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.