Norman, Paul E., Davis, Wendy A., Coughlan, Melinda T., Forbes, Josephine M., Golledge, Jonathan, and Davis, Timothy M.E. (2009) Serum carboxymethyllysine concentrations are reduced in diabetic men with abdominal aortic aneurysms: health in men study. Journal of Vascular Surgery, 50 (3). pp. 626-631.

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Abstract

Objective: Abdominal aortic aneurysms (AAAs) share common risk factors with atherosclerosis, except for diabetes which appears protective. The reason for this is unknown. Although increased circulating concentrations of advanced glycation endproducts (AGEs) such as carboxymethyllysine (CML) are associated with occlusive vascular disease, it is possible that their effects on the aortic wall explain the paradoxically low incidence of AAAs in diabetes.

Methods: We studied 234 community-dwelling men aged 65 to 79 years. The cases comprised all identifiable diabetic men with AAA (aortic diameter ≥30 mm on ultrasound; n = 27) and randomly-selected non-diabetic men with AAA (n = 67). Controls were age-matched randomly-selected diabetic men (n = 69) and age-matched randomly-selected non-diabetic men (n = 71) without AAA (aortic diameter 18 to 22 mm). Serum CML concentrations were measured by validated indirect enzyme-linked immunosorbent assay (ELISA).

Results: Serum CML concentrations were significantly lower in men with AAAs than those without (6627 ± 1544 vs 7309 ± 1490 nmol/mol lysine; P = .001). Variables positively associated with AAA were height, diastolic blood pressure, smoking, a history of coronary heart disease, and serum creatinine (P ≤ .040), while serum CML (odds ratio [95% confidence interval] per 1000 nmol/mol lysine; 0.80 [0.64-0.98]) and a history of diabetes were inversely associated (P ≤ .040). After adjusting, the interaction between diabetes status and serum CML was negatively associated with AAA (P = .016).

Conclusion: These cross-sectional data show that circulating concentrations of CML are reduced in diabetic men with AAAs. This is in contrast to studies of the relationship between AGEs and occlusive manifestations of cardiovascular disease and could explain the inverse association between diabetes and AAA.

Clinical Relevance: In contrast to most manifestations of cardiovascular disease, diabetes protects against abdominal aortic aneurysms (AAAs). The basis for this is unknown. We assessed a circulating marker of the glycation pathway, carboxymethyllysine (CML), and found levels to be significantly lower in diabetic men with AAAs compared with those without AAAs, supporting the hypothesis that advanced glycation may play a role in the negative association between diabetes and AAA. This may be of relevance to the pathogenesis of AAAs, and in the context of diabetes, may be important in the assessment of drugs that inhibit AGE formation.

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