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Abstract

The purpose of this review article was to examine the empirical evidence supporting depression as a risk factor for diabetes complications and associated burden. A database search using keywords located recent clinical and population studies addressing the association between depression and type 2 diabetes. Both cross-sectional and cohort studies were reviewed. Depression appears to exacerbate the progression of type 2 diabetes. The evidence is strong supporting the hypothesis that depression in persons with diabetes increases the risk of diabetes-related burden, including suboptimal glycemic control, complications, functionality, mortality, and health care utilization. Screening for depression among patients with diabetes should be increased in primary care. Newer approaches to diabetes care management may help to slow the progression of diabetes.

Keywords

depression diabetes diabetes complications screening mortality

Chronic hyperglycemia in persons with diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.^1-4 Despite this evidence and advances in literature related to known modifiable risk factors for diabetes, diabetes-related complications, and effective intervention strategies, the disease epidemic continues to burgeon.^5-7 To date, more than 23.6 million people (>8.0% of the US population) in the United States have diabetes, and 23.5 million of them are adults 20 years and older.^8,9 A recent study estimates that the prevalence of diabetes will more than double between 2005 and 2050.¹⁰ This is due to several factors that include unhealthy lifestyle (eg, unhealthy diets and inadequate physical activity), the obesity epidemic, and demographic changes (eg, aging and increased growth of at-risk populations).¹¹ The total annual economic cost of diabetes in the United States is estimated to be $174 billion ($116 billion direct costs; $58 billion indirect cost due to reduced productivity), accounting for more than 5% of the US health care budget.¹²

Optimal diabetes management through improved glycemic control has been shown to reduce the risk of developing diabetes-related complications.⁴ Nevertheless, it is estimated that the majority (>67%) of persons with type 2 diabetes (T2D) do not achieve optimal glycemic control.^13-16 Diabetes is one of the most behaviorally and psychologically demanding chronic conditions, especially with regard to self-management.¹⁷ Evidence suggests that 95% of routine diabetes care, essential for optimal glycemic control, is provided by the person with diabetes.^15,18,19 As reported by Sousa et al,¹⁸ optimal self-care practices must be adopted via diabetes education and development of self-care skills, social support, self-efficacy, and effective lifestyle changes.

Because of the aforementioned burden, it is not surprising that as with other chronic diseases (eg, AIDS and cancer), persons with T2D are at increased risk of developing psychological disorders such as stress and depression. Increased prevalence of depression in persons with diabetes has been reported for more than 200 years. However, not until recently has research confirmed an association between depression and diabetes. The number of research articles addressing the relationship between depression and diabetes has increased within the past 20 years as compared with the years prior.^20,21 Drivers of the increase in interest in this topic include the development of valid and reliable approaches to psychiatric diagnosis and the exponential increase in diabetes prevalence within the past 2 decades. Chronic diseases such as diabetes are known to increase risk of depression. The extent to which comorbid depression (CD) may cause or exacerbate diabetes is less fully understood. The volume of recent research requires a review to summarize the findings.

Methods

Primary sources published from January 2000 to April 2009 were gathered from MEDLINE, EMBASE, CINAHL, PsycARTICLES, SocINDEX with Full text, PsycINFO, Cochrane Databases, and Cochrane Database of Systematic Reviews. Depression and diabetes were used as the main key words for the searches and in some instances as subject headings (eg, MeSH). To maximize the search and minimize potential publication bias, the following additional sources were explored: books, doctoral theses, non-peer-reviewed journals, references listed in reviews and/or primary sources, and meeting (eg, annual American Diabetes Association meetings) abstracts. Only articles that were written in English were included. Only studies that included adult participants were included because T2D is more prevalent in adults compared with children and youth. The database search yielded several publications, including review articles whose findings are reviewed and discussed within the following sections.

The Relationship Between Diabetes and Depression

Most studies investigating the relationship between diabetes and depression do not distinguish between the various types of depression. As reported by Carney and Freedland,²² this is because dysphoric mood, syndromal depression, and all forms of unipolar and bipolar depressive disorders have been shown to have an adverse impact on the management and progression of chronic medical illness, including diabetes. Of note, the term depression will be used in the current review to describe any of the aforementioned forms of depression.

