Diabetic foot complications tied to increased risk of all-cause mortality in type 2 diabetes patients

Amputation exhibited the strongest association, surpassing the influence of gangrene/ulcer, while revascularization alone showed a relatively modest effect.

Diabetic foot ulcers (DFUs) are common long-term complications of diabetes that occur in 19 to 34% of patients during their lifetime, with recurrence rates of ~ 65% at 3–5 years. They are associated with increased mortality, particularly from cardiovascular disease, though not many studies have investigated the independent contribution of these events to the risk of death.

To fill this knowledge gap, Giuseppe Pugliese, “La Sapienza” University, Via di Grottarossa, Rome, Italy, and colleagues aimed to evaluate the association of history of diabetic foot with all-cause mortality in individuals with T2D, independent of cardiovascular risk factors, other comorbidities and complications by conducting a prospective cohort study.

The study enrolled 15,773 Caucasian patients in 19 Italian centers from 2006–2008. Prior lower extremity, cerebrovascular, and coronary events and major comorbidities were ascertained by medical records, diabetic kidney disease by albuminuria and estimated glomerular filtration rate, diabetic retinopathy by fundoscopy, and cardiovascular risk factors by standard methods. All-cause mortality was retrieved for 15,656 patients on 31 October 2015.

The study revealed the following findings:

· At baseline, 5.7% of patients had a history of diabetic foot, including ulcer/gangrene and/or amputation (3.58%), with (0.80%) or without (2.78%) lower limb revascularization, and revascularization alone (2.09%).

· History of diabetic foot was associated with all-cause death over a 7.42-year follow-up (adjusted hazard ratio, 1.502), independent of confounders, among which age, male sex, haemoglobin A1c, smoking, current treatments, other complications, comorbidities and, inversely, physical activity level and total and HDL cholesterol were correlated independently with mortality.

· Both ulcer/gangrene and amputation alone were independently associated with death, with a higher strength of association for amputation than for ulcer/gangrene (1.874 versus 1.567).

· Both ulcer/amputation/gangrene and lower limb revascularization alone were independently associated with death; mortality risk was much higher for ulcer/gangrene/amputation than for revascularization (1.641 versus 1.229) and further increased only slightly for combined ulcer/gangrene/amputation and revascularization (1.733).

"In patients with type 2 diabetes from the RIACE cohort, a history of diabetic foot events, including ulcer/gangrene, lower limb revascularization, and amputation, was associated with a ~ 50% increased risk of subsequent death from any cause, independent of cardiovascular disease risk factors, other complications and severe comorbidities, which were also significantly associated with mortality," the researchers wrote.

"The association with mortality was greatest for amputation, whereas that for revascularization alone was relatively modest," they concluded.

Reference:

Vitale, M., Orsi, E., Solini, A. et al. Independent association of history of diabetic foot with all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. Cardiovasc Diabetol 23, 34 (2024). https://doi.org/10.1186/s12933-023-02107-9