Advanced Glycation End Products, Oxidation Products, and the Extent of Atherosclerosis During the VA Diabetes Trial and Follow-up Study.
To determine whether plasma levels of advanced glycation end products and oxidation products play a role in the development of atherosclerosis in patients with type 2 diabetes (T2D) over nearly 10 years of the VA Diabetes Trial and Follow-up Study.



Baseline plasma levels of methylglyoxal hydroimidazolone, Nε-carboxymethyl lysine, Nε-carboxyethyl lysine (CEL), 3-deoxyglucosone hydroimidazolone and glyoxal hydroimidazolone (G-H1), 2-aminoadipic acid (2-AAA), and methionine sulfoxide were measured in a total of 411 participants, who underwent ultrasound assessment of carotid intima-media thickness (CIMT), and computed tomography scanning of coronary artery calcification (CAC) and abdominal aortic artery calcification (AAC) after an average of 10 years of follow-up.



In risk factor-adjusted multivariable regression models, G-H1 was associated with the extent of CIMT and CAC. In addition, 2-AAA was strongly associated with the extent of CAC, and CEL was strongly associated with the extent of AAC. The combination of specific advanced glycation end products and oxidation products (G-H1 and 2-AAA) was strongly associated with all measures of subclinical atherosclerosis.



Specific advanced glycation end products and metabolic oxidation products are associated with the severity of subclinical atherosclerosis over the long term and may play an important role in the "negative metabolic memory" of macrovascular complications in people with long-standing T2D.
Phoenix VA Health Care System, Phoenix, AZ ari_saremi@yahoo.com peter.reaven@va.gov.
Aramesh
A
Saremi
PreventAGE Health Care, Lebanon, NH.
Scott
S
Howell
Phoenix VA Health Care System, Phoenix, AZ.
Dawn C
DC
Schwenke
Cooperative Studies Program Coordinating Center, Hines, IL.
Gideon
G
Bahn
PreventAGE Health Care, Lebanon, NH.
Paul J
PJ
Beisswenger
Phoenix VA Health Care System, Phoenix, AZ ari_saremi@yahoo.com peter.reaven@va.gov.
Peter D
PD
Reaven
D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis; D001786:Blood Glucose / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D002784:Cholesterol / Q000097:blood; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007093:Imidazoles / Q000097:blood; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011765:Pyruvaldehyde / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D014280:Triglycerides; C117197:imidazolone; C048496:N(6)-carboxymethyllysine; D011765:Pyruvaldehyde; D002784:Cholesterol; D003847:Deoxyglucose; C016350:3-deoxyglucosone; D008239:Lysine