Elsevier

Psychoneuroendocrinology

Volume 36, Issue 9, October 2011, Pages 1276-1286
Psychoneuroendocrinology

Review
The relationship of depression and diabetes: Pathophysiological and treatment implications

https://doi.org/10.1016/j.psyneuen.2011.03.005Get rights and content

Summary

Diabetes is a highly prevalent, chronic disease that requires ongoing, multi-specialty medical care combined with patient self-management, family support, and education to prevent or delay end-organ morbidity and mortality. There is clearly an increased prevalence of major depressive disorder, a relatively common and costly central nervous system syndrome, in diabetic patients. During the past two decades, multiple studies reveal that not only are depressive symptoms a risk factor for the development of type 2 diabetes, but they have also been shown to contribute to hyperglycemia, diabetic complications, functional disability and all-cause mortality among diabetic patients. This article reviews studies examining the relationship between depression and diabetes, neurochemical underpinnings of the two disorders, and the diagnosis and treatment of depression associated with diabetes. We examine the validity of rating scales used to diagnose depression in diabetic patients and review the literature on psychotherapeutic and psychopharmacologic management for these patients. The challenges of optimal depression screening and treatment in primary care settings of diabetic patients are currently under close scrutiny, especially regarding their potential impact related to improvements in diabetes-related outcomes and decreased health care costs, be it “depression” or “diabetes” relevant. Much of the current literature regarding the intertwined nature of diabetes and depression is cross-sectional in nature. Future research should focus on longitudinal, prospective studies to determine causal factors. What is clear from the research reviewed in this article is that depression and diabetes should be treated together rather than as isolated diseases. The mind/body dualism is a false dichotomy and a truly team-based approach is necessary to address both issues of depression and diabetes. Collaborative care and the “patient-centered medical home” have emerged as potentially effective interventions to improve quality of care and patient outcomes in patients with depression and medical illnesses such as diabetes.

Introduction

Diabetes is a chronic disease that requires ongoing, multi-specialty medical care combined with patient self-management, family support, and education to prevent or delay end-organ morbidity and mortality (ADA, 2010). The prevalence of diabetes (which includes the four clinical classes of type 1, type 2, gestational, and diabetes due to other causes) was estimated at 2.8% world-wide in the year 2000 (Wild et al., 2004). Due to factors such as population aging and urbanization, 4.4% of the world's population is expected to have diabetes by 2030 (Wild et al., 2004). Within the United States, 17.5 million persons have been diagnosed with diabetes resulting in a total estimated annual cost of $174 billion (ADA, 2008). This includes $116 billion in excess medical expenditures and $58 billion in reduced national productivity (ADA, 2008). The actual national burden of diabetes is likely greater due to the social cost of intangibles such as pain and suffering, care provided by unpaid caregivers, excess medical costs due to undiagnosed diabetes, and other diabetes-attributed health care costs (ADA, 2008).

Another relatively common and costly central nervous system syndrome, major depression, occurs in many patients with diabetes. During the past two decades, multiple studies reveal that not only are depressive symptoms a risk factor for the development of type 2 diabetes, but they are also associated with premature onset of diabetes complications. We conducted multiple MEDLINE searches using terms such as “diabetes,” “depression,” and “pathophysiology” for the period, 2000–2010. This article reviews studies examining the relationship between depression and diabetes, neurochemical underpinnings of the two disorders, and the diagnosis and treatment of depression associated with diabetes. We examine the validity of rating scales used to diagnose depression in diabetic patients and review the literature on psychotherapeutic and psychopharmacologic management for these patients. The challenges of optimal depression screening and treatment in primary care settings of diabetic patients are currently under close scrutiny, especially regarding their potential impact related to improvements in diabetes-related outcomes and decreased health care costs, be it “depression” or “diabetes” relevant.

Section snippets

Epidemiological studies of depression and diabetes

The prevalence of clinically significant elevations in depressive symptoms or the presence of major depressive disorder (MDD) has long been recognized to be higher among persons with diabetes compared to non-diabetic populations (Anderson et al., 2001). Table 1 displays studies documenting increased rates of depression in diabetic populations. In 2001, Anderson and colleagues performed a meta-analysis of twenty controlled, cross-sectional studies, each containing a non-diabetic comparison group

The negative impact of depression on patients with diabetes: poorer glycemic control and premature diabetes-related complications and mortality

Considerable evidence indicates that depression is associated with poor glycemic control (Lustman et al., 2000a). A meta-analytic review of the literature showed a small to moderate, consistent effect size of 0.17 [95% CI 0.13–0.21] (Lustman et al., 2000a). This effect size was similar in studies of type 1 or type 2 diabetes, and increased upon the implementation of standardized interviews and diagnostic criteria to assess depression (Lustman et al., 2000a). Depression is also strongly

Pathophysiology of depression and diabetes

The epidemic of type 2 diabetes in the United States was increasingly recognized during the “Decade of the Brain” (1990–2000). During the subsequent decade of 2000–2010, increased attention focused upon adverse metabolic and thrombovascular consequences of depression through certain biologic pathways. Relevant in this regard are the hypothalamic–pituitary–adrenal axis hyperactivity and mental stress-induced sympathomedullary activation in many patients with major depression, which can

Diagnosis of depression in patients with diabetes

There are multiple conceptual approaches to the diagnosis of major depression in medically ill patients, including the exclusive and inclusive approaches (McDaniel et al., 1995). The exclusive approach maximizes specificity by eliminating somatic symptoms such as anorexia and fatigue, which frequently are elements of medical disorders (McDaniel et al., 1995). The inclusive approach includes all depressive symptoms to diagnose major depressive disorder in the medically ill and maximizes

Treatment of depression in patients with diabetes

Lustman and colleagues at Washington University in St. Louis have performed the vast majority of the research on treatment of depression in diabetic populations. Table 5 lists the results of double-blind, randomized controlled trials examining the psychotherapeutic and psychopharmacological treatment of depression in patients with diabetes. A randomized, controlled trial was conducted to determine the efficacy of cognitive behavioral therapy (CBT) in the treatment of major depression in

Future directions in treatment of depression in patients with diabetes

Collaborative care, structured care involving a greater role for non-medical specialists to augment primary care, has emerged as a potentially effective intervention to improve quality of care and patient outcomes in patients with depression and medical illnesses such as diabetes (Gilbody et al., 2006). A cumulative meta-analysis (examining 37 randomized studies including 12,355 patients with depression receiving primary care) showed that depression outcomes among patients receiving

Conclusions

Two common disorders, depression and diabetes, are complex diseases with manifold genetic and environmental contributors to pathogenesis. There is clearly an increased prevalence of depression among diabetic patients. Depressive symptoms serve as a risk factor for the development of diabetes and have been shown to contribute to hyperglycemia, diabetic complications, functional disability and all-cause mortality among diabetic patients. Despite the fact that depression complicates medical

Financial disclosures

James K. Rustad M.D., has no financial disclosures to report.

Dominique L. Musselman, M.D., M.S., received grant support from the National Institute of Mental Health (NIMH), The DANA Foundation, and Forest Laboratories, Inc.

Charles B. Nemeroff, M.D., Ph.D., served on the Board of Directors of NovaDel Pharma and Mt. Cook Pharma. He served on the Scientific Advisory Board of AstraZeneca Pharmaceuticals, CeNeRx BioPharma, NovaDel Pharma, PharmaNeuroboost, the American Foundation for Suicide

Role of the funding source

Not applicable for this manuscript.

Contributors

With the exception of the three authors, there are no other contributors to this manuscript.

Acknowledgement

There are no acknowledgements for this manuscript.

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