Oxidative stress and cardiovascular risk in type 1 diabetes mellitus: Insights from the DCCT/EDIC study

DCCT/EDIC Research Group

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2 Scopus citations


Background--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 F isoprostanes, and its metabolite, 2,3 dinor-8 iso prostaglandin F. 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 F, 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 F, P=0.0092). In contrast, the oxidative markers myeloperoxidase and F 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.

Original languageEnglish (US)
Article numbere008368
JournalJournal of the American Heart Association
Issue number10
StatePublished - May 15 2018

Bibliographical note

Funding Information:
The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017), and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, MD. The research in this ancillary study to the DCCT/EDIC was supported by National Institutes of Health grants P01HL076491, R01HL128300, and 3R01DK080732-01A1S1.

Funding Information:
This 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).

Publisher Copyright:
© 2018 The Authors.


  • Diabetes mellitus
  • F2Isoprostane
  • Free radical
  • Paraoxonase

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