Increased Resting-state Functional Connectivity as a Compensatory Mechanism for Reduced Brain Volumes in Prediabetes and Type 2 Diabetes

<p> </p> <p><strong>OBJECTIVE</strong></p> <p>To investigate the contribution of alterations in the brain structure and function to cognitive function and their interactions in prediabetic individuals and patients with type 2 diabetes mellitus (T2DM).</p> <p><strong>RESEARCH DESIGN AND METHODS</strong></p> <p>This population-based study included 2483 participants who had undergone structural magnetic resonance imaging (sMRI) (569 normal glucose metabolism (NGM),1353 prediabetes and 561 T2DM) and cognitive testing. Of these, 2145 participants also had functional magnetic resonance imaging (fMRI) (496 NGM, 1170 prediabetes and 479 T2DM). Multivariate linear regression models were used to assess the association of brain volumes and functional connectivity with cognition, as well as the association of brain volumes and functional connectivity.</p> <p><strong>RESULTS</strong></p> <p>Compared with NGM participants, those with T2DM had lower brain volumes in a wide range of brain regions and stronger functional connectivity between bilateral thalamus and brain functional network (visual network and default mode network), and prediabetes had lower brain volumes in the specific local regions (subcortical gray matter volume and subcortical subregions (bilateral thalamus, bilateral nucleus accumbens and right putamen)) and stronger functional connectivity between right thalamus and visual network. The cognition was associated with higher right thalamus volume and lower functional connectivity between right thalamus and visual network. The functional connectivity between right thalamus and visual network was associated with lower right thalamus volume. </p> <p><strong>CONCLUSIONS</strong></p> <p>Cognition was associated with higher brain volumes and lower functional connectivity in T2DM. Increased functional connectivity may indicate a compensatory mechanism for reduced brain volumes that begin in the prediabetic phase.</p>