Unconscious uncoupling: dysfunctional neurovascular responses to low glucose in type 1 diabetes and impaired hypoglycemia awareness
Stephanie A Amiel, Fernando O Zelaya
Stephanie A Amiel, Fernando O Zelaya
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Commentary

Unconscious uncoupling: dysfunctional neurovascular responses to low glucose in type 1 diabetes and impaired hypoglycemia awareness

Abstract

Approximately 25% of individuals with type 1 diabetes (T1D) experience impaired awareness of hypoglycemia (IAH), a weakening of symptomatic neurohumoral responses to falling glucose levels that sharply increases risk of severe hypoglycemia. A recent study by Filip et al. used MRI-based arterial spin labeling to compare regional cerebral blood flow (CBF) responses to experimental hypoglycemia across 3 groups: individuals without T1D and individuals with T1D, with or without IAH. All groups showed a CBF response to hypoglycemia in brain regions involved in learning and interoception, among others, but the responses were qualitatively different between groups and blunted in the presence of IAH. The association between the regional CBF and the hormonal responses to hypoglycemia was inverted in IAH, compared with that in individuals with preserved awareness. The findings add to work linking changes in cognitive processing to IAH development and its persistence in some individuals.

Authors

Stephanie A Amiel, Fernando O Zelaya

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Figure 1

Altered CBF responses associated with IAH may underlie ineffective counterregulatory responses to falling blood glucose levels.

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Altered CBF responses associated with IAH may underlie ineffective count...
In most individuals, hypoglycemia evokes protective responses that involve activation of and enhanced CBF to brain regions involved in decision making, interoception, and detection of salience. These brain regions coordinate counterregulatory responses to falling glucose levels that mobilize glucose stores and elicit food-seeking behavior to avoid progression to severe hypoglycemia. However, a subset of individuals with T1D experience IAH accompanied by failure to mount a counterregulatory response, raising their risk of life-threatening severe hypoglycemia. Using MRI imaging of CBF combined with experimental hypoglycemia, Filip et al. (6) observed alterations in CBF and hormonal responses to hypoglycemia in individuals with T1D and IAH that may represent progressive neurovascular dysfunction. The findings raise the question of whether intrinsic differences in neurovascular responsiveness may predispose some individuals with T1D to develop IAH despite adequate control of blood glucose.