Patients with type 2 diabetes (T2D) and peripheral artery disease may be at increased risk for major adverse limb events, according to a study published in Diabetic Medicine.
The study included 14,752 patients (mean age 62 years, 38% female) with T2D from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. In the new analysis, patients were assessed for major adverse limb events—such as non-traumatic amputation, lower-extremity revascularization, and gangrene—for follow-up at 3.2 years later.
Only, 523 (3.55%) patients had more than 1 major adverse limb event for a total of 736 events. Patients who experienced negative outcomes were older (P <.001), tended to be male and white (P <.001), or were previous smokers (P <.0001). They also had cardiovascular disease and a longer history of diabetes. The negative outcomes included 247 amputations, 218 endovascular revascularizations, 166 episodes of gangrene, and 105 surgical revascularizations.
Major adverse limb events were associated with peripheral artery disease (hazard ratio [HR], 4.83; 95% CI, 3.94-5.92; P <.0001), prior foot ulcer (HR, 2.16; 95% CI, 1.63-2.87; P <.0001), prior amputation (HR, 2.00; 95% CI, 1.53-2.64; P <.0001), insulin use (HR, 1.86; 95% CI, 1.52-2.27; P <.0001), male gender (HR, 1.64; 95% CI, 1.31-2.06; P <.0001), coronary artery disease (HR, 1.67; 95% CI, 1.38-2.03; P <.0001), current smoker status (HR, 2.00; 95% CI, 1.54-1.72; P <.0001), and baseline glycated hemoglobin (HR, 1.24; 95% CI, 1.13-1.36; P <.0001).
On the basis of these associations, investigators developed a major adverse limb events risk score comprising age, gender, ethnicity, cardiovascular disease risk factors, glycated hemoglobin level, history of foot ulcer or amputation, insulin use, neuropathy status, and smoking status. The score ranged from 6 (low risk) to 96 (high risk). Patients with a score of £40 points had a £0.8% (95% CI, 0.7%-1.0%) risk for MACE at 3 years, a score of 65-69 points corresponded with a 11.8% (95% CI, 10.7%-12.9%) risk, and among those with a score of 85-89 points, a MALE risk of 64.5% (95% CI, 58.0%-71.7%). The risk score had a C-index of 0.822 (95% CI, 0.803-0.841).
The study data indicated patients with T2D and peripheral artery disease were at greater risk for major adverse limb events at 3 years. Additional risk factors included prior foot ulcers or amputations, insulin use, and smoking.
“Although risk scores exist to predict amputation in specific subgroups of people with type 2 diabetes, no risk score exists to predict all lower extremity events among a broader cohort of people with type 2 diabetes,” the authors wrote.
This study was limited by not testing the major adverse limb events risk score among an independent cohort.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Weissler E H, Clare R M, Lokhnygina Y, et al. Predicting Major Adverse Limb Events in Individuals With Type 2 Diabetes: Insights From the EXSCEL Trial. Diabet Med. 2021;e14552. doi:10.1111/dme.14552.