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Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Eighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic\u2013euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>While glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (<jats:italic>p<\/jats:italic>&lt;0.001). Metabolomics revealed an increase in the most common NEFAs (<jats:italic>p<\/jats:italic>&lt;0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>In conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov NCT05095259<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-024-06116-5","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T15:04:08Z","timestamp":1709305448000},"page":"1095-1106","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Metabolic effect of adrenaline infusion in people with type 1 diabetes and healthy individuals"],"prefix":"10.1007","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-6419","authenticated-orcid":false,"given":"Rui","family":"She","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2583-4912","authenticated-orcid":false,"given":"Tommi","family":"Suvitaival","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-9720","authenticated-orcid":false,"given":"Henrik U.","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-5919","authenticated-orcid":false,"given":"Eva","family":"Hommel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1620-8271","authenticated-orcid":false,"given":"Kirsten","family":"N\u00f8rgaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-3408","authenticated-orcid":false,"given":"J\u00f8rgen F. 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The authors thank Ismo Mattila from Steno Diabetes Center Copenhagen (Herlev, Denmark) and Betina Bolgren and Johan Onslev from the Department of Nutrition, Exercise and Sports, University of Copenhagen (Copenhagen, Denmark) for insightful discussions on the data and their technical assistance. Some of the data were presented as an abstract at the EASD meeting in 2023.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"All data supporting the findings of this study are available within the paper and . Additional datasets are available from the corresponding author upon reasonable request.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This study was funded by the Novo Nordisk Foundation (grant number NNF17OC0028358) and the Research Foundation at Nordsj\u00e6llands Hospital. The funding bodies were not involved in the design of the study, collection, analysis or interpretation of data, or writing the report, and did not impose any restrictions regarding publication of the report.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"KN serves as a consultant for Medtronic, Abbott, Convatec and Novo Nordisk, owns stocks in Novo Nordisk, has received research funding from Novo Nordisk, Zealand Pharma, Dexcom and Medtronic, and has received speaking fees from Medtronic, Novo Nordisk and Dexcom. JFPW has current collaborations with Novo Nordisk and Pfizer, unrelated to the present study. HUA owns stocks in Novo Nordisk, has served as an advisor to Novo Nordisk, Abbott and Astra Zeneca, and has received a lecture fee from Nordic Infucare. UP-B is a member of the editorial board of <i>Diabetologia<\/i>, has served as an advisor to Novo Nordisk, Sanofi and Vertex, and has received lecture fees from Abbott, Novo Nordisk and Sanofi. RS, TS, EH and CL-Q 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":"UP-B and RS contributed to the conceptualisation of the aims of this study. UP-B, RS and JFPW contributed to development of the methodological design. RS, UP-B, KN, HUA and EH contributed to recruitment of participants and execution of the study. RS, TS, UP-B and CL-Q contributed to the data analysis. RS wrote the first draft of the manuscript. UP-B, KN, CL-Q, TS, JFPW, HUA and EH contributed to review and editing of the manuscript. All authors reviewed the results and approved the final version of the manuscript. UP-B is the guarantor of this work, had full access to all the data in the study, and takes responsibility for the integrity and accuracy of the data and data analysis.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}