Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study
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Published:2018-05-15
Issue:10
Volume:7
Page:
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ISSN:2047-9980
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Container-title:Journal of the American Heart Association
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language:en
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Short-container-title:JAHA
Author:
Tang W.H. Wilson12, McGee Paula3, Lachin John M.3, Li Daniel Y.1, Hoogwerf Byron4, Hazen Stanley L.12, 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., Singerman L., Smith‐Brewer S., Novak M., Quin J., Genuth Saul, Palmert M., Brown E., McConnell J., Pugsley P., Crawford P., Dahms W., Gregory N.S., Lackaye M.E., Kiss S., Chan R., Orlin A., Rubin M., Brillon D., Reppucci V., Lee T., Heinemann M., Chang S., Levy B., Jovanovic L., Richardson M., Bosco B., Dwoskin A., Hanna R., Barron S., Campbell R., Bhan A., Kruger D., Jones J.K., Edwards P.A., Bhan A., Carey J.D., Angus E., Thomas A., Galprin A., McLellan M., Whitehouse F., Bergenstal R., Johnson M., Gunyou K., Thomas L., Laechelt J., Hollander P., Spencer M., Kendall D., Cuddihy R., Callahan P., List S., Gott J., Rude N., Olson B., Franz M., Castle G., Birk R., Nelson J., Freking D., Gill L., Mestrezat W., Etzwiler D., Morgan K., Aiello L.P., Golden E., Arrigg P., Asuquo V., Beaser R., Bestourous L., Cavallerano J., Cavicchi R., Ganda O., Hamdy O., Kirby R., Murtha T., Schlossman D, Shah S., Sharuk G., Silva P., Silver P., Stockman M., Sun J., Weimann E., Wolpert H., Aiello L.M., Jacobson A., Rand L., Rosenzwieg J., Nathan D.M., Larkin M.E., Christofi M., Folino K., Godine J., Lou P., Stevens C., Anderson E., Bode H., Brink S., Cornish C., Cros D., Delahanty L., eManbey ., Haggan C., Lynch J., McKitrick C., Norman D., Moore D., Ong M., Taylor C., Zimbler D., Crowell S., Fritz S., Hansen K., Gauthier‐Kelly C., Service F.J., Ziegler G., Barkmeier A., Schmidt L., French B., Woodwick R., Rizza R., Schwenk W.F., Haymond M., Pach J., Mortenson J., Zimmerman B., Lucas A., Colligan R., Luttrell L., Lopes‐Virella M., Caulder S., Pittman C., Patel N., Lee K., Nutaitis M., Fernandes J., Hermayer K., Kwon S., Blevins A, Parker J., Colwell J., Lee D., Soule J., Lindsey P., Bracey M., Farr A., Elsing S., Thompson T., Selby J., Lyons T., Yacoub‐Wasef S., Szpiech M., Wood D., Mayfield R., Molitch M., Adelman D., Colson S., Jampol L., Lyon A., Gill M., Strugula Z., Kaminski L., Mirza R., Simjanoski E., Ryan D., Johnson C., Wallia A., Ajroud‐Driss S., Astelford P., Leloudes N., Degillio A., Schaefer B., Mudaliar S., Lorenzi G, Goldbaum M., Jones K., Prince M., Swenson M., Grant I., Reed R., Lyon R., Kolterman O., Giotta M., Clark T., Friedenberg G., Sivitz W.I., Vittetoe B., Kramer J., Bayless M., Zeitler R., Schrott H., Olson N., Snetselaar L., Hoffman R., MacIndoe J., Weingeist T., Fountain C., Miller R., Johnsonbaugh S., Patronas M., Carney M., Mendley S., Salemi P., Liss R., Hebdon M., Counts D., Donner T., Gordon J., Hemady R., Kowarski A., Ostrowski D., Steidl S., Jones B., Herman W.H., Martin C.L., Pop‐Busui R., Greene D.A., Stevens M.J., Burkhart N., Sandford T., Floyd J., Bantle J., Flaherty N., Terry J., Koozekanani D., Montezuma S., Wimmergren N., Rogness B., Mech M., Strand T., Olson J., McKenzie L., Kwong C., Goetz F., Warhol R., Hainsworth D., Goldstein D., Hitt S., Giangiacomo J., Schade D.S, Canady J.L., Burge M.R., Das A., Avery R.B., Ketai L.H., Chapin J.E., Schluter M.L., Rich J., Johannes C., Hornbeck D., Schutta M., Bourne P.A., Brucker A., Braunstein S., Schwartz S., Maschak‐Carey B.J., Baker L., Orchard T., Cimino L., Songer T., Doft B., Olson S., Becker D., Rubinstein D., Bergren R.L., Fruit J., Hyre R., Palmer C., Silvers N., Lobes L., Rath P. Paczan, Conrad P.W., Yalamanchi S., Wesche