Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC
Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, John M Lachin, Neil H White, Dean P Hainsworth, Wanjie Sun, Patricia A Cleary, David M Nathan, Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, John M Lachin, Neil H White, Dean P Hainsworth, Wanjie Sun, Patricia A Cleary, David M Nathan
Abstract
The Diabetes Control and Complications Trial (DCCT) demonstrated that a mean of 6.5 years of intensive therapy aimed at near-normal glucose levels reduced the risk of development and progression of retinopathy by as much as 76% compared with conventional therapy. The Epidemiology of Diabetes Interventions and Complications study (EDIC) observational follow-up showed that the risk of further progression of retinopathy 4 years after the DCCT ended was also greatly reduced in the former intensive group, despite nearly equivalent levels of HbA1c, a phenomenon termed metabolic memory. Metabolic memory was shown to persist through 10 years of follow-up. We now describe the risk of further progression of retinopathy, progression to proliferative diabetic retinopathy, clinically significant macular edema, and the need for intervention (photocoagulation or anti-VEGF) over 18 years of follow-up in EDIC. The cumulative incidence of each retinal outcome continues to be lower in the former intensive group. However, the year-to-year incidence of these outcomes is now similar, owing in large part to a reduction in risk in the former conventional treatment group.
Trial registration: ClinicalTrials.gov NCT00360815 NCT00360893.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Figures
References
- The Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986
- Diabetes Control and Complications Trial Research Group . Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. J Pediatr 1994;125:177–188
- Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care 1999;22:99–111
- The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group . Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000;342:381–389
- White NH, Cleary PA, Dahms W, Goldstein D, Malone J, Tamborlane WV; Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group . Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT). J Pediatr 2001;139:804–812
- Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group . Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002;287:2563–2569
- Martin CL, Albers J, Herman WH, et al. .; DCCT/EDIC Research Group . Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion. Diabetes Care 2006;29:340–344
- White NH, Sun W, Cleary PA, et al. . 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. Arch Ophthalmol 2008;126:1707–1715
- White NH, Sun W, Cleary PA, et al. .; DCCT-EDIC Research Group . Effect of prior intensive therapy in type 1 diabetes on 10-year progression of retinopathy in the DCCT/EDIC: comparison of adults and adolescents. Diabetes 2010;59:1244–1253
- Nathan DM, Bayless M, Cleary P, et al. .; DCCT/EDIC Research Group . Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study at 30 years: advances and contributions. Diabetes 2013;62:3976–3986
- Nathan DM; DCCT/EDIC Research Group . The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study at 30 years: overview. Diabetes Care 2014;37:9–16
- Aiello LP; DCCT/EDIC Research Group . Diabetic retinopathy and other ocular findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Diabetes Care 2014;37:17–23
- de Boer IH, Sun W, Gao P, et al.; for the DCCT/EDIC research group. Effect of intensive diabetes treatment on albuminuria in type 1 diabetes: long-term follow-up of the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study. Lancet Diabetes Endocrinol. 17 July 2014 [Epub ahead of print]
- Diabetes Control and Complications Trial Research Group. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Ophthalmology 1995;102:647–661
- Early Treatment Diabetic Retinopathy Study Research Group . Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Ophthalmology 1991;98(Suppl.):823–833
- Odell PM, Anderson KM, D’Agostino RB. Maximum likelihood estimation for interval-censored data using a Weibull-based accelerated failure time model. Biometrics 1992;48:951–959
- Turnbull BW. The empirical distribution function with arbitrarily censored and truncated data. J R Stat Soc [Ser B] 1976;38:290–295
- Hastie TJ. Generalized additive models. In Statistical Models in S. Chambers JM, Hastie TJ, Eds. Pacific Grove, CA, Wadsworth & Brooks/Cole, 1992
- Agesti A. Categorical Data Analysis. New York, John Wiley & Sons, 1990, p. 80–91, 235–236
- Sparling YH, Younes N, Lachin JM, Bautista OM. Parametric survival models for interval-censored data with time-dependent covariates. Biostatistics 2006;7:599–614
- MacKinnon DP. Introduction to Statistical Mediation Analysis. New York, Erlbaum, 2008
Source: PubMed