The prevalence of diabetes mellitus worldwide is projected to rise from 2.8% in 2000 to 4.4% in 2030.1 Studies have reported a high prevalence of diabetes in the Middle East, with rates as high as 31.6% in Saudi Arabia, 29% in Oman, 25.4% in Kuwait, 25% in Bahrain, and 25% in the United Arab Emirates.2
Major depressive disorder (referred to as “depression” for the purpose of this article) is a major public health problem, associated with substantial suffering, reduced functioning, lost productivity, decreased quality of life along with higher health care utilization and costs, and disability.3-5 Furthermore, depression is more prevalent in patients with chronic illness in general and diabetes in particular, and it leads to poor adherence to medical regimens in patients with comorbid medical illness. A WHO survey found that the comorbid state of depression with chronic diseases incrementally worsens health compared with depression alone, with any of the chronic diseases alone, and with any combination of chronic diseases without depression.6 Diabetes is unique in that it places the burden of invasive blood glucose monitoring, regimentation of diet and exercise, and often multiple daily insulin injections into the hands of the individual.7 Notably, the coexistence of diabetes and depression is associated with a significantly increased risk of death from all causes, beyond that due to having either diabetes or depression alone.8,9 In most instances, comorbidity remains undetected and even when recognized, it usually meets inadequate care.
Diabetes and Depression: Association and Direction of Causality.
Diabetes (both type 1 and type 2) is associated with an increased risk and prevalence of depression.10-13 The presence of diabetes roughly doubles the odds of comorbid depression and this is observed across ethnically diverse groups. The overall risk estimate generalizes across community and clinical settings despite differences in prevalence rates between these settings. Nonetheless, it has been noted that several factors claimed to be linked to depression are not limited to those with diabetes and may be related to the general psychological distress of having a chronic disease.
The relationship between depression and diabetes has been argued to be essentially bi-directional (Figure 1). Brown et al. have concluded that depression increases the risk of diabetes rather than vice-versa.14 Both physiological and behavioral factors seem to play a role in the relationship between depression and diabetes. Depression is potentially related to impaired glucose tolerance and central obesity.15 Additionally, poor health behaviors (i.e., smoking, physical inactivity, caloric intake) found in depressed individuals may increase the risk of diabetes type 2.16 Depression is associated with physiological abnormalities, including activation of the hypothalamic-pituitary-adrenal axis, sympathetic nervous system, and pro-inflammatory cytokines, which can induce insulin resistance and contribute to diabetes risk.17
Poor Glycemic Control and Depression
Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes,18,19 though some researchers have contended the relationship to be more strongly established in the type 1 variant.20-22 Overall, evidence is more in favor of depression leading to hyperglycemia rather than the other way round. In a prospective representative study of patients with type 2 diabetes, baseline depression predicted problems with medication adherence, problems with health-related behaviors, and unsatisfactory glycemic control at follow-up.23 Another prospective study on the clinical impact of depressive episodes on glycemic control showed that the number of depressive episodes correlated with a higher glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes.24
Depression does not seem to have a direct effect on glycemic control; rather, the relationship is indirect via self-care behaviors.25 Depression impedes the adoption of effective self-management behaviors (including physical activity, appropriate dietary behavior, foot care, and appropriate self-monitoring of blood glucose behavior) through a decrease in social motivation, probably leading to poor glycemic control. While there is a direct relationship between depression and behavior, social motivation exists in this predicted pathway, and is potentially modifiable through diabetes educational efforts.26
Complications of Diabetes and Depression
The development of depression has often been considered a secondary response to the onset of diabetes complications but depression might also play a primary role in the development or exacerbation of complications.27 Arguably, temporal relationships between depressive symptoms and complications warrant clarification. As prospectively studied, among people with type 2 diabetes, depression is associated with an increased risk of clinically significant micro vascular and macro vascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities.28 Similar findings have been reported for patients with type 1 diabetes.29 Meta-analytic reviews have demonstrated a significant and consistent association of diabetes complications (in both type 1 and type 2 diabetes) and depressive symptoms, although effect sizes were in the small to moderate range.27 Expectedly, an increase in depressive symptoms is associated with an increase in the severity or number of diabetes complications.27 Neuropathy, nephropathy, retinopathy, peripheral vascular disease, and sexual dysfunction have all been independently associated with depression in diabetes mellitus.
Treatment of Depression in Patients with Diabetes
Available research data suggests that effective psychological and/or pharmacological treatment of depression may not only improve depressive symptoms, but may also have a positive impact on glycemic control and behavioral risk factors, though not uniformly and simplistically. Differential treatment effects might exist depending on the time-course and etiology of depressive disorders.30
In depressed patients with diabetes type 2, selective serotonin reuptake inhibitors (SSRIs) are the only class of antidepressants with confirmed favorable effects on glycemic control.31 Noradrenergic substances (and possibly also dual acting antidepressants), in contrast, may deteriorate glucose tolerance. The effects of other antidepressants, like bupropion, mirtazapine or newer agents, require further investigation before reliable conclusions can be made.32 In diabetic neuropathy, perhaps due to the fact that catecholamine and serotonin may both be implicated in pain pathways, dual-action antidepressants, like duloxetine and tricyclic antidepressants (TCAs) appear more effective at lower doses than do specific serotonergic agents.33 Dopamine and norepinephrine influences appear to be hyperglycemic. Serotonergic influences, in the presence of mono amine oxidase inhibitors (MAOIs), which decrease serotonin metabolism, are in contrast hypoglycemic. SSRIs may be hypoglycemic (causing as much as a 30% decrease in fasting plasma glucose) and anorectic (causing an approximately 2-lb decrease), while possibly improving alertness.34
Depression is significantly associated with diabetes, from incidence to mortality. It may thus be recommended that all patients with diabetes should be screened for depression. Co-occurrence of the two dreaded Ds leads to poor symptom control; greater symptom severity; increased disease burden, disability, work impairment and use of health care services; poor quality of life; substantially higher health care costs; and a greater risk of death. Treatment of depression may not only improve depressive symptoms, but may also have a positive impact on glycemic control and health care behaviors in those with diabetes.
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