Depression is common in people with diabetes. In the United States, depressive symptoms in people with either type 1 diabetes (T1D) or type 2 diabetes (T2D) is approximately 30%, and 11% show signs of major depressive disorder [MDD]. A 2020 study found similar rates of depression in people with diabetes in other countries as well.  Additionally, depression was not limited to people with a confirmed clinical diagnosis of diabetes. Research published in 2021 in the American Journal of Psychiatry reported a positive association between prediabetes and MDD (hazard ratio [HR], 2.66; 95% CI, 1.13-6.27).2

Potential diabetic and depression pathways

Although the precise underlying mechanisms remain unclear, the association between diabetes and depression appears to be bidirectional. Experts have proposed insulin resistance might represent a shared factor in the pathogenesis of both depression and severity of diabetes, with recent findings showing insulin resistance predicted MDD at a 9-year follow-up in patients with no previous history of depression.2-3

Contributing factors of the potential influence of depression on people with diabetes includes “poor health behaviors such as low self-care and treatment adherence, as well as by psychobiological changes such as dysregulation of the autonomic nervous system and increased inflammatory processes due to depressive symptoms, which may lead to glycemic variations,” according to a paper written by Jung et al in 2020.4


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Depression and diabetes: risk factors and outcomes

Women with diabetes seem to be at a heightened risk for symptoms of depression. Other potential risk factors related to depression in people with diabetes include diabetes-related complications, poor glycemic control, low socioeconomic status, a family history of diabetes, insulin as a starting treatment, and experiencing acute hypoglycemia or hyperglycemia in the 12 months prior to symptons.1,4-5

One study also reported that the risk of depression was 57% higher (odds ratio, 1.57; 95% CI, 1.13–2.28; P =.011) in individuals with an earlier age of onset of T2D (<40 years) vs the usual age of onset disease (≥40 years).5

Comorbid depression in diabetes may result in poor treatment adherence, hospitalization, cardiovascular and other complications, and all-cause mortality, underscoring the need to ensure effective mental health treatment for people  experiencing depression.6

Antidepressants and interaction with diabetic health challenges

Emerging research suggests treatment of depression with antidepressants may decrease the risk of developing diabetes-related complications, although other research suggests there may be complications related to their use.  

A retrospective cohort study published in 2021 examined the association between the risk of developing T2D with antidepressant use in a sample of 46,201 individuals with depression, compared with matched controls without depression.   The risk of developing T2D was 39% higher in people who did not receive antidepressants, and 11%-48% lower (depending on drug type) in those who did receive antidepressants.7 

In another 2021 retrospective cohort study of 36,276 patients with depression and newly treated diabetes, regular vs poor adherence to antidepressant medication was associated with reductions in the risk of microvascular complications (8%) and all-cause mortality (14%). Study authors suggested “clinicians should emphasize antidepressant treatment adherence among patients with depression and diabetes mellitus.”8

Other research has linked antidepressant use to an increased risk of developing diabetes.  A retrospective cohort study of 90,530 participants (45,265 new users of antidepressants and 45,265 non-users) showed antidepressant use was associated with increased diabetes risk which was both time-dependent and dose-dependent (adjusted HR [aHR], 1.27; 95% CI, 1.16-1.39 for short-term, low-dose use; and aHR, 3.95; 95% CI, 3.31-4.72 for long-term, high-dose use).9

Other studies suggested people with diabetes who reduced the dosage or discontinued the use of antidepressants demonstrated lower glycated hemoglobin (HbA1c) levels (F 2,49] = 8.17; P <.001).Similarly, a 2020 cohort study of 63,999 women showed an increased risk of T2D in those taking antidepressants compared to nonusers (HR, 1.34; 95% CI, 1.12-1.61).10

These conflicting findings highlight the need for further research to elucidate the relationship between diabetes risk and antidepressant use, and underscore the importance of understanding the complex relationship between people with diabetes, depressive symptoms, and health outcomes.

