Diabetes, Lower-Extremity Amputation, and Death

Ole Hoffstad; Nandita Mitra; Jonathan Walsh; David J. Margolis


Diabetes Care. 2015;38(10):1852-1857. 

In This Article

Abstract and Introduction


Objective The goal of the study was to determine whether complications of diabetes well-known to be associated with death such as cardiovascular disease and renal failure fully explain the higher rate of death in those who have undergone a lower-extremity amputation (LEA).

Research Design and Methods This was a longitudinal cohort study of patients cared for in the Health Improvement Network. Our primary exposure was LEA and outcome was all-cause death. Our "risk factor variables" included a history of cardiovascular disease (a history of myocardial infarctions, cerebrovascular accident, and peripheral vascular disease/arterial insufficiency), Charlson index, and a history of chronic kidney disease. We estimated the effect of LEA on death using Cox proportional hazards models.

Results The hazard ratio (HR) for death after an LEA was 3.02 (95% CI 2.90, 3.14). The fully adjusted (all risk factor variables) LEA HR was diminished only by ~22% to 2.37 (2.27, 2.48). Furthermore, LEA had an area under the receiver operating curve (AUC) of 0.51, which is poorly predictive, and the fully adjusted model had an AUC of 0.77, which is better but not strongly predictive. Sensitivity analysis revealed that it is unlikely that there exists an unmeasured confounder that can fully explain the association of LEA with death.

Conclusions Individuals with diabetes and an LEA are more likely to die at any given point in time than those who have diabetes but no LEA. While some of this variation can be explained by known complications of diabetes, there remains a large amount of unexplained variation.


Worldwide, every 30 s, a limb is lost to diabetes.[1,2] Nearly 2 million people living in the U.S. are living with limb loss.[1] According to the World Health Organization, lower-extremity amputations (LEAs) are 10 times more common in people with diabetes than in persons who do not have diabetes. In the U.S. Medicare population, the incidence of diabetic foot ulcers is ~6 per 100 individuals with diabetes per year and the incidence of LEA is 4 per 1,000 persons with diabetes per year.[3] LEA in those with diabetes generally carries yearly costs between $30,000 and $60,000 and lifetime costs of half a million dollars.[4] In 2012, it was estimated that those with diabetes and lower-extremity wounds in the U.S. Medicare program accounted for $41 billion in cost, which is ~1.6% of all Medicare health care spending.[4–7] In 2012, in the U.K., it was estimated that the National Health Service spent between £639 and 662 million on foot ulcers and LEA, which was approximately £1 in every £150 spent by the National Health Service.[8]

LEA does not represent a traditional medical complication of diabetes like myocardial infarction (MI), renal failure, or retinopathy in which organ failure is directly associated with diabetes.[2] An LEA occurs because of a disease complication, usually a foot ulcer that is not healing (e.g., organ failure of the skin, failure of the biomechanics of the foot as a unit, nerve sensory loss, and/or impaired arterial vascular supply), but it also occurs at least in part as a consequence of a medical plan to amputate based on a decision between health care providers and patients.[9,10] Many researchers have reported a large increase in the incidence of death among LEA patients. The surgical procedure itself is associated with a risk of death that is based on the American Society of Anesthesiologist physical status classification system and is not dependent on risks inherent to the procedure. However, 30-day postoperative mortality can approach 10%, with most mortality associated with those receiving an LEA as an emergency procedure or with the presence of preoperative sepsis.[11,12] Previous reports have estimated that the 1-year post-LEA mortality rate in people with diabetes is between 10 and 50%, and the 5-year mortality rate post-LEA is between 30 and 80%.[4,13–15] More specifically, in the U.S. Medicare population mortality within a year after an incident LEA was 23.1% in 2006, 21.8% in 2007, and 20.6% in 2008.[4] In the U.K., up to 80% will die within 5 years of an LEA.[8] In general, those with diabetes with an LEA are two to three times more likely to die at any given time point than those with diabetes who have not had an LEA.[5] For perspective, the 5-year death rate after diagnosis of malignancy in the U.S. was 32% in 2010.[16]

Evidence on why individuals with diabetes and an LEA die is based on a few mainly small (e.g., <300 subjects) and often single center–based[13,17–20] studies or <1 year duration of evaluation.[11] In these studies, death is primarily associated with a previous history of cardiovascular disease and renal insufficiency, which are also major complications of diabetes; these complications are also associated with an increased risk of LEA. The goal of our study was to determine whether complications of diabetes well-known to be associated with death in those with diabetes such as cardiovascular disease and renal failure fully explain the higher rate of death in those who have undergone an LEA.