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

CONTEXT: Individuals with type 1 diabetes (T1DM) have alterations in brain activity which have been postulated to contribute to the adverse neurocognitive consequences of T1DM; however, the impact of T1DM and hypoglycemic unawareness on the brain's resting state activity remains unclear.

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 healthy control volunteers participated in the study.

INTERVENTION: All participants underwent BOLD resting state fMRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60mg/dl) clamp.

OUTCOME: Changes in resting state functional connectivity.

RESULTS: Using two separate methods of functional connectivity analysis, we identified distinct differences in the resting state brain responses to mild hypoglycemia amongst HC, T1DM-Aware 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 amongst individuals with T1DM.