Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates

Background: Although insulin resistance (IR) and cardiometabolic syndrome are prevalent in patients with bi-polar disorder (BD), only a few studies have attempted to precisely assess the degree and clinical impact of IR in BD.Methods: A comprehensive search was conducted from multiple research databases through May 2022, following a pre-defined protocol (PROSPERO: CRD42022359259). We extracted neuroimaging, cognition, illness course, and treatment response findings from individuals with BD with evidence of IR compared with euglycemic BD individuals.Results: Of 1436 identified articles, 10 reports fulfilling inclusion criteria were included (n = 1183). BD patients with IR displayed worse composite verbal memory scores and worse executive function and exhibited smaller hippocampal volumes along with prefrontal neurochemical alterations compared to euglycemic BD patients. Fixed-effect meta-analysis revealed that BD patients with impaired glucose metabolism (IGM) were more likely to develop a chronic and rapid cycling course when compared with euglycemic BD patients (k = 2, OR = 2.96, 95 % CI 1.69-5.17, OR = 2.88, 95 % CI 1.59-5.21, p < 0.001, respectively), with a trend for significantly lower Global Assessment of Functioning scores (k = 5, MD =-4, 95 % CI -8.23-0.23, p = 0.06). BD patients with IGM displayed a higher rate of poor response to mood stabilizers when compared with euglycemic BD patients (k = 2, OR = 6.74, 95 % CI 1.04-43.54, p = 0.04).Limitations: Cross-sectional design and small sample sizes of studies included limit the generalizability of results.Conclusion: IR is associated with worse clinical outcomes of BD and inadequate treatment response. Imple-menting strategies to prevent and treat IR in BD is crucial to improve the prognosis of such a difficult-to-treat population.

Automated summary

Insulin resistance (IR) is associated with poorer clinical outcomes and inadequate treatment response in patients with bipolar disorder (BD). BD patients with IR exhibit impairments in verbal memory and executive function, as well as smaller hippocampal volumes and prefrontal neurochemical alterations. They are also more likely to have chronic and rapid cycling courses and lower Global Assessment of Functioning scores. BD patients with impaired glucose metabolism also have a higher rate of poor response to mood stabilizers.