Early intensive glycemic control decreases the long-term risk of diabetic foot ulcers (DFUs) in patients with type 1 diabetes (T1D), according to a study in Diabetes Care.
Researchers evaluated the effects of intensive treatment (INT) vs conventional treatment (CON) in patients with T1D from the Diabetes Control and Complications Trial (DCCT) on the subsequent risk of DFU and lower-extremity amputations (LEA) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study.
A total of 1441 participants aged 13 to 39 years with a T1D duration of 1 to 15 years were enrolled in DCCT from 1983 to 1989. After an average 6.5 years of follow-up in 1993, 1422 individuals completed a closeout visit. In 2017, after 23 years of follow-up, 1190 participants continued to be followed. The analysis in this current study is based on the data of 1408 participants with follow-up from the EDIC study in years 1 to 23.
A total of 699 patients who received INT (mean age, 33.4 years; 49% female) and 709 patients who received CON (mean age, 32.8 years; 46% female) were followed in EDIC. Of the cohort, 195 participants had at least 1 DFU, and 48 had multiple DFUs.
Diabetic foot ulcers occurred in 86 participants in the INT group and in 109 from the CON group (incidences of 6.0 and 7.8 per 1000 person-years, respectively). The risk of first-recorded DFU was nominally, but not statistically significantly lower, among INT participants (hazard ratio [HR] 0.78 [95% CI, 0.59-1.03]).
A total of 117 DFUs, including first and subsequent lesions, occurred in INT participants and 153 in CON participants (incidences of 7.3 and 9.6 per 1000 person-years, respectively). The risk for all DFUs was 23% lower among INT participants (0.77 [0.60, 0.97]).
Of the 36 amputations that were reported, 15 occurred in the INT group and 21 in the CON group (incidences of 1.0 and 1.4 per 1000 person-years, respectively). The risk of amputation for INT participants was 30% lower than in CON participants but not statistically significant (HR 0.70 [95% CI, 0.36- 1.36]).
After adjustment for age, sex, and diabetes duration at DCCT closeout, the common risk factors for DFU and LEA were time-weighted mean DCCT/EDIC glycated hemoglobin (HbA1c) serum triglyceride concentration, sustained estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, albumin excretion rate (AER) ≥30 mg/24 hours, confirmed clinical neuropathy, lower sural nerve conduction velocity, cardiovascular autonomic neuropathy (CAN), any retinopathy, and macular edema.
In further adjustment for time-weighted mean DCCT/EDIC HbA1c, any retinopathy was the only statistically significant risk factor in common between DFU and LEA. Confirmed clinical neuropathy, lower sural nerve conduction velocity, and CAN remained associated with higher DFU risk. Sustained estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, sustained microalbuminuria (AER) ≥30 mg/24 hours, and macular edema statistically significantly predicted the risk of LEA.
The investigators noted that lower-extremity complications were not designated as major outcomes in the DCCT/EDIC follow-up, which limited their analysis. Also, the ankle-brachial pressure index, noted by the study authors as “an established clinical predictor of peripheral artery disease” was “limited by falsely high readings owing to vessel incompressibility.”
“Diabetic foot ulcers can be added to the list of complications potentially preventable by intensive glycemic treatment, further reinforcing the importance of optimal glycemic control implemented as early as possible for individuals with T1D to prevent this outcome,” the researchers stated.
Boyko EJ, Zelnick LR, Braffett BH, et al. Risk of foot ulcer and lower-extremity amputation among participants in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2022;45(2):357-364. doi:10.2337/dc21-1816