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evident
Original paper
1993NEJMEndocrinology/Metabolism

DCCT

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus

RCTType 1 diabetes

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Overview

In type 1 diabetes, intensive insulin reduced new-retinopathy risk 76% (primary-prevention) and slowed existing retinopathy 54% (secondary-intervention); severe hypoglycemia rose.

Clinical takeaway

Treat type 1 diabetes intensively to delay new retinopathy if the retina is still clear, and to slow existing mild retinopathy. Expect more severe hypoglycemia.

Key result

Primary-prevention cohort: 76% lower adjusted mean risk of developing retinopathy (95% CI 62-85%). Secondary-intervention cohort: 54% slower retinopathy progression (95% CI 39-66%).

Practice impact

Use intensive insulin in type 1 diabetes to prevent and slow microvascular disease; counsel about a two-to-threefold rise in severe hypoglycemia.

Evidence

Study design

Randomized trial of intensive versus conventional insulin therapy in insulin-dependent diabetes mellitus, with separate primary-prevention and secondary-intervention cohorts.

Enrollment

1,441

Follow-up

Mean 6.5 years.

Geography

Not listed

Clinical question

Does intensive insulin therapy aimed at near-normal blood glucose reduce the development and progression of retinopathy and other long-term complications in insulin-dependent diabetes mellitus?

Population

  • 1441 patients with insulin-dependent diabetes mellitus.
  • Primary-prevention cohort: 726 with no retinopathy at baseline.
  • Secondary-intervention cohort: 715 with mild retinopathy at baseline.

Intervention

Intensive therapy with an external insulin pump or three or more daily insulin injections, guided by frequent blood glucose monitoring.

Comparator

Conventional therapy with one or two daily insulin injections.

Primary outcome

Appearance of retinopathy in the primary-prevention cohort and progression of retinopathy in the secondary-intervention cohort.

Keep the cohorts separate. Primary-prevention: 76% lower adjusted mean risk of developing retinopathy (95% CI 62-85%). Secondary-intervention: 54% slower retinopathy progression (95% CI 39-66%).

Adjusted mean risk reduction / 76 / 95% CI 62-85%

Key results

  • In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76% (95% CI 62-85%) compared with conventional therapy.
  • In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54% (95% CI 39-66%) and reduced the development of proliferative or severe nonproliferative retinopathy by 47% (95% CI 14-67%).
  • In the two cohorts combined, intensive therapy reduced microalbuminuria (urinary albumin excretion ≥40 mg per 24 hours) by 39% (95% CI 21-52%), albuminuria (≥300 mg per 24 hours) by 54% (95% CI 19-74%), and clinical neuropathy by 60% (95% CI 38-74%).

Harms

  • The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.

Clinical Use

Practice impact

  • Offer intensive insulin therapy in type 1 diabetes to delay new retinopathy (primary-prevention) and to slow existing mild retinopathy (secondary-intervention). Combined-cohort analyses also showed less microalbuminuria, albuminuria, and clinical neuropathy.
  • Warn patients about a two-to-threefold increase in severe hypoglycemia.

Applicability

  • Primary-prevention findings apply to insulin-dependent diabetes without retinopathy at baseline.
  • Secondary-intervention findings apply to insulin-dependent diabetes with mild retinopathy at baseline.

Limitations

  • Retinopathy results are cohort-specific; do not quote a single pooled retinopathy effect as the main result.
  • Albuminuria and neuropathy estimates combine both cohorts.
  • The abstract does not report hemoglobin A1c values or event counts.

Common misinterpretations

  • Do not collapse the primary-prevention and secondary-intervention cohorts into one retinopathy result.
  • This is a trial in insulin-dependent (type 1) diabetes, not a glycemic-target trial in type 2 diabetes.

Related evidence

UKPDS - Later TrialACCORD - Later Trial

Citation

Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, et al. 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;329(14):977-986. doi:10.1056/NEJM199309303291401

Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.