Risk Factors for Diabetic Peripheral Neuropathy and Cardiovascular Autonomic Neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

Diabetes. 2020 May;69(5):1000-1010. doi: 10.2337/db19-1046. Epub 2020 Feb 12.


The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated that intensive glucose control reduced the risk of developing diabetic peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). We evaluated multiple risk factors and phenotypes associated with DPN and CAN in this large, well-characterized cohort of participants with type 1 diabetes, followed for >23 years. DPN was defined by symptoms, signs, and nerve conduction study abnormalities in ≥2 nerves; CAN was assessed using standardized cardiovascular reflex tests. Generalized estimating equation models assessed the association of DPN and CAN with individual risk factors measured repeatedly. During DCCT/EDIC, 33% of participants developed DPN and 44% CAN. Higher mean HbA1c was the most significant risk factor for DPN, followed by older age, longer duration, greater height, macroalbuminuria, higher mean pulse rate, β-blocker use, and sustained albuminuria. The most significant risk factor for CAN was older age, followed by higher mean HbA1c, sustained albuminuria, longer duration of type 1 diabetes, higher mean pulse rate, higher mean systolic blood pressure, β-blocker use, estimated glomerular filtration rate <60 mL/min/1.73 m2, higher most recent pulse rate, and cigarette smoking. These findings identify risk factors and phenotypes of participants with diabetic neuropathy that can be used in the design of new interventional trials and for personalized approaches to neuropathy prevention.

Trial registration: ClinicalTrials.gov NCT00360815 NCT00360893.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autonomic Nervous System / physiopathology
  • Blood Glucose
  • Cardiovascular Diseases / pathology*
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetic Neuropathies / pathology*
  • Female
  • Glycated Hemoglobin
  • Humans
  • Longitudinal Studies
  • Male
  • Multivariate Analysis
  • Risk Factors
  • Young Adult


  • Blood Glucose
  • Glycated Hemoglobin A

Associated data

  • ClinicalTrials.gov/NCT00360815
  • ClinicalTrials.gov/NCT00360893