Although associated mechanisms are poorly understood, recent research has demonstrated an increased risk of depression in persons with diabetes.^2,23,24

Ali et al²³ conducted a systematic review and meta-analysis to estimate the prevalence and odds of developing or having depression in persons with T2D. Using 10 controlled trials including 51331 people for analysis, the prevalence of depression was significantly higher in persons with T2D as compared with those without T2D (17.6% vs 9.8%; odds ratio [OR] = 1.6; 95% confidence interval [CI]: 1.2-2.0). This confirmed findings from a similar meta-analysis by Anderson et al² that analyzed findings across 42 studies. Anderson et al determined that diabetes doubles the odds of developing CD (OR = 2.0; 95% CI: 1.8-2.2).

Proposed Mechanisms

A plausible mechanism for this association is that depression results from the stresses and pressures resulting from the diagnosis of diabetes and the associated burden—for example, stigma, complex T2D management and control practices, and difficulties in adapting to diabetes-related complications.²⁵ According to Carney and Freedland,²² many persons with diabetes and CD have depressive episodes well before they develop diabetes. Considering genomics as a potential mechanism, a positive family history of depression has been found to be associated with CD in persons with diabetes compared with nondepressed persons with diabetes.^26-28

Biological mechanisms have also been suggested as possible mechanisms linking diabetes and depression. Evidence reports common biological substrates in diabetes and depression. For example, alterations in the hypothalamic-pituitary-adrenal axis (HPA) have been observed in persons with diabetes as well as depressed patients.²⁵ Physiological mechanisms that are central to persons with diabetes such as reduction of glucose use and insulin resistance have been found in depressed persons without diabetes.^22,25 In a 5-year prospective study to assess the course of depression in persons with diabetes, Lustman et al²⁹ found that CD in persons with diabetes may be attributed to neurochemical changes (partly as a result of diabetes-related neuropathy) associated with advancing diabetes.

Impact of Depression on Diabetes Care and Outcomes

Depression has been shown to have adverse effects on optimal diabetes management and control. Ciechanowski et al³⁰ conducted a cross-sectional study to examine the effects of depressive symptoms on diabetes self-care, adherence to prescribed medication regimens, functioning, and health care costs. Associated findings included a significant association between the severity of depressive symptoms and nonadherence to healthy self-care practices and medication (P < .05). Compared with persons with low-severity depression symptoms, those with medium and high severity also showed significantly poorer physical and mental functioning and higher total health care costs (86% higher; P < .05). In a related study, Gonzalez et al³¹ found that all levels of depression (ie, low, medium, and high) were significantly associated with suboptimal adherence to diabetes medication in persons with diabetes (P < .01). It should be noted that these findings are subject to recall bias as adherence was self-reported. A prospective study by Gilmer et al³² found that depression was associated with a 50% increase in health care costs in persons with T2D and CD compared with those without CD ($31967 vs $21609; P < .05).

In 2008, Rush et al³³ investigated whether depressive symptoms are associated with achievement of recommended goals for controlling glucose. In this study, 1223 adults with diabetes were randomly recruited from a prospective cohort study (Project QUEST) for secondary data analysis. Persons with diabetes and CD were found less likely to have optimal glycemic control as compared with those without CD (43% vs 50%; P = .0176). Associated study findings also support that treatment with antidepressants increased the likelihood of achieving optimal glycemic control (48% vs 38%; P = .0517).

In another recent study, Egede and Ellis³⁴ conducted a cross-sectional study on 201 adults with T2D from an indigent care clinic to assess differences in diabetes knowledge, diabetes self-management practices, and perceived control in participants with versus those without CD. Persons with T2D and CD were found to more likely report self-control issues (P < .001) and less likely to report positive attitude (P < .001), self-care ability (P < .001), and self-care adherence (P < .001).

Several studies have evaluated the association of depression and diabetes-related complications. Twenty-seven of these studies were examined in a meta-analysis whose objective was to assess the strength and consistency of this association in a combined total of 5374 persons with T1D and/or T2D.³ Because the studies varied considerably by depression assessment procedures, diabetes type, and diabetic complications, de Groot et al³ stratified studies by the aforementioned variables. After adjusting for these variables and conducting meta-analyses on each subgroup, a significant association was found between depression and both microvascular (diabetic retinopathy, neuropathy, and nephropathy) and macrovascular (coronary artery disease, ischemic heart disease, and atherosclerotic vascular diseases) complications (P < .00001). The meta-analysis yielded a moderate weighted effect size (r = 0.25; P < .0001) for studies that reported adequate data (n = 22).

