TY - JOUR
T1 - Advanced glycation end products, oxidation products, and incident cardiovascular events in patients with type 2 diabetes
AU - Koska, Juraj
AU - Saremi, Aramesh
AU - Howell, Scott
AU - Bahn, Gideon
AU - De Courten, Barbora
AU - Ginsberg, Henry
AU - Beisswenger, Paul J.
AU - Reaven, Peter D.
N1 - Funding Information:
VADT study participants and study staff and the investigators at the Phoenix, San Diego, Long Beach, Hines, Pittsburgh, Tucson, and Miami VA Medical Centers for participating in this study. The authors also acknowledge the contributions of the Hines VA Cooperative Studies Program Coordinating Center. Funding. This work was supported by the Veterans Affairs Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development. Additional support was received from the National Institutes of Health (R01-HL110418 [to H.G.] and R01-067690 and 5R01-094775 [to P.D.R.]), the American Diabetes Association (to P.D.R.), and the National Institute of Diabetes and Digestive and Kidney Diseases (Small Business Innovation Research grant 4R44-DK101226-01A1 [to P.J.B.]). B.D.C. is supported by a National Heart Foundation Future Leader Fellowship (no. 100864). Duality of Interest. S.H. and P.J.B. are employed by PreventAGE Healthcare, where the assays of AGE and OP were performed. No other potential conflicts of interest relevant to this article were reported. Author Contributions. J.K., A.S., and P.D.R. conceived and designed the study, analyzed and interpreted the data, and wrote the manuscript. S.H. and P.J.B. measured AGE and OP values. G.B. advised on statistical analysis methods and acquired the data. B.D.C. reviewed and edited the manuscript. H.G. designed the study and reviewed the manuscript. P.D.R. was the principal investigator. All authors reviewed and edited the manuscript, approved the final version, and are accountable for all aspects of the work. J.K. and P.D.R. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Part of this study was presented in abstract form for a late-breaking poster presentation at the 76th Scientific Sessions of the American Diabetes Association, New Orleans, LA, 10–14 June 2016.
Publisher Copyright:
© 2017 by The American Diabetes Association.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - OBJECTIVE The goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes. RESEARCH DESIGN AND METHODS Five specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-Aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1) a subcohort of the Veterans Affairs Diabetes Trial (VADT) (n = 445) and 2) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (n = 271). RESULTS Increased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A1c. In the VADT, increased risk of incident CVD events (n = 107) was associated with lowerMetSOafter adjusting for age, race/ethnicity, sex, prior CVDevent, kidney function, treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28-0.99; P = 0.047). Individualswith both lowMetSO and high 3-deoxyglucosone hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01). In the ACCORD study, those with incident CVD events (n = 136) had lower MetSO (by 14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by 18%and 15%, respectively; P = 0.04 for both); however, only the difference inMetSO remained significant after adjustment for prior CVD event (P = 0.002). CONCLUSIONS Lower levels ofMetSO and higher levels of select AGE are associated with increased incident CVD and may help account for the limited benefit of intensive glucose lowering in type 2 diabetes.
AB - OBJECTIVE The goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes. RESEARCH DESIGN AND METHODS Five specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-Aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1) a subcohort of the Veterans Affairs Diabetes Trial (VADT) (n = 445) and 2) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (n = 271). RESULTS Increased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A1c. In the VADT, increased risk of incident CVD events (n = 107) was associated with lowerMetSOafter adjusting for age, race/ethnicity, sex, prior CVDevent, kidney function, treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28-0.99; P = 0.047). Individualswith both lowMetSO and high 3-deoxyglucosone hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01). In the ACCORD study, those with incident CVD events (n = 136) had lower MetSO (by 14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by 18%and 15%, respectively; P = 0.04 for both); however, only the difference inMetSO remained significant after adjustment for prior CVD event (P = 0.002). CONCLUSIONS Lower levels ofMetSO and higher levels of select AGE are associated with increased incident CVD and may help account for the limited benefit of intensive glucose lowering in type 2 diabetes.
UR - http://www.scopus.com/inward/record.url?scp=85042585990&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042585990&partnerID=8YFLogxK
U2 - 10.2337/dc17-1740
DO - 10.2337/dc17-1740
M3 - Article
C2 - 29208654
AN - SCOPUS:85042585990
SN - 1935-5548
VL - 41
SP - 570
EP - 576
JO - Diabetes Care
JF - Diabetes Care
IS - 3
ER -