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Lancet. 2010 Aug 7;376(9739):419-30. doi: 10.1016/S0140-6736(10)60576-4. Epub 2010 Jun 30.

Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial.

Collaborators (1236)

Friedewald WT, Buse JB, Bigger JT, Byington RP, Cushman WC, Ismail-Beigi F, Gerstein HC, Ginsberg HN, Goff DC Jr, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Gerstein HC, Yusuf S, Punthakee Z, Russo R, Anand S, Chrysler K, Cracknell B, Cukierman-Yaffe T, Gafni A, Guyatt G, Hall S, Kaszyca J, Lonn E, Mackie P, Reiding V, Shehadeh N, Tadeson B, Thompson K, Vallis M, Vasudeva V, Wilderman I, Wright D, Grimm RH Jr, Kirpach BR, Bartkoske MM, Boyce CM, Druckman N, Gillett AM, Levin JA, Livingston GJ, Murray AM, Wood H, Margolis KL, Bigger JT, Lopez-Jimenez CR, Bornholdt R, Busaca L, Ginsberg HN, Gonzales P, Gosh D, Love P, Kosok A, Robinson E, Steinman R, Watson C, Reyes G, Genuth S, Ismail-Beigi F, Thibonnier M, Vargo L, Kelly C, Bongorno T, Dolish A, Pavlik L, Tiktin M, Isteitieh S, Bartlett A, Kulow T, Goff DC Jr, Summerson JH, Crago L, Blackwell CS, Bertoni A, Blaine RL, Kirk JK, Spach RL, Williamson J, Calles J, Katula J, Wishnietsky DB, Cushman WC, Geraci TS, Walsh SM, Coley LG, Elam MB, Pickering DI, Huff C, Probstfield JL, Kingry C, Line AS, Corson MA, Knopp R, Lipkin E, Sullivan MD, Johnson J, Griswold C, Liebert K, Brown A, Juliano D, Kurashige EM, Moberg S, Leader J, Punthakee Z, Smith A, Stanton I, Capes S, Manjoo P, Valla T, Danby S, Harper W, Harvey P, Hunt D, Moroso A, Otto R, Prebtani A, Punthakee Z, Davis A, Capes S, Hill KL, McCarthy V, Edwards AL, Mitchell DJ, Clearwaters MA, Dielissen C, Gillam M, Hammond B, Jensen H, Kherani A, Lau D, Pringle V, Rabi D, Sigal R, Smith C, Walker M, Williams G, Joyce C, Parsons M, Rowe B, Burton J, Chandurkar V, Coady-McDonald S, Gibbons D, Kovacs C, Murphy B, Smart R, Varghese S, Mereu L, Ryan E, Senior P, Kirkland P, Abe J, Dalton K, Gendall W, Germsheid J, Hartmann D, Jeffrys A, Kumar U, MacDonald C, Makhani N, Mawani S, Morales F, Paty B, Pick M, Schwanke B, Stark A, Tennant M, Varma S, Weiss-Aburto D, Werbiski-Wood P, Woloschuk B, Zimmerman W, Bélanger A, Gauthier S, Bahsali G, Barbeau C, Caponi E, Duchesne R, Dumas R, Gauthier P, Girouard J, Kandalaft N, Labbé M, Palardy J, Pilon M, Raymond J, Schiffrin A, Hramiak I, Tereschyn S, Driscoll M, Gehring M, Gonder J, Lincoln C, McBeth W, McDonald C, McDonald T, Pauli P, Paul T, Powers S, Ronald N, Trinh V, Vancer L, Walsh G, Lochnan H, Ooi TC, Maranger J, Bradley L, Buhrmann R, Cyr M, Gilchrist C, Hanlon B, Harley M, Jay K, Leech T, Malcolm J, McLean M, Parker E, Sigal R, Sullivan K, Yale JF, Segal SA, Al Ansari G, Renouf N, Allaire N, Alawadhi MA, Belfer B, Blank DW, Bouchard F, Buoy-Phang S, Carter J, Coppin L, Dalpe D, Delpech I, Doran PM, Emmian F, Fortin S, Garfield N, Gosselin M, Horan S, Kalergis M, Koutelias S, Légaré C, Lombardo A, Morais JA, Quigley M, Renouf N, Riopel C, Riopel S, Rivera JA, Rochon G, Roy M, Salera M, Sherman