We identified 624,968 veterans with diabetes in FY 2000. Veterans were excluded for prior lower limb amputations (25,660, 4.1%), bipolar disorder (24,660, 3.9%), schizophrenia (20,160, 3.2%), death prior to the index date (14,327, 2.3%), and no visits after the index date (22,549, 3.6%) (not mutually exclusive groups), leaving 531,973 eligible patients. Of these, 84,984 (16.0%) met our definition of depression, 63,615 (12.0%) by ICD-9-CM codes and 21,369 (4.0%) by antidepressant use. There were 10,194 veterans using antidepressants with diagnoses of anxiety or PTSD but not depression whom we considered non-depressed. Among 63,615 veterans with depression codes, the most common diagnoses were depressive disorder, not otherwise specified (43,242, 68.0%); major depressive disorder, recurrent episode (14,406, 22.6%); dysthymia (13,124, 20.6%); and major depressive disorder, single episode (10,430, 16.4%).
Clinical and demographic characteristics of the cohort by depression status are shown in . On average, the sample was elderly and mostly male. Compared to the non-depressed group, the depressed group was younger and had slightly more female, Caucasian, Native American, unmarried, homeless, and disabled veterans. The depressed group had more insulin use and diabetes complications, but HbA1c was equivalent between the groups (although there was a high proportion of missing data for this variable) (see Methods). The depressed group also had more hospitalizations, more outpatient visits, and higher medical and mental health comorbidity.
There were 3,830 incident lower limb amputations (1,289 major and 2,541 minor) over a mean of 4.1 years of follow up. The depressed group had 643 amputations (252 major and 391 minor), and the non-depressed group had 3,187 amputations (1,037 major and 2,150 minor). shows unadjusted amputation incidence rates by depression status.
Unadjusted incidence rates for non-traumatic lower limb amputation by depressed status
shows the HR for lower limb amputations, comparing veterans with and without diagnosed depression. In unadjusted models, veterans with diabetes and diagnosed depression had a 15% higher risk of any lower limb amputation (HR 1.15, 95% CI: 1.05, 1.25) and a 38% higher risk of major amputation (HR 1.38, 95% CI: 1.21, 1.59), compared to those without diagnosed depression. This effect remained statistically significant after adjusting for all covariates (HR 1.12, 95% CI: 1.02, 1.22 for any amputation and HR 1.33, 95% CI: 1.15, 1.55 for major amputation). There were no significant multiplicative interactions between depression and age, gender, race/ethnicity, or PTSD. There was not an increased risk of minor amputations associated with diagnosed depression in any model. See for Kaplan Meier curve for any amputation by depressed status.
Cox regression models for non-traumatic lower limb amputation, comparing patients with diagnosed depression to patients without diagnosed depression
Kaplan Meier curve for any amputation by depressed status (black=non-depressed, gray=depressed)
We performed several fully adjusted sensitivity analyses. The results were similar to the primary analysis if depression was defined only by codes (HR 1.10, 95% CI: 0.99, 1.22 for any amputation and HR 1.29, 95% CI: 1.08, 1.53 for major amputation). The primary analysis did not include HbA1c, but a complete case analysis including only patients with non-missing values for HbA1c gave similar results to the primary analysis (HR 1.20, 95% CI: 1.04, 1.38 for any amputation and HR 1.37, 95% CI: 1.08, 1.73 for major amputation). We also examined the potential effect of antidepressant treatment in the year following depression diagnosis, and there was also no substantial difference in major amputation risk associated with depression between treated patients (HR 1.11, 95% CI: 0.99, 1.24 for any amputation and HR 1.30, 95% CI: 1.08, 1.57 for major amputation) and untreated patients (HR 1.12, 95% CI: 0.97, 1.29 for any amputation and HR 1.40, 95% CI: 1.13, 1.74 for major amputation). The results were also similar when the risk of amputation was compared between veterans with depression, anxiety, or PTSD and veterans with none of these mental health disorders (HR 1.10, 95% CI: 1.00, 1.20 for any amputation and HR 1.31, 95% CI: 1.13, 1.52 for major amputation).