Posted on

Comorbid depression and diabetes mellitus: a double whammy

Dr. Girish Banwari

By Dr. Girish Banwari

Dr. Girish Banwari is a psychiatrist at Education: M.B.B.S. from NHL Municipal Medical College, Ahmedabad, India and M.D. (Psychiatry) with a Gold Medal from BJ Medical College, Ahmedabad, India.

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.

Contact Dr Banwari

1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047–53.
2. Meo SA, Usmani AM, Qalbani E. Prevalence of type 2 diabetes in the Arab world: impact of GDP and energy consumption. Eur Rev Med Pharmacol Sci 2017;21:1303-12.
3. Eren I, Erdi O, Mehmet S. The effect of depression on quality of life of patients with type II diabetes mellitus. Depress Anxiety 2008;25:98–106.
4. Pennix BW, Leveille S, Ferrucci L, van Eijk JT, Guralnik JM. Exploring the effects of depression of physical disability: longitudinal evidence established populations for epidemiologic studies of the elderly. Am J Public Health 1999;89:1346–52.
5. Stewart WF, Ricci JA, Chee E, Hahn SR, Morganstein D. Cost of lost productive work time among US workers with depression. JAMA 2003;289:3135–44.
6. Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 2007;370:851–8.
7. Harris MD. Psychosocial aspects of diabetes with an emphasis on depression. Curr Diab Rep 2003;3:49-55.
8. Egede LE, Nietert PJ, Zheng D. Depression and all-cause and coronary heart disease mortality among adults with and without diabetes. Diabetes Care 2005;28:1339–45.
9. Zhang X, Norris SL, Gregg EW, Cheng YJ, Beckles G, Kahn HS. Depressive symptoms and mortality among persons with and without diabetes. Am J Epidemiol 2005;161:652–60.
10. Ali S, Stone MA, Peters JL, Davies MJ, Khunti K. The prevalence of co-morbid depression in adults with Type 2 diabetes: a systematic review and meta-analysis. Diabet Med 2006;23:1165–73.
11. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001;24:1069–78.
12. Barnard KD, Skinner TC, Peveler R. The prevalence of co-morbid depression in adults with Type 1 diabetes: systematic literature review. Diabet Med 2006;23:445–8.
13. Lin EH, von Korff M, Alonso J, Angermeyer MC, Anthony J, Bromet E, et al. Mental disorders among persons with diabetes–results from the World Mental Health Surveys. J Psychosom Res 2008;65:571–80.
14. Brown LC, Majumdar SR, Newman SC, Johnson JA. Type 2 diabetes does not increase risk of depression. CMAJ 2006;175:42-6.
15. Weber B, Schweiger U, Deuschle M, Heuser I. Major depression and impaired glucose tolerance. Exp Clin Endocrinol Diabetes 2000;108:187–90.
16. Strine T, Mokdad A, Dube S, Balluz L, Gonzalez O, Berry J, et al. The association of depression and anxiety with obesity and unhealthy behaviors among community-dwelling US adults. Gen Hosp Psychiatry 2008;30:127–37.
17. Golden SH. A review of the evidence for a neuroendocrine link between stress, depression and diabetes mellitus. Curr Diabetes Rev 2007;3:252-9.
18. Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE. Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care 2000;23:934-42.
19. Sahota PK, Knowler WC, Looker HC. Depression, diabetes, and glycemic control in an American Indian community. J Clin Psychiatry 2008;69:800-9.
20. Ciechanowski PS, Katon WJ, Russo JE, Hirsch IB. The relationship of depressive symptoms to symptom reporting, self-care and glucose control in diabetes. Gen Hosp Psychiatry 2003;25:246-52.
21. de Groot M, Jacobson AM, Samson JA, Welch G. Glycemic control and major depression in patients with type 1 and type 2 diabetes mellitus. J Psychosom Res 1999;46:425-35.
22. Van Tilburg MA, McCaskill CC, Lane JD, Edwards CL, Bethel A, Feinglos MN, et al. Depressed mood is a factor in glycemic control in type 1 diabetes. Psychosom Med 2001;63:551-5.
23. Mathew CS, Dominic M, Isaac R, Jacob JJ. Prevalence of depression in consecutive patients with type 2 diabetes mellitus of 5-year duration and its impact on glycemic control. Indian J Endocrinol Metab 2012;16:764-8.
24. Dirmaier J, Watzke B, Koch U, Schulz H, Lehnert H, Pieper L, et al. Diabetes in primary care: prospective associations between depression, nonadherence and glycemic control. Psychother Psychosom 2010;79:172-8.
25. Eren I, Erdi O, Ozcankaya R. Relationship between blood glucose control and psychiatric disorders in type II diabetic patients. Turk Psikiyatri Derg 2003;14:184-91.
26. Egede LE, Osborn CY. Role of motivation in the relationship between depression, self-care, and glycemic control in adults with type 2 diabetes. Diabetes Educ 2010;36:276-83.
27. de Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ. Association of depression and diabetes complications: a meta-analysis. Psychosom Med 2001;63:619-30.
28. Lin EH, Rutter CM, Katon W, Heckbert SR, Ciechanowski P, Oliver MM, et al. Depression and advanced complications of diabetes: a prospective cohort study. Diabetes Care 2010;33:264-9.
29. Lloyd CE, Matthews KA, Wing RR, Orchard TJ. Psychosocial factors and complications of IDDM. The Pittsburgh Epidemiology of Diabetes Complications Study. VIII. Diabetes Care 1992;15:166-72.
30. Baumeister H, Hutter N, Bengel J. Psychological and pharmacological interventions for depression in patients with diabetes mellitus and depression. Cochrane Database Syst Rev 2012;12:CD008381.
31. Deuschle M. Effects of antidepressants on glucose metabolism and diabetes mellitus type 2 in adults. Curr Opin Psychiatry 2013;26:60-5.
32. Hennings JM, Schaaf L, Fulda S. Glucose metabolism and antidepressant medication. Curr Pharm Des 2012;18:5900-19.
33. Goodnick PJ. Use of antidepressants in treatment of comorbid diabetes mellitus and depression as well as in diabetic neuropathy. Ann Clin Psychiatry 2001;13:31-41.
34. Goodnick PJ, Henry JH, Buki VM. Treatment of depression in patients with diabetes mellitus. J Clin Psychiatry 1995;56:128-36.