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Diabetes. 2020 Feb 12. pii: db191046. doi: 10.2337/db19-1046. [Epub ahead of print]

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.

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George Washington University, Biostatistics Center, 6110 Executive Blvd, Suite 750, Rockville, MD 20852;
Case Western Reserve University, Rainbow Babies and Children's Hospital, Suite 737, Box 6004, Cleveland, OH 44106.
University of Michigan Medical School, 5329 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105.
Washington University School of Medicine in St. Louis, 660 S Euclid Ave, Box 8116, St Louis, MO 63110.
University of Pittsburgh, Pitt Public Health, 130 De Soto Street, Pittsburgh, PA 15261.
Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425.
George Washington University, Biostatistics Center, 6110 Executive Blvd, Suite 750, Rockville, MD 20852.


The 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 longer duration, older age, 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 longer duration, higher mean HbA1c, sustained albuminuria, higher mean and most recent pulse rate, higher mean systolic blood pressure, β-blocker use, eGFR<60 mL/min/1.73m2, and current 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.


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