74 A recent large study of 4000 patients with diabetes has also shown that comorbid depression in patients with diabetes was associated with a twofold increased risk of development of foot ulcers.75 A second large study that included over half a

million Veterans with diabetes showed that comorbid depression was associated with a 33% increased risk of having a nontraumatic lower-limb amputation over a 4year period.76 Black and colleagues found in the abovedescribed prospective study of aging Hispanic respondents that having diabetes was associated with an increased risk of 1.37 (95% CI 1.16, 1.62) for macrovascular complications and 9.30 (95% CI 7.38, Inhibitors,research,lifescience,medical 11.15) for microvascular complications compared with controls without

diabetes or depression.72 Inhibitors,research,lifescience,medical Those with depression and diabetes had an increased risk compared with those without history of diabetes or depression of 2.64 (95% CI 1.73, 4.04) for macrovascular complications and 11.32 (95% CI 8.76, 15.43) for microvascular complications.72 Both depression and diabetes Inhibitors,research,lifescience,medical have been found in multiple studies to be independent risk factors for development of dementia.77 A recent study of over 4000 patients with type 2 diabetes found that patients with comorbid depression compared with those with diabetes alone had a 2.7-fold increase in development of dementia over a 5year period.78 Functional impairment Interest in the adverse effect of depression on functional impairment was Inhibitors,research,lifescience,medical stimulated by findings from the Medical Outcomes survey. This large study showed that patients with depression were at least as functionally impaired as patients with chronic medical illnesses such as diabetes, CHD, and arthritis.22 Moreover, when depression was comorbid Inhibitors,research,lifescience,medical with chronic physical illness, there was additive functional impairment.22 One of the methodological challenges in assessing functioning in patients with depression is whether reported impairments result from true MK-2206 datasheet deficits or from reporting

bias. Methodologists others have attempted to understand this problem by comparing more “objective” impairment such as length of time a patient walks on a stress treadmill test to more “subjective” functional measures. Recent data have shown that depressed patients also have significant deficits on these more “objective” measures. For instance, depressed patients whose cardiac function is tested by stress treadmill EKG have been found to be more likely to stop the test due to fatigue prior to an adequate length of time for assessment.79 Patients with depression with congestive heart failure (CHF) also have been shown to have poorer performance on the standard 6-minute walk compared with those with CHF alone.