Effect of prior intensive therapy in type 1 diabetes on 10-year progression of retinopathy in the DCCT/EDIC: comparison of adults and adolescents

Abstract

Objective: The aim of this study was to examine differences between adolescents and adults in persistence of the benefits of intensive therapy 10 years after completion of the Diabetes Control and Complications Trial (DCCT).

Research design and methods: During the Epidemiology of Diabetes Interventions and Complications (EDIC) study, progression of retinopathy from DCCT closeout to EDIC year 10 was evaluated in 1,055 adults and 156 adolescents.

Results: During 10 years of follow-up, HbA(1c) (A1C) was similar between original intensive (INT) and conventional (CON) groups and between former adolescents and adults. At EDIC year 10, adults in the former INT group continued to show slower progression of diabetic retinopathy than those in the CON group (adjusted hazard reduction 56%, P < 0.0001), whereas in adolescents this beneficial effect had disappeared (32%, P = 0.13). Seventy-nine percent of observed differences in the prolonged treatment effect between adults and adolescents at year 10 were explained by differences in mean A1C during DCCT between adolescents and adults (8.9 vs. 8.1%), particularly between INT adolescents and adults (8.1 vs. 7.2%).

Conclusions: Prior glycemic control during DCCT is vital for the persistence of the beneficial effects of INT therapy 10 years later. Lowering A1C to as close to normal as safely possible without severe hypoglycemia and starting as early as possible should be attempted for all subjects with type 1 diabetes. These results underscore the importance of maintaining A1C at target values for as long as possible because the benefits of former INT treatment wane over time if A1C levels rise.

Trial registration: ClinicalTrials.gov NCT00360815 NCT00360893.

FIG. 1.

Prevalence of further 3-step progression of retinopathy from the level at DCCT closeout at years 4 and 10 of EDIC, among patients free of scatter laser photocoagulation during the DCCT and evaluated for retinopathy at EDIC year 10, by DCCT treatment group, for adolescents (A) and for adults (B). Patients with prior scatter photocoagulation during DCCT (7 adolescents and 29 adults) were excluded. Odds reduction was for intensive therapy (INT) compared with conventional therapy (CON). P values are from Mantel-Haenszel test and GEE models.

FIG. 2.

Estimated cumulative incidence of further 3-step progression of retinopathy from DCCT closeout, by DCCT treatment group, through EDIC year 4, for adolescents (A) and for adults (B); through EDIC year 10, for adolescents (C) and for adults (D). Subjects with prior scatter photocoagulation during DCCT (7 adolescents and 29 adults) were excluded from analyses. Based on Weibull regression models adjusted for the level of retinopathy at the end of the DCCT, primary vs. secondary cohort, the A1C value on entry to the DCCT, and diabetes duration at DCCT baseline. Hazard reduction was for intensive therapy compared with conventional therapy.

FIG. 3.

Sensitivity of further retinopathy progression in EDIC to difference in DCCT mean A1C for adolescents and adults, for a 10% increase in A1C in INT (A) and CON (B), and a 10% decrease in A1C in INT (C) and CON (D). Based on separate Weibull regression models in INT and CON, adjusted for the level of retinopathy at the end of the DCCT, primary vs. secondary cohort, A1C value on entry to the DCCT, diabetes duration at DCCT baseline, log transformation of DCCT mean A1C, age (adult vs. adolescent), and interaction of DCCT mean A1C and age.