Research Articles in Diabetes and Diabetic Retinopathy

The Effect of Intensive Diabetes Treatment on the Progression of Diabetic Retinopathy in Insulin-Dependent Diabetes Mellitus: The Diabetes Control and Complications Trial

(From Archives of Ophthalmology 1995;113:36-51, The Diabetes Control and Complications Trial Research Group)

OVERVIEW:

This study of the Diabetes Control and Complications Trial Research Group (DCCT) was a prospective, randomized trial involving over 1400 patients with insulin dependent diabetes. Follow-up time ranged from three to nine years. The objective of the study was to determine the magnitude of the decrease in the risk of diabetic retinopathy progression observed with "intensive" treatment of the underlying diabetes. Relationships to baseline retinopathy severity and duration of follow-up were also determined.

In this study, insulin dependent diabetes is defined as deficient c-peptide secretion. Subjects were generally in good health, without hypertension or elevated cholesterol. Subjects either had no retinopathy at baseline, or only mild to moderate non-proliferative retinopathy.

1441 patients were enrolled with ages ranging from 13 to 39. 726 of these had no baseline retinopathy, and had a duration of diabetes of 1 to 5 years. This group was termed the "primary prevention cohort". The remaining 715 patients had very mild to moderate diabetic retinopathy at baseline, with a duration of diabetes ranging from 1 to 15 years. This group was termed the "secondary prevention cohort".

"Intensive Treatment" of the underlying diabetes consisted of 3 or more injections of insulin daily, or of the use of an external pump. The insulin dosage was adjusted based on self-monitored blood glucose four times daily. Before meal blood glucose was to be kept between 70 and 120, and after meal blood glucose less than 180. The goal of the treatment was normoglycemia, with a monthly glycosylated hemoglobin (HbA1c) level within the normal range (less than 6.05%).

"Conventional Treatment" of the diabetes consisted of 1 to two insulin injections daily, with daily urine glucose monitoring, blood glucose monitoring, and modifications in diet and exercise. The goal of the treatment was freedom from symptoms of hyper- and hypoglycemia, and normal growth and development of an ideal body weight.

RESULTS:

• Successfulness of Intensive treatment of diabetes at maintaining normoglycemia:

  • The Intensively treated group maintained a statistically significant reduction in HbA1c throughout the years of the study, compared to the Conventionally treated group. The Intensively treated group's HbA1c ranged approximately from 6.5% to 7.9% over the years of the study, with a low point 6 months after beginning intensive treatment.

  • The Conventionally treated group's HbA1c ranged approximately from 7.8% to 10.2% over the years of the study.

  • 44% of Intensively treated patients achieved the goal of an HbA1c of less than 6.05% at least once during the study, but less than 5% maintained an average value within this range.

  • The Intensively treated group had a three-fold incidence in severe hypoglycemia and weight gain compared to the conventionally treated group.
     

• Progression of diabetic retinopathy:

  • In the Primary Prevention Cohort (no baseline retinopathy),
    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 (some baseline retinopathy),
    Of those Conventionally treated there was a 49.2% cumulative 8.5 year progression rate of retinopathy.
    Of those Intensively treated there was an 17.1% cumulative 8.5 year progression rate.

  • 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.
     

• Types of diabetic retinopathy:

  • The 9 year rate for severe or worse non-proliferative retinopathy was 32% in the Conventionally treated group, and 9% in the Intensively treated group.

  • The 9 year rate for proliferative retinopathy was 24% in the Conventionally group, and 8% in the Intensively treated group.

  • The 9 year rate for diabetic macular edema in the Conventionally treated group was 27%, and 15% in the Intensively treated group.
     

• There was noted to be a phenomenon termed "Early Worsening" of diabetic retinopathy in the Intensively treated group. Over the first 2 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).

CONCLUSIONS:
Overall, Intensive treatment substantially slowed the progression of retinopathy, and this effect increased with time and was consistent among all of the groups studied. There was some degree of early worsening of retinopathy with Intensive Treatment, so patients should be monitored closely with eye examinations when beginning Intensive treatment.

 

For information about diabetic eye disease in general, and for an explanation of terminology used below, go to Diabetic Eye Disease.

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