Depression and incident lower limb amputations in veterans with diabetes.

PROBLEM: Depression is associated with a higher risk of macrovascular and microvascular complications and mortality in diabetes, but whether depression is linked to an increased risk of incident amputations is unknown. We examined the association between diagnosed depression and incident non-traumatic lower limb amputations in veterans with diabetes. METHODS: This was a retrospective cohort study from 2000-2004 that included 531,973 veterans from the Diabetes Epidemiology Cohorts, a national Veterans Affairs (VA) registry with VA and Medicare data. Depression was defined by diagnostic codes or antidepressant prescriptions. Amputations were defined by diagnostic and procedural codes. We determined the HR and 95% CI for incident non-traumatic lower limb amputation by major (transtibial and above) and minor (ankle and below) subtypes, comparing veterans with and without diagnosed depression and adjusting for demographics, health care utilization, diabetes severity and comorbid medical and mental health conditions. RESULTS: Over a mean 4.1 years of follow-up, there were 1289 major and 2541 minor amputations. Diagnosed depression was associated with an adjusted HR of 1.33 (95% CI: 1.15-1.55) for major amputations. There was no statistically significant association between depression and minor amputations (adjusted HR 1.01, 95% CI: 0.90-1.13). CONCLUSIONS: Diagnosed depression is associated with a 33% higher risk of incident major lower limb amputation in veterans with diabetes. Further study is needed to understand this relationship and to determine whether depression screening and treatment in patients with diabetes could decrease amputation rates.

Identifying Persons at Highest Risk of Melanoma Using Self-Assessed Risk Factors.

OBJECTIVE: To develop a self-assessed melanoma risk score to identify high-risk persons for screening METHODS: We used data from a 1997 melanoma case-control study from Washington State, USA, where 386 cases with invasive cutaneous melanoma and 727 controls were interviewed by telephone. A logistic regression prediction model was developed on 75% of the data and validated in the remaining 25% by calculating the area under the receiver operating characteristic curve (AUC), a measure of predictive accuracy from 0.5-1 (higher scores indicating better prediction). A risk score was calculated for each individual, and sensitivities for various risk cutoffs were calculated. RESULTS: The final model included sex, age, hair color, density of freckles, number of severe sunburns in childhood and adolescence, number of raised moles on the arms, and history of non-melanoma skin cancer. The area under the receiver operating characteristic curve(AUC) was 0.70 (95% CI: 0.64, 0.77). The top 15% risk group included 50% of melanomas (sensitivity 50%). CONCLUSIONS: This self-assessed score could be used as part of a comprehensive melanoma screening and public education program to identify high-risk individuals in the general population. This study suggests it may be possible to capture a large proportion of melanomas by screening a small high-risk group. Further study is needed to determine the costs, feasibility, and risks of this approach.

Depression and incident diabetic foot ulcers: a prospective cohort study.

OBJECTIVE: To test whether depression is associated with an increased risk of incident diabetic foot ulcers. METHODS: The Pathways Epidemiologic Study is a population-based prospective cohort study of 4839 patients with diabetes in 2000-2007. The present analysis included 3474 adults with type 2 diabetes and no prior diabetic foot ulcers or amputations. Mean follow-up was 4.1 years. Major and minor depression assessed by the Patient Health Questionnaire-9 were the exposures of interest. The outcome of interest was incident diabetic foot ulcers. We computed the hazard ratio and 95% confidence interval (CI) for incident diabetic foot ulcers, comparing patients with major and minor depression with those without depression and adjusting for sociodemographic characteristics, medical comorbidity, glycosylated hemoglobin, diabetes duration, insulin use, number of diabetes complications, body mass index, smoking status, and foot self-care. Sensitivity analyses also adjusted for peripheral neuropathy and peripheral arterial disease as defined by diagnosis codes. RESULTS: Compared with patients without depression, patients with major depression by Patient Health Questionnaire-9 had a 2-fold increase in the risk of incident diabetic foot ulcers (adjusted hazard ratio 2.00; 95% CI, 1.24-3.25). There was no statistically significant association between minor depression by Patient Health Questionnaire-9 and incident diabetic foot ulcers (adjusted hazard ratio 1.37; 95% CI, 0.77-2.44). CONCLUSION: Major depression by Patient Health Questionnaire-9 is associated with a 2-fold higher risk of incident diabetic foot ulcers. Future studies of this association should include better measures of peripheral neuropathy and peripheral arterial disease, which are possible confounders or mediators.

Depression in relation to long-term control of glycemia, blood pressure, and lipids in patients with diabetes.

