Plasma advanced glycation end products are associated with incident cardiovascularevents in individuals with type 2 diabetes: A Case-Cohort study with a median follow-Up of 10 years (EPIC-NL)

Nordin M.J. Hanssen, Joline W.J. Beulens, Susan Van Dieren, Jean L.J.M. Scheijen, Daphne L. Van Der A, Annemieke M.W. Spijkerman, Yvonne T. Van Der Schouw, Coen D.A. Stehouwer, Casper G. Schalkwijk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Experimental data suggest a role for advanced glycation end products (AGEs) in cardiovascular disease (CVD), particularly in type 2 diabetes (T2DM). However, epidemiological evidence of an association between high plasma AGEs and increased cardiovascular risk remains inconclusive. Therefore, in a case-cohort study comprising 134 cardiovascular case subjects and a random subcohort of 218 individuals (including 65 cardiovascular case subjects), all with T2DM and nested in the European Prospective Investigation into Cancer and Nutrition in the Netherlands (EPIC-NL) study, plasma levels of proteinbound Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and pentosidine were measured with liquid chromatography. AGEs were loge-transformed, combined in a z-score, and the association with incident cardiovascular eventswas analyzed with Cox proportional hazard regression, adapted for case-cohort design (Prentice method). After multivariable adjustment (sex, age, cohort status, diabetes duration, total cholesterol to HDL-cholesterol ratio, smoking, systolic blood pressure, BMI, blood pressure-, cholesterol- and glucose-lowering treatment, prior cardiovascular events, and triglycerides), higher plasma AGE z-scores were associated with higher risk of incident cardiovascular events in individuals without prior cardiovascular events (hazard ratio 1.31 [95% CI: 1.06-1.61]). A similar trend was observed in individuals withprior cardiovascular events (1.37 [0.63-2.98]). In conclusion, high plasma AGEs were associated with incident cardiovascular events in individuals with T2DM. These results underline the potential importance of AGEs in development of CVD.

Original languageEnglish
Pages (from-to)257-265
Number of pages9
Issue number1
Publication statusPublished - 1 Jan 2015

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