Mood disorders and medical illnessRelationship of depression to diabetes types 1 and 2: epidemiology, biology, and treatment
Introduction
“How sad and bad and mad it was, but then, how it was sweet!”—Browning (1864)
In the United States, 17 million Americans have diabetes (almost 8% of the adult population and 19% of the population over the age of 65 years) (Harris et al 1998). Several racial and ethnic groups are at high risk for diabetes, including blacks, Hispanics, Asians and Pacific Islanders, and Native Americans 1995, Lindgren and Hirschhorn, 2001. Accounting for ∼8% of total US health care expenditures ($78 billion) in 1997 (American Diabetes Association 1998), diabetes is the leading cause of nontraumatic limb amputation, new cases of end stage renal disease (Centers for Disease Control 1993), and blindness in adults (Klein et al 1984). The sixth leading cause of death, diabetes further contributes to cardiac and stroke-related morbidity and mortality (Centers for Disease Control and Prevention 2002).
The epidemic of type 2 diabetes dwarfs the prevalence of type 1 and other types of diabetes due to genetic defects of β-cell function or insulin action, disease of the exocrine pancreas, endocrinopathies, infections, gestational, and drug- or chemical-induced (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2003). Of the 800,000 new cases of diabetes per year in the United States, most are type 2, due to the combined impact of sedentary lifestyles, increased prevalence of obesity, and the rising age of the population (Nathan 2002). Moreover, as many as 50% (over 8 million) of those with type 2 diabetes remain undiagnosed and unaware of their condition (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2003).
Diabetes mellitus is a heterogeneous metabolic disease in which hyperglycemia is a central feature. The associated abnormalities in protein, carbohydrate, and fat metabolism are the result of insufficient insulin action on peripheral target tissues due to insufficient insulin secretion (type 1), diminished tissue response to insulin (type 2), or some combination of both. The requisite β-cell loss for type 1 diabetes, which develops in most individuals by age 20, apparently stems from a combination of genetic susceptibility and an autoimmune reaction presumably stimulated by an environmental insult. Although debate continues, type 2 diabetes likely stems from a combination of inadequate insulin secretion and increased insulin resistance. Patients with type 2 diabetes have insulin levels that are considerably higher than in patients with type 1 diabetes but insufficient to overcome the challenge of insulin resistance involving both the liver, muscle, and adipose tissue. In type 2 diabetes, the defect in insulin action occurs largely at the postreceptor level, although exact mechanisms remain poorly understood. The genetic contribution to type 2 diabetes is even stronger than in type 1, with a concordance rate over 90% in identical twins (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2003).
Recent studies have demonstrated that depression constitutes a major risk factor in the development of type 2 diabetes and may accelerate the onset of diabetes complications. Since the mid-1980s, multiple longitudinal and cross-sectional studies have scrutinized the association of diabetes with depressive symptoms and major depression. Utilizing the search terms depressive disorders, psychiatry, diabetes, and pathophysiology in MEDLINE searches (1966–2003), this article reviews studies investigating pathophysiological alterations related to glucose intolerance and diabetes in depressed patients. Understanding the bidirectional relationship between depression and diabetes, including the biological, psychological, and sociocultural pathways of influence, is critical to the treatment and prevention of diabetes.
Section snippets
Diagnosis of depression in patients with diabetes
In contrast to the debate regarding criteria for the diagnosis of major depression in patients with cancer (McDaniel et al 1995), scrutiny of the depression symptom patterns in diabetic patients has been less controversial Bradley, 1994, Lustman et al., 1983. Indeed, sophisticated receiver operating characteristics analyses have confirmed the sensitivity and specificity of a self-report instrument, the Beck Depression Inventory (BDI) (Beck et al 1961), in screening for the syndrome of major
Biology
Depression is associated with important pathophysiologic alterations that may contribute to the increased vulnerability of depressed patients to type 2 diabetes and/or complications from both type 1 and type 2 diabetes. Although the underlying mechanisms are poorly understood despite intense scrutiny, depression is associated with abnormalities in metabolically significant biologic pathways: increased counter-regulatory hormone release and action, alterations in glucose transport function, and
Critique of the empirical literature
Despite the increased prevalence of major depression in patients with diabetes, no large-scale, randomized, controlled trials for the psychiatric treatment of depression and diabetes exist (please see review by Snoek and Skinner 2002). Surprisingly, there has been only one controlled study of psychotherapy and two controlled studies of antidepressant medication in diabetic patients with depression (see Table 4 ). A major finding is that nortriptyline decreased depression but had an adverse
Future directions for research
The principal unanswered questions in this field remain primarily prognostic, etiologic, and treatment-related. By what mechanisms do dysphoria and other symptoms such as hostility (Surwit et al 2002) affect glucoregulatory systems? Conversely, will treatment of depression prevent or reduce incidence of diabetes and diabetes-associated complications? Investigative strategies should certainly include additional prospective (rather than cross-sectional) studies of diabetic patients with comorbid
Acknowledgements
This research was supported by grants RR-00039 from the National Institutes of Health, Bethesda, Maryland and HS-07922 (LSP) and DK063302 (DLM). We are grateful for the assistance of Barbara Rothbaum, Ph.D., Ms. Alice Huang, Mr. Brett Galvin, Ms. Mary Lou Mojonnier, and the nursing and laboratory staff of the Emory General Clinical Research Center, Emory University Hospital, and the Diabetes Clinic at Grady Memorial Hospital. We apologize to those colleagues whose work could not be cited due to
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