Linear regression models were adopted to explore the association between 25(OH)D₃ and SAF with adjustment for confounders. Interaction terms were tested to identify effect modification. The study was conducted in the general community. 2746 community-dwelling participants (age ≥ 45 years) from the Rotterdam Study were included. Serum 25(OH)D₃ inversely associated with SAF and explained 1.5% of the variance (unstandardized B = - 0.002 (95% CI[- 0.003, - 0.002]), standardized β = - 0.125), independently of known risk factors and medication intake. The association was present in both diabetics (B = - 0.004 (95% CI[- 0.008, - 0.001]), β = - 0.192) and non-diabetics (B = - 0.002 (95% CI[- 0.003, - 0.002]), β = - 0.122), both sexes, both smokers and non-smokers and in each RS subcohort. Serum 25(OH)D₃ concentration was significantly and inversely associated with SAF measured prospectively, also after adjustment for known risk factors for high SAF and the number of medication used, but the causal chain is yet to be explored in future studies.Clinical Trial Registry (1) Netherlands National Trial Register: Trial ID: NTR6831 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831 ). (2) WHO International Clinical Trials Registry Platform: under shared catalogue number NTR6831 ( www.who.int/ictrp/network/primary/en/ ).

SUBMITTER: Chen J

PROVIDER: S-EPMC6325991 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAdvanced glycation end products (AGEs) have been linked to cardiovascular disease (CVD), especially coronary heart disease (CHD), but their role in CVD pathogenesis remains unclear. Therefore, we investigated cross-sectional associations of skin AGEs with subclinical atherosclerosis, arterial stiffness, and hypertension after confirming their relation with CHD.MethodsIn the population-based Rotterdam Study, skin AGEs were measured as skin autofluorescence (SAF). Prevalent MI was obtained from digital medical records. Carotid plaques, carotid intima-media thickness (IMT), coronary artery calcification (CAC), pulse wave velocity (PWV), and hypertension were assessed. Associations of SAF with endophenotypes were investigated in logistic and linear regression models adjusting for common cardiovascular risk factors. Effect modification by sex, diabetes mellitus, and chronic kidney disease (CKD) was tested.Results3001 participants were included (mean age 73 (SD 9) years, 57% women). One unit higher SAF was associated with the presence of carotid plaques (OR 1.2 (0.92, 1.57)), a higher max IMT (0.08 SD (0.01, 0.15)), higher CAC (OR 2.2 (1.39, 3.48)), and PWV (0.09 SD (0.01, 0.16)), but not with hypertension (OR 0.99 (0.81, 1.21)). The associations with endophenotypes were more pronounced in men and participants with diabetes or CKD with significant interactions.ConclusionsPreviously documented associations between SAF and CVD, also found in our study, may be explained by the endophenotypes atherosclerosis and arterial stiffness, especially in men and individuals with diabetes or CKD, but not by hypertension. Longitudinal studies are needed to replicate these findings and to test if SAF is an independent risk factor or biomarker of CVD.Trial registrationThe Rotterdam Study has been entered into the Netherlands National Trial Register (NTR; www.trialregister.nl ) and the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/ ) under shared catalogue number NTR6831.

Project description:BackgroundAdvanced glycation end products (AGEs) are involved in age-related diseases, but the interaction of gut microbiota with dietary AGEs (dAGEs) and tissue AGEs in the population is unknown.ObjectiveOur objective was to investigate the association of dietary and tissue AGEs with gut microbiota in the population-based Rotterdam Study, using skin AGEs as a marker for tissue accumulation and stool microbiota as a surrogate for gut microbiota.DesignDietary intake of three AGEs (dAGEs), namely carboxymethyl-lysine (CML), N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1), and carboxyethyl-lysine (CEL), was quantified at baseline from food frequency questionnaires. Following up after a median of 5.7 years, skin AGEs were measured using skin autofluorescence (SAF), and stool microbiota samples were sequenced (16S rRNA) to measure microbial composition (including alpha-diversity, beta-dissimilarity, and taxonomic abundances) as well as predict microbial metabolic pathways. Associations of both dAGEs and SAF with microbial measures were investigated using multiple linear regression models in 1052 and 718 participants, respectively.ResultsdAGEs and SAF were not associated with either the alpha-diversity or beta-dissimilarity of the stool microbiota. After multiple-testing correction, dAGEs were not associated with any of the 188 genera tested, but were nominally inversely associated with the abundance of Barnesiella, Colidextribacter, Oscillospiraceae UCG-005, and Terrisporobacter, in addition to being positively associated with Coprococcus, Dorea, and Blautia. A higher abundance of Lactobacillus was associated with a higher SAF, along with several nominally significantly associated genera. dAGEs and SAF were nominally associated with several microbial pathways, but none were statistically significant after multiple-testing correction.ConclusionsOur findings did not solidify a link between habitual dAGEs, skin AGEs, and overall stool microbiota composition. Nominally significant associations with several genera and functional pathways suggested a potential interaction between gut microbiota and AGE metabolism, but validation is required. Future studies are warranted, to investigate whether gut microbiota modifies the potential impact of dAGEs on health.

