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dc.contributor.authorWilson Tang, W.H.
dc.contributor.authorMcGee, P.
dc.contributor.authorLachin, J.M.
dc.date.accessioned2019-06-21T18:46:36Z
dc.date.available2019-06-21T18:46:36Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85046955072&doi=10.1161%2fJAHA.117.008368&partnerID=40&md5=d44e91299074228c57fcc839df329f0a
dc.identifier.urihttp://hdl.handle.net/10713/9809
dc.description.abstractBackground-- Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results-- A random subcohort of 349 participants was selected from the DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT, and 1 to 2 years post‐DCCT (EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F2α. Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F2α, an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P<0.003; −5.3% risk for 10% higher 2,3 dinor‐8 iso prostaglandin F2α, P=0.0092). In contrast, the oxidative markers myeloperoxidase and F2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions-- Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. Copyright 2018 The Authors.en_US
dc.description.sponsorshipThis study was supported by JSPS KAKENHI (15K09082 to Morita) and Tailor-made Medical Treatment Program with the BioBank Japan Project (BBJ) from Japan Agency for Medical Research and Development (AMED) (15km0305015h0101 to Morita).en_US
dc.description.urihttps://dx.doi.org/10.1161/JAHA.117.008368en_US
dc.language.isoen-USen_US
dc.publisherAmerican Heart Association Inc.en_US
dc.relation.ispartofJournal of the American Heart Association
dc.subjectDiabetes mellitusen_US
dc.subjectF2Isoprostaneen_US
dc.subjectFree radicalen_US
dc.subjectParaoxonaseen_US
dc.titleOxidative stress and cardiovascular risk in type 1 diabetes mellitus: Insights from the DCCT/EDIC studyen_US
dc.typeArticleen_US
dc.identifier.doi10.1161/JAHA.117.008368


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