MH, Shingler M, Staples HE, Ulyatt L, Yared Z, Leiter LA, Booth G, Sparrow L, Choi H, Bedard DC, Berger A, Berndl LA, Cheng A, Evalmplev V, Goguen J, Hanna A, Josse RG, Kalas JA, Perry S, Pike M, Elliott T, Dawson K, Kong J, Albiani D, Inducil M, Al Amoudi R, Broughton T, Hall L, Harrison B, Hirvi N, Lee R, Merkur A, Norman E, Paty B, Potter M, Stevenson D, Vafadaran A, Woo V, Berard L, Anderlic T, Austman K, Bernard A, Catte D, Darvill P, Hak D, Hutchison K, Janzen L, Klopak T, Mandock C, Mathen M, Mawani S, Mawani A, Murphy L, Nyomba G, Penner B, Pockett S, Russell S, Stockl F, Studney J, Sukkau R, Abbott C, Ur E, Yuille M, Archibald M, Clayton D, Cruess A, Davis N, Fong H, Frizzell S, Hanway B, Hoskin-Mott A, Imran A, Ingraham C, McCarthy G, Murdock H, Palmer T, Patterson AM, Ransom T, Shu D, Tuttle J, Kempainen S, Madden M, Fareed MT, Hall K, Moor R, Wood K, Bergenstal R, Cuddihy R, Davick B, Hokanson J, Johnson M, Lausch M, List S, Monk A, Robinson R, Smith K, Whipple D, Damberg G, Hahn R, Koenig V, Magadan M, Sabin-Smith S, Stewart P, Strock E, Peremislov D, Gunyou K, Passi R, Ashanti C, Thomas L, Stoffels D, Seaquist ER, Mech MV, Benedict LE, Demmon DJ, Kumar AF, Martinson SM, Miller SA, Pease C, Rao JP, Redmon JB, Swanson JE, Wimmer JK, Okorocha Y, Stiles M, Kodl C, Chadha C, Peterson KA, Seaquist LA, Boese C, Cruciani M, Dodds E, Ek FP, Feldman JL, Fontaine P, Lange CJ, Mendenhall TJ, Peterson AM, Rudelt A, Schrock TM, Spielman DP, Velasco S, Weinhand JC, Sperl-Hillen JM, O'Connor PJ, Busch ME, Chung A, Klein BK, Krugen N, Bunkers-Lawson T, Ekstrom HL, Gunderson HS, Johnson BM, MacIndoe JH, Prewedo DJ, Rawl JL, Roethke CM, Quinlan M, Fox CR, Bate BM, Cao QT, Ohnstad MM, Meyers PJ, Sivitz WI, Wayson SM, Lower TA, Larson L, Ahrens LA, Bayless M, Beck SE, Chahal J, Chenard C, Doelle GC, Guzman VM, Kabadi UM, Ochs KA, Rahhal A, Spanheimer RG, Snetselaar L, Smith K, Wells D, Schubart UK, Mendoza M, Goswami G, Laufer A, Russo J, Vincenty N, Alderman MH, Carroll L, Sanguily MJ, Gorkin JU, Mayer AC, Ramos L, Sessoms V, Stewart AF, Brillon D, Cordero J, Richardson MA, Wei E, Ganz F, Meyer BR, Paley J, Anderson S, Charles C, Dwoskin A, Chiong R, Hyams K, Lorber DL, Arenstein T, Depree P, Elmorsy AA, Wendel JM, Zintl LL, August P, Beck M, Goldberg MD, Hofacker MJ, Marotta-Kollarus M, Ocampo EJ, Resta CA, Tibaldi JM, Bastien A, Grudzinski S, Niblack P, Abreu L, Brobyn T, Brown K, Casale M, Dougherty D, Haddad G, Heintz K, Kelly M, Linneman D, Olivia C, Salvador MA, Zee P, Hyman D, Brautigam DF, Fischer R, Chiarot JM, Scharf DM, Nunn B, Carlson J, Flanders C, Hagen MR, Newman S, Gordon TA, Goland R, Tuck CH, Kringas P, Hey-Hadavi J, Montes J, Vargas-Jerez J, Salas-Spiegel J, Getaneh A, Ramirez J, Vasquez EF, Kranwinkel G, Durant SA, Donovan DS, Febres G, Hernandez C, Jonaitis MA, Mesa L, Banerji MA, Norton M, Patel P, Daly V, Hirsch S, Jazmin C, Khillan R, Mendonca D, Relingado A, Sandoval E, Tiewala M, Banerji MA, Norton M, Patel P, Daly V, Hirsch S, Jazmin