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

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.

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Publication Details

Journal
Journal of Clinical Investigation
Published
2026-04-14
DOI
https://doi.org/10.1172/jci205273
Primary Topic
Diabetes Management and Research
Type
article
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article

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

Fernando Zelaya, Stephanie A Amiel
Journal of Clinical Investigation
Diabetes Management and Research
article

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

Fernando Zelaya, Stephanie A Amiel
article en

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.

Journal of Clinical InvestigationVol. 136(8)
King's College London (GB), King's College Hospital NHS Foundation Trust (GB), Diabetes UK (GB)
Openalex Percentile: Top 12%
Diabetes Management and Research
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Unconscious uncoupling: dysfunctional neurovascular responses to low glucose in type 1 diabetes and impaired hypoglycemia awareness — Fernando Zelaya, Stephanie A Amiel · Journal of Clinical Investigation (2026) | TGRS Research Map | TGRS