Reduced gray matter volume in the default-mode network associated with insulin resistance

Insulin resistance may lead to structural and functional abnormalities of the human brain. However, the mechanism by which insulin resistance impairs the brain remains elusive. In this study, we used two large neuroimaging databases to investigate the brain regions where insulin resistance was associated with the gray matter volume and to examine the resting-state functional connectivity between these brain regions and each hypothalamic nucleus. Insulin resistance was associated with reduced gray matter volume in the regions of the default-mode and limbic networks in the cerebral cortex in older adults. Resting-state functional connectivity was prominent between these networks and the paraventricular nucleus of the hypothalamus, a hypothalamic interface connecting functionally with the cerebral cortex. Furthermore, we found a significant correlation in these networks between insulin resistance-related gray matter volume reduction and network paraventricular nucleus of the hypothalamus resting-state functional connectivity. These results suggest that insulin resistance-related gray matter volume reduction in the default-mode and limbic networks emerged through metabolic homeostasis mechanisms in the hypothalamus.

Methods
Data from the Bunkyo Health Study, which aimed to prevent diseases requiring long-term care in older people, was used in the present study. Of 1629 participants in the database, insulin-dependent T2DM patients were excluded, and then the data of 1609 without any missing data were analyzed. We analyzed the gray matter volumes using a VBM software implemented in SPM12 and insulin resistance (HOMA-IR) was calculated using fasting blood sampling data.

We also analyzed the functional connectivity between the HOMA-IR-related cerebral region and the hypothalamic nuclei. For this analysis, we used the data of resting-state functional images of HCP (N = 418).