Association between advanced glycation end products, their soluble receptor, and mortality in the general population: Results from the CARLA study.

BACKGROUND: Advanced glycation end products (AGEs) in the plasma are associated with a number of age-related diseases that possibly lead to reduced longevity. However, previous studies showed large inconsistencies in the association between AGEs or their soluble receptor (sRAGE) and mortality. We studied this association in a cohort study of general population and assessed the potential changes in this association over time. METHODS: We used data of 958 men and 802 women from the general population in Halle, Germany with a follow up of 12 years. The associations were assessed by means of Kaplan-Meyer survival curves and multivariable and time-varying Cox-regression. RESULTS: AGEs and sRAGE were either not or only weakly (and in the other direction than expected) associated with all-cause mortality after 12 years follow-up in men and women (AGEs: Hazard ratio (HR) = 0.93, 95% confidence interval (95%CI) = 0.83-1.05 for men; HR = 0.88, 95%CI = 0.74-1.05 for women; sRAGE: HR = 1.08, 95%CI = 0.95-1.23 for men; HR = 1.10, 95%CI = 0.92-1.30 for women). There was no change of the predictive values over the follow up time. Sub-analyses with participants with and without AGEs-related conditions (diabetes mellitus and decreased renal function), with age stratified groups (younger (<65 years) and older (≥65 years) participants), with cardiovascular disease mortality as the outcome and the AGE/sRAGE ratio as predictor provided similar results. CONCLUSIONS: Our findings suggest a lack of the expected association with mortality and contribute to the inconsistent findings for plasma-measured AGEs, sRAGE, and AGE/sRAGE ratio.

Advanced glycation end products and their ratio to soluble receptor are associated with limitations in physical functioning only in women: results from the CARLA cohort.

BACKGROUND: Advanced glycation end products (AGEs), modifications of proteins or amino acids, are increasingly produced and accumulated with age-related diseases. Recent studies suggested that the ratio of AGEs and their soluble receptor (sRAGE) is a more accurate biomarker for age-related diseases than each separately. We aim to investigate whether this also applies for physical functioning in a broad age-spectrum. METHODS: AGE and sRAGE levels, and physical functioning (SF-12 questionnaire) of 967 men and 812 women (45-83 years) were measured in the CARLA study. We used ordinal logistic regression to examine associations between AGEs, sRAGE, and AGE/sRAGE ratio with physical functioning in sex- and age-stratified models. RESULTS: Higher levels of AGEs and AGE/sRAGE ratio were associated with lower physical functioning only in women, even after consideration of classical lifestyle and age-related factors (education, BMI, smoking, alcohol consumption, diet, creatinine clearance, diabetes mellitus, lipid lowering and antihypertensive drugs) (odds ratio (OR) =0.86, 95%confidence interval = 0.74-0.98 and OR = 0.86, 95%CI = 0.75-0.98 for AGEs and AGE/sRAGE ratio respectively). We could not demonstrate a significant difference across age. CONCLUSIONS: We showed a sex-specific association between physical functioning and AGEs and AGE/sRAGE, but no stronger associations of the latter with physical functioning. Further investigation is needed in the pathophysiology of this association.