title: Diabetes, lower-extremity amputation, and death.
abstract: 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).
  
  
  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.
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Ole
authors.initials: O
authors.lastname: Hoffstad
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Walsh
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA margo@mail.med.upenn.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Margolis
mesh_terms: D000368:Aged; D000671:Amputation, Surgical / Q000401:mortality*; D003925:Diabetic Angiopathies / Q000401:mortality*; D017719:Diabetic Foot / Q000401:mortality / Q000601:surgery; D003928:Diabetic Nephropathies / Q000401:mortality; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D006113:United Kingdom / Q000453:epidemiology