{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:13:12Z","timestamp":1784887992409,"version":"3.55.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["2018PG-TID06"],"award-info":[{"award-number":["2018PG-TID06"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","award":["P30DK036836"],"award-info":[{"award-number":["P30DK036836"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Diabetes Sci Technol"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>An increasing number of individuals with type 1 diabetes (T1D) manage glycemia with insulin pumps containing short-acting insulin. If insulin delivery is interrupted for even a few hours due to pump or infusion site malfunction, the resulting insulin deficiency can rapidly initiate ketogenesis and diabetic ketoacidosis (DKA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>To detect an event of accidental cessation of insulin delivery, we propose the design of ketone-based alert system (K-AS). This system relies on an extended Kalman filter based on plasma 3-beta-hydroxybutyrate (BOHB) measurements to estimate the disturbance acting on the insulin infusion\/injection input. The alert system is based on a novel physiological model capable of simulating the ketone body turnover in response to a change in plasma insulin levels. Simulated plasma BOHB levels were compared with plasma BOHB levels available in the literature. We evaluated the performance of the K-AS on 10 in silico subjects using the S2014 UVA\/Padova simulator for two different scenarios.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The K-AS achieves an average detection time of 84 and 55.5 minutes in fasting and postprandial conditions, respectively, which compares favorably and improves against a detection time of 193 and 120 minutes, respectively, based on the current guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The K-AS leverages the rapid rate of increase of plasma BOHB to achieve short detection time in order to prevent BOHB levels from rising to dangerous levels, without any false-positive alarms. Moreover, the proposed novel insulin-BOHB model will allow us to understand the efficacy of treatment without compromising patient safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19322968231209339","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T01:15:36Z","timestamp":1699578936000},"page":"683-691","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Ketone-Based Alert System for Insulin Pump Failures"],"prefix":"10.1177","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5129-8829","authenticated-orcid":false,"given":"Eleonora M.","family":"Aiello","sequence":"first","affiliation":[{"name":"Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, MA, USA"},{"name":"Sansum Diabetes Research Institute, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9675-3001","authenticated-orcid":false,"given":"Lori M.","family":"Laffel","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Elizabeth","family":"Patti","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3293-9114","authenticated-orcid":false,"suffix":"III","given":"Francis J.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, MA, USA"},{"name":"Sansum Diabetes Research Institute, Santa Barbara, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobme.2021.100312"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1379"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-7560(199911\/12)15:6<412::AID-DMRR72>3.0.CO;2-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10201."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122093"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296817700545."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1549-7."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681000400429."},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2011.0259."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0078."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.11708."},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.5.817"},{"issue":"1","key":"e_1_3_3_14_2","article-title":"Model of the kinetics of ketone bodies in humans","volume":"243","author":"Cobelli C","year":"1982","unstructured":"Cobelli C, Nosadini R, Toffolo G, et al. Model of the kinetics of ketone bodies in humans. Am J Physiol. 1982;243(1):R7-R17.","journal-title":"Am J Physiol"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37836-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296819882058"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/19322968211042656"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296819881452."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681200600518."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2012.2227256."},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3182\/20140824-6-za-1003.02733."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1109\/TIE.2015.2417501."},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1109\/MED.2006.328697."},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1109\/PAHCE.2009.5158384."},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.29.11.926"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2006.8.67"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296813514502"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2017.2784101"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ces.2022.118321."},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.automatica.2016.12.024"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/19322968211008185"},{"issue":"8","key":"e_1_3_3_32_2","first-page":"2673","article-title":"Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients","volume":"84","author":"Guerci B","year":"1999","unstructured":"Guerci B, Meyer L, Sall\u00e9 A, et al. Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients. J Clin Endocrinol Metab. 1999;84(8):2673-2678.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_33_2","article-title":"6. Glycemic targets: standards of medical care in diabetes","volume":"42","author":"American Diabetes Association Professional Practice Committee","year":"2022","unstructured":"American Diabetes Association Professional Practice Committee. 6. Glycemic targets: standards of medical care in diabetes. Diabetes Care. 2022;42:S61-S70.","journal-title":"Diabetes Care"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.2337\/dci19-0028"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-2482."},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-1608"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ifacol.2017.08.271."},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296817750404."},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1109\/acc.2011.5990951."},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296816663962."},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2021.0542."},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ifacol.2020.12.279"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1109\/MCS.2017.2766322."}],"container-title":["Journal of Diabetes Science and Technology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19322968231209339","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/19322968231209339","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19322968231209339","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:16:42Z","timestamp":1777400202000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/19322968231209339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,9]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1177\/19322968231209339"],"URL":"https:\/\/doi.org\/10.1177\/19322968231209339","relation":{},"ISSN":["1932-2968","1932-2968"],"issn-type":[{"value":"1932-2968","type":"print"},{"value":"1932-2968","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,9]]}}}