Understanding brain responses to hypoglycaemia in type 1 diabetes and impaired awareness of hypoglycaemia and their susceptibility to hypoglycaemia awareness restoration
: studies in functional magnetic resonance imaging

Student thesis: Doctoral ThesisDoctor of Philosophy


Hypoglycaemia-induced changes in cerebral blood flow (CBF) within cortical and subcortical brain regions are implicated in the aetiology of impaired awareness of hypoglycaemia in type 1 diabetes, a major risk factor for severe hypoglycaemia. This thesis characterises the brain responses to hypoglycaemia in adults without diabetes, adults with type 1 diabetes and intact hypoglycaemia awareness and adults with type 1 diabetes and impaired awareness of hypoglycaemia (IAH). The cerebral impact of hypoglycaemia awareness restoration, a previously unexplored area, is examined. This work furthers the understanding of the mechanisms behind IAH and provides evidence for potential therapeutic strategies to treat IAH.
Brain responses to hypoglycaemia were examined in fifteen non-diabetic healthy controls (HC), fifteen adults with type 1 diabetes and preserved hypoglycaemia awareness (HA) and nineteen adults with type 1 diabetes and IAH using pseudo-continuous arterial spin labelling functional neuroimaging. Twelve IAH participants underwent a repeat scan after eight months of an intervention designed to avoid hypoglycaemia and reduce risk of severe hypoglycaemia.
Hypoglycaemia induced changes in the thalamus, prefrontal cortex, temporal cortex and hippocampus of HC and HA. HA participants had comparable symptom and thalamofrontal responses to hypoglycaemia to their HC counterparts, despite a significantly reduced adrenaline response. IAH had significantly attenuated thalamic and frontal responses to hypoglycaemia when compared to HA. Restoration of subjective hypoglycaemia awareness was associated with increased cerebral blood flow to the anterior cingulate cortex (ACC), but thalamofrontal responses to hypoglycaemia remained unchanged.
Results indicate that the thalamus, prefrontal cortex and hippocampus, regions involved in arousal, executive function and memory, contribute to the cerebral response to hypoglycaemia. This is the first study to show increases of cerebral blood flow within a region involved in internal self-awareness and complex decision-making (ACC) after restoration of subjective hypoglycaemia awareness, suggesting partial recovery of the brain responses lost in IAH. Thalamofrontal resistance may imply that current methods of awareness restoration require a more cognitive and behavioural focus, or that some with IAH are predisposed to developing the condition due to inherent cerebral responses to stress. Based on these data, I hypothesise that IAH is a syndrome of symptom and counterregulatory hormone loss, thalamocortical dysfunction and maladaptive behaviour; assessing and addressing each factor may be a more successful therapeutic strategy than current methods comprising of education and technology alone.
Date of Award1 Dec 2020
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorPratik Choudhary (Supervisor) & Fernando Zelaya (Supervisor)

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