{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:17:32Z","timestamp":1777526252158,"version":"3.51.4"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]},{"name":"U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["RO1 DK085623"],"award-info":[{"award-number":["RO1 DK085623"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Digit. Med."],"DOI":"10.1038\/s41746-025-01679-y","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T18:40:21Z","timestamp":1746556821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Human-machine co-adaptation to automated insulin delivery: a randomised clinical trial using digital twin technology"],"prefix":"10.1038","volume":"8","author":[{"given":"Boris P.","family":"Kovatchev","sequence":"first","affiliation":[]},{"given":"Patricio","family":"Colmegna","sequence":"additional","affiliation":[]},{"given":"Jacopo","family":"Pavan","sequence":"additional","affiliation":[]},{"given":"Jenny L.","family":"Diaz Casta\u00f1eda","sequence":"additional","affiliation":[]},{"given":"Maria F.","family":"Villa-Tamayo","sequence":"additional","affiliation":[]},{"given":"Chaitanya L. K.","family":"Koravi","sequence":"additional","affiliation":[]},{"given":"Giulio","family":"Santini","sequence":"additional","affiliation":[]},{"given":"Carlene","family":"Alix","sequence":"additional","affiliation":[]},{"given":"Meaghan","family":"Stumpf","sequence":"additional","affiliation":[]},{"given":"Sue A.","family":"Brown","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"1679_CR1","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1056\/NEJMoa1907863","volume":"381","author":"SA Brown","year":"2019","unstructured":"Brown, S. A. et al. For the iDCL Trial Research Group. Six-month randomized multicenter trial of closed-loop control in type 1 diabetes. N. Engl. J. Med. 381, 1707\u20131717 (2019).","journal-title":"N. Engl. J. Med."},{"key":"1679_CR2","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1056\/NEJMoa2004736","volume":"383","author":"MD Breton","year":"2020","unstructured":"Breton, M. D. et al. For the iDCL Trial Research Group. A randomized trial of closed-loop control in children with type 1 diabetes. N. Engl. J. Med. 383, 836\u2013845 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1679_CR3","doi-asserted-by":"crossref","unstructured":"Brown, S. A. et al. For the Omnipod 5 Research Group. Multicenter trial of a tubeless, on-body automated insulin delivery system with customizable glycaemic targets in pediatric and adult participants with type 1 diabetes. Diabetes Care 44, 1630\u20131640 (2021).","DOI":"10.2337\/dc21-0172"},{"key":"1679_CR4","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1056\/NEJMoa2203913","volume":"387","author":"MJ Burnside","year":"2022","unstructured":"Burnside, M. J. et al. Open-source automated insulin delivery in type 1 diabetes. N. Engl. J. Med. 387, 869\u2013881 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1679_CR5","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1056\/NEJMoa2210834","volume":"388","author":"RP Wadwa","year":"2023","unstructured":"Wadwa, R. P. et al. For the PEDAP Trial Study Group. Trial of hybrid closed-loop control in young children with type 1 diabetes. N. Engl. J. Med. 388, 991\u20131001 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1679_CR6","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1056\/NEJMoa2205225","volume":"387","author":"Bionic Pancreas Research Group et al.","year":"2022","unstructured":"Bionic Pancreas Research Group et al. Multicenter, randomized trial of a bionic pancreas in type 1 diabetes. N. Engl. J. Med. 387, 1161\u20131172 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1679_CR7","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1056\/NEJMoa2203496","volume":"387","author":"CK Boughton","year":"2022","unstructured":"Boughton, C. K. et al. For the CLOuD Consortium. Closed-loop therapy and preservation of C-peptide secretion in type 1 diabetes. N. Engl. J. Med. 387, 882\u2013893 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1679_CR8","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1056\/NEJMoa2303911","volume":"389","author":"TTM Lee","year":"2023","unstructured":"Lee, T. T. M. et