As reported by several studies,^35-39 depression increases the likelihood of mortality in the general population, and the same is true for CD in chronic conditions. Using longitudinal data from the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-Up Study (1982-1992) in a survival analysis, Zhang et al⁴⁰ revealed that the presence of depressive symptoms significantly increased the mortality risk by approximately 54% for persons with diabetes and CD when compared with those without CD, after controlling for important confounding factors (hazard ratio [HR] = 1.54; 95% CI: 1.15-2.07). In a related 3-year prospective cohort study that assessed 4000 health maintenance organization (HMO) patients with T2D, Katon et al⁴¹ found that after adjusting for potential confounders, participants with minor depression were 1.67 times, whereas those with major depression were 2.3 times, at increased risk for mortality than those without depression (P = .003 and P < .0001, respectively).

Treatment of Depression in Persons With Diabetes

Many treatment options, including pharmacotherapy and behavioral therapy, are available to treat and manage depression. Nearly 75% of people taking antidepressants at a therapeutic dosage will report improvements.⁴² Considering previously mentioned evidence that consistently supports that CD is associated with an increased risk of suboptimal diabetes management and control and adverse diabetes-related outcomes, several studies have evaluated whether these treatment options modify this risk.

A multicenter (ie, 18 clinical sites from 8 health care organizations) randomized controlled trial examined the efficacy of collaborative and enhanced depression care in older (mean age, 71.2 years) persons with diabetes and CD. HbA1c levels were obtained for 293 participants at baseline, 6 months, and 12 months. At baseline, participants were randomly assigned to either a usual care group or to the IMPACT (Improving Mood-Promoting Access to Collaborative Treatment) intervention group, which provided collaborative depression care for 12 months. In comparison to the control group (usual care group), associated study findings indicated less severe depression (P < .001), greater improvement in overall functioning (P < .001), and increased weekly exercise days (P = .001) in the intervention group. HbA1c levels were not affected by the intervention; however, it should noted that participants in both groups had good glycemic control at baseline, thereby limiting the power of the study to detect small but clinically significant improvements.^43,44

Using data from another multisite, randomized trial, PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial)⁴⁵ supplemented with data from the National Health Index Plus, Bogner et al⁴⁶ investigated the relationship between diabetes, depression treatment, and all-cause mortality in 584 older adults (>60 years). After adjusting for baseline differences in the comparison groups, patients in the intervention (ie, PROSPECT, a collaborative care model) group were significantly less likely to have died as compared with the control group (HR = 0.49; 95% CI: 0.24-0.98). In 2004, a meta-analysis of 12 controlled trials by Ismail et al⁴⁷ found that psychological interventions for persons with diabetes suggested significant long-term benefits with regards to their glycemic control (P < .001).

Despite the aforementioned evidence, findings from a retrospective cohort study⁴⁸ suggest that only 31% of persons with diabetes and CD received adequate antidepressant treatment, and up to 96.3% received less than 4 sessions of outpatient psychotherapy visits during a 12-month period. This suboptimal therapy level calls for better and improved management of CD in persons with diabetes.

Screening for Depression

Most patients with diabetes and CD seek care from a primary care physician (PCP) rather than a specialist; therefore, PCPs must be able to identify, diagnose, and treat this important comorbid condition. However, appropriate depression diagnosis and management is affected by several factors that include brief visits, poor integration with specialized psychological health care, and a false perception by some PCPs who still believe that CD is a plausible and justifiable outcome of diabetes.^21,49,50 Consequently, treatment for these patients may be limited to diabetes education, social support, and other therapies that are not effective in treating CD. As reported by Williams et al,⁵¹ another barrier is related to limited knowledge of available and essential diagnostic elements or concern over their validity and reliability in persons with diabetes. In other cases, patients, especially men, rarely spontaneously describe their emotional feelings, and PCPs generally do not have the time to conduct formal psychodiagnostic interviews and/or evaluations.⁵¹ Persons with diabetes have been reported to generally have several comorbidities^51,52; hence, another contributing reason to the underrecognition and/or treatment of depression may be due to competing clinical explanation. For example, fatigue is associated with depression and/or diabetes, and patients and/or health care providers may then associate fatigue with hyperglycemia instead of depression.⁵³

Despite the fact that depression is more prevalent in persons with diabetes, CD is identified in only 25% of this population group compared with the 50% depression recognition rate in the general population.^54,55 Consequently, nearly 67% of depressed persons with diabetes do not receive antidepressant therapy.^48,49 From a global standpoint, the World Health Organization (WHO)⁵⁶ reports that approximately 450 million people globally have clinically relevant psychosocial or mental health issues, but most do not receive accurate diagnosis or effective treatment.

