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Our hypothesis was that premeal insulin administration would lead to greater myocardial microvascular blood flow (MBF) via blunting postprandial hyperglycaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      People with type 1 diabetes between 18 and 35 years of age with BMI &lt;30 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      underwent two protocols with a 1:1 randomised crossover design wherein prandial insulin was injected either 15 min before or 15 min after meal intake began. To provide a physiological comparison, age-, sex- and BMI-matched control participants completed one study where they consumed the same meal but received no exogenous insulin. Glucose, insulin, vascular function (including ultrasound measures of myocardial and skeletal muscle microvascular perfusion, aortic stiffness, brachial artery endothelial function) and biomarkers of systemic inflammation and endothelial dysfunction were assessed at baseline and then 2 h after meal ingestion within each protocol. The primary outcome was change in myocardial MBF within each protocol. Study personnel assessing outcomes were masked to group assignment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eighteen people with type 1 diabetes and 18 matched control participants were analysed within each protocol. Glucose area under the curve was significantly greater (\n                      <jats:italic>p<\/jats:italic>\n                      =0.015) in the postmeal insulin study compared with the premeal insulin study in participants with type 1 diabetes. Myocardial microvascular flow velocity significantly increased (\n                      <jats:italic>p<\/jats:italic>\n                      =0.031) with premeal insulin administration in people with type 1 diabetes and this consequently led to greater myocardial MBF (\n                      <jats:italic>p<\/jats:italic>\n                      =0.044). There were no changes in myocardial MBF within the other protocols. Changes in vital signs were similar between all protocols.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Appropriately timed premeal insulin led to lower postprandial blood glucose along with increased myocardial MBF in people with type 1 diabetes. Further work is needed to determine the underlying aetiology of these changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT04730882<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06806-2","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:50:47Z","timestamp":1783723847000},"page":"2882-2896","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Premeal insulin administration lowers postprandial blood glucose and increases myocardial microvascular blood flow in people with type 1 diabetes: a randomised, crossover clinical trial"],"prefix":"10.1007","volume":"69","author":[{"given":"William B.","family":"Horton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara C.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin M.","family":"Love","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda A.","family":"Jahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee M.","family":"Hartline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Patrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Solga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelmina J.","family":"Awan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Thakur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana L.","family":"Schalk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason G.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E.","family":"Kuzas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Aylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene J.","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"issue":"25","key":"6806_CR1","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.1056\/NEJMoa052187","volume":"353","author":"DM Nathan","year":"2005","unstructured":"Nathan DM, Cleary PA, Backlund JY et al (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. 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Liu (University of Virginia School of Medicine) for helpful discussions during the development of the study. The authors also thank J. Bourque (University of Virginia School of Medicine) for guidance on presentation of myocardial microvascular blood flow data. This work used assay services in the Center for Human Therapeutics cGMP Core Facility (RRID: SCR_025475; which is supported by the University of Virginia School of Medicine) and the Flow Cytometry Core Facility (RRID: SCR_017829; which is supported by the University of Virginia School of Medicine and partially supported by the NCI grant P30-CA044579).","order":1,"name":"Ethics","label":"Acknowledgements","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The datasets generated and analysed during the current study are stored in a password-protected electronic database. Access to these datasets is available immediately from the corresponding author upon reasonable request. Access will include a unique password that provides user access to the datasets. Those seeking access will be granted a 30 day period wherein they may analyse primary and secondary outcome data.","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"WBH was supported by a career development award from the American Heart Association (grant number: 941481) and a strategic research agreement with Breakthrough T1D (3-SRA-2023-1236-M-B). The study sponsors\/funders were not involved in the design of the study; the collection, analysis and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.","order":3,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}},{"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","label":"Authors\u2019 relationships and activities","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"WBH designed the study, collected\/analysed data, wrote the first draft of the manuscript and reviewed\/edited the manuscript in its entirety. KCA, KML, LAJ, LMH, JL, MDS, WJA, AT, DLS, MGB, CEK and KWA collected\/analysed data and reviewed\/edited the manuscript. JTP analysed all data and reviewed\/edited the manuscript. EJB contributed to study design and reviewed\/edited the manuscript. All authors approved the final version of the manuscript. EJB is the guarantor of the work and, as such, had full access to all data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis.","order":5,"name":"Ethics","label":"Contribution statement","group":{"name":"EthicsHeading","label":"Ethics"}}]}}