The Diabetes Control and Complications Trial (DCCT) was a prospective, randomized trial involving more than 1,400 patients with type 1 (insulin-dependent) diabetes. The objective of the study was to determine the magnitude of the decrease in the risk of diabetic retinopathy progression observed with "intensive" treatment (three or more injections of insulin daily, or use of an external pump) of the underlying diabetes. Relationships to baseline retinopathy severity and duration of follow-up were also determined.
Of the 1,441 patients enrolled (ages 13 to 39 years), 726 had no baseline retinopathy and had a duration of diabetes of one to five years; this group was termed the "primary prevention cohort." The remaining 715 patients had very mild to moderate retinopathy at baseline, with a duration of diabetes ranging from one to 15 years; this group was termed the "secondary prevention cohort."
Patients receiving intensive treatment maintained a statistically significant reduction in HbA1c throughout the years of the study, compared to those who received "conventional" treatment (one to two insulin injections daily, with daily urine glucose monitoring, blood glucose monitoring and modifications in diet and exercise). In the primary prevention cohort, of those conventionally treated, there was a 54.1% cumulative 8.5-year progression rate of retinopathy; of those intensively treated, there was an 11.5% cumulative 8.5-year progression rate. In the secondary prevention cohort, of those conventionally treated, there was a 49.2% cumulative 8.5-year progression rate of retinopathy, versus a 17.1% cumulative 8.5-year progression rate among those intensively treated. Overall, intensive treatment provided a 78.5% reduction of risk for retinopathy in the primary cohort and a 64.5% reduction of risk in the secondary cohort.
As for type of diabetic retinopathy, the 9-year rate for severe or worse nonproliferative diabetic retinopathy (NPDR) was 32% in the conventionally treated group and 9% in the intensively treated group. The 9-year rate for proliferative diabetic retinopathy (PDR) was 24% in the conventionally treated group and 8% in the intensively treated group. With regard to diabetic macular edema, the 9-year rate was 27% among conventionally treated patients and 15% among those receiving intensive treatment. Investigators observed a phenomenon they termed "Early Worsening" of diabetic retinopathy in the intensively treated group. Over the first two years of intensive treatment, there was a slight worsening of diabetic retinopathy as compared to the conventionally treated group; this was more evident in the secondary prevention cohort (some baseline retinopathy).
Overall, intensive treatment substantially showed the progression of retinopathy, and this effect increased with time and was consistent among all groups studied. The phenomenon of early worsening with intensive treatment implies that patients should be monitored closely with eye examinations when beginning intensive treatment.
Selected Publications
Diabetes Control and Complications Trial Research Group. The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial. Diabetes 1996;45:1289-1298.
Diabetes Control and Complications Trial Research Group. Lifetime benefits and costs of intensive therapy as practiced in the Diabetes Control and Complications Trial. JAMA 1996;276:1409-1415.
Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968-983.
Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development of progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-986.
Ferris FL III, Davis MD, Aiello LM. Treatment of diabetic retinopathy. N Engl J Med 1999;341:667-678.
Click on the highlighted citations for summaries of studies
The Wisconsin Epidemiologic Study
Early Treatment Diabetic Retinopathy Study Research Group
The Diabetic Retinopathy Study Research Group
Diabetic Retinopathy Vitrectomy Study Research Group
UK Prospective Diabetes Study
This web resource is made possible through an unrestricted educational grant from Eli Lilly and Company.
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