{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:23:41Z","timestamp":1777350221645,"version":"3.51.4"},"reference-count":41,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["13\/0004653"],"award-info":[{"award-number":["13\/0004653"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004374","name":"Medtronic","doi-asserted-by":"publisher","award":["A 2265657"],"award-info":[{"award-number":["A 2265657"]}],"id":[{"id":"10.13039\/100004374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D) is a major risk factor for severe hypoglycemia (SH) and is associated with atypical responses to hypoglycemia in brain regions involved in arousal, decision making, and memory. Whether restoration of hypoglycemia awareness alters these responses is unknown. We sought to investigate the impact of awareness restoration on brain responses to hypoglycemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Twelve adults with T1D and IAH underwent pseudocontinuous arterial spin labeling functional MRI during a hypoglycemic clamp (5\u20132.6 mmol\/L) before and after a hypoglycemia avoidance program of structured education (Dose Adjustment for Normal Eating), specialist support, and sensor-augmented pump therapy (Medtronic MiniMed 640G). Hypoglycemic cerebral blood flow (CBF) responses were compared pre- and postintervention using predefined region-of-interest analysis of the thalamus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and hippocampus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Postintervention, Gold and Clarke scores fell (6.0 \u00b1 1.0 to 4.0 \u00b1 1.6, P = 0.0002, and 5.7 \u00b1 1.7 to 3.4 \u00b1 1.8, P = 0.0008, respectively), SH rates reduced (1.5 \u00b1 2 to 0.3 \u00b1 0.5 episodes per year, P = 0.03), hypoglycemic symptom scores increased (18.8 \u00b1 6.3 to 27.3 \u00b1 12.7, P = 0.02), and epinephrine responses did not change (P = 0.2). Postintervention, hypoglycemia induced greater increases in ACC CBF (P = 0.01, peak voxel coordinates [6, 40, \u22122]), while thalamic and OFC activity did not change.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Increased blood flow is seen within brain pathways involved in internal self-awareness and decision making (ACC) after restoration of hypoglycemia awareness, suggesting partial recovery of brain responses lost in IAH. Resistance of frontothalamic networks, involved in arousal and emotion processing, may explain why not all individuals with IAH achieve awareness restoration with education and technology alone.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc20-1250","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T22:16:11Z","timestamp":1608156971000},"page":"533-540","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":13,"title":["Restoration of Hypoglycemia Awareness Alters Brain Activity in Type 1 Diabetes"],"prefix":"10.2337","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7200-6004","authenticated-orcid":false,"given":"Munachiso","family":"Nwokolo","sequence":"first","affiliation":[{"name":"Department of Diabetes, School of Life Course Sciences, King\u2019s College London, London, U.K."},{"name":"King\u2019s College Hospital NHS Foundation Trust, London, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2686-5531","authenticated-orcid":false,"given":"Stephanie A.","family":"Amiel","sequence":"additional","affiliation":[{"name":"Department of Diabetes, School of Life Course Sciences, King\u2019s College London, London, U.K."},{"name":"King\u2019s College Hospital NHS Foundation Trust, London, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen","family":"O\u2019Daly","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian A.","family":"Macdonald","sequence":"additional","affiliation":[{"name":"School of Life Sciences, MRC-Arthritis Research UK Centre of Excellence in Musculoskeletal Ageing, Nottingham University Medical School, Queen\u2019s Medical Centre, Nottingham, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando O.","family":"Zelaya","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pratik","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Department of Diabetes, School of Life Course Sciences, King\u2019s College London, London, U.K."},{"name":"King\u2019s College Hospital NHS Foundation Trust, London, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"2022031300253550800_B1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.2337\/diacare.17.7.697","article-title":"Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia","volume":"17","author":"Gold","year":"1994","journal-title":"Diabetes Care"},{"key":"2022031300253550800_B2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/j.1464-5491.2010.03006.x","article-title":"Frequency of biochemical hypoglycaemia in adults with type 1 diabetes with and without impaired awareness of hypoglycaemia: no identifiable differences using continuous glucose monitoring","volume":"27","author":"Choudhary","year":"2010","journal-title":"Diabet Med"},{"key":"2022031300253550800_B3","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1172\/JCI116302","article-title":"Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. 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