Oxidative stress and cardiovascular risk in type 1 diabetes mellitus: Insights from the DCCT/EDIC study
- Citation data:
Journal of the American Heart Association, ISSN: 2047-9980, Vol: 7, Issue: 10
- Publication Year:
- Repository URL:
- https://hsrc.himmelfarb.gwu.edu/sphhs_epibiostats_facpubs/494; https://ohsu.pure.elsevier.com/en/publications/82079417-3d7c-48bc-aade-7c1f4469a748
- Medicine; Diabetes mellitus; F2Isoprostane; Free radical; Paraoxonase; Cardiology and Cardiovascular Medicine; Biostatistics; Endocrine System Diseases; Endocrinology, Diabetes, and Metabolism; Epidemiology
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 Fisoprostanes, 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 Fisoprostanes 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.