{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:19:24Z","timestamp":1790785164910,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Bipolar disorder (BD) is increasingly recognized as a multisystem condition in which metabolic abnormalities, particularly insulin resistance (IR), may be linked to illness severity and neuroprogression. Despite growing evidence linking IR to adverse clinical outcomes, the data is heterogeneous and preliminary, and its specific association in hospitalized patients with BD remains underexplored. Methods: This cross-sectional study included 86 inpatients with a primary diagnosis with BD at the IRCCS Ospedale Policlinico San Martino, Genoa, Italy, between July 2023 and January 2024. Sociodemographic, clinical, and metabolic characteristics were systematically investigated. IR was defined as a HOMA-IR index \u2265 2.5. Results: Twenty-eight patients met criteria for IR. Insulin resistant patients showed a significantly longer illness duration, more frequent residual symptoms, and higher rates of \u22655 lifetime psychiatric hospitalizations. They also exhibited greater polypharmacy (\u22654 psychotropics at discharge) and daily alcohol use. Furthermore, the IR subgroup was significantly associated with higher body mass index and triglycerides, lower HDL cholesterol and physical activity levels. Conclusions: Our findings indicate that IR is associated with markers of greater illness burden in BD. While these results are consistent with emerging hypotheses on metabolic dysfunction in BD, longitudinal studies are required to clarify temporal and causal relationships. These associations suggest that IR may represent a clinically relevant component of BD rather than a secondary metabolic consequence. Routine metabolic screening and the preferential use of metabolically neutral agents may improve long-term outcomes and align with the emerging paradigm of precision psychiatry.<\/jats:p>","DOI":"10.3390\/jpm16010047","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:25:23Z","timestamp":1768213523000},"page":"47","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Insulin Resistance in Bipolar Disorder: A Real-World Cross-Sectional Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2003-2101","authenticated-orcid":false,"given":"Andrea","family":"Aguglia","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Largo Paolo Daneo 3, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Meinero","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Largo Paolo Daneo 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Aprile","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Largo Paolo Daneo 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Cerisola","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Largo Paolo Daneo 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuditta","family":"Mazzarello","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Largo Paolo Daneo 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Oggianu","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6387-6462","authenticated-orcid":false,"given":"Alessandra","family":"Costanza","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Geneva University (UNIGE), 24 Rue du General-Dufour, 1211 Geneva, Switzerland"},{"name":"Department of Psychiatry, Faculty of Biomedical Sciences, University of Italian Switzerland (USI), via Buffi 13, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Amore","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Largo Paolo Daneo 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-340X","authenticated-orcid":false,"given":"Andrea","family":"Amerio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Largo Paolo Daneo 3, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-856X","authenticated-orcid":false,"given":"Gianluca","family":"Serafini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Largo Paolo Daneo 3, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1001\/archgenpsychiatry.2011.12","article-title":"Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative","volume":"68","author":"Merikangas","year":"2011","journal-title":"Arch. 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