BACKGROUND: Little information is available about the association of depression with long-term control of glycemia, blood pressure, or lipid levels in patients with diabetes. OBJECTIVE: To determine whether minor and major depression at study enrollment compared with no depression are associated with higher average HbA(1c), systolic blood pressure (SBP) and LDL cholesterol over the long term in patients with an indication for or receiving drug treatment. DESIGN: Cohort study. PATIENTS: A total of 3,762 patients with type 2 diabetes mellitus enrolled in the Pathways Epidemiologic Study in 2001-2002 and followed for 5 years. MAIN MEASURES: Depression was assessed at study enrollment using the Patient Health Questionnaire-9 (PHQ-9). SBP and information on cardiovascular co-morbidity were abstracted from medical records, and LDL cholesterol and HbA(1c) measured during clinical care were obtained from computerized laboratory data during a median of 4.8 years' follow-up. KEY RESULTS: Among those with an indication for or receiving drug treatment, after adjustment for demographic and clinical characteristics, average long-term HbA(1c), SBP, and LDL cholesterol did not differ in patients with comorbid diabetes and minor or major depression compared with those with diabetes alone. CONCLUSIONS: The adverse effect of depression on outcomes in patients with diabetes may not be mediated in large part by poorer glycemic, blood pressure, or lipid control. Further study is needed of the biologic effects of depression on patients with diabetes and their relation to adverse outcomes.

Comorbid depression is associated with an increased risk of dementia diagnosis in patients with diabetes: a prospective cohort study.

BACKGROUND: Both depression and diabetes have been found to be risk factors for dementia. This study examined whether comorbid depression in patients with diabetes increases the risk for dementia compared to those with diabetes alone. METHODS: We conducted a prospective cohort study of 3,837 primary care patients with diabetes (mean age 63.2 +/- 13.2 years) enrolled in an HMO in Washington State. The Patient Health Questionnaire (PHQ-9) was used to assess depression at baseline, and ICD-9 diagnoses for dementia were used to identify cases of dementia. Cohort members with no previous ICD-9 diagnosis of dementia prior to baseline were followed for a 5-year period. The risk of dementia for patients with both major depression and diabetes at baseline relative to patients with diabetes alone was estimated using cause-specific Cox proportional hazard regression models that adjusted for age, gender, education, race/ethnicity, diabetes duration, treatment with insulin, diabetes complications, nondiabetes-related medical comorbidity, hypertension, BMI, physical inactivity, smoking, HbA(1c), and number of primary care visits per month. RESULTS: Over the 5-year period, 36 of 455 (7.9%) patients with major depression and diabetes (incidence rate of 21.5 per 1,000 person-years) versus 163 of 3,382 (4.8%) patients with diabetes alone (incidence rate of 11.8 per 1,000 person-years) had one or more ICD-9 diagnoses of dementia. Patients with comorbid major depression had an increased risk of dementia (fully adjusted hazard ratio 2.69, 95% CI 1.77, 4.07). CONCLUSIONS: Patients with major depression and diabetes had an increased risk of development of dementia compared to those with diabetes alone. These data add to recent findings showing that depression was associated with an increased risk of macrovascular and microvascular complications in patients with diabetes.

Depression and advanced complications of diabetes: a prospective cohort study.

OBJECTIVE: To prospectively examine the association of depression with risks for advanced macrovascular and microvascular complications among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A longitudinal cohort of 4,623 primary care patients with type 2 diabetes was enrolled in 2000-2002 and followed through 2005-2007. Advanced microvascular complications included blindness, end-stage renal disease, amputations, and renal failure deaths. Advanced macrovascular complications included myocardial infarction, stroke, cardiovascular procedures, and deaths. Medical record review, ICD-9 diagnostic and procedural codes, and death certificate data were used to ascertain outcomes in the 5-year follow-up. Proportional hazard models analyzed the association between baseline depression and risks of adverse outcomes. RESULTS: After adjustment for prior complications and demographic, clinical, and diabetes self-care variables, major depression was associated with significantly higher risks of adverse microvascular outcomes (hazard ratio 1.36 [95% CI 1.05-1.75]) and adverse macrovascular outcomes (1.24 [1.0-1.54]). CONCLUSIONS: Among people with type 2 diabetes, major depression is associated with an increased risk of clinically significant microvascular and macrovascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities. Clinical and public health significance of these findings rises as the incidence of type 2 diabetes soars. Further research is needed to clarify the underlying mechanisms for this association and to test interventions to reduce the risk of diabetes complications among patients with comorbid depression.

Relationship styles and mortality in patients with diabetes.