To learn more about depressive symptoms in people with T2D and how clinicians can evaluate their patients, Endocrinology Advisor interviewed Lawrence Fisher, PhD, a professor and researcher with the Department of Family and Community Medicine at the  University of California, San Francisco.

What is known about the association between depression and type 2 diabetes?

Dr Fisher: Rates of major depressive disorder [MDD]  among adults with type 2 diabetes (T2D) are not much higher than in community samples, but these individuals experience elevated symptoms of depression or diabetes-related distress (DRD). [It is] important to make a distinction between DRD and MDD.

In clinical settings, depression is usually measured by something like the Patient Health Questionnaire-9 (PHQ-9), but MDD can only be diagnosed by clinician interview. Symptoms of depression among those with diabetes correspond in many ways to symptoms of hyperglycemia – such as emotional lability, irritability, trouble sleeping, and general malaise – which can distort measures of depression and lead to overdiagnosis.11-12

What are the screening recommendations for endocrinologists when assessing their T2D patients for depression and diabetes-related distress?

Dr Fisher: The ADA has published guidelines on this. They don’t discourage screening for depression, but the way clinical settings are moving now is to also screen for distress associated with managing diabetes.13

There are several good scales to screen patients for DRD in the office. Probably the most comprehensive scale for T2D is a new one called the Type 2 Diabetes Distress Assessment System (T2-DDAS). The T2-DDAS enables clinicians to assess the intensity of distress and the various sources of distress, whether it’s related to food, stigma, family issues, etc, which can inform targeted interventions.14-15 

How does major depressive disorder affect diabetes management?

Dr Fisher: Patients with clinical depression can experience intense symptoms, and they are more likely to be sedentary and less likely to respond to the demands of diabetes management. Clinical depression is very disruptive to all aspects of disease management, including medication, diet, lifestyle, stress management, and self-care behaviors.

What is known about the effects of antidepressant medication in people with diabetes and clinical depression?

Dr Fisher: The treatment of clinical depression with antidepressant medications is effective. Clinicians will probably want to monitor glucose profiles in patients with diabetes to make sure there are no interactions, but this generally isn’t an issue with antidepressants; antipsychotic medications are more of a concern in terms of potential interactions.

By and large, the data are pretty clear that most antidepressants are safe and effective in this population. Patients with T2D who are on insulin are going to be more reactive, as endocrinologists know.

What are the treatment suggestions for patients with diabetes-related distress?

Dr Fisher: The ADA guidelines are clear on treatment for both depression and distress in diabetes. Diabetes-related distress is also very disruptive and, given the much higher prevalence of DRD in this population, we are trying to encourage diabetes providers to learn to address these issues in practice. Most mental health clinicians know little about diabetes and the emotional issues that people with diabetes experience. The people who know about these issues are the providers treating these patients for diabetes.

Diabetes-related distress reflects the emotional distress of living with diabetes and should be included as part of regular diabetes care. There is no reason why diabetes care professionals can’t learn to manage the emotional aspect of the disease as well.

We have a website and resource center with scales available for use at diabetesdistress.org. Patients can complete the assessments online and receive a PDF of the results. Additional resources are provided by the JDRF and by the ADA with support from the Helmsley foundation.16-18

What should the next steps be in terms of research and education?

Dr Fisher: We are currently exploring how we can provide the tools and protocols for diabetes clinicians to address these needs directly in the office. Doing so may necessitate somewhat of a culture shift because most diabetes providers have little experience dealing with the emotional side of diabetes. But we are seeing many clinics and practices overcome various hurdles to get these aspects of treatment and care integrated into endocrinology practice.

