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 bipolar 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. Implementing strategies to prevent and treat IR in BD is crucial to improve the prognosis of such a difficult-to-treat population.
Competing Interests: Conflict of interest Dr. Romo-Nava is supported in part by a National Institute of Mental Health K23 Award (K23MH120503) and a 2017 NARSAD Young Investigator Award from the Brain and Behavior Research Foundation; has a U.S. Patent and Trademark Office patent # 10,857,356; receives consultant fees from Otsuka Pharmaceutical and has received non-financial research support from Soterix Medical. Dr. Prieto served on an advisory board of Janssen and received grant support from ANID FONDECYT Regular 1181365, FONDEF ID19I10116 and Basal Funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024. Dr. Nuñez is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685. Dr. Frye is supported by a grant from the Assurex Health, Mayo Foundation and Intellectual property licensed to Chymia LLC. He received honoraria from the Carnot Laboratories and the American Physician Institute. Other authors have no conflicts of interest to declare that are relevant to the content of this article.
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