Differential Resting State Connectivity Responses to Glycemic State in Type 1 Diabetes

Abstract

Context Individuals with type 1 diabetes mellitus (T1DM) have alterations in brain activity that 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 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, 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 among individuals with T1DM.

Altered functional connectivity during hypoglycaemia in type 1 diabetes

“…A recent study has shown important differences in the DMN connectivity response in people with diabetes and normal awareness of hypoglycaemia that is lost in impaired awareness. 34 The DMN has been widely studied and is known to be disrupted in numerous disease states. 35 The impact of awareness status on the effect of hypoglycaemia induction in resting state networks, other than the DMN, has not been explored in previous connectivity studies.…”

“…The study does have some limitations. Previous resting state analyses have had, at most, 12 participants with IAH 34 and this is the largest resting state functional neuroimaging study investigating hypoglycaemia in diabetes of which we are aware. Despite this, we may have lacked power and missed important changes in brain connectivity due to hypoglycaemia.…”

Alterations in intra- and inter-network connectivity associated with cognition impairment in insulinoma patients

“…An analysis by Nicolas et al ( 22) has examined the alterations of RSNs during the induction of hypoglycemia in diabetic and control subjects, and found changes in multiple RSNs, such as DMN, SMN, play an important role in awareness and behavioral response to hypoglycemia. Parikh et al (23) also found the decreased connectivity in angular gyrus within DMN was correlated with greater symptoms of hypoglycemia as well as higher scores of perceived stresses. Alterations in brain network responses to hypoglycemia are increasingly described, and the brain regions and networks that are sensitive to variations in plasma glucose levels have been identified (24).…”

“…Parikh et al. ( 23 ) also found the decreased connectivity in angular gyrus within DMN was correlated with greater symptoms of hypoglycemia as well as higher scores of perceived stresses. Alterations in brain network responses to hypoglycemia are increasingly described, and the brain regions and networks that are sensitive to variations in plasma glucose levels have been identified ( 24 ).…”

Low‐calorie diet‐induced weight loss is associated with altered brain connectivity and food desire in obesity

“…We used the novel fMRI technique, intrinsic connectivity distribution (ICD), to measure synchronous brain activity during a visual task, identifying patterns of correlated neural activity and providing insights into how brain regions interact with each other in response to different conditions [22,23]. ICD uses a whole-brain voxel-wise approach that does not require a prior selection of predefined brain regions (seed-based) [22,24] to determine brain connectivity and can be performed across different types of tasks [23,25]. The absence of seed region selection ensures a data-driven approach, allowing the identification of connectivity patterns that may not have been considered in advance.…”