THE EFFECT OF INTENSIVE TREATMENT OF DIABETES ON THE DEVELOPMENT ANDPROGRESSION
OF LONG-TERM COMPLICATIONS IN INSULIN-DEPENDENT DIABETESMELLITUS
AbstractBackground Long-term microvascular and neurologic complications cause major morbidity
and mortality in patients with insulin-dependent diabetes mellitusIDDM).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.
MethodsA total of 1441 patients withIDDM - 726 with no retinopathy at base line (the primary-prevention cohort)
and 715 with mild retinopathy (the secondaryintervention 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.
Results 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 therapyslowed the progression of retinopathy by 54 percent (Q5 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 albuminexcretion of ^40 mg per 24 hours) by 39 percent (95 percent confidence
interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion
of ^300 mg. per 24 hours) by 54 percent95percent confidence interval, 19 to 74 percent), and that of clinical neuropathy
by 60 percent (95 percent confidenceinterval 38 to 74 percent). The chief
adverse event associated with intensive therapy was a two-to-threefold
increase in severe hypoglycemia.]
Conclusions Intensive therapy effectively delays the onset and slows the progression
of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
