Abstract-Arterial stiffening, as characterized by an increase in carotid-femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid-femoral pulse-wave velocity (sβ 0.10; 95% confidence interval, 0.03-0.17 and 0.10; 0.04-0.16, respectively) and central pulse pressure (sβ 0.08; 95% confidence interval 0.01-0.15 and 0.07; 0.01-0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid-femoral pulsewave velocity were more pronounced in individuals with type 2 diabetes mellitus (P-interaction<0.10). These results support the hypothesis that accumulation of advanced glycation end products is involved in arterial stiffening and may explain part of the increased risk of cardiovascular disease in individuals with type 2 diabetes mellitus. carotid to femoral pulse-wave velocity (cfPWV) or pulse pressure, both measures of aortic stiffening, in a population-based setting, including individuals with normal glucose metabolism (NGM), impaired glucose metabolism (IGM), and T2DM. In view of these considerations, the aims of our study were, first, to evaluate the independent association between SAF and plasma AGEs on the one hand and measures of arterial stiffening, ie, cfPWV, central pulse pressure, and 24-hour ambulatory pulse pressure, on the other. Second, to examine whether these associations differed between individuals with NGM, IGM, or T2DM. Methods Study Population and DesignIn this study, we used data from The Maastricht Study, an observational prospective population-based cohort study. The rationale and methodology have been described previously. 22 In brief, the study focuses on the cause, pathophysiology, complications, and comorbidities of type 2 diabetes mellitus (T2DM) and is characterized by an extensive phenotyping approach. Eligible for participation were all individuals aged between 40 and 75 years and living in the southern part of the Netherlands. Participants were recruited through mass media campaigns and from the municipal registries and the regional Diabetes Patient Registry via mailings. Recruitment was stratified according to known T2DM status for reasons of efficiency. The present report includes cross-sectional data from the ...

BackgroundAdvanced glycation endproducts (AGEs) may play a role in the development of coronary artery calcification (CAC) in type 1 diabetes (T1DM). We studied plasma AGEs in association with T1DM and CAC, and whether or not the latter association could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED).MethodsWe studied 165 individuals with and 169 without T1DM. CAC was quantified in a CAC score based on CT-scanning. Plasma levels of protein-bound pentosidine, Nϵ-(carboxymethyl)lysine (CML) and Nϵ-(carboxyethyl)lysine (CEL) were measured with HPLC/UPLC with fluorescence detection or tandem-mass spectrometry. Tetrahydropyrimidine (THP) was measured with ELISA, as were HsCRP, and sVCAM-1 and vWF, as markers for LGI and ED, respectively. Associations were analyzed with ANCOVA and adjusted for age, sex, BMI, waist-to-hip ratio, smoking, blood pressure, lipid profile, eGFR and T1DM.ResultsIndividuals with T1DM had higher plasma levels of pentosidine, CML and THP compared with controls; means (95% CI) were 0.69 (0.65-0.73) vs. 0.51 (0.48-0.54) nmol/mmol LYS, p < 0.001; 105 (102–107) vs. 93 (90–95) nmol/mmol LYS, p < 0.001; and 126 (118–134) vs. 113 (106–120) U/mL, p = 0.03, respectively. Levels of pentosidine were higher in individuals with T1DM with a moderate to high compared with a low CAC score, means (95% CI) were 0.81 (0.70-0.93) vs. 0.67 (0.63-0.71) nmol/mmol LYS, p = 0.03, respectively. This difference was not attenuated by adjustment for LGI or ED.ConclusionsWe found a positive association between pentosidine and CAC in T1DM. These results may indicate that AGEs are possibly involved in the development of CAC in individuals with T1DM.

We found inverse associations of SAF (a noninvasive marker for tissue AGEs) with cognitive performance, which were attenuated after adjustment for vascular risk factors and depression.

Our results suggest that MGO-derived THP may reflect endothelial dysfunction among individuals with and without type 1 diabetes, and therefore may potentially play a role in the development of atherosclerosis and vascular disease.

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