Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study

Medientyp: E-Artikel
Titel: Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study
Beteiligte: Tang, W.H. Wilson; McGee, Paula; Lachin, John M.; Li, Daniel Y.; Hoogwerf, Byron; Hazen, Stanley L.; Nathan, D.M.; Zinman, B.; Crofford, O.; Genuth, S.; Brown‐Friday, J.; Crandall, J.; Engel, H.; Engel, S.; Martinez, H.; Phillips, M.; Reid, M.; Shamoon, H.; Sheindlin, J.; Gubitosi‐Klug, R.; Mayer, L.; Pendegast, S.; Zegarra, H.; Miller, D.; [...]
Erschienen: Ovid Technologies (Wolters Kluwer Health), 2018
Erschienen in: Journal of the American Heart Association
Sprache: Englisch
DOI: 10.1161/jaha.117.008368
ISSN: 2047-9980
Schlagwörter: Cardiology and Cardiovascular Medicine
Entstehung:
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Beschreibung: <jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en">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.</jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> A random subcohort of 349 participants was selected from the <jats:styled-content style="fixed-case">DCCT</jats:styled-content> / <jats:styled-content style="fixed-case">EDIC</jats:styled-content> (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 <jats:styled-content style="fixed-case">DCCT</jats:styled-content> baseline, year 1, and closeout of <jats:styled-content style="fixed-case">DCCT</jats:styled-content> , and 1 to 2 years post‐ <jats:styled-content style="fixed-case">DCCT</jats:styled-content> ( <jats:styled-content style="fixed-case">EDIC</jats:styled-content> years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F <jats:sub>2α</jats:sub> isoprostanes, and its metabolite, 2,3 dinor‐8 <jats:italic>iso</jats:italic> prostaglandin F <jats:sub>2α</jats:sub> . 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 <jats:italic>iso</jats:italic> prostaglandin F <jats:sub>2α</jats:sub> , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, <jats:italic>P</jats:italic> <0.003; −5.3% risk for 10% higher 2,3 dinor‐8 <jats:italic>iso</jats:italic> prostaglandin F <jats:sub>2α</jats:sub> , <jats:italic>P</jats:italic> =0.0092). In contrast, the oxidative markers myeloperoxidase and F <jats:sub>2α</jats:sub> isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between <jats:styled-content style="fixed-case">DCCT</jats:styled-content> intensive and conventional treatment groups in the change in all biomarkers across time segments. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en">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.</jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Clinical Trial Registration</jats:title> <jats:p xml:lang="en"> <jats:styled-content style="fixed-case">URL</jats:styled-content> : <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</jats:ext-link> . Unique identifiers: <jats:styled-content style="fixed-case">NCT</jats:styled-content> 00360815 and <jats:styled-content style="fixed-case">NCT</jats:styled-content> 00360893. </jats:p> </jats:sec>
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