J., Bratkowksi M., Arslanian S., Rinkoff J., Warnicki J., Curtin D., Steinberg D., Vagstad G., Harris R., Steranchak L., Arch J., Kelly K., Ostrosaka P., Guiliani M., Good M., Williams T., Olsen K., Campbell A., Shipe C., Conwit R., Finegold D., Zaucha M., Drash A., Morrison A., Malone J.I., Bernal M.L., Pavan P.R., Grove N., Tanaka E.A., McMillan D., Vaccaro‐Kish J., Babbione L., Solc H., DeClue T.J., Dagogo‐Jack S., Wigley C., Ricks H., Kitabchi A., Chaum E., Murphy M.B., Moser S., Meyer D., Iannacone A., Yoser S., Bryer‐Ash M., Schussler S., Lambeth H., Raskin P., Strowig S., Basco M., Cercone S., Zinman B., Barnie A., Devenyi R., Mandelcorn M., Brent M., Rogers S., Gordon A., Bakshi N., Perkins B., Tuason L., Perdikaris F., Ehrlich R., Daneman D., Perlman K., Ferguson S, Palmer J., Fahlstrom R., de Boer I.H., Kinyoun J., Van Ottingham L., Catton S., Ginsberg J., McDonald C., Harth J., Driscoll M., Sheidow T., Mahon J., Canny C., Nicolle D., Colby P., Dupre J., Hramiak I., Rodger N.W., Jenner M., Smith T., Brown W., May M., Lipps Hagan J., Agarwal A., Adkins T., Lorenz R., Feman S., Survant L., White N.H., Levandoski L., Grand G., Thomas M., Joseph D., Blinder K., Shah G., Burgess D., Boniuk I., Santiago J., Tamborlane W., Gatcomb P., Stoessel K., Ramos P., Fong K., Ossorio P., Ahern J., Gubitosi‐Klug R., Meadema‐Mayer L., Beck C., Farrell K., Genuth S., Quin J, Gaston P., Palmert M., Trail R., Dahms W., Lachin J., Backlund J., Bebu I., Braffett B., Diminick L., Gao X., Hsu W., Klumpp K., Pan H., Trapani V., Cleary P., McGee P., Sun W., Villavicencio S., Anderson K., Dews L., Younes Naji, Rutledge B., Chan K., Rosenberg D., Petty B., Determan A., Kenny D., Williams C., Cowie C., Siebert C., Steffes M., Arends V., Bucksa J., Nowicki M., Chavers B., O'Leary D., Polak J., Harrington A., Funk L., Crow R, Gloeb B., Thomas S., O'Donnell C., Soliman E.Z., Zhang Z.M., Li Y., Campbell C., Keasler L., Hensley S., Hu J., Barr M., Taylor T., Prineas R., Feldman E.L., Albers J.W., Low P., Sommer C., Nickander K., Speigelberg T., Pfiefer M., Schumer M., Moran M., Farquhar J., Ryan C., Sandstrom D., Williams T., Geckle M., Cupelli E., Thoma F., Burzuk B., Woodfill T., Danis R., Blodi B., Lawrence D., Wabers H., Gangaputra S., Neill S., Burger M., Dingledine J., Gama V., Sussman R., Davis M., Hubbard L., Budoff M., Darabian S., Rezaeian P., Wong N., Fox M., Oudiz R., Kim L, Detrano R., Cruickshanks K., Dalton D., Bainbridge K., Lima J., Bluemke D., Turkbey E., der Geest ., Liu C., Malayeri A., Jain A., Miao C., Chahal H., Jarboe R., Nathan D.M., Monnier V., Sell D., Strauch C., Hazen S., Pratt A., Tang W., Brunzell J., Purnell J., Natarajan R., Miao F., Zhang L., Chen Z., Paterson A., Boright A., Bull S., Sun L., Scherer S., Lopes‐Virella M., Lyons T.J., Jenkins A., Klein R., Virella G., Jaffa A., Carter R., Stoner J., Garvey W.T., Lackland D., Brabham M., McGee D., Zheng D., Mayfield R.K., Maynard J., Wessells H., Sarma A, Jacobson A., Dunn R., Holt S., Hotaling J., Kim C., Clemens Q., Brown J., McVary K.,
Affiliation:
1. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 2. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 3. The Biostatistics Center, George Washington University, Rockville, MD 4. Cleveland Clinic (Emeritus), Cleveland, OH
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
2α
isoprostanes, and its metabolite, 2,3 dinor‐8
iso
prostaglandin F
2α
. 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
2α
, 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
2α
,
P
=0.0092). In contrast, the oxidative markers myeloperoxidase and F
2α
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.
Clinical Trial Registration
URL
:
https://www.clinicaltrials.gov
. Unique identifiers:
NCT
00360815 and
NCT
00360893.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
7 articles.
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