Log in to MyACC
Diabetes Control and Complications Trial - DCCT
Description:
Intensive vs. conventional glycemic control for diabetic complications.
Hypothesis:
Intensive therapy will prevent the development of diabetic retinopathy in patients with no retinopathy, and will delay the progression of retinopathy in patients with early retinopathy.
Study Design
Study Design:
Patients Screened: Not given
Patients Enrolled: 1,441
Mean Follow Up: 6.5 years
Mean Patient Age: 27
Female: 47
Patient Populations:
Insulin-dependence, as evidenced by evidenced C-peptide secretion
Age >13 < 39 years
Primary prevention cohort:
IDDM for 1 to 5 years
No retinopathy as detected by 7-field stereoscopic fundus photography
Urinary albumin excretion of < 40 mg/24 h
Secondary prevention cohort
IDDM for 1 to 15 years
Very mild to moderate nonproliferative retinopathy
Urinary albumin excretion of < 200 mg/24 h
Exclusions:
Hypertension
Hypercholesterolemia
Severe diabetic complications or medical conditions
Primary Endpoints:
Diabetic retinopathy, defined as a change of > 3 steps on fundus photography, sustained over a 6-month period
Secondary Endpoints:
Renal outcomes
Neurologic outcomes
Cardiovascular outcomes
Neuropsychological outcomes
Adverse effects of treatment regimens
Drug/Procedures Used:
Conventional therapy
1 or 2 daily injections of insulin, including mixed intermediate and rapid-acting insulins
Daily self-monitoring of urine or blood glucose
Education about diet and exercise
Intensive therapy
Administration of
Concomitant Medications:
Not stated
Principal Findings:
Primary prevention cohort:
Similar results in both groups for first 36 months.
From 5 years onward, cumulative incidence of retinopathy in intensive therapy group was approximately 50% less than in conventional-therapy group.
During mean of 6 years of follow-up, retinopathy developed in 91 patients in conventional therapy group, 23 patients in intensive-therapy group. Intensive therapy adjusted the mean risk of retinopathy by 76% (95% confidence interval, 62 to 82 %). The reduction in risk increased with time.
Secondary prevention cohort:
Intensive-therapy patients had higher cumulative incidence of sustained progression of retinopathy during first year than conventional-therapy patients, but a lower cumulative incidence beginning at 36 months and continuing for the rest of the study.
Intensive therapy reduced the average risk of such progression by 54% (95% confidence interval, 39 to 66%).
Combined cohorts:
Intensive therapy reduced the occurrence of microalbuminuria by 39% (95% confidence interval, 21 to 52%); that of albuminuria by 54% (95% confidence interval, 19 to 74%) ; that of clinical neuropathy by 60% (95% confidence interval, 38 to 74%).
The chief adverse event associated with intensive therapy was a 2- to 3-fold increase in severe hypoglycemia. A total of 65% percent of patients in the intensive group vs. 35% of patients in the conventional group had at least one episode of severe hypoglycemia by the study end; the overall rates of severe hypoglycemia were 61.2 per 100 patient-years vs. 18.7 per 100 patient-years in the intensive and conventional treatment groups, respectively.
The number of combined major macrovascular events was almost twice as high in the conventionally treated group (40 events) as in the intensive-treatment group (23 events), although the differences were not statistically significant (p = 0.08).
Implementing intensive rather than conventional therapy in this population would result in an incremental cost per year of life gained of $28,661.
Interpretation:
Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM. Intensive therapy for type 1 diabetes helps sustain endogenous insulin secretion, which, in turn, is associated with better metabolic control and lower risk for hypoglycemia and chronic complications. These observations underscore the importance of initiating intensive diabetic management as early as safely possible after type 1 diabetes is diagnosed.
References:
1. N Engl J Med 1993;329:977-86. Final results
2. Am J Cardiol 1995;75:894-903. Macrovascular outcomes
3. JAMA 1996;276:1409-15. Cost-effectiveness analysis
4. Diabetes 1997;46(2):271-86. Hypoglycemia
5. Ann Int Med 1998;128(7):517-23. Residual beta-cell function
Keywords: Follow-Up Studies, Insulin, Short-Acting, C-Peptide, Hypoglycemia, Photography, Diabetic Retinopathy, Diabetes Complications, Blood Glucose, Confidence Intervals, Diet, Diabetes Mellitus, Type 1
< Back to Listings
