Intensive insulin therapy reduced microvascular and neurologic outcomes in type 1diabetes mellitus
ACP J Club. 1994 Mar-April;120:30. doi:10.7326/ACPJC-1994-120-2-030
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329:977-86.
To evaluate the effectiveness of intensive diabetes therapy in reducing chronic microvascular and neurologic complications in patients with type 1 diabetes mellitus.
Randomized controlled trial with a mean follow-up of 6.5 years.
29 centers in North America.
1441 patients (mean age 27 y, 53% men, 96% white) with type 1 diabetes and without hypertension, hypercholesterolemia, severe diabetic complications, and severe medical conditions. Patients who had type 1 diabetes for 1 to 5 years, no retinopathy, and a urinary albumin excretion < 40 mg/24 h were included in the primary-prevention cohort (n = 726). Patients who had type 1 diabetes for 1 to 15 years, mild-to-moderate nonproliferative retinopathy, and a urinary albumin excretion < 200 mg/24 h were included in the secondary-intervention cohort (n = 715). Follow-up was 99%.
Randomization was stratified by primary-prevention and secondary-intervention cohorts. 711 patients received intensive therapy (348 in the primary-prevention cohort and 363 in the secondary-prevention cohort) with insulin administered ≥ 3 times daily by injection or an external pump guided by frequent blood glucose monitoring. 730 patients received conventional therapy (378 in the primary prevention cohort and 352 in the secondary prevention cohort) with 1 or 2 insulin injections daily.
Main outcome measures
Retinopathy and nephropathic, neurologic, cardiovascular, neuropsychologic, and quality-of-life outcomes.
In the primary-prevention cohort, fewer patients in the intensive-therapy group developed retinopathy than did those in the conventional-therapy group; in the secondary-intervention cohort, fewer patients in the intensive-therapy group had sustained progression of retinopathy than did thosein the conventional-therapy group (Table). In the 2 cohorts combined, intensive therapy reduced the risk for the development and sustained progression of retinopathy by 63% (CI 52% to 71%), for severe retinopathy by 47% (CI 15% to 67%), for microalbuminuria by 39% (CI 21% to 52%), for albuminuria by 54% (CI 19% to 74%), and for clinical neuropathy at 5 years by 60% (CI 38% to 74%).
Intensive insulin therapy delayed the onset and slowed the progression of retinopathy, nephropathy, and neuropathy in patients with type 1 diabetes mellitus.
Source of funding: National Institutes of Health.
For article reprint: DCCT Research Group, Box NDIC/DCCT, Bethesda, MD 20892, USA.
Table. Intensive vs conventional therapy for retinopathy at a mean follow-up of 6 years in type 1 diabetes by patient cohort*
|Cohort||Intensive therapy||Conventional therapy||RRR (95% CI)||NNT (CI)|
|Primary prevention||7%||24%||73% (58 to 82)||6 (4 to 8)|
|Secondary prevention||21%||41%||48% (34 to 59)||5 ( 4 to 8)|
*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
All who routinely care for patients with diabetes can sigh with relief because now there are good experimental data to support our long-held belief that intensive treatment of diabetes leads to reduced risk for microvascular complications. But the sigh can only be brief because our responsibilities to our patients have now been considerably increased and, for many of us, it is not clear whether resources necessary to achieve these results are available.
The DCCT was an efficacy, not an effectiveness, trial. In the optimal conditions of this trial, with highly motivated patients and specially trained treatment team members, microvascular disease progression was slowed. The study by Reichard and colleagues also included much more interaction with patients than occurs in usual practice settings. Can we achieve the same results in our own practices? Perhaps.
What are the "take home" messages? First, to achieve these results, a long-term strategy would have to be adopted; it took 36 months for the groups to diverge, and, in both the DCCT and the study by Reichard and colleagues, existent retinopathy worsened early in the trial. Second, complete prevention of complications may require absolute normalization of glucose from the day of diagnosis because even the intensive-treatment group developed some complications. It is important to note, however, that lowering of the glucose to some degree still achieved partial reduction in complications. Third, intensive therapy is costly from both a human point of view and a monetary point of view: The incidence of severe hypoglycemia was increased and patients were contacted frequently by study personnel. Cost-effectiveness analyses from the DCCT show an additional cost of $33 746 over a lifetime for intensive compared with conventional therapy. The cost per year of life saved is $28 661, which is considered to be cost-effective. The United Kingdom Prospective Diabetes Study, which was completed in 1998, has extended these results to patients with type 2 diabetes who use a variety of treatments. Glycemic control should be a high priority for persons with diabetes, whether type 1 or 2, based on these 2 large, long-term trials.
Finally, physicians and nurses treating patients with diabetes need to take a proactive role in initiating change in our usual patterns of diabetic care. Our treatment community is not consistently doing simple things to prevent complications, such as screening regularly for retinopathy or examining feet to prevent amputations. We must strive to address all the prevention and screening needs of our patients with diabetes in addition to improving glucose control. We also need to become active in the political process to ensure that funds are sufficient to support the nursing care, equipment, supplies, and education required to achieve our new and more ambitious goals.
Jacqueline A. Pugh, MD
The University of TexasSan Antonio, Texas, USA