C, Khillan R, Mendonca D, Relingado A, Sandoval E, Tiewala M, Bastien A, Grudzinski S, Niblack P, Abreu L, Brobyn T, Brown K, Casale M, Dougherty D, Haddad G, Heintz K, Kelly M, Linneman D, Olivia C, Salvador MA, Zee P, Hyman D, Ismail-Beigi F, Krikorian A, Moore L, Richardson L, Coles-Herman E, Yee K, Frankino J, Jing M, Sood A, Hustak L, Julius M, Pavlik L, Ross T, Long L, Schwing W, Tiktin M, Sullivan MK, Strauss L, Behm K, Eskandari F, Hall C, Hayes D, Horowitz K, Isteitieh S, Madhun Z, Seeholzer E, Shina J, Taylor H, Schnall A, Huang S, Heeg M, Tang J, Belkin J, Lee MS, Joly T, Sadler LS, Griffith M, Hornsby A, Klyn K, Ospelt E, Long L, DeSmit M, McCann P, Schmidt NP, Gottfried C, Kulow T, Zaletal J, Kapadia MS, Smith L, Schnall AM, Dragmen L, Ellert R, Smith J, Leksan J, Sussman T, Huang S, Heeg M, Tang J, Belkin J, Lee MS, Joly T, Ismail-Beigi F, Hustak L, Julius M, Schwing W, Tiktin M, Anselmo J, Eskandari F, Daymeyer S, Hall C, Hayes D, Horowitz K, Isteitieh S, Johnson C, Kern E, Richmond MA, Richardson L, Roberts K, Shina J, Sood A, Suhan P, Taylor H, Watts S, Martin J, Moor L, Burtch B, Ober S, Strauss GJ, Leone A, Belkin J, Huang S, Frank K, Stephens D, Lee MS, Joly T, Hoogwerf BJ, Brakeman J, Matzinger M, Newsome J, Becker J, Bizjack S, Clingman B, Curtas-Thomas S, Depietro G, Ellert R, Horner C, Bunae G, Hamrahian A, Hawkins A, Head T, Iannica S, Jones L, Kaiser P, McCoy R, Mehta A, Olansky L, Orasko A, Reddy S, Ross D, Shockley L, Siraj E, Williams M, Zimmerman R, Hamaty M, Weiss D, Fagan KA, Hanslik TM, Farrell J, Brys P, Oligny M, Prokop K, Lenardic K, Karapanzcik T, Huang S, Heeg M, Tang J, Belkin J, Lee MS, Joly T, Akpunonu B, Franco-Saenz R, Gilmore J, Gilmore M, Godfrey L, Ross P, Bauer B, Chrisstie M, Lopez A, Mulrow P, Peters C, Pop-Busui R, Roman J, Smith C, Bick J, Blust Z, Nelsen PT, Marcus D, Osei K, Dziengelewski EA, Breedlove H, Boland D, Boyer CC, Cataland S, Kearns PA, Irwin JE, Schuster DP, Varga-Spangler JL, Bowles T, Weiland K, Arnold K, Evans T, Bouttamy J, Letson A, Craig E, Davidorf F, Cohen RM, Burton K, Craig J, Carter B, Harrer J, Hurd R, Lopez-Stickney D, Pritchard C, Pfefferman A, Ramlo-Halsted BA, McCormick C, Riley C, Strominger M, Knittel A, Groff G, Bailey C, Howald A, Anderson N, Bierschbach JL, Tyzinski M, Smith B, Krug S, Hershberger V, Hutchins RK, Raymond LA, Thomas A, Kahkonen DM, Cushman T, Roman M, Stys AM, White K, Austin M, Chatterton C, Francis JK, Jones C, Kruger D, McLellan A, Whitehouse F, Higgins E, Levy S, Schoenherr A, Edwards P, Grunberger G, Aman LC, Bandagi AH, Russell KM, Tucker C, Abidova Y, Amirikia A, Narduccio M, Billingsly B, Feinglos MN, Jones J, Mason MB, Furst MA, Bean WJ, Gedon-Lipscomb G, Green JB, Parham T, Satterwhite BM, Thacker CR, Padhiar D, Noel R, Padhiar N, West S, Braden J, Francis A, Atkinson HH, Dibari M, Allen J, Stanfield J, Delvalle-Fagan T, Gordineer LJ, Gordon L, Gordon M, Smith SL, Yates H, Pedley CF, Zurek G, Baird M, Dunn B, Kinder W, Mauney S, Buse JB, Duclos