Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus: 10 years after the diabetes control and complications trial

Neil H. White, Wanjie Sun, Patricia A. Cleary, Ronald P. Danis, Matthew D. Davis, Dean P. Hainsworth, Larry D. Hubbard, John M. Lachin, David M. Nathan, O. Crofford, J. Crandall, M. Phillips, M. Reid, J. Brown-Friday, S. Engel, J. Sheindlin, H. Martinez, H. Shamoon, H. Engel, W. DahmsM. Palmert, R. Gubitosi-Klug, L. Mayer, S. Pendegras, H. Zegarra, D. Miller, L. Singerman, S. Smith-Brewer, M. Novak, P. Gaston, S. Genuth, D. Brillon, M. E. Lackaye, V. Reppucci, T. Lee, M. Heinemann, F. Whitehouse, M. McLellan, D. Kruger, J. D. Carey, E. Angus, M. Croswell, A. Galpirn, R. Bergenstal, M. Johnson, M. Spencer, K. Morgan, D. Etzwiler, D. Kendall, D. Noller, A. Jacobson, E. Golden, R. Beaser, O. Ganda, O. Hamdy, J. Rosenzweig, H. Wolpert, P. G. Sharuk, P. Arrigg, A. Burwood, L. Rand, D. M. Nathan, M. Larkin, J. Godine, D. Moore, E. Cagliero, P. Lou, S. Fritz, J. Service, G. Ziegler, J. Pach, R. Colligan, M. Lopes-Virella, J. Colwell, K. Hermayer, M. Brabham, J. Soule, A. Blevins, J. Parker, D. Lee, P. Lindsey, M. Bracey, K. Lee, M. Nutaitis, A. Farr, S. Elsing, T. Thompson, J. Selby, T. Lyons, S. Yacoub-Wasef, M. Szpiech, D. Wood, R. Mayfield, M. Molitch, B. Schaefer, L. Jampol, A. Lyon, M. Gill, Z. Strugula, L. Kaminski, J. Shankle, P. Astlesford, D. Blackburn, S. Ajroud-Driss, O. Stone, C. West, I. Burnett-Zeigler, O. Kolterman, G. Lorenzi, M. Goldbaum, K. Harvey, H. Ferreyra, W. Sivitz, M. Bayless, T. Weingeist, E. Stone, H. Culver Boldt, K. Gehres, S. Russell, J. Bayless, J. Kramer, J. Long, R. Zeither, M. Hebdon, T. Donner, S. Johnsonbaugh, J. Gordon, R. Hemady, A. Kowarski, D. Ostrowski, S. Steidl, B. Jones, D. Counts, W. Herman, C. Martin, R. Pop-Busui, A. K. Vine, S. Elner, E. Feldman, J. Albers, D. Greene, M. J. Stevens, J. Bantle, B. Rogness, T. Olsen, E. Steuer, P. Rath, D. Hainsworth, S. Hitt, J. Giangiacom, D. Goldstein, D. Schade, J. Canady, J. M. Schluter, A. Das, D. Hornbeck, S. Schwartz, P. A. Bourne, B. J. Maschak-Carey, L. Baker, S. Braunstein, A. Brucker, T. Orchard, N. Silvers, C. Ryan, T. Songer, B. Doft, S. Olson, R. L. Bergren, L. Lobes, P. Paczan Rath, D. Becker, A. Drash, A. Morrison, J. Vaccaro-Kish, M. L. Bernal, J. Malone, P. R. Pavan, N. Grove, M. N. Iyer, A. F. Burrows, E. A. Tanaka, R. Gstalder, S. Dagogo-Jack, C. Wigley, H. Ricks, A. Kitabchi, M. B. Murphy, S. Moser, D. Meyer, A. Iannacone, E. Chaum, S. Yoser, M. Bryer-Ash, S. Schussler, H. Lambeth, Philip Raskin, S. Strowig, Rafael Ufret-Vincenty, Yu-Guang He, A. Edwards, J. Alappatt, C. Wilson, S. Park, B. Zinman, A. Barnie, S. MacLean, R. Devenyi, M. Mandelcorn, M. Brent, S. Rogers, A. Gordon, J. Palmer, S. Catton, J. Brunzell, J. Ginsberg, J. Kinyoun, L. Van Ottingham, J. Dupre, J. Harth, D. Nicolle, C. Canny, M. May, J. Lipps, A. Agarwal, T. Adkins, L. Survant, R. Lorenz, S. Feman, N. White, L. Levandoski, I. Boniuk, G. Grand, M. Thomas, D. Burgess, D. Joseph, K. Blinder, G. Shah, J. Santiago, W. Tamborlane, P. Gatcomb, K. Stoessel, K. Taylor, R. Trail, J. Quin, M. Lachin, P. Cleary, D. Kenny, J. Backlund, W. Sun, B. Rutledge, B. Waberski, K. Klumpp, K. Chan, L. Diminick, D. Rosenberg, B. Petty, A. Determan, C. Williams, L. Dews, M. Hawkins, C. Cowie, J. Fradkin, C. Siebert, R. Eastman, R. Danis, M. Davis, L. Hubbard, P. Geithman, L. Kastorff, M. Neider, D. Badal, B. Esser, K. Miner, H. Wabers, K. Glander, J. Joyce, N. Robinson, C. Hurtenbach, C. Hannon, M. Steffes, J. Bucksa, B. Chavers, D. O'Leary, L. Funk, J. Polak, A. Harrington, R. Crow, B. Gloeb, S. Thomas, C. O'Donnell, R. Prineas, C. Campbell, D. Sandstrom, T. Williams, M. Geckle, E. Cupelli, F. Thoma, B. Burzuk, T. Woodfill, P. Low, C. Sommer, K. Nickander, R. Detrano, N. Wong, M. Fox, L. Kim, R. Oudiz, G. Weir, C. Clark, R. D'Agostino, M. Espeland, B. Klein, T. Manolio, D. Singer, M. Stern, W. T. Garvey, T. J. Lyons, A. Jenkins, R. Klein, G. Virella, A. A. Jaffa, D. Lackland, D. McGee, D. Zheng, R. K. Mayfield, A. Paterson, A. Boright, S. Bull, L. Sun, S. Scherer, J. Hokanson, S. Marcovina, J. Purnell, S. Sibley, S. Deeb, K. Edwards

Research output: Contribution to journalArticle

245 Scopus citations


Objective: To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at nearnormal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy. Methods: Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome. Results: After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conventional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; P<.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (P<.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion: The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning. Trial Registration: Identifiers: NCT00360815 and NCT00360893.

Original languageEnglish (US)
Pages (from-to)1707-1715
Number of pages9
JournalArchives of Ophthalmology
Issue number12
StatePublished - Dec 1 2008

ASJC Scopus subject areas

  • Ophthalmology

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    White, N. H., Sun, W., Cleary, P. A., Danis, R. P., Davis, M. D., Hainsworth, D. P., Hubbard, L. D., Lachin, J. M., Nathan, D. M., Crofford, O., Crandall, J., Phillips, M., Reid, M., Brown-Friday, J., Engel, S., Sheindlin, J., Martinez, H., Shamoon, H., Engel, H., ... Edwards, K. (2008). Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus: 10 years after the diabetes control and complications trial. Archives of Ophthalmology, 126(12), 1707-1715.