Alterations in effective connectivity within the Papez circuit are correlated with insulin resistance in T2DM patients without mild cognitive impairment

Insulin resistance (IR) can significantly affect the hippocampus, a component of a larger memory circuit called the Papez circuit. This study was performed to identify altered effective connectivity within the Papez circuit in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) and to determine the relationships between these alterations and IR. T2DM patients without MCI ( n = 105) and age-, sex-, and education-matched healthy controls ( n = 106) were included in this study. Granger causality analysis (GCA) with seed regions in the hippocampus was performed to identify abnormal effective connectivity in the brains of T2DM patients without MCI. Furthermore, correlation analysis was conducted to detect the association between aberrant effective connectivity and IR in T2DM patients without MCI. Compared to healthy controls, T2DM patients without MCI demonstrated abnormal directional connectivity both to and from the hippocampus; the main abnormalities were located in several brain areas, including the cingulate cortex, amygdala, and prefrontal cortex, all of which are components of the Papez circuit. This altered effective connectivity network in the Papez circuit was correlated with IR in T2DM patients without MCI. Effective connectivity network alterations within the Papez circuit occurred prior to the appearance of mild cognitive deficits in T2DM patients and were correlated with IR. The current study may improve our understanding of the IR-related neurological mechanisms involved in T2DM.