In light of this and as supported by researchers,³ the American Diabetes Association (ADA) incorporated a standard of psychosocial assessment into its 2005 Clinical Practice Recommendations.⁵⁷ Within these recommendations, the ADA emphasizes the need for screening and highlights several opportunities for screening for depression and ensuring that appropriate referrals are made. Some of these opportunities include screening at diagnosis of diabetes, when suboptimal diabetes management (eg, issues with glycemic control or adherence) and/or complications are discovered, and during management visits. Based on evidence supporting that patients coped best when physicians identified depression symptoms and ensured appropriate treatment, the US Preventive Services Task Force (USPSTF) also recommended and encouraged PCPs to routinely screen chronic disease patients for CD.⁵⁸ Hence, predictive models or related questions should be employed into diabetes office visits.

Despite the aforementioned barriers to appropriate depression diagnosis and management, as well as overlap between depression and physiological diabetes symptoms, screening tools that have shown adequate sensitivity and validity in persons with T2D exist. In a review of screening tools used in primary care settings, Sharp and Lipsky⁵⁹ recommended the Beck Depression Inventory (BDI),⁶⁰ the Center for Epidemiologic Studies Depression Scale (CES-D), and the Zung Self-Rating Depression Scale (Zung’s SDS)⁵⁹ as showing adequate sensitivity and specificity. As reported by Katon et al,⁴⁸ the BDI and the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)⁶¹ criteria are effective and beneficial screening tools that can identify persons with diabetes in need for management of depression or other psychosocial conditions. The depression protocol of 9-symptom checklist of the Patient Health Questionnaire (PHQ-9) and the CES-D have also been shown to retain sensitivity and specificity in people with both type 1 diabetes (T1D) and T2D.⁶² The PHQ-9 has demonstrated high sensitivity (88%) and specificity (88%) in the screening of major depression based on structured psychiatric interviews.⁶³

Because of the convenience sampling or recruiting approaches employed by most of the studies included in the current review, associated findings may be subject to selection bias, thereby limiting their ability to generalize findings to the general population of persons with T2D. For example, most studies of depression as a risk factor for T2D complications recruited participants from managed care populations, primary care sites, specialized hospitals, and subpopulations (eg, specific racial/ethnic and economically disadvantaged population groups). In addition, most of these studies used a cross-sectional study design to assess the relationship between diabetes and depression, thereby limiting any interpretations associated with causal relationships. Needed are more longitudinal studies employing representative samples.

Conclusions

As indicated by the current literature review, recent research advances have provided valuable insight on the criticality of CD in persons with diabetes. Depression in persons with T2D has been associated with adverse implications on diabetes management, glycemic control, functioning, diabetes-related morbidity, mortality, and health care utilization. The current review revealed that screening for depression in persons with diabetes is not only feasible but efficacious, beneficial, cost-effective, and recommended in diabetes management and control guidelines defined by the ADA. Although further research is needed to investigate ways to reduce the high rates of recurrence and unresponsiveness to available depression treatment, the effectiveness of depression therapy via various approaches is well established and has been shown to improve diabetes-related outcomes and delay progression of diabetes. Despite this, evidence suggests that depression is underrecognized and consequently undertreated in persons with diabetes. Therefore, as recommended by the ADA, improved recognition and management of CD in persons with diabetes is essential to optimize diabetes management and control. This review highlights the primary care setting as a crucial point of possible intervention and the important task that PCPs have in maintaining increased suspicion and high alert for the possibility of depression in persons with T2D. Hence, insight on risk factors and/or predictors for developing or having depression in persons with T2D might be valuable to enable researchers and PCPs to identify high-risk groups.

Footnotes

Acknowledgements

I thank Dr James Rohrer, Dr Georjean Stoodt, and Dr Reginald Taylor for their guidance and assistance in the literature review.

The author is employed by Eli Lilly and Company; however, none of the information included in this review is associated with any specific pharmaceutical medication.

The author received no financial support for the research and/or authorship of this article.

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Is Depression a Modifiable Risk Factor for Diabetes Burden?

Abstract

Keywords

Methods

The Relationship Between Diabetes and Depression

Proposed Mechanisms

Impact of Depression on Diabetes Care and Outcomes

Treatment of Depression in Persons With Diabetes

Screening for Depression

Conclusions

Footnotes

Acknowledgements

References