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      The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus

      New England Journal of Medicine
      Massachusetts Medical Society

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          Abstract

          Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

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          Most cited references1

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          The Pittsburgh insulin-dependent diabetes mellitus (IDDM) morbidity and mortality study. Mortality results.

          A follow-up study of 1966 patients with insulin-dependent diabetes mellitus (IDDM) who were diagnosed at Children's Hospital of Pittsburgh (CHP) between 1950 and 1981 has been completed. The mean age of the population at follow-up was 21.2 yr with a mean duration of IDDM of 12.9 yr. Nine percent of the patients were deceased, a sevenfold excess in mortality compared with the U.S. population. The relative increase in mortality was greater for females than males and greater for blacks than whites. Before age 20, the primary excess in mortality was at onset of IDDM, or within 6 mo after onset, and was due to acute diabetic complications. After age 20, the annual mortality risk was approximately 2%, which was more than 20 times greater than for the U.S. population. Renal disease was responsible for the majority of these deaths. There was a reduced risk of dying for diabetic patients who were diagnosed between 1966 and 1971 compared with patients diagnosed during earlier years.
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            Author and article information

            Journal
            New England Journal of Medicine
            N Engl J Med
            Massachusetts Medical Society
            0028-4793
            1533-4406
            September 30 1993
            September 30 1993
            : 329
            : 14
            : 977-986
            Article
            10.1056/NEJM199309303291401
            8366922
            81d23beb-08a0-40dd-934d-9ab01cf622b3
            © 1993
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