medwireNews: Early intensive glycemic control may reduce the long-term risk for foot ulcers in people with type 1 diabetes, suggest data from the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) study.
The DCCT included 1408 people with type 1 diabetes who completed an average of 6.5 years of intensive (target glycated hemoglobin [HbA1c] <6.05% [42.6 mmol/mol]) or conventional (no specific glycemic target) diabetes treatment and subsequently underwent 23 years of follow-up in the EDIC study.
During this period, 195 participants developed at least one diabetic foot ulcer (48 people had multiple events) and 36 needed lower extremity amputation.
Edward Boyko (University of Washington, Seattle, USA) and co-authors report in Diabetes Care that the individuals who were assigned to intensive glycemic control in DCCT (n=699) had a significant 23% lower risk for diabetic foot ulcer than those who received conventional treatment (n=709), with respective incidence rates of 7.3 and 9.6 per 1000 person–years.
The amputation rate was 1.0 per 1000 person–years in the intensive treatment group versus 1.4 per 1000 person–years in the conventional treatment group. The corresponding 30% lower risk with intensive treatment was not statistically significant, “likely because of the low power to detect associations given the very few amputations observed,” the researchers remark.
After adjustment for age, sex, diabetes duration at DCCT closeout, and mean DCCT HbA1c, Boyko and team found that age at DCCT closeout was significantly associated with future risk for both ulcers and amputation, at hazard ratios (HRs) of 1.46 and 1.85 per 10-year increase, respectively.
In addition, albuminuria (sustained albumin excretion rate ≥30 mg/24 h; HR=1.67) and cardiovascular autonomic neuropathy (HR=1.43) were associated with a significantly increased risk for foot ulcers, while macular edema (HR=4.15) and increasing BMI (HR=1.88 per 5 kg/m2) and triglyceride levels (HR=1.11 per 20 mg/dL) were associated with significantly increased amputation risk.
The investigators then assessed the temporal change in risk factors for ulcers and amputation. After adjustment for age, sex, diabetes duration at DCCT closeout, and time-weighted mean DCCT/EDIC HbA1c, they found that clinical neuropathy (HR=2.18) and cardiovascular autonomic neuropathy (HR=1.68) were associated with a significantly increased risk for foot ulcers.
Sustained estimated glomerular filtration rate below 60 mL/min per 1.73 m2 (HR=2.63), albuminuria (HR=2.23), and macular edema (HR=3.13) were associated with a significantly increased risk for amputation.
Furthermore, increasing time-weighted mean DCCT/EDIC HbA1c was associated with a significantly increased risk for both ulcers (HR=1.33 per 10% increment) and amputation (HR=2.37 per 10% increment).
Boyko et al conclude that 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 [type 1 diabetes] to prevent this outcome.”
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