Depression as a Comorbidity to Diabetes: Implications for Management

Andrea A. Riley; Mindy L. McEntee; Linda Gerson; Cheryl R. Dennison


Journal for Nurse Practitioners. 2009;5(7):523-535. 

In This Article

Relationship between Diabetes and Depression

The high prevalence of comorbid depression and diabetes suggests that these disorders may be related.[33] Depression has been proposed as both a result of and precursor to diabetes, with this relationship attributed to a variety of mechanisms. Studies have examined a number of psychosocial and biological correlates of depression and diabetes, yet the causal relationship between these disorders, its direction, and underlying mechanisms remain unclear.[31,34]

Depression as a Result of Diabetes

Some authors have proposed that depression may stem from the psychosocial burden and/or biochemical changes related to diabetes and its treatment.[1,17,18] This hypothesis may help explain why depression is more prevalent in diabetics than in the general population and is supported by the temporal finding among type 1 diabetics, in which diabetes typically precedes the onset of major depressive disorder (MDD).[34] While there is little empirical data on the psychosocial facet of this theory, there is some evidence that emotional distress is mediated by perceived threat of illness,[35,36] self-esteem,[37,38] self-efficacy,[35] coping skills,[39] and social support.[35,37]

Sociodemographic factors including younger age,[21,26,40] female gender,[1,21,26,40–44] low socioeconomic status,[26,43,45] ethnic minority status,[21,31,41,46] chronic stressors, and negative life events[47] have also been identified as predictors of depression among individuals with diabetes, although a causal relationship has not been established.

The biological component of this hypothesis speculates that the metabolic consequences of diabetes lead to structural and functional changes in the brain that increase susceptibility to stress and depression,[48] although data thus far have been inconclusive. The relationship between depression and glycemic control remains subject to debate; a meta-analysis of 26 studies found a significant relationship with comparable effect sizes in both type 1 and type 2 diabetes,[17] yet other research did not find this correlation,[42,49,50] or found it significant only for individuals with type 1 diabetes.[51,52] The connection between diabetic complications and depression has also produced mixed results;[18,31,44,53–57] these discrepancies may suggest that biochemical mechanisms have greater influence on the duration of depression rather than its initial onset.[34]

Depression as a Precursor to Diabetes

An alternative hypothesis in which depression precedes and predisposes individuals to diabetes may explain the development of type 2 diabetes among patients diagnosed with depression several years earlier.[58] This theory proposes that diabetes may develop via the psychosocial effects of depression, including adiposity and negative health behaviors like poor diet, physical activity, smoking, and medication adherence; and/or as a result of biological mechanisms such as activation of the HPA axis[45,59–62] and inflammatory responses[63–66] that contribute to insulin resistance and decreased glucose uptake. A meta-analysis of 9 longitudinal studies showed that adults who were depressed were 37% more likely to develop type 2 diabetes than their non-depressed counterparts.[67] Other studies have shown that this increased risk remains significant after controlling for known demographic and clinical risk factors.[57,68–75] Adults receiving treatment for depression were still prone to developing diabetes,[75,76] with those taking a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI) concurrently at greater risk (60%) than those prescribed either a TCA (44%) or SSRI (37%) alone.[77]

While research supports a trend in which depression precedes type 2 diabetes, causal mechanisms for this association remain speculative. A recent meta-analysis of 13 prospective studies found that while adverse psychosocial factors were associated with poor diabetes control in both type 1 and type 2 diabetes, they were not related to incidence of diabetes.[78] Variations in the extent to which depression increased the risk of type 2 diabetes after accounting for known risk factors suggest that additional factors affect this relationship.[44,57,70] Inflammatory markers interleukin-6 and C-reactive protein were elevated in depressed individuals and have been identified as risk factors for developing type 2 diabetes, yet models accounting for these variables were still unable to explain the association between depression and the incidence of type 2 diabetes in Golden et al.[44] Knol et al found that insulin resistance was not related to depressive symptoms, further challenging the proposed mechanisms underlying this relationship.[79]

A Bidirectional Relationship

Contradictory research findings suggest the relationship between depression and diabetes is complex and may differ for type 1 and type 2 diabetes. The factors underlying this relationship may be bidirectional and consist of multiple mechanisms and/or indirect causation. Golden et al found evidence for a bidirectional relationship within the same cohort; adults with treated type 2 diabetes who were depression-free at baseline were 52% more likely to experience depressive symptoms than non-diabetics, while adults with elevated depression scores were 21% more likely than those with low or normal symptoms to develop type 2 diabetes after adjusting for clinical, demographic, and lifestyle risk factors.[44]