MD, Kirby RE, Largay JF, McDermott NM, Goley A, Braithwaite SS, Dostou JM, Fasy EA, Kelly DC, Metz CE, Jeffries J, Rubin D, Vukojicik K, Miller JL, Besterman W, Norton SM, Weatherly J, Bishop S, Cross B, Nuss K, Surgenor M, Alley D, Farmer A, Foard J, White J, Wood Y, Dulin M, Konen J, Barringer T, Andrews K, Hoffman C, Morris C, Norton S, Tochiki P, Reinblatt G, Bruner P, Peace R, Stuart DO, Strickland J, Cummings L, Craig D, Stanfield J, Peace R, Stuart DO, Strickland J, Cummings L, Craig D, Stanfield J, Crouse JR, Menon L, Marion S, Davis D, Cabrera B, Calles J, Chandler T, Ellis J, Kouba E, Riddle P, Myers E, Fonseca V, John-Kalarickal J, McDuffie RH, Asafu-Adjaye NO, Leger SM, Reilly P, Afner G, Arrey F, Asnani S, Borshard E, Boyd D, Cemo A, Chennur S, Dupart P, Garg R, Girindra GP, Gouda B, Itoua-N'Ganongo W, Innocent-Ituah I, Johnson C, Kuhadiya N, Kukreja M, Mangan-Mbondi I, Mason S, McLain C, Naylyanya J, Nazereth K, Nazereth S, Singh S, Thethi T, Varnado K, Williams R, Barzilay JI, Eley M, Bader K, Curry-Ball D, Goodman S, Stevens M, Elam MB, Thompson CW, Lichtermann L, Peeples S, Turner-Bates J, Heimberg M, Childress D, Turner J, Jasper J, Coley J, Hamilton BP, Hamilton J, Kuzbida G, Hatten W Jr, Lancaster A, Haywood J, Luck J, Bannerman-Wood D, Felicetta J, Bourne-Collo M, Svoboda ME, Clothier D, Deitz M, Flaugher C, Hayward P, Scheibe T, Velarde S, Heritage S, Nelson JP, Heritage D, Martinez C, Sweeney ME, Harrelson D, McConnell S, Watson F, Johnson R, Whittington L, Nanes M, Salles M, Rice C, Cowden C, Basile J, Ham DB, North-Lee B, Baig HA, Rehman SU, Mixson J, Nelson D, Sonny GV, Kirchner KA, Hinton LA, Mack L, Adair C, James B, Spencer A, Jones A, Katz L, Richardson EA, Goldberg AG, Nieves A, Russo JE, Adams J, Sochalski SA, Coles M, Anderson S, Williams M, Hoffman D, Papademetriou V, Gregory B, Alignay R, Nylen E, Rajendran B, Hodges R, Amodeo S, Ross A, Notargiacomo A, Metcalfe M, Narayan P, Wojackovski D, Giddings S, Clark E, Pittler A, Davis R, Harris P, Waidmann K, Conwill L, Felton S, Chen A, Simmons DL, Cooper JJ, Dishongh K, Bates R, Bhaghayath K, Choksi P, Conley S, Elbein S, Faas F, Hamid Z, Johnson J, Johnson P, Mayo A, Moriarty MS, Nair G, Rani D, Rasouli N, Said S, Rassouli N, Rodriguez M, Thomas K, Watson K, Williams D, Makdissi A, Byington RP, Ambrosius WT, Anderson RT, Barnes J, Beal J, Bell C, Bonds DE, Burton S, Collins C, Cook D, Craven B, Craven T, Dunbar D, Evans GW, Feeney P, Furberg CD, Greven CM, Griffin J, Harvin L, Hepler J, Howard L, Howard-Perdue LT, Hough M, Hwang W, Kimel A, Lefkowitz D, Lopina A, Lovato J, Lovato LC, Miller ME, Reboussin D, Rushing S, Sanders L, Sims L, Stowe C, Walkup M, Wilmoth S, Wilson K, Woolard N, Raisch D, Ringer R, Sather M, DelCurto B, Garnand D, Prineas R, Campbell C, Zhang Z, Kesler L, Hall S, Hensley S, Li Y, Solomon E, Milne D, Marcovina S, Chmielewski J, Gadbois K, Gaur V, Strylewicz G, Ramirez M, Waddell S, Mehan M, Bryan RN, Davatzkios C, Moonis G, Desiderio L, D'Arcy S, Davis M, Danis