References

1. Aschner P, Gagliardino JJ, Ilkova H, et al. High prevalence of depressive symptoms in patients with type 1 and type 2 diabetes in developing countries: results from the International Diabetes Management Practices Study. Diabetes Care. 2021;44(5):1100-1107. doi:10.2337/dc20-2003

2. Lyra E Silva NM, Lam MP, Soares CN, et al. Insulin resistance as a shared pathogenic mechanism between depression and type 2 diabetes. Front Psychiatry. 2019;14;10:57. doi:10.3389/fpsyt.2019.00057

3. Watson KT, Simard JF, Henderson VW, et al. Incident major depressive disorder predicted by three measures of insulin resistance: a Dutch cohort study. Am J Psychiatry. 2021;178(10):914-920. doi:10.1176/appi.ajp.2021.20101479

4. Jung A, Du Y, Nübel J, et al. Are depressive symptoms associated with quality of care in diabetes? Findings from a nationwide population-based study. BMJ Open Diabetes Res Care. 2021;9(1):e001804. doi:10.1136/bmjdrc-2020-001804

5. Riaz BK, Selim S, Neo M, Karim MN, Zaman MM. Risk of depression among early onset type 2 diabetes mellitus patients. Dubai Diabetes Endocrinol J. 2021;27:55-65. doi:10.1159/000515683

6. Guerrero Fernández de Alba I, Gimeno-Miguel A, Poblador-Plou B, et al. Association between mental health comorbidity and health outcomes in type 2 diabetes mellitus patients. Sci Rep. 2020;10(1):19583. doi:10.1038/s41598-020-76546-9

7. Fang YJ, Wu TY, Lai JN, Lin CL, Tien N, Lim YP. Association between depression, antidepression medications, and the risk of developing type 2 diabetes mellitus: a nationwide population-based retrospective cohort study in Taiwan. Biomed Res Int. 2021;2021:8857230. doi:10.1155/2021/8857230

8. Wu CS, Hsu LY, Pan YJ, Wang SH. Associations between antidepressant use and advanced diabetes outcomes in patients with depression and diabetes mellitus. J Clin Endocrinol Metab. 2021;106(12):e5136-e5146. doi:10.1210/clinem/dgab443

9. Miidera H, Enomoto M, Kitamura S, Tachimori H, Mishima K. Association between the use of antidepressants and the risk of type 2 diabetes: a large, population-based cohort study in Japan. Diabetes Care. 2020;43(4):885-893. doi:10.2337/dc19-1175

10. Azevedo Da Silva M, Fournier A, Boutron-Ruault MC, et al. Increased risk of type 2 diabetes in antidepressant users: evidence from a 6-year longitudinal study in the E3N cohort. Diabet Med. 2020;37(11):1866-1873. doi:10.1111/dme.14345

11. Perrin NE, Davies MJ, Robertson N, Snoek FJ, Khunti K. The prevalence of diabetes-specific emotional distress in people with Type 2 diabetes: a systematic review and meta-analysis. Diabet Med. 2017;34(11):1508-1520. doi:10.1111/dme.13448

12. Fisher L, Hessler DM, Polonsky WH, et al. Prevalence of depression in type 1 diabetes and the problem of over-diagnosis. Diabet Med. 2016;33(11):1590-1597. doi:10.1111/dme.12973

13. Young-Hyman D, de Groot M, Hill-Briggs F, Gonzalez JS, Hood K, Peyrot M. Psychosocial care for people with diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2016;39(12):2126-2140. doi:10.2337/dc16-2053

14. Behavioral Diabetes Institute. Scales and measures: Type 2 Diabetes Distress Assessment System. Accessed online January 21, 2022.

15. Polonsky WH, Fisher L, Hessler D, Desai U, King SB, Perez-Nieves M. Toward a more comprehensive understanding of the emotional side of type 2 diabetes: A re-envisioning of the assessment of diabetes distress. J Diabetes Complications. 2022;36(1):108103. doi:10.1016/j.jdiacomp.2021.108103

16. JDRF. Dealing with diabetes distress. Accessed online January 21, 2022.

17. American Diabetes Association. Mental health provider diabetes education program.  Accessed online January 21, 2022.

18. Hemsley Trust. Mental health provider diabetes education program receives nearly $1 million grant from Helmsley.  Accessed online January 21, 2022.