Patients With Type 2 Diabetes and Major Depression at Greater Risk for Significant Cardiovascular Complications
By Nancy Fowler Larson
Medscape Medical News
December 8, 2009 — Adults with type 2 diabetes who have major depression face a greater risk for life-altering microvascular and macrovascular complications regardless of their self-care habits or the degree to which their disease is controlled, according to a study published online November 23 in Diabetes Care.
"A meta-analysis of 27 studies found a significant association between depression and a wide variety of diabetes complications (neuropathy, retinopathy, nephropathy, macrovascular complications, and sexual dysfunction). The conclusions that can be drawn from individual studies are limited given their relatively small samples that included patients with both type 1 and type 2 diabetes," write Elizabeth H.B. Lin, MD, MPH, from the Group Health Research Institute in Seattle, Washington, and other study authors. "The greatest limitation of these studies was their cross-sectional design. Cross-sectional studies can not clarify whether patients are depressed because they have disabling and worrisome diabetic complications or whether having depression could actually precede occurrence of severe and clinically significant diabetic complications."
Researchers collected a longitudinal cohort of 4623 adults with type 2 diabetes. Between 2000 and 2002, participants self-assessed any minor and major depression symptoms using the Patient Health Questionnaire 9, based on criteria from the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. The study also noted subjects' prior complications of diabetes.
Five years later, between 2005 and 2007, researchers collected data on 3922 of the original patients (85.1%) regarding the development of advanced complications of diabetes, both microvascular (eg, blindness, end-stage renal disease, amputations, and renal failure deaths) and macrovascular (eg, myocardial infarction, stroke, cardiovascular procedures, and deaths). This information was obtained through medical records; International Classification of Diseases, Ninth Revision; diagnostic and procedural codes; and death certificates.
Researchers found that participants who reported major depression had a 36% increased risk of developing advanced microvascular complications and a 25% greater risk of developing significant macrovascular issues compared with those with mild or no depression. Adjusting for disparities in glycemic control (eg, treatment adherence and diet) and self-care habits (eg, physical activity, smoking, and HbA1c results — a measure of how well diabetes is being controlled) lowered the association between depression and macrovascular issues, but not between depression and microvascular complications.
"After adjustment for prior complications, demographic, clinical and diabetes self-care variables, major depression was associated with significantly higher risks of adverse microvascular outcomes [hazard ratio (HR) 1.36, 95% confidence interval (CI): 1.05 to 1.75], and adverse macrovascular outcomes [HR: 1.24, 95% CI: 1.0 to 1.54]," the authors write.
Limitations include the fact that no depression data were collected on individuals before their participation in the study and that it took place in a single geographic area.
Researchers posit that both biologic and behavioral factors may affect the association between depression and diabetes complications. Depression and ongoing stress can trigger the hypothalamic-pituitary-adrenal axis, arouse the sympathetic nervous system, elevate inflammatory and platelet aggregation, and negatively affect the patient's glycemic control and self-care, which can also increase the risk for complications. According to the authors, the importance of this and related future studies will continue to escalate.
"Clinical and public health significance of these findings rises as the incidence of type 2 diabetes soars," the authors write. "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 co-morbid depression."
The National Institutes of Health supported this study. All study procedures were approved by institutional review boards at Group Health, a mixed-model prepaid health plan, and the University of Washington. The study authors have disclosed no relevant financial relationships.
Diabetes Care. Published online November 23, 2009.
