{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:40:42Z","timestamp":1787856042544,"version":"build-2784847793"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>The physiological basis of the well-described neurocognitive decrements and structural brain changes in type 1 diabetes is unclear. We aimed to assess differences in cerebral blood flow (CBF) and neural activity before, during and after induced hypoglycaemia and hyperglycaemia in adolescents with type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An observational hyperinsulinaemic clamp and functional MRI study was conducted. Parallel study arms assessed participants during three consecutive glycaemic phases: baseline euglycaemia (5.0\u00b10.5 mmol\/l), either hypoglycaemia (2.6\u00b10.5 mmol\/l) or hyperglycaemia (18\u201320 mmol\/l), and euglycaemic recovery (5.0\u00b10.5 mmol\/l). During each glycaemic phase, CBF\/brain perfusion was measured with arterial spin labelling and brain neural activity was measured with fractional amplitude of low frequency fluctuations. Comparative analyses were based on the seven regional functional parcellation areas (networks) of the cerebral cortex. A Bayesian multi-level regression model was employed to test regional differences in CBF and brain neural activity between the various glycaemic conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty adolescents with type 1 diabetes participated: ten in each of the hypoglycaemic and hyperglycaemic study arms. Relative to baseline, acute hypoglycaemia was associated with substantially reduced brain neural activity (six of seven functional networks); no significant differences in CBF were evident. By contrast, acute hyperglycaemia was associated with widespread increases in brain activity (five of seven functional networks) and decreased perfusion (six of seven functional networks). Hypoglycaemia and hyperglycaemia had symmetrically opposite effects on brain neural activity in the visual, ventral attention, dorsal attention, frontoparietal and default networks. Recovery from both hypoglycaemia and hyperglycaemia was associated with persistent alterations in both brain perfusion and neural activity, relative to baseline, despite &gt;45 min of sustained euglycaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Across widespread areas of the brain, both brain perfusion and neural metabolic activity are altered by acute hypoglycaemia and hyperglycaemia in adolescents with type 1 diabetes. Recovery from glycaemic extremes is delayed. These findings offer important further insights into the acute cerebral responses to abnormal blood glucose levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-025-06548-7","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T22:03:34Z","timestamp":1759874614000},"page":"2670-2681","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Acute brain responses to hypoglycaemia and hyperglycaemia in adolescents with type 1 diabetes"],"prefix":"10.1007","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4003-956X","authenticated-orcid":false,"given":"Michele A.","family":"O\u2019Connell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Beare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Messazos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth A.","family":"Northam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles","family":"Clarkson Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc L.","family":"Seal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fergus J.","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"issue":"1","key":"6548_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/jc.2011-1927","volume":"97","author":"RJ McCrimmon","year":"2012","unstructured":"McCrimmon RJ (2012) Update in the CNS response to hypoglycemia. 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We also acknowledge T. Jones and N. Paramalingam (Telethon Kids Institute, Perth, Western Australia) for their assistance and shared expertise in the conduct of hyperinsulinaemic clamp studies, as well as the technical assistance of M. Kean and the research MRI and neurodevelopmental imaging teams at Murdoch Children\u2019s Research Institute Melbourne.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Datasets generated from this study are available from the corresponding author on reasonable request.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Open Access funding enabled and organized by CAUL and its Member Institutions. This work was supported by a pilot and feasibility grant awarded by a network of collaborating clinical research organisations involved in T1D research (\u2018the T1DCRN\u2019) that has sites across Australia funded by Breakthrough T1D and the Commonwealth of Australia through the Australian Research Council\u2019s (\u2018ARC\u2019) Special Research Initiative for Type 1 Juvenile Diabetes. The research was also supported by a Pfizer Australia Australasian Paediatric Endocrine Care (APEC) grant. This work was investigator-initiated and led. Funding sources had no role in study design or conduct, nor in the writing of this report.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"EAN and FJC were responsible for the study concept. MAOC, EAN, MLS, RB and FJC contributed to the experimental protocol and study design. MAOC, BM, EAN, MCF and FJC were responsible for participant recruitment and the conduct of the study. BM, EAN, MCF, RB and MLS collected and assembled data for analyses. RB and MLS designed the fMRI paradigm and analysed the fMRI data. MAOC drafted the manuscript, and all authors reviewed, edited and approved the final version of the manuscript.\u00a0MAOC, RB and MLS are the guarantors of this work and, as such, have had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of data analysis.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}