Abstract

Objective: To evaluate the impact of former intensive- versus conventional insulin treatment on neuropathy in DCCT intensive and conventional treatment subjects with type 1 diabetes 13-14 years after DCCT closeout, during which time the two groups had achieved similar hemoglobin A1c (HbA1c) levels.

Research Design and Methods: Clinical and nerve conduction studies (NCSs) performed during DCCT were repeated during EDIC by examiners masked to treatment status on 603 former intensive- and 583 former conventional-treatment subjects. Clinical neuropathy was defined by symptoms, sensory signs, or reflex changes consistent with distal polyneuropathy and confirmed with NCS abnormalities involving ≥ 2 nerves among the median, peroneal, and sural nerves.

Results: The prevalence of neuropathy increased 13-14 years after DCCT closeout from 9% to 25% in former intensive- and from 17% to 35% in former conventional treatment groups, but the difference between groups remained significant (P<0.001) and the incidence of neuropathy remained lower among former intensive- (22%) than former conventional treatment subjects (28%) (P=0.0125). Analytic models of incident neuropathy that adjusted for differences in NCS results at DCCT closeout showed no significant risk reduction associated with former intensive treatment during follow-up (OR=1.17; CI=0.84-1.63). However, a significant persistent treatment group effect was observed for several NCS measures. Longitudinal analyses of overall glycemic control showed a significant association between mean HbA1c and measures of incident and prevalent neuropathy.

Conclusions: The benefits of former intensive insulin treatment persisted for 13-14 years after DCCT closeout and provide evidence of a durable effect of prior intensive treatment on neuropathy.