And Depression

Depression has important clinical relevance to diabetes due to its potential association with poor glycemic control and decreased adherence to treatment regimens. However, it is still unclear what etiology is behind the strong association between these two illnesses. There are several possible mechanisms to explain the relationship between depressive symptoms and DM, and none have been absolutely supported by an evidence-base to date. A very recent study (30) examined the bidirectional relationship between diabetes and depressive symptoms using a multi-ethnic, longitudinal cohort of men and women with atherosclerosis and determined that persons with depressive symptoms are at a significantly increased risk of developing diabetes even after controlling for demographic, metabolic, and inflammatory factors. What is clear is that there exists clinical and neurological evidence that diabetes and depression are linked, primarily through dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis (see Neuroendocrine Findings Associated with Depression), but the direction of the causality remains under debate (30, 31).

Diabetes as a Risk Factor for Depression

One view is that depressive symptoms are triggered by the existence of diabetes. Depressive symptoms are associated with biochemical changes related to the diabetes (i.e., hyperglycemia, inflammation, activation of the hypothalamic-pituitary-adrenal axis, stress) and may be important factors in disrupting overall metabolic control (7, 32, 33). Further, the presence of depression and depressive symptoms may present as a result of lifestyle choices (i.e., poor diet, no physical activity) and psychological stress associated with managing the illness that are frequently associated with the presence of diabetes. Treated type II diabetes has been associated with a significantly higher chance of developing depressive symptoms, even after controlling for BMI and co-morbidities (30), and well-functioning older adults with diabetes are at nearly twice the risk of developing depressive symptoms than those without diabetes (34).

Depression as a Risk Factor for Diabetes

An alternative explanation for the relationship between depression and diabetes views the development of diabetes as the result of pre-existing depression. This view suggests that (1) neurohormonal changes induced by depression, such as hypercortisolism, can lead to insulin resistance and to the development of diabetes, and (2) behavioral factors associated with depression, including lack of physical activity and poor diet, increase the risk for the development of diabetes (24, 32, 35-38).

The presence of depression may adversely impact the function of a number of neurotransmitters, including serotonin, norepinephrine, dopamine, acetylcholine, and GABA (7). Depressive symptoms are also associated with increased inflammation (39) and inflammatory markers are established risk factors for type II diabetes (40). Further, depressive symptoms and major depression can cause abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis and other hormonal irregularities (41). Meta-analyses have identified an association between depression and hyperglycemia, but the mechanism and directionality of the association have not been determined (7, 23).

The increase in glycosylated hemoglobin (HgbAlc) levels attributed to depression alone has ranged from 1.8 to 3.3% (23, 42). A meta-analysis of depression and studies of glycemic control confirmed the association of depression with hyperglycemia, but was unable to reveal the mechanism or the direction of the association (23). The association between depression and glycemic control has recently been observed in ethnic minority groups with diabetes as well (43). In addition, treatment and subsequent improvement in depression has been significantly associated with improvement in glycemic control (see also: Treatment Considerations).

Diabetes and Depression as Clinical Outcomes of a Common Pathophysiologic Pathway

It is extremely difficult to establish an evidence-base for either of these explanations due to the lack of control populations and standardized measurements. The role of stress in the development of depression as well as in glucose regulation has been well established, and the impact of stress can be nearly impossible to disentangle in studies of diabetes and depression. While the relationship between diabetes and depression clearly exists, the causative nature of this relationship may always be difficult to determine due to the circular directionality of these two illnesses. Depression may be a cause or a result of diabetes and both the direction and the mechanism of this relationship may vary over time. There is a growing research base that confirms the bidirectional association between diabetes and depression (30, 44). Regardless of the etiology of these illnesses in a patient, the outcomes for both illnesses worsen when they co-occur, than with either illness alone. Providers should be aware of the strong relationship between diabetes and depression and provide appropriate treatment and management of both illnesses.

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