al. For the AiDAPT Collaborative Group. Automated insulin delivery in women with pregnancy complicated by type 1 diabetes. N. Engl. J. Med. 389, 1566\u20131578 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1679_CR9","doi-asserted-by":"publisher","DOI":"10.1111\/dme.15196","volume":"41","author":"BE Amer","year":"2024","unstructured":"Amer, B. E., Yaqout, Y. E., Abozaid, A. M., Afifi, E. & Aboelkhier, M. M. Does fully closed-loop automated insulin delivery improve glycaemic control in patients with type 2 diabetes? A meta-analysis of randomized controlled trials. Diabet. Med. 41, e15196 (2024).","journal-title":"Diabet. Med."},{"key":"1679_CR10","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1089\/dia.2023.0569","volume":"26","author":"C Bauza","year":"2024","unstructured":"Bauza, C. et al. Use of the community-derived open-source automated insulin delivery loop system in type 2 diabetes. Diabetes Technol. Ther. 26, 494\u2013497 (2024).","journal-title":"Diabetes Technol. Ther"},{"key":"1679_CR11","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1111\/dom.14424","volume":"23","author":"J Da Silva","year":"2021","unstructured":"Da Silva, J. et al. Real-world performance of the MiniMed\u2122 670G system in Europe. Diabetes Obes. Metab. 23, 1942\u20131949 (2021).","journal-title":"Diabetes Obes. Metab"},{"key":"1679_CR12","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1089\/dia.2021.0203","volume":"24","author":"JD Silva","year":"2022","unstructured":"Silva, J. D. et al. Real-world performance of the MiniMed\u2122 780G system: first report of outcomes from 4120 users. Diabetes Technol. Ther. 24, 113\u2013119 (2022).","journal-title":"Diabetes Technol. Ther"},{"key":"1679_CR13","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.2337\/dc22-1217","volume":"45","author":"BP Kovatchev","year":"2022","unstructured":"Kovatchev, B. P., Singh, H., Mueller, L. & Gonder-Frederick, L. A. Biobehavioral changes following transition to automated insulin delivery: a large real-life database analysis. Diabetes Care 45, 2636\u20132643 (2022).","journal-title":"Diabetes Care"},{"key":"1679_CR14","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1089\/dia.2023.0578","volume":"26","author":"GP Forlenza","year":"2024","unstructured":"Forlenza, G. P. et al. Real-world evidence of Omnipod\u00ae 5 automated insulin delivery system use in 69,902 people with type 1 diabetes. Diabetes Technol. Ther.26, 514\u2013525 (2024).","journal-title":"Diabetes Technol. Ther."},{"key":"1679_CR15","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1089\/dia.2023.0414","volume":"26","author":"S Lablanche","year":"2024","unstructured":"Lablanche, S. et al. 12-Month real-life efficacy of the MiniMed 780G advanced closed-loop system in patients living with type 1 diabetes: a French observational, retrospective, multicentric study. Diabetes Technol. Ther. 26, 426\u2013432 (2024).","journal-title":"Diabetes Technol. Ther."},{"key":"1679_CR16","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1089\/dia.2022.0558","volume":"25","author":"RW Beck","year":"2023","unstructured":"Beck, R. W. et al. A meta-analysis of randomized trial outcomes for the t:slim X2 insulin pump with control-iq technology in youth and adults from age 2 to 72. Diabetes Technol. Ther. 25, 329\u2013342 (2023).","journal-title":"Diabetes Technol. Ther"},{"key":"1679_CR17","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.2337\/dc23-0504","volume":"46","author":"B Zeng","year":"2023","unstructured":"Zeng, B., Gao, L., Yang, Q., Jia, H. & Sun, F. Automated insulin delivery systems in children and adolescents with type 1 diabetes: a systematic review and meta-analysis of outpatient randomized controlled trials. Diabetes Care 46, 2300\u20132307 (2023).","journal-title":"Diabetes Care"},{"key":"1679_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-40423-y","volume":"13","author":"M Jabari","year":"2023","unstructured":"Jabari, M. Efficacy and safety of closed-loop control system for type one diabetes in adolescents a meta analysis. Sci. Rep. 13, 13165 (2023).","journal-title":"Sci. Rep."