Oxidative stress and cardiovascular risk in type 1 diabetes mellitus

Insights from the DCCT/EDIC study

DCCT/EDIC Research Group

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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
Volume7
Issue number10
DOIs
StatePublished - May 15 2018

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Diabetes Complications
Type 1 Diabetes Mellitus
Epidemiology
Oxidative Stress
Aryldialkylphosphatase
Dinoprost
Cardiovascular Diseases
F2-Isoprostanes
Peroxidase
Antioxidants
Biomarkers
Hyperglycemia

Keywords

  • Diabetes mellitus
  • F2Isoprostane
  • Free radical
  • Paraoxonase

Cite this

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

In: Journal of the American Heart Association, Vol. 7, No. 10, e008368, 15.05.2018.

Research output: Contribution to journalArticle

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title = "Oxidative stress and cardiovascular risk in type 1 diabetes mellitus: Insights from the DCCT/EDIC study",
abstract = "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 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.",
keywords = "Diabetes mellitus, F2Isoprostane, Free radical, Paraoxonase",
author = "{DCCT/EDIC Research Group} and {Wilson Tang}, {W. H.} and Paula McGee and Lachin, {John M.} and Li, {Daniel Y.} and Byron Hoogwerf and Hazen, {Stanley L.} and Nathan, {D. M.} and B. Zinman and O. Crofford and S. Genuth and J. Brown-Friday and J. Crandall and H. Engel and S. Engel and H. Martinez and M. Phillips and M. Reid and H. Shamoon and J. Sheindlin and R. Gubitosi-Klug and L. Mayer and S. Pendegast and H. Zegarra and D. Miller and L. Singerman and S. Smith-Brewer and M. Novak and J. Quin and Saul Genuth and M. Palmert and E. Brown and J. McConnell and P. Pugsley and P. Crawford and W. Dahms and Gregory, {N. S.} and Lackaye, {M. E.} and S. Kiss and R. Chan and A. Orlin and M. Rubin and D. Brillon and V. Reppucci and T. Lee and M. Heinemann and S. Chang and B. Levy and L. Jovanovic and M. Richardson and B. Bosco",
year = "2018",
month = "5",
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doi = "10.1161/JAHA.117.008368",
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T1 - Oxidative stress and cardiovascular risk in type 1 diabetes mellitus

T2 - Insights from the DCCT/EDIC study

AU - DCCT/EDIC Research Group

AU - Wilson Tang, W. H.

AU - McGee, Paula

AU - Lachin, John M.

AU - Li, Daniel Y.

AU - Hoogwerf, Byron

AU - Hazen, Stanley L.

AU - Nathan, D. M.

AU - Zinman, B.

AU - Crofford, O.

AU - Genuth, S.

AU - Brown-Friday, J.

AU - Crandall, J.

AU - Engel, H.

AU - Engel, S.

AU - Martinez, H.

AU - Phillips, M.

AU - Reid, M.

AU - Shamoon, H.

AU - Sheindlin, J.

AU - Gubitosi-Klug, R.

AU - Mayer, L.

AU - Pendegast, S.

AU - Zegarra, H.

AU - Miller, D.

AU - Singerman, L.

AU - Smith-Brewer, S.

AU - Novak, M.

AU - Quin, J.

AU - Genuth, Saul

AU - Palmert, M.

AU - Brown, E.

AU - McConnell, J.

AU - Pugsley, P.

AU - Crawford, P.

AU - Dahms, W.

AU - Gregory, N. S.

AU - Lackaye, M. E.

AU - Kiss, S.

AU - Chan, R.

AU - Orlin, A.

AU - Rubin, M.

AU - Brillon, D.

AU - Reppucci, V.

AU - Lee, T.

AU - Heinemann, M.

AU - Chang, S.

AU - Levy, B.

AU - Jovanovic, L.

AU - Richardson, M.

AU - Bosco, B.

PY - 2018/5/15

Y1 - 2018/5/15

N2 - 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 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.

AB - 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 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.

KW - Diabetes mellitus

KW - F2Isoprostane

KW - Free radical

KW - Paraoxonase

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U2 - 10.1161/JAHA.117.008368

DO - 10.1161/JAHA.117.008368

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VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

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