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 ≥ 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 ≥5 lifetime psychiatric hospitalizations. They also exhibited greater polypharmacy (≥4 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.
Aguglia et al. (2026) studied this question.