},{"key":"1679_CR19","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s00592-024-02284-3","volume":"61","author":"T Teixeira","year":"2024","unstructured":"Teixeira, T. et al. Efficacy of automated insulin delivery in pregnant women with type 1 diabetes: a meta-analysis and trial sequential analysis of randomized controlled trials. Acta Diabetol. 61, 831\u2013840 (2024).","journal-title":"Acta Diabetol."},{"key":"1679_CR20","doi-asserted-by":"publisher","first-page":"e64","DOI":"10.1016\/S2589-7500(19)30218-3","volume":"2","author":"BP Kovatchev","year":"2020","unstructured":"Kovatchev, B. P. et al. Evening and overnight closed-loop control versus 24\/7 continuous closed-loop control for type 1 diabetes: a randomized crossover trial. Lancet Digit. Health 2, e64\u2013e73 (2020).","journal-title":"Lancet Digit. Health"},{"key":"1679_CR21","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.2337\/dc17-1188","volume":"40","author":"E Dassau","year":"2017","unstructured":"Dassau, E. et al. 12-week 24\/7 ambulatory artificial pancreas with weekly adaptation of insulin delivery settings: effect on hemoglobin A1c and hypoglycemia. Diabetes Care 40, 1719\u20131726 (2017).","journal-title":"Diabetes Care"},{"key":"1679_CR22","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1177\/193229681300700234","volume":"7","author":"RM Bergenstal","year":"2013","unstructured":"Bergenstal, R. M. et al. Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the ambulatory glucose profile. J. Diabetes Sci. Technol. 7, 562\u2013578 (2013).","journal-title":"J. Diabetes Sci. Technol."},{"key":"1679_CR23","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.2337\/db23-1055-P","volume":"72","author":"S Huang","year":"2023","unstructured":"Huang, S., Liang, Y., Li, J. & Li, X. J. Clinical decision support systems (CDSSs) in diabetes management\u2014a scoping review. Diabetes 72, 1055\u2013105 (2023).","journal-title":"Diabetes"},{"key":"1679_CR24","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1096325","volume":"13","author":"DP Zaharieva","year":"2023","unstructured":"Zaharieva, D. P. et al. Adding glycaemic and physical activity metrics to a multimodal algorithm-enabled decision-support tool for type 1 diabetes care: Keys to implementation and opportunities. Front. Endocrinol.13, 1096325 (2023).","journal-title":"Front. Endocrinol."},{"key":"1679_CR25","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1109\/RBME.2023.3331297","volume":"17","author":"PG Jacobs","year":"2024","unstructured":"Jacobs, P. G. et al. Artificial intelligence and machine learning for improving glycaemic control in diabetes: best practices, pitfalls, and opportunities. IEEE Rev. Biomed. Eng. 17, 19\u201341 (2024).","journal-title":"IEEE Rev. Biomed. Eng."},{"issue":"S1","key":"1679_CR26","doi-asserted-by":"publisher","first-page":"S70","DOI":"10.1089\/dia.2023.2505","volume":"25","author":"R Nimri","year":"2023","unstructured":"Nimri, R., Phillip, M. & Kovatchev, B. Closed-loop and artificial intelligence-based decision support systems. Diabetes Technol. Ther. 25(S1), S70\u2013S89 (2023).","journal-title":"Diabetes Technol. Ther"},{"key":"1679_CR27","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/s43588-024-00607-6","volume":"4","author":"R Laubenbacher","year":"2024","unstructured":"Laubenbacher, R., Mehrad, B., Shmulevich, I. & Trayanova, N. Digital twins in medicine. Nat. Comput. Sci. 4, 184\u2013191 (2024).","journal-title":"Nat. Comput. Sci."},{"key":"1679_CR28","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1177\/193229680900300106","volume":"3","author":"BP Kovatchev","year":"2009","unstructured":"Kovatchev, B. P., Breton, M. D., Dalla Man, C. & Cobelli, C. In silico preclinical trials: a proof of concept in closed-loop control of type 1 diabetes. J. Diabetes Sci. Technol. 3, 44\u201355 (2009).","journal-title":"J. Diabetes Sci. Technol."},{"key":"1679_CR29","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1177\/19322968231195081","volume":"17","author":"C Cobelli","year":"2023","unstructured":"Cobelli, C. & Kovatchev, B. Developing the UVA\/Padova type 1 diabetes simulator: modeling, validation, refinements, and utility. J. Diabetes Sci. Technol. 17, 1493\u20131505 (2023).","journal-title":"J. Diabetes Sci. Technol."