Insulin Resistance, Diabetes Mellitus, and Brain Structure in Bipolar Disorders

Abstract

Type 2 diabetes mellitus (T2DM) damages the brain, especially the hippocampus, and frequently co-occurs with bipolar disorders (BD). Reduced hippocampal volumes are found only in some studies of BD subjects and may thus be secondary to the presence of certain clinical variables. Studying BD patients with abnormal glucose metabolism could help identify preventable risk factors for hippocampal atrophy in BD. We compared brain structure using optimized voxel-based morphometry of 1.5T MRI scans in 33 BD subjects with impaired glucose metabolism (19 with insulin resistance/glucose intolerance (IR/GI), 14 with T2DM), 15 euglycemic BD participants and 11 euglycemic, nonpsychiatric controls. The group of BD patients with IR, GI or T2DM had significantly smaller hippocampal volumes than the euglycemic BD participants (corrected p ¼ 0.02) or euglycemic, nonpsychiatric controls (corrected p ¼ 0.004). Already the BD subjects with IR/GI had smaller hippocampal volumes than euglycemic BD participants (t(32) ¼ À 3.15, p ¼ 0.004). Age was significantly more negatively associated with hippocampal volumes in BD subjects with IR/GI/T2DM than in the euglycemic BD participants (F(2, 44) ¼ 9.96, p ¼ 0.0003). The gray matter reductions in dysglycemic subjects extended to the cerebral cortex, including the insula. In conclusion, this is the first study demonstrating that T2DM or even prediabetes may be risk factors for smaller hippocampal and cortical volumes in BD. Abnormal glucose metabolism may accelerate the age-related decline in hippocampal volumes in BD. These findings raise the possibility that improving diabetes care among BD subjects and intervening already at the level of prediabetes could slow brain aging in BD.

Insulin resistance in bipolar disorder: relevance to routine clinical care

“…With progression of BD over time, some patients appear to develop neurocognitive deficits and brain changes, evident on magnetic resonance imaging (MRI). Our recent spectroscopic and functional MRI studies are the first to show that some of the neurochemical and morphological changes found in BD may be associated with impaired glucose metabolism . Further, our group replicated earlier findings of impairment in measures of verbal memory and decreased visual processing speed and accuracy among patients with BD.…”

Association Between Diabetes and Hippocampal Atrophy in Elderly Japanese: The Hisayama Study

“…Since insulin receptors are selectively distributed in the hippocampus and cerebral cortex (20), insulin resistance and hyperinsulinemia may particularly contribute to atrophy in these areas. Some observational studies reported that insulin resistance was associated with brain and hippocampal atrophy (21,22), which supports this hypothesis.…”

Cardiometabolic risks and omega‐3 index in recent‐onset bipolar I disorder

“…[4][5][6] In 2015, the American Heart Association published a scientific statement recognizing major depression and bipolar disorder in adolescents as moderaterisk conditions for cardiovascular disease. 7 In addition to increasing cardiovascular disease risk in bipolar I disorder, cardiometabolic risk factors including elevated triglyceride and C-reactive protein (CRP) levels, [8][9][10] and insulin resistance 11 may accelerate central pathological processes, and worsen psychiatric outcomes. [12][13][14][15] One potential risk factor for metabolic dysregulation in bipolar disorder is exposure to second-generation antipsychotic and/ or mood-stabilizer medications.…”