Which Came First – Depression or Diabetes?

A recent study in JAMA reported that patients treated for type 2 diabetes are at risk for developing depression. The study also reported that patients with depression are at risk for developing type 2 diabetes.

The study confirmed what other studies have reported, and clinicians have seen in practice, that symptoms of depression place patients at an increased risk for developing diabetes. Depressive symptoms including being overweight, poor eating habits, smoking, and a sedentary lifestyle are all known risk factors for developing impaired glucose tolerance and type 2 diabetes. However, lifestyle factors only partly explain the association between depression and diabetes.

Another study published in Diabetes Care found an association between antidepressant medication use and the development of type 2 diabetes. This study concluded that individuals already at high risk for developing type 2 diabetes who took antidepressant medications did develop diabetes at an increased rate. However, individuals with depressive symptoms, but not treated with an antidepressant medication, did not experience an increased risk of type 2 diabetes. These findings built on yet another study that found that the concurrent use of two distinct antidepressant medications — a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI) — had a greater risk of developing type 2 diabetes than patients who took only a TCA to treat their depression.

However, some antidepressant medications have common side effects that duplicate risk factors for type 2 diabetes. TCA’s, for example, are associated with weight gain and may increase blood glucose levels. (SSRI’s, on the other hand, are not associated with weight gain and may actually improve insulin sensitivity.) No study has been able to explain the mechanism by which antidepressant medications may influence the onset of type 2 diabetes. Some researchers suggest that antidepressant use may just be a marker for a history of recurrent or severe depression, which may have physiologic and biochemical effects on the body that leads to impaired glucose tolerance.

To confound the proverbial chicken-and-egg debate, the study published in JAMA demonstrated that patients treated for type 2 diabetes were at risk for developing depressive symptoms. These patients were also more likely to have high blood pressure and protein in their urine, suggestive of kidney damage. Interestingly, patients with pre-diabetes, or impaired fasting glucose, and patients with type 2 diabetes who were not being treated were less likely to experience depression.

Many studies have reported that patients with diabetes are nearly twice as likely to experience depression, compared to non-diabetics. The psychological stress associated with intense management of a chronic disease such as diabetes is thought to contribute to depressive symptoms. More research is needed to confirm these findings, but many clinicians suggest screening patients with diabetes for depression. Lifestyle modification, including diet, exercise, and stress management, is crucial in mitigating the morbidity and mortality associated with both diabetes and depression.

The use of antidepressant medications and the prevalence of type 2 diabetes are rising rapidly in the United States. Currently, at least 4 million people with pre-diabetes are taking antidepressants. Healthcare providers must be aware of the association and potential risk factors among diabetes, depression, and antidepressant medications and take appropriate measures to educate and inform patients of the risks, benefits, and screening tools related to treatment options. Patients should not change their current treatment regimens based on current findings, but should discuss any concerns with their healthcare provider.


BROWN, L., MAJUMDAR, S., JOHNSON, J. (2008). Type of antidepressant therapy and risk of type 2 diabetes in people with depression. Diabetes Research and Clinical Practice, 79(1), 61-67. DOI: 10.1016/j.diabres.2007.07.009

Golden, S.H., Lazo, M., Carnethon, M., Bertoni, A.G., Schreiner, P.J., Roux, A.V., Lee, H.B., Lyketsos, C. (2008). Examining a Bidirectional Association Between Depressive Symptoms and Diabetes. JAMA: The Journal of the American Medical Association, 299(23), 2751-2759. DOI: 10.1001/jama.299.23.2751

Rubin, R.R., Ma, Y., Marrero, D.G., Peyrot, M., Barrett-Connor, E.L., Kahn, S.E., Haffner, S.M., Price, D.W., Knowler, W.C. (2007). Elevated Depression Symptoms, Antidepressant Medicine Use, and Risk of Developing Diabetes During the Diabetes Prevention Program. Diabetes Care, 31(3), 420-426. DOI: 10.2337/dc07-1827

Jennifer Gibson, PharmD

Jennifer Gibson, PharmD, is a practicing clinical pharmacist and medical writer/editor with experience in researching and preparing scientific publications, developing public relations materials, creating educational resources and presentations, and editing technical manuscripts. She is the owner of Excalibur Scientific, LLC.
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