The Advanced Glycation End Product Nε-Carboxymethyllysine Is Not a Predictor of Cardiovascular Events and Renal Outcomes in Patients With Type 2 Diabetic Kidney Disease and Hypertension

Plasma Advanced Glycation End Products Are Associated With Incident Cardiovascular Events in Individuals With Type 2 Diabetes: A Case-Cohort Study With a Median Follow-up of 10 Years (EPIC-NL)

“…These findings indicate that AGEs may indeed play an important role in the development of cardiovascular events in humans. However, epidemiological studies using plasma measurements of AGEs, which are more feasible than plaque measurements, have generated inconsistent associations with incident cardiovascular events (15)(16)(17)(18)(19)(20). These results may be conflicting because they were based on semiquantitative ELISA-based techniques to measure AGEs (measuring mostly one AGE only) instead of specific liquid chromatographybased techniques and did not take potential confounding factors (consistently) into account.…”

“…Other studies focusing on plasma AGEs and incident cardiovascular events found associations between higher plasma CML and higher risk of incident cardiovascular events in older individuals (15,16), while no associations were found in individuals with T2DM (17). In hemodialysis patients, even associations between higher CML levels and lower risk of incident cardiovascular events have been described (18).…”

“…Finally, Kilhovd et al (19,20) have found that higher serum levels of AGEs and 5-hydro-5-methylimidazolone were associated with higher risk of incident cardiovascular events, but only in nondiabetic women. The majority of previous studies have used stepwise regression models (17,18) or selected covariates based on significance in univariable analyses (15,16). These analyses are less appropriate for etiological analyses, as they are not hypothesis driven.…”

“…Thus, selection of the covariates may be based more on statistical power of the study than on underlying biology and subsequently yield inconsistent models. Indeed, most studies adjusted for BMI (15,16,19,20), but others did not (17,18), and no study adjusted for glucose-, blood pressure-, and cholesterol-lowering medication. We consistently found that CEL in particular was strongly associated with incident cardiovascular events.…”

Advanced glycation end-products induce cell cycle arrest and hypertrophy in podocytes

“…After glycation, AGE-BSA was characterized by a 58-fold higher N ε -carboxy-methyl-lysine (CML) concentration than Co-BSA (11.6 nmol/mg protein versus 0.2 nmol/mg protein in Co-BSA) and 6-fold higher pentosidine (4.9 pmol/mg protein versus 0.8 pmol/mg protein in Co-BSA) concentrations. CML was measured by an ELISA (Roche Diagnostics, Mannheim, Germany) whereas pentosidine was determined by HPLC (Merck-Hitachi, Darmstadt, Germany) as previously described [18].…”