Aim: The brain senses hypoglycemia and governs symptomatic, hormonal and behavioral responses to it. This study aimed to understand the differences in regional brain responses to experimental hypoglycemia between adults with type 1 diabetes (T1D) with intact hypoglycemia awareness [HA] and impaired awareness of hypoglycemia [IAH] and evaluate the impact of intensive hypoglycemia avoidance on these responses.

Methods: We performed ASL fMRI scans to measure global and regional cerebral blood flow [CBF and rCBF] and measured symptomatic and hormonal responses to experimental hypoglycemia [47 mg/dl] in 15 HA T1D subjects and 22 subjects with IAH matched for age, HbA1c and duration of diabetes. Those with IAH underwent a hypoglycemia avoidance program including education, frequent contact and additional technology where required, including sensor augmented pump therapy with predictive low glucose suspend before being restudied with ASL FMRI at hypoglycemia.

Results: Baseline scans: Global CBF increased in response to hypoglycemia in HA and IAH [HA 6.3% p=0.01; IAH 8.0%, p=0.03; HA vs. IAH p=NS]. There was greater increase in rCBF in thalamus, prefrontal cortex and orbitofrontal cortex in HA vs. IAH and greater reduction in rCBF in the hippocampus. Repeat scans: The hypoglycemia avoidance program improved subjective awareness [Gold score 6 ±1 vs. 4.2±1.9; p = 0.001] in the 12 completers. Compared to baseline scans, there was a trend to greater increase in rCBF in the anterior cingulate cortex in response to hypoglycemia [p=0.058], but no changes in the thalamus, prefrontal or orbitofrontal cortices.

Conclusion: Intensive education and support can improve hypoglycemia awareness with some restoration of activation in the anterior cingulate cortex, but frontal changes are not restored suggesting cognitive responses to hypoglycemia may not be changed by these interventions.


P. Choudhary: Speaker's Bureau; Self; Medtronic MiniMed, Inc., Novo Nordisk Inc.. Advisory Panel; Self; Becton, Dickinson and Company, Sanofi-Aventis, Roche Diabetes Care Health and Digital Solutions, Lilly. M. Nwokolo: None. O. O'Daly: None. S.A. Amiel: Advisory Panel; Self; Medtronic MiniMed, Inc., Novo Nordisk A/S, Roche Diabetes Care Health and Digital Solutions. F.O. Zelaya: None.

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