Neuropathy and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study

Abstract

OBJECTIVE To describe the development and progression of neuropathy and related findings among patients with type 1 diabetes who participated in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. RESEARCH DESIGN AND METHODS The main diabetic peripheral neuropathy (DPN) outcome was assessed using clinical symptoms, signs, and nerve conduction study results during DCCT and repeated in EDIC year 13/14. Cardiovascular autonomic neuropathy (CAN) was assessed by R-R response to paced breathing, Valsalva ratio, and blood pressure response to standing during DCCT and in EDIC years 13/14 and 16/17. Additionally, symptoms reflecting neuropathic pain and autonomic function (including hypoglycemia awareness) were collected yearly in EDIC using standardized questionnaires; peripheral neuropathy was also assessed annually using the Michigan Neuropathy Screening Instrument. Assessments of genitourinary function were collected at EDIC year 10. RESULTS Intensive therapy during the DCCT significantly reduced the risk of DPN and CAN at DCCT closeout (64% and 45%, respectively, P < 0.01). The prevalence and incidence of DPN and CAN remained significantly lower in the DCCT intensive therapy group compared with the DCCT conventional therapy group through EDIC year 13/14. CONCLUSIONS The persistent effects of prior intensive therapy on neuropathy measures through 14 years of EDIC largely mirror those observed for other diabetes complications. DCCT/EDIC provides important information on the influence of glycemic control, and the clinical course of diabetic neuropathy, and, most important, on how to prevent neuropathy in type 1 diabetes.

Figure 1

Flow diagram of DCCT/EDIC subject participation in CAN and DPN assessments at EDIC year 13/14. *Percentage based on the original number of EDIC participants (n = 1,375). †Percentage based on number of active EDIC participants at year 13/14 (n = 1,274). ‡Percentages shown for R-R variation and Valsalva ratio are based on number of EDIC participants with CAN test at EDIC year 13/14 (n = 1,226). DCCT/EDIC CAN testing included R-R variation during deep breathing, Valsalva maneuver, and postural testing. DPN testing included history and examination by a board-certified neurologist and nerve conduction studies. Adapted with permission from Pop-Busui et al. (16).