Effects of medical therapies on retinopathy progression in type 2 diabetes

Abstract

Background: We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy.

Methods: In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy.

Results: At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29).

Conclusions: Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)

Figure 1. Subgroup Effects in the ACCORD Glycemia Trial

The estimated odds ratios for progression of diabetic retinopathy are indicated as squares (with the area proportional to the sample size). The vertical dashed line is the overall treatment effect. Data were missing for some patients in some subgroups. The comparison between the subgroup enrolled in the ACCORD Lipid trial and the subgroup enrolled in the ACCORD Blood-Pressure trial was not specified within the protocol. Race was self-reported. The body-mass index (BMI) is the weight in kilograms divided by the square of the height in meters. A logarithmic scale is used on the x axis.

Figure 2. Subgroup Effects in the ACCORD Lipid Trial

The estimated odds ratios for progression of diabetic retinopathy are indicated as squares (with the area proportional to the sample size). The vertical dashed line is the overall treatment effect. Data were missing for some patients in some subgroups. Two comparisons were not specified within the protocol: the comparison between the subgroup with triglyceride levels of 204 mg per deciliter (2.3 mmol per liter) or higher and high-density lipoprotein (HDL) cholesterol levels of 34 mg per deciliter (0.9 mmol per liter) or less and the subgroup with lower triglyceride levels or higher HDL cholesterol levels, and the comparison between the subgroup with some retinopathy and the subgroup with none. Race was self-reported. The body-mass index (BMI) is the weight in kilograms divided by the square of the height in meters. To convert values for cholesterol to millimoles per liter, multiply by 0.02586. To convert values for triglycerides to millimoles per liter, multiply by 0.01129. LDL denotes low-density lipoprotein. A logarithmic scale is used on the x axis.

Figure 3. Subgroup Effects in the ACCORD Blood-Pressure Trial

The estimated odds ratios for progression of diabetic retinopathy are indicated as squares (with the area proportional to the sample size). The vertical dashed line is the overall treatment effect. Data were missing for some patients in some subgroups. The last four comparisons shown in the figure were not specified in the protocol. Race was self-reported. The body-mass index (BMI) is the weight in kilograms divided by the square of the height in meters. A logarithmic scale is used on the x axis.