Type 2 diabetes mellitus: A potentially modifiable risk factor for neurochemical brain changes in bipolar disorders

Background: Neuroimaging changes in bipolar disorder (BD) may be secondary to the presence of certain clinical factors. Type 2 diabetes mellitus (T2DM) damages the brain and frequently co-occurs with BD. Studying patients with both T2DM and BD could help identify preventable risk factors for neuroimaging changes in BD. Methods: We used 1.5T magnetic resonance spectroscopy to measure prefrontal N-acetylaspartate (NAA), which is mainly localized in neurons, and total creatine (tCr), an energy metabolite, in 19 BD patients with insulin resistance/glucose intolerance (BD + IR/GI), 14 BD subjects with T2DM (BD + T2DM), 15 euglycemic BD participants, and 11 euglycemic, nonpsychiatric control. Results: The levels of NAA and tCr were lowest among BD + T2DM, intermediate in the BD + IR/GI, and highest among the euglycemic BD and control subjects (F_3,55 = 4.57, p = .006; F_3,55 = 2.92, p = .04, respectively). Even the BD + IR/GI subjects had lower NAA than the euglycemic participants (t₄₃ = 2.13, p = .04). Total Cr was associated with NAA (β = .52, t₅₆ = 5.57, p = .000001). Both NAA and tCr correlated with Global Assessment of Functioning scores (r₄₆ = .28, p = .05; r₄₆ = .48, p = .0004, respectively). Conclusions: T2DM, but also prediabetes, may be risk factors for prefrontal neurochemical alterations in BD. These changes were associated with poor psychosocial functioning and could indicate impaired energy metabolism. The findings emphasize the importance of improving diabetes care in BD and suggest potential options for treatment of neuroimaging alterations.