R, Johnson S, Robinson N, Hubbard L, Esser B, Thayer D, Neider M, Glader K, Burger M, Simons-Morton DG, Cooper L, Domanski M, Nwachuku C, Rosenberg Y, Salive M, Savage P, Fleg JL, Cutler JA, Geller N, Follmann D, Proschan M, Jennings C, Schaeffer E, Mills P, Bittner J, Kirby R, Frommer P, Fine L, Chan J, Fradkin J, Malozowski S, Meyers C, Hostetter T, Launer L, Chew EY, Albright A, Narayan KM, Engelgau M, Zhang P, Ariani K, Karunaratne K, Azizad M, Chow C, Gutierrez H, Partamian J, Toven J, Toven J, Mular J, Sanders S, Haywood LJ, Kamdar V, DeQuattro DL, Wang L, Song Z, Becerra L, Cai AQ, Pruitt C, DeQuattro V, Failor R, Ellsworth A, Jackson N, Miller C, Britt D, Dobie S, Hirsch I, Khakpour D, Quaempts R, Stoffel W, Neighbor W, Cappocia K, Hawkins V, Tapp L, Force R, Macdonald M, Pettingill K, Liday C, Koester S, Pettinger T, Solbrig R, Waldron C, Woodhouse W, Hoover B, Lusk S, Wilcox T, Hachey D, Linz PE, Pepper PV, Kozlowski J, Chase C, Griffin C, Samuelson D, Gutierrez P, Gonzales C, Engle M, Coopersmith J, Griffin S, Lammers R, Leon J, Zirkle D, Hollingsworth S, Riddle MC, Hanavan KA, McDaniel PA, Swift R, Ahmann AJ, Gammell-Matthews SC, Karl DM, Burden V, MacNeil B, MacMurray M, Weiss J, Carlson C, DesRochers SK, Negreanu D, Stephens EA, Gale D, Wysham C, Weeks D, Kuntsmann L, Maxwell L, Yedinak S, Pena H, Kistler J, White J, Dudl J, Lyons L, House B, Murray M, Stevenson R, Wu P, Palma A, Briere S, Wilson T, Becker D, Harden K, Hawley C, Dailey G, Baron M, Gianella A, Jacobson M, Farro E, Philis-Tsimikas A, Banares A, Bravo-Medina A, Horne J, Esquer E, Morrissey R.

Author information

  • 1Department of Medicine, Division of Clinical and Molecular Endocrinology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4951, USA. faramarz.ismail-beigi@case.edu

Erratum in

  • Lancet. 2010 Oct 30;376(9751):1466.

Abstract

BACKGROUND:

Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes.

METHODS:

ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA(1c) concentrations (>7.5%), and cardiovascular disease (or >or=2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A(1c) [HbA(1c)] of <6.0%) or standard (7.0-7.9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291.7 micromol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620.

FINDINGS:

10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1.00, 95% CI 0.88-1.14; p=1.00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0.96, 0.89-1.02; p=0.19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0.95, 95% CI 0.85-1.07, p=0.42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0.95, 0.89-1.01, p=0.12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0.05).

INTERPRETATION:

Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia.

FUNDING:

US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

Copyright 2010 Elsevier Ltd. All rights reserved.

Comment in

PMID:
20594588
[PubMed - indexed for MEDLINE]
PMCID:
PMC4123233
Free PMC Article

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