Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Authors

Edward J. Boyko, Veterans Affairs Puget Sound Health Care System, Seattle, WA.
Leila R. Zelnick, Department of Medicine, University of Washington, Seattle, WA.
Barbara H. Braffett, Biostatistics Center, George Washington University, Rockville, MD.
Rodica Pop-Busui, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
Catherine C. Cowie, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
Gayle M. Lorenzi, University of California, San Diego, La Jolla, CA.
Rose Gubitosi-Klug, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH.
Bernard Zinman, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Ian H. de Boer, Veterans Affairs Puget Sound Health Care System, Seattle, WA.

Document Type

Journal Article

Publication Date

2-1-2022

Journal

Diabetes care

Volume

45

Issue

2

DOI

10.2337/dc21-1816

Abstract

OBJECTIVE: Intensive glycemic control reduces the risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces the risk of lower-extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFUs) and lower-extremity amputations (LEAs) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS: DCCT participants (n = 1,441) completed 6.5 years on average of intensive versus conventional diabetes treatment, after which 1,408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox proportional hazard regression models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. RESULTS: Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFUs (hazard ratio 0.77 [95% CI 0.60, 0.97]) and a similar magnitude but nonsignificant risk reduction for first-recorded DFUs (0.78 [0.59, 1.03]) and first LEAs (0.70 [0.36, 1.36]). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity, and cardiovascular autonomic neuropathy were associated with higher DFU risk; estimated glomerular filtration rate <60 mL/min/1.73 m2, albuminuria, and macular edema with higher LEA risk; and any retinopathy and greater time-weighted mean DCCT/EDIC HbA1c with higher risk of both outcomes (P < 0.05). CONCLUSIONS: Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.

APA Citation

Boyko, Edward J.; Zelnick, Leila R.; Braffett, Barbara H.; Pop-Busui, Rodica; Cowie, Catherine C.; Lorenzi, Gayle M.; Gubitosi-Klug, Rose; Zinman, Bernard; and de Boer, Ian H., "Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study" (2022). GW Authored Works. Paper 353.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/353

Department

Epidemiology