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

Alessandro Miola, Neri A. Alvarez-Villalobos, Fernando Gerardo Ruiz-Hernandez, Eleanna De Filippis, Marin Veldic, Miguel L. Prieto, Balwinder Singh, Jorge A. Sanchez Ruiz, Nicolas A. Nunez, Manuel Gardea Resendez, Francisco Romo-Nava, Susan L. McElroy, Aysegul Ozerdem, Joanna M. Biernacka, Mark A. Frye, Alfredo B. Cuellar-Barboza*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalJournal of Affective Disorders
StatePublished - 1 Aug 2023

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© 2023 Elsevier B.V.


  • Bipolar disorder
  • Clinical course
  • Insulin resistance
  • Systematic review
  • Treatment response


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