},{"key":"1679_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2023.107830","volume":"242","author":"CJL Diaz","year":"2023","unstructured":"Diaz, C. J. L., Villa-Tamayo, M. F., Moscoso-Vasquez, M. & Colmegna, P. Simulation-driven optimization of insulin therapy profiles in a commercial hybrid closed-loop system. Comput. Methods Prog. Biomed. 242, 107830 (2023).","journal-title":"Comput. Methods Prog. Biomed"},{"key":"1679_CR31","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1109\/JBHI.2022.3209090","volume":"27","author":"P Colmegna","year":"2023","unstructured":"Colmegna, P. et al. Evaluation of a web-based simulation tool for self-management support in type 1 diabetes: a pilot study. IEEE J. Biomed. Health Inf. 27, 515\u2013525 (2023).","journal-title":"IEEE J. Biomed. Health Inf."},{"key":"1679_CR32","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1089\/dia.2023.0399","volume":"26","author":"P Colmegna","year":"2024","unstructured":"Colmegna, P. et al. Adaptive biobehavioral control: a pilot analysis of human-machine coadaptation in type 1 diabetes. Diabetes Technol. Ther. 26, 644\u2013651 (2024).","journal-title":"Diabetes Technol. Ther"},{"key":"1679_CR33","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1089\/dia.2023.0433","volume":"26","author":"P Choudhary","year":"2024","unstructured":"Choudhary, P. et al. Celebrating the data from 100,000 real-world users of the MiniMed\u2122 780G system in Europe, Middle East, and Africa collected over 3 years: from data to clinical evidence. Diabetes Technol. Ther. 26, 32\u201337 (2024).","journal-title":"Diabetes Technol. Ther"},{"key":"1679_CR34","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1089\/dia.2023.0341","volume":"26","author":"R Graham","year":"2024","unstructured":"Graham, R. et al. Real-world use of control-IQ technology is associated with a lower rate of severe hypoglycemia and diabetic ketoacidosis than historical data: results of the control-IQ observational (CLIO) prospective study. Diabetes Technol. Ther. 26, 24\u201332 (2024).","journal-title":"Diabetes Technol. Ther"},{"key":"1679_CR35","doi-asserted-by":"publisher","DOI":"10.1177\/19322968241262112","volume":"17","author":"G Cappon","year":"2024","unstructured":"Cappon, G. & Facchinetti, A. Digital twins in type 1 diabetes: a systematic review. J. Diabetes Sci. Technol. 17, 19322968241262112 (2024).","journal-title":"J. Diabetes Sci. Technol."}],"container-title":["npj Digital Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41746-025-01679-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-025-01679-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-025-01679-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T18:40:23Z","timestamp":1746556823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41746-025-01679-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1679"],"URL":"https:\/\/doi.org\/10.1038\/s41746-025-01679-y","relation":{},"ISSN":["2398-6352"],"issn-type":[{"value":"2398-6352","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"assertion":[{"value":"1 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"B.P.K. reports research grants handled by the University of Virginia from the National Institutes of Health, Novo Nordisk, Dexcom, and Tandem Diabetes Care. Additionally, B.P.K. has patents with royalties paid to Dexcom and Novo Nordisk, handled by the University of Virginia Licensing and Ventures Group. P.C. is at present an employee of Dexcom, Inc.; the work presented in this article was performed as part of his UVA appointment and is independent of his employment with Dexcom, Inc. J.P. has received research support through his previous institution from Dexcom. J.D.C. is at present an employee of Insulet Corp.; the work presented in this article was performed as part of her UVA appointment and is independent of her employment with Insulet. M.V.T., C.L.K., G.S., C.A. declare no conflicts. M.S. has received support to her institution from Dexcom, Insulet and Tandem Diabetes Care. S.A.B. has received research support through her institution from Dexcom, Insulet, Roche Diagnostics, Tandem Diabetes Care and Tolerion and has participated on a data monitoring board for MannKind.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"253"}}