Munachiso Nwokolo1,2, Stephanie A Amiel3,2, Owen O'Daly4, Megan L Byrne3, Bula M Wilson3, Andrew Pernet3, Sally M Cordon5, Ian A Macdonald5, Fernando O Zelaya4, Pratik Choudhary3,2. 1. Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K. munachiso.nwokolo@kcl.ac.uk. 2. King's College Hospital NHS Foundation Trust, London, U.K. 3. Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K. 4. Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, U.K. 5. School of Life Sciences, MRC Arthritis Research UK Centre of Excellence in Musculoskeletal Ageing, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, U.K.
Abstract
OBJECTIVE: Impaired awareness of hypoglycemia (IAH) affects one-quarter of adults with type 1 diabetes and significantly increases the risk of severe hypoglycemia. Differences in regional brain responses to hypoglycemia may contribute to the susceptibility of this group to problematic hypoglycemia. This study investigated brain responses to hypoglycemia in hypoglycemia aware (HA) and IAH adults with type 1 diabetes, using three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) functional MRI to measure changes in regional cerebral blood flow (CBF). RESEARCH DESIGN AND METHODS: Fifteen HA and 19 IAH individuals underwent 3D pCASL functional MRI during a two-step hyperinsulinemic glucose clamp. Symptom, hormone, global, and regional CBF responses to hypoglycemia (47 mg/dL [2.6 mmol/L]) were measured. RESULTS: In response to hypoglycemia, total symptom score did not change in those with IAH (P = 0.25) but rose in HA participants (P < 0.001). Epinephrine, cortisol, and growth hormone responses to hypoglycemia were lower in the IAH group (P < 0.05). Hypoglycemia induced a rise in global CBF (HA P = 0.01, IAH P = 0.04) but was not different between groups (P = 0.99). IAH participants showed reduced regional CBF responses within the thalamus (P = 0.002), right lateral orbitofrontal cortex (OFC) (P = 0.002), and right dorsolateral prefrontal cortex (P = 0.036) and a lesser decrease of CBF in the left hippocampus (P = 0.023) compared with the HA group. Thalamic and right lateral OFC differences survived Bonferroni correction. CONCLUSIONS: Responses to hypoglycemia of brain regions involved in arousal, decision making, and reward are altered in IAH. Changes in these pathways may disrupt IAH individuals' ability to recognize hypoglycemia, impairing their capacity to manage hypoglycemia effectively and benefit fully from conventional therapeutic pathways to restore awareness.
OBJECTIVE: Impaired awareness of hypoglycemia (IAH) affects one-quarter of adults with type 1 diabetes and significantly increases the risk of severe hypoglycemia. Differences in regional brain responses to hypoglycemia may contribute to the susceptibility of this group to problematic hypoglycemia. This study investigated brain responses to hypoglycemia in hypoglycemia aware (HA) and IAH adults with type 1 diabetes, using three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) functional MRI to measure changes in regional cerebral blood flow (CBF). RESEARCH DESIGN AND METHODS: Fifteen HA and 19 IAH individuals underwent 3D pCASL functional MRI during a two-step hyperinsulinemic glucose clamp. Symptom, hormone, global, and regional CBF responses to hypoglycemia (47 mg/dL [2.6 mmol/L]) were measured. RESULTS: In response to hypoglycemia, total symptom score did not change in those with IAH (P = 0.25) but rose in HA participants (P < 0.001). Epinephrine, cortisol, and growth hormone responses to hypoglycemia were lower in the IAH group (P < 0.05). Hypoglycemia induced a rise in global CBF (HA P = 0.01, IAH P = 0.04) but was not different between groups (P = 0.99). IAHparticipants showed reduced regional CBF responses within the thalamus (P = 0.002), right lateral orbitofrontal cortex (OFC) (P = 0.002), and right dorsolateral prefrontal cortex (P = 0.036) and a lesser decrease of CBF in the left hippocampus (P = 0.023) compared with the HA group. Thalamic and right lateral OFC differences survived Bonferroni correction. CONCLUSIONS: Responses to hypoglycemia of brain regions involved in arousal, decision making, and reward are altered in IAH. Changes in these pathways may disrupt IAH individuals' ability to recognize hypoglycemia, impairing their capacity to manage hypoglycemia effectively and benefit fully from conventional therapeutic pathways to restore awareness.
Authors: Peter Jacob; Munachiso Nwokolo; Sally M Cordon; Ian A Macdonald; Fernando O Zelaya; Stephanie A Amiel; Owen O'Daly; Pratik Choudhary Journal: J Cereb Blood Flow Metab Date: 2022-02-25 Impact factor: 6.960
Authors: Ruth McManus; Seva Ioussoufovitch; Elizabeth Froats; Keith St Lawrence; Stan Van Uum; Mamadou Diop Journal: Sci Rep Date: 2020-12-04 Impact factor: 4.379
Authors: Ioannis Bakolis; Nicole de Zoysa; Stephanie A Amiel; Laura Potts; Kimberley Goldsmith; Peter Jacob; Emma L Smith; Linda Gonder-Frederick; Simon Heller; Elena Toschi; Augustin Brooks; Dulmini Kariyawasam; Pratik Choudhary; Marietta Stadler; Helen Rogers; Mike Kendall; Nick Sevdalis Journal: Nat Commun Date: 2022-04-28 Impact factor: 17.694
Authors: Yu Kuei Lin; Danielle Groat; Owen Chan; Man Hung; Anu Sharma; Michael W Varner; Ramkiran Gouripeddi; Julio C Facelli; Simon J Fisher Journal: Diabetes Technol Ther Date: 2020-10-13 Impact factor: 6.118
Authors: Evita C Wiegers; Bastiaan E de Galan; Lian A van Meijel; Jack J A van Asten; Joanes Grandjean; Arend Heerschap; Cornelis J Tack; Marinette van der Graaf Journal: BMJ Open Diabetes Res Care Date: 2022-03