OBJECTIVE Prior research has shown that less social support is associated with increased mortality in individuals with chronic illnesses. We set out to determine whether lower propensity to seek support as indicated by relationship style, based on attachment theory, is associated with mortality in patients with diabetes. RESEARCH DESIGN AND METHODS A total of 3,535 nondepressed adult patients with type 1 and type 2 diabetes enrolled in a health maintenance organization in Washington State were surveyed at baseline and followed for 5 years. Relationship style was assessed at baseline. Patients with a greater propensity to seek support were classified as having an interactive relationship style and those less inclined to seek support as having an independent relationship style. We collected Washington State mortality data and used Cox proportional hazards models to estimate relative risk (RR) of death for relationship style groups. RESULTS The rate of death in the independent and interactive relationship style groups was 39 and 29 per 1,000 individuals, respectively. Unadjusted RR of death was 1.33 (95% CI 1.12-1.58), indicating an increased risk of death among individuals with an independent relationship style. After adjustment for demographic and clinical covariates, those with an independent relationship style still had a greater risk of death compared with those with an interactive relationship style (hazard ratio 1.20 [95% CI 1.01-1.43]). CONCLUSIONS In a large sample of adult patients with diabetes, a lower propensity to reach out to others is associated with higher mortality over 5 years. Further research is needed to examine possible mechanisms for this relationship and to develop appropriate interventions.

How does change in depressive symptomatology influence weight change in patients with diabetes? Observational results from the Pathways longitudinal cohort.

BACKGROUND: Little is known about how change in depressive symptoms over time is associated with change in weight. METHODS: Longitudinal associations between change in depression (Patient Health Questionnaire-9 [PHQ-9]) and weight (self-reported and chart abstracted) were examined in 2,600 patients with type 2 diabetes (mean age 62, SD = 11.6) who were surveyed by telephone in 2001-2002 and 5 years later as part of the Pathways study. Mixed effects regression analyses compared a) patients with persistently low depression symptoms with those whose depression worsened (increased at least 5 points on PHQ-9) over 5 years and b) patients with persistently high depression symptoms with those who improved (decreased at least 5 points on PHQ-9) over 5 years. RESULTS: Those who worsened in comparison to those with persistently low depression symptoms did not differ in their pattern of weight change (z = 1.54, p = .12). Both groups weighed approximately 92 kg at baseline and lost approximately 2 kg. A significantly different pattern of change over time was observed for those with persistently high depression symptoms in comparison to those whose depression improved (z = 1.98, p = .04). Although the groups had almost identical weight at baseline (approximately 100 kg), at the 5-year assessment, those with persistently high depression symptoms had about half the weight loss (M = -1.71, SD = 9.08) in comparison to those whose depression improved (M = -3.62, SD = 19.93). CONCLUSION: In persons with diabetes who have clinically significant levels of depressive symptoms, improvement in depression is accompanied by significantly greater, clinically significant weight loss.

Diabetes and poor disease control: is comorbid depression associated with poor medication adherence or lack of treatment intensification?

OBJECTIVE: To hypothesize that patients with comorbid depression and diabetes and poor disease control will have poorer adherence to disease control medication and less likelihood of physician intensification of treatment. Many patients with diabetes fail to achieve American Diabetes Association Guidelines for glycemic, blood pressure and lipid control. Depression is a common comorbidity and may affect disease control through adverse effects on adherence and physician intensification of treatment. METHODS: In a cohort of 4117 patients with diabetes, depression was measured at baseline with the Patient Health Questionnaire-9 (PHQ-9). Patient adherence and physician intensification of treatment were measured in those who had evidence of poor disease control (HbA(1c) >or=8.0%, LDL >or=130 mg/dL, systolic blood pressure >or=140 mm Hg) over this 5-year period. Poor adherence was defined as having medication refill gaps for >or=20% of days covered for medications prescribed for each of these conditions. Treatment intensification was defined as an increased medication dosage in a class, an increase in the number of medication classes, or a switch to a different class within 3-month periods before and after notation of above target levels. RESULTS: Among patients with diabetes and poor disease control, depression was associated with an increased likelihood of poor adherence to diabetes control medications (odds ratio [OR] = 1.98; 95% Confidence Interval [CI] = 1.31, 2.98), antihypertensives (OR = 2.06; 95% CI = 1.47, 2.88), and LDL control medications (OR = 2.43; 95% CI = 1.19, 4.97). In patients with poor disease control who were adherent to medication or not yet started on a medication, depression was not associated with differences in likelihood of physician intensification of treatment. CONCLUSIONS: In patients with diabetes and poor disease control, depression is an important risk factor for poor patient adherence to medications, but not lack of treatment intensification by physicians.