Project description:Advanced glycation end-products (AGEs), which bind to type 1 collagen in bone and skin, have been implicated in reduced bone quality. The AGE reader™ measures skin autofluorescence (SAF), which might be regarded as a marker of long-term accumulation of AGEs in tissues. We investigated the association of SAF with bone mineral density (BMD) and fractures in the general population. We studied 2853 individuals from the Rotterdam Study with available SAF measurements (median age, 74.1 years) and with data on prevalent major osteoporotic (MOFs: hip, humerus, wrist, clinical vertebral) and vertebral fractures (VFs: clinical + radiographic Genant's grade 2 and 3). Radiographs were assessed 4 to 5 years before SAF. Multivariate regression models were performed adjusted for age, sex, BMI, creatinine, smoking status, and presence of diabetes and additionally for BMD with interaction terms to test for effect modification. Prevalence of MOFs was 8.5% and of VFs 7%. SAF had a curvilinear association with prevalent MOFs and VFs and therefore, age-adjusted, sex stratified SAF quartiles were used. The odds ratio (OR) (95% confidence interval [CI]) of the second, third and fourth quartiles of SAF for MOFs were as follows: OR 1.60 (95% CI, 1.08-2.35; p = .02); OR 1.30 (95% CI, 0.89-1.97; p = .20), and OR 1.40 (95% CI, 0.95-2.10; p = .09), respectively, with first (lowest) quartile as reference. For VFs the ORs were as follows: OR 1.69 (95% CI, 1.08-2.64; p = .02), OR 1.74(95% CI, 1.11-2.71; p = .01), and OR 1.73 (95% CI, 1.12-2.73; p = .02) for second, third, and fourth quartiles, respectively. When comparing the top three quartiles combined with the first quartile, the OR (95% CI) for MOFs was 1.43 (95% CI, 1.04-2.00; p = .03) and for VFs was 1.72 (95% CI, 1.18-2.53; p = .005). Additional adjustment for BMD did not change the associations. In conclusion, there is evidence of presence of a threshold of skin AGEs below which there is distinctly lower prevalence of fractures. Longitudinal analyses are needed to confirm our cross-sectional findings. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Project description:ContextAdvanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports.Evidence acquisitionEvidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles.ResultsPharmacological approaches in humans include aminoguanidine, pyridoxamine, benfotiamine, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statin, ALT-711 (alagebrium) and thiazolidinediones. The most recent promising anti-AGEs agents are statins, alagebrium and thiazolidinediones. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years. Compounds with anti-AGEs activity but still not available for clinical scenarios are ALT-946, OPB-9195, tenilsetam, LR-90, TM2002, sRAGE and PEDF.ConclusionsDespite most studies confirm the efficacy of these pharmacological approaches, other reports produced conflicting evidences; in almost any case, these drugs were well tolerated. At present, AGEs measurement has still not taken a precise role in clinical practice, but its relevance as a marker of disease has been widely shown; therefore, it is important for clinicians to understand the value of new cardiovascular risk factors. Findings from the current and future clinical trials may help in determining the role of AGEs and the benefits of anti-AGEs treatment in cardiovascular disease.

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Serum 25-hydroxyvitamin D₃ is associated with advanced glycation end products (AGEs) measured as skin autofluorescence: The Rotterdam Study.

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Serum 25-hydroxyvitamin D₃ is associated with advanced glycation end products (AGEs) measured as skin autofluorescence: The Rotterdam Study.