Serum carboxymethyllysine concentrations are reduced in diabetic men with abdominal aortic aneurysms: Health In Men Study.
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 > or =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 < or = .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 < or = .040). After adjusting, the interaction between diabetes status and serum CML was negatively associated with AAA (P = .016).


CONCLUSIONS
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.
Norman
Paul E
PE
School of Surgery, University of Western Australia, Freemantle, Australia. paul.norman@uwa.edu.au
Davis
Wendy A
WA
Coughlan
Melinda T
MT
Forbes
Josephine M
JM
Golledge
Jonathan
J
Davis
Timothy M E
TM
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000453:epidemiology; D015536:Down-Regulation; D006801:Humans; D016015:Logistic Models; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D054526:Men's Health; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D014904:Western Australia / Q000453:epidemiology
C048496:N(6)-carboxymethyllysine; D008239:Lysine