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

Abstract

Objective: Intensive glycemic control reduces risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces 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 (DFU) and lower extremity amputations (LEA) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. <p>Research Design and Methods: DCCT participants [n=1441] completed 6.5 years on average of intensive vs conventional diabetes treatment, after which 1408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. </p> <p>Results: Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFU (Hazard Ratio [HR] 0.77, 95% CI 0.60 to 0.97), and a similar magnitude but nonsignificant risk reduction for first recorded DFU (HR 0.78, 95% CI 0.59 to 1.03) and first LEA (HR 0.70, 95% CI 0.36 to 1.36). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity and cardiovascular autonomic neuropathy were associated with higher DFU risk; eGFR < 60 mL/min/1.73 m<sup>2</sup>, 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).</p> <p>Conclusions: Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.</p>