The Impact Of Insulin Resistance On The Course Of Bipolar Disorder

Type 2 diabetes is two to three times more prevalent among people with bipolar disorder than among the general population, with over half of all people with bipolar disorder having either insulin resistance (also known as “pre-diabetes”) or type 2 diabetes. The development of type 2 diabetes typically follows a progression from normal glucose metabolism to insulin resistance, then glucose intolerance, and eventually diabetes. 

Previous studies by our research group at Dalhousie University have demonstrated that people with bipolar disorder and insulin resistance or type 2 diabetes are more likely to have a chronic course of bipolar disorder and are less likely to respond to mood stabilizing medications than people with bipolar disorder who do not have insulin resistance or type 2 diabetes.

Until recently, the relationship between insulin resistance/type 2 diabetes and the course of bipolar disorder had only been demonstrated in cross-sectional studies, which assess relationships between variables at a single point in time. Though valuable, cross-sectional studies do not provide evidence of causal relationships – in this case, whether insulin resistance causes a change in the course of bipolar disorder from episodic to chronic, or whether a worsening course of bipolar disorder causes insulin resistance. 

To investigate how the development of insulin resistance relates to the course of bipolar disorder over time, we collected data to recreate the lifetime course of illness for six patients with bipolar disorder who also had insulin resistance. All patients provided informed consent for their data to be used in this study. The course of illness was determined by obtaining a detailed history for each patient through patient and family member interviews, as well as a thorough review of each patient’s medical records. Blood work results from medical records were used to determine when the patients developed insulin resistance.

These data were recorded using a chart that allowed for values to be calculated to represent overall bipolar disorder severity. With this chart, we compared each patient’s severity values from before and after they developed insulin resistance. For all six patients, the value increased following the onset of insulin resistance. This reflects greater frequency, length, and/or severity of episodes, compared to the episodes that occurred while the patients had normal glucose metabolism. 

As the onset of insulin resistance preceded the worsening of each patient’s course of illness, we suggest that insulin resistance may be a causal factor in patients’ change of course of illness from episodic to chronic. Previous research has demonstrated that insulin resistance is associated with inflammation and neurodegeneration in the brain, conditions that are likely to worsen a pre-existing brain disorder, such as bipolar disorder. 

Insulin resistance may represent a testable, modifiable factor in the process of bipolar illness progression. We have recommended screening for insulin resistance and implementing diet and exercise interventions in the treatment of insulin-resistant patients with bipolar disorder, as this could delay or prevent progression to a chronic course of illness. We are currently studying the efficacy of an insulin-sensitizing drug in treating insulin resistance as a strategy to improve outcomes for patients with chronic bipolar disorder who are not yet diabetic. 

Though our results were consistent across all six patients, it is important to bear in mind that further research will be required to support our preliminary findings. Only long-term studies that follow a greater number of stable patients with bipolar disorder over time and identify the onset of both insulin resistance and mood instability will provide more conclusive evidence for a causal relationship between insulin resistance and a worsening course of bipolar disorder.

These findings are described in the article entitled Course of bipolar illness worsens after onset of insulin resistance, recently published in the Journal of Psychiatric Research. This work was conducted by Kathleen Cairns from the Nova Scotia Health Authority, Terrence McCarvill from Dalhousie University and the Operational Trauma/Stress Support Centre, and Martina Ruzickova and Cynthia V. Calkin from Dalhousie University.

Reference:

1. Cairns, K., McCarvill, T., Ruzickova, M., & Calkin, C. V. (2018). Course of bipolar illness worsens after onset of insulin resistance. Journal of Psychiatric Research, 102(March), 34–37. https://linkinghub.elsevier.com/retrieve/pii/S0022395617314000