Altered functional connectivity between brain structures in adults with type 1 diabetes and polyneuropathy

Objective: Alterations of the central nervous system are increasingly being recognized as a part of diabetes, especially in the thalamus and the default mode network (DMN). However, the functional involvement in diabetic peripheral neuropathy (DPN) is poorly understood. This study aimed to investigate functional connectivity of thalamus and DMN in individuals with DPN and the associations to clinical characteristics. Methods: Forty-seven type 1 diabetes mellitus (T1DM) individuals with DPN and 28 healthy controls underwent resting-state functional magnetic resonance imaging. Seed-to-voxel and ROI-to-ROI analyses were performed for thalamus and DMN. The connectivity for both thalamus and DMN were correlated to clinical parameters. Results: Alterations in the functional connectivity of the thalamus and DMN were observed in individuals with T1DM and DPN. Thalamus showed decreased connectivity to the middle frontal, superior frontal, and precentral cortex (all p _{FWE-corrected}<0.05). DMN ROIs showed increased connectivity to the superior frontal cortex (all p _uncorrected<0.05). A trend towards increased overall connectivity within DMN was observed in the T1DM compared to healthy controls (p=0.051). The subgroup with painful DPN had significantly increased overall connectivity compared to healthy controls (p=0.038). No associations were found to clinical parameters. Conclusion: Individuals with DPN had disrupted connectivity between thalamus/DMN and other brain structures and disrupted overall mean connectivity within DMN. Our findings support the existing knowledge of central nervous system involvement in diabetes and provide support for the involvement of thalamus and DMN in people with T1DM and DPN.