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Advanced glycation end products, oxidation products tied to CVD risk in type 2 diabetes
Adults with type 2 diabetes may be at increased risk for cardiovascular disease with low levels of the oxidation product methionine sulfoxide and high levels of certain advanced glycation end products, according to findings published in Diabetes Care.
These associations may account for the limited benefit of intensive glucose lowering in adults with type 2 diabetes, according to the researchers.
Juraj Koska, MD, PhD, of the department of endocrinology at Phoenix VA Health Care System, and colleagues evaluated data on adults with type 2 diabetes from a subcohort of the Veterans Affairs Diabetes Trial (VADT; n = 445) and a nested case-control subgroup from ACCORD (n = 271) to determine whether plasma levels of advanced glycation end products (AGEs) and oxidation products predict CVD incidence.
At the baseline of each study, participants were measured for five specific AGEs — methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone and glyoxal hydroimidazolone — and two oxidation products — 2-aminodipic acid and methionine sulfoxide.
At baseline among participants in ACCORD, the mean age of those with CVD was 64 years, 76% were men and 72% were white; the mean age of those without CVD was 64 years, 75% were men and 68% were white. At baseline among participants in VADT, the mean age of those with CVD was 60 years, 99% were men and 72% were white; the mean age of those without CVD was 58 years, 96% were men and 60% were white.
During a median follow-up of 2.3 years, 107 participants in the VADT subcohort had a CVD event. A lower risk for CVD events was associated with higher plasma methionine sulfoxide concentrations (HR = 0.53; 95% CI, 0.28-0.99) independent of age, race/ethnicity, sex, prior CVD event, kidney function, treatment assignment and diabetes duration. Incident CVD was associated with 3-deoxyglucosone hydroimidazolone (HR = 1.51; 95% CI, 1.003-2.27) and methionine sulfoxide (HR = 0.45; 95% CI, 0.27-0.85) in stepwise modeling that evaluated all AGEs and oxidation products.
Participants with prior CVD in the ACCORD trial had higher glyoxal hydroimidazolone (P < .0001), 3-deoxyglucosone hydroimidazolone (P = .002) and carboxymethyl lysine (P = .0004) compared with those without prior CVD, but after adjustment for age, race/ethnicity, sex, diabetes duration and kidney function, only higher glyoxal hydroimidazolone remained significant. Participants with incident CVD had lower methionine sulfoxide (P = .007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (P = .004 for both) compared with those without incident CVD; after adjustment CVD history, only the difference in methionine sulfoxide remained significant.
“Our results indicate that lower levels of [methionine sulfoxide] and higher levels of select AGE are associated with incident cardiovascular events over 3 to 7 years of follow-up in patients with long-standing [type 2 diabetes],” the researchers wrote. “This may help explain the limited benefit of intensive glucose-lowering therapy in these moderate-duration studies.” – by Amber Cox
Disclosures: Koska reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.