Differential resting state connectivity responses to glycemic state in type 1 diabetes

Objective: To determine whether individuals with T1DM and hypoglycemia unawareness (T1DM-Unaware) had changes in the brain resting state functional connectivity compared to healthy controls (HC) and those with T1DM and hypoglycemia awareness (T1DM-Aware). Design: Observational study. Setting: Academic medical center. Participants: 27 individuals with T1DM and 12 HC volunteers participated in the study. Intervention: All participants underwent blood oxygenation level dependent (BOLD) resting state functional magnetic brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/ dL)-hypoglycemic (60 mg/dL) clamp. Outcome: Changes in resting state functional connectivity. Results: Using 2 separate methods of functional connectivity analysis, we identified distinct differences in the resting state brain responses to mild hypoglycemia between HC, T1DMAware, and T1DM-Unaware participants, particularly in the angular gyrus, an integral component of the default mode network (DMN). Furthermore, changes in angular gyrus connectivity also correlated with greater symptoms of hypoglycemia (r = 0.461, P = 0.003) as well as higher scores of perceived stress (r = 0.531, P = 0.016). Conclusion: These findings provide evidence that individuals with T1DM have changes in the brain's resting state connectivity patterns, which may be further associated with differences in awareness to hypoglycemia. These changes in connectivity may be associated with alterations in functional outcomes among individuals with T1DM.