Diabetic retinopathy and other ocular findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study

Abstract

OBJECTIVE To evaluate whether intensive treatment (INT) with the goal of achieving blood glucose levels as close to the nondiabetic range as safely possible reduced the risk of onset and progression of diabetic retinopathy (DR) in subjects with type 1 diabetes (T1D) compared with conventional therapy (CON). RESEARCH DESIGN AND METHODS The Diabetes Control and Complications Trial (DCCT) (1982-1993) was a multicenter, controlled clinical trial comparing INT with CON for onset and progression of DR. The Epidemiology of Diabetes Interventions and Complications (EDIC) study (1994-present) is an observational follow-up of the DCCT cohort. RESULTS Of the 1,441 DCCT subjects, 726 had no DR (primary prevention cohort) and 715 had mild DR (secondary intervention cohort) at baseline. Subjects were followed for a mean of 6.5 years. INT median HbA1c was 7% compared with CON median of 9%. INT reduced the adjusted mean risk for the development of DR by 76% and slowed progression of DR by 54% compared with CON. Following DCCT, the HbA1c levels in the original INT and CON groups converged (year 8, INT 7.98%; CON 8.07%); nevertheless, the groups continued to have a durable effect of initial assigned therapy with significantly lower incidence of further DR progression in the INT group (hazard reduction 53-56%). Severe retinal outcomes and procedures to treat them were reduced by 50% in the original INT group. CONCLUSIONS INT delays the onset and slows the progression of DR. Furthermore, the early effects of metabolic control continue to accrue over many years despite subsequent comparable glycemic control (metabolic memory). These results emphasize the need for optimizing glycemic control as early as possible in patients with diabetes.

Figure 1

Cumulative incidence of DR progression (three-step or greater by ETDRS criteria [6]) in the DCCT primary prevention cohort. There was little difference in percentage of patients with retinopathy progression between the INT and CON groups over the first 3 years; however, there was a 76% risk reduction for DR progression evident at the conclusion of the DCCT after mean follow-up of 6.5 years (14).

Figure 2

Cumulative incidence of DR progression in the DCCT secondary intervention cohort. By the conclusion of the DCCT, there was a 54% reduction in the risk of retinopathy (≥ three-step) progression in the secondary intervention cohort for those in the INT group as compared with the CON group (11,14).

Figure 3

Cumulative incidence for onset of severe NPDR in the DCCT secondary intervention cohort. There was a 61% risk reduction in the development of severe NPDR in the INT cohort compared with the CON cohort.

Figure 4

The risk of DR progression as related to mean HbA_1c during DCCT. The rate of DR progression per 100 patient-years (100 PYR) was similar and highly associated with HbA_1c in the DCCT for both the INT and the CON groups (12).

Figure 5

After adjustment for DR severity at DCCT closeout, the cumulative incidence of further DR progression during the first 10 years of EDIC follow-up is shown (8).

Figure 6

The cumulative incidence of any major eye disease end point (PDR, CSME, application of laser, or development of blindness) is shown in relation to diabetes duration. DCCT CON (open squares) and INT (solid circles) groups are presented. Also presented is the cumulative incidence of these major eye disease end points observed in the observational Pittsburgh Epidemiology of Diabetes Complications (EDC) study (solid triangles) (15).