Advanced Glycation End Products, Oxidation Products, and the Extent of Atherosclerosis During the VA Diabetes Trial and Follow-up Study
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OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Higher levels of circulating AGEs are positively correlated with the incidence of cardiovascular disorders and severity of coronary atherosclerosis and coronary artery disease independent of diabetic status.
“Additionally, higher levels of circulating AGEs are positively correlated with the incidence of cardiovascular disorders and severity of coronary atherosclerosis and coronary artery disease independent of diabetic status62–64, suggesting a causal role of AGEs in cardiovascular diseases.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [64]
AGEs have a causal role in cardiovascular diseases.
“Additionally, higher levels of circulating AGEs are positively correlated with the incidence of cardiovascular disorders and severity of coronary atherosclerosis and coronary artery disease independent of diabetic status62–64, suggesting a causal role of AGEs in cardiovascular diseases.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [64]
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- Authors
- Saremi, A., Howell, S., Schwenke, D. C., Bahn, G., Beisswenger, P. J., Reaven, P. D., & for the VADT Investigators
- Affiliations
- Phoenix VA Health Care System (US)
- PreventAGE Health Care (United States) (US)
- Cooperative Studies Program Coordinating Center, Hines, IL
- Corresponding author
- Saremi, Aramesh
- Reaven, Peter D.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2017-02-01
- Volume
- 40
- Issue
- 4
- Pages
- 591-598
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC5360279
- OpenAlex
- W2584038420
- Cited by
- 90
- References
- 41
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 15 · 2022: 11 · 2021: 12 · 2020: 11 · 2019: 10 · 2018: 12 · 2017: 3
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Veterans Affairs Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development
- National Institutes of Health (R01-067690, 5R01-094775)
- American Diabetes Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- advanced glycation end products, oxidative stress, type 2 diabetes, subclinical atherosclerosis, carotid intima-media thickness, coronary artery calcification, abdominal aortic calcification, 2-aminoadipic acid, Nε-(carboxyethyl)lysine, carboxymethyllysine, methionine sulfoxide, macrovascular complications
- MeSH terms
- Aged, Blood Glucose, Cholesterol, Deoxyglucose, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Humans, Imidazoles, Lysine, Male, Middle Aged, Oxidation-Reduction, Pyruvaldehyde, Triglycerides, Glycation End Products, Advanced, Atherosclerosis, Carotid Intima-Media Thickness
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