Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy

Abstract

Background: Among patients with type 1 diabetes mellitus, intensive therapy (with the aim of achieving near-normal blood glucose and glycosylated hemoglobin concentrations [hemoglobin A1c]) markedly reduces the risk of microvascular complications as compared with conventional therapy. To assess whether these benefits persist, we compared the effects of former and intensive conventional therapy on the recurrence and severity of retinopathy and nephropathy for four years after the end of the Diabetes Control and Complications Trial (DCCT).

Methods: At the end of the DCCT, the patients in the conventional-therapy group were offered intensive therapy, and the care of all patients was transferred to their own physicians. Retinopathy was evaluated on the basis of centrally graded fundus photographs in 1208 patients during the fourth year after the DCCT ended, and nephropathy was evaluated on the basis of urine specimens obtained from 1302 patients during the third or fourth year, approximately half of whom were from each treatment group.

Results: The difference in the median glycosylated hemoglobin values between the conventional-therapy and intensive-therapy groups during the 6.5 years of the DCCT (average, 9.1 percent and 7.2 percent, respectively) narrowed during follow-up (median during 4 years, 8.2 percent and 7.9 percent, respectively, P<0.001). Nevertheless, the proportion of patients who had worsening retinopathy, including proliferative retinopathy, macular edema, and the need for laser therapy, was lower in the intensive-therapy group than in the conventional-therapy group (odds reduction, 72 percent to 87 percent, P<0.001). The proportion of patients with an increase in urinary albumin excretion was significantly lower in the intensive-therapy group.

Conclusions: The reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persists for at least four years, despite increasing hyperglycemia.

Figures

Figure 1

Distribution of Glycosylated Hemoglobin (Hemoglobin A1c) Values in the Conventional-Therapy and Intensive-Therapy Groups at the End of the Diabetes Control and Complications Trial (DCCT), in Each of the Four Years of the Epidemiology of Diabetes Interventions and Complications (EDIC) Study, and Averaged over the Four Years of the EDIC Study. Data are for the 1208 patients who had an eye evaluation in year 4 of the EDIC study. The boxes represent the second and third quartiles of the distribution, the center lines the medians, and the plus signs the means.

Figure 2

Prevalence of More Severe Retinopathy as Compared with the Level of Retinopathy at Entry into the Diabetes Control and Complications Trial (DCCT), at the End of the DCCT, and after an Additional Four Years of Follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study among 1208 Patients Evaluated at Year 4 of the EDIC Study. There were 603 patients in the conventional-therapy group and 605 in the intensive-therapy group. Patients who underwent scatter photocoagulation after entry into the DCCT were counted as having worsening retinopathy, and those who underwent focal photocoagulation were counted as having macular edema. Adjusted odds ratios were computed after stratification according to the level of retinopathy at the end of the DCCT, as shown in Table 1. The percent reduction in the likelihood of worsening retinopathy was computed as (1-OR)×100, where OR is the odds ratio for intensive therapy as compared with conventional therapy. Panel A shows the percentage of subjects with progression of retinopathy (three or more steps) after DCCT entry. Panel B shows the percentage of patients with development of proliferative or severe nonproliferative retinopathy. Panel C shows the percentage of patients with clinically significant macular edema. Panel D shows the percentage of patients who underwent photocoagulation (scatter or focal).

Figure 2

Prevalence of More Severe Retinopathy as Compared with the Level of Retinopathy at Entry into the Diabetes Control and Complications Trial (DCCT), at the End of the DCCT, and after an Additional Four Years of Follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study among 1208 Patients Evaluated at Year 4 of the EDIC Study. There were 603 patients in the conventional-therapy group and 605 in the intensive-therapy group. Patients who underwent scatter photocoagulation after entry into the DCCT were counted as having worsening retinopathy, and those who underwent focal photocoagulation were counted as having macular edema. Adjusted odds ratios were computed after stratification according to the level of retinopathy at the end of the DCCT, as shown in Table 1. The percent reduction in the likelihood of worsening retinopathy was computed as (1-OR)×100, where OR is the odds ratio for intensive therapy as compared with conventional therapy. Panel A shows the percentage of subjects with progression of retinopathy (three or more steps) after DCCT entry. Panel B shows the percentage of patients with development of proliferative or severe nonproliferative retinopathy. Panel C shows the percentage of patients with clinically significant macular edema. Panel D shows the percentage of patients who underwent photocoagulation (scatter or focal).

Figure 3

Cumulative Incidence of Further Progression of Retinopathy (an Increase of at Least Three Steps from the Level at the End of the Diabetes Control and Complications Trial [DCCT]) in the Former Conventional-Therapy and Intensive-Therapy Groups. The data are based on regression analysis adjusted for the level of retinopathy at the end of the DCCT, whether patients received therapy as primary prevention or secondary intervention, and both the duration of diabetes and the glycosylated hemoglobin value on enrollment in the DCCT. Patients who underwent scatter photocoagulation during the DCCT were excluded from the analysis (22 in the conventional-therapy group and 9 in the intensive-therapy group). Bars denote 95 percent confidence intervals.