{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:52:46Z","timestamp":1777557166724,"version":"3.51.4"},"reference-count":52,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["R01DK114504"],"award-info":[{"award-number":["R01DK114504"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["R01MD015974"],"award-info":[{"award-number":["R01MD015974"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Istituto di Ricerca Pediatrica","award":["Starting Grant 2020, Padova"],"award-info":[{"award-number":["Starting Grant 2020, Padova"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Diabetes Sci Technol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Lactate is not considered just a \u201cwaste product\u201d of anaerobic glycolysis anymore. It has been proved to play a key role in several metabolic diseases, such as in the metabolic dysfunction\u2013associated steatotic liver disease, obesity, and diabetes. The capability of simulating glucose-insulin-lactate interaction would be useful to design and test drugs targeting lactate metabolism in such pathological conditions. Minimal models are available, which describe and quantify glucose-lactate interaction but models to simulate postprandial glucose-insulin-C-peptide-lactate time courses are missing. The aim of this study is to fill this gap.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Starting from the Padova Type 2 Diabetes Simulator (T2DS), we first added a description of glucose-lactate kinetics and then created a population of 100 in silico subjects to match glucose-insulin-C-peptide-lactate data of 44 adolescents with\/without obesity who underwent a standard oral glucose tolerance test (OGTT) of 75 g.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The developed model accurately predicts all molecules time courses, guaranteeing precise model parameter estimates (percent coefficient of variation [CV%] median [25th-75th percentile] = 19 [9-29]%). The generated in silico population shows good agreement with the clinical data in terms of area under the curve (AUC) (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .6, .6, .9, .6 for glucose, insulin, C-peptide, and lactate, respectively) and parameter distributions (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &gt; .1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We have developed a simulator to describe glucose, insulin, C-peptide, and lactate kinetics during an OGTT, which captures the behavior of a real population of adolescents with\/without obesity both in terms of average and intersubject variability. Such simulator can be used to investigate the pharmacodynamics of drugs targeting lactate metabolic pathway in various pathological conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19322968241266825","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T04:38:18Z","timestamp":1722314298000},"page":"143-152","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Modeling Glucose, Insulin, C-Peptide, and Lactate Interplay in Adolescents During an Oral Glucose Tolerance Test"],"prefix":"10.1177","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4097-7943","authenticated-orcid":false,"given":"Jacopo","family":"Bonet","sequence":"first","affiliation":[{"name":"Department of Information Engineering, University of Padua, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9503-4147","authenticated-orcid":false,"given":"Emiliano","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Section of Pediatrics, Department of Translational Sciences, University of Naples Federico II, Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-4173","authenticated-orcid":false,"given":"Nicola","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Department of Medicine and Health Sciences, \u201cV. Tiberio\u201d University of Molise, Campobasso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-0596","authenticated-orcid":false,"given":"Chiara","family":"Dalla Man","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, University of Padua, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2016-0438"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10040762"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23621"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1587"},{"key":"e_1_3_2_6_2","first-page":"208","volume-title":"Circulation, Respiration, and Metabolism","author":"Brooks GA","unstructured":"Brooks GA. Lactate:glycolytic end product and oxidative substrate during sustained exercise in mammals\u2014the \u201clactate shuttle.\u201d In: Gilles R, ed. Circulation, Respiration, and Metabolism. Berlin, Germany: Springer; 1985:208-218."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.058701"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004210100516"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP280955"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0300258"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229680700100414"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40279-017-0751-x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology5040038"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.77"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i42.5280"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.710420"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.11.028"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2014.05.007"},{"key":"e_1_3_2_19_2","first-page":"3296","article-title":"Lactate and glycerol release from adipose tissue in lean, obese, and diabetic women from South Africa","volume":"86","author":"Van der Merwe M-T","year":"2001","unstructured":"Van der Merwe M-T, Schlaphoff GP, Crowther NJ, et al. Lactate and glycerol release from adipose tissue in lean, obese, and diabetic women from South Africa. J Clin Endocrinol Metab. 2001;86:3296-3303.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(92)90185-D"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14364-4"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031314"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1540"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2021.3124143"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296813514502"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2020.0110"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2017.2652062"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2022.106973"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00304.2001"},{"key":"e_1_3_2_31_2","volume-title":"A Physiologic Model of Glucose Metabolism in Man and Its Use to Design and Assess Improved Insulin Therapies for Diabetes","author":"Sorensen JT.","year":"1985","unstructured":"Sorensen JT. A Physiologic Model of Glucose Metabolism in Man and Its Use to Design and Assess Improved Insulin Therapies for Diabetes. Cambridge, MA: Massachusetts Institute of Technology; 1985."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2015.2505507"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-51-3-520"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.41.3.368"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17091450"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-7412"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00473.2004"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2016.2535241"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1214\/aoms\/1177731909"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1954.10501232"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1995.10476572"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2024.3352153"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296815610124"},{"key":"e_1_3_2_44_2","unstructured":"MATLAB Version: 9.13.0 (R2022b). Natick MA: The MathWorks Inc.; 2022."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/52.3-4.591"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-2753-6"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.2008.21.1.31"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2013-305718"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1373"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.13113"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12562"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1177\/1932296813514502"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107697"}],"container-title":["Journal of Diabetes Science and Technology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19322968241266825","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/19322968241266825","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19322968241266825","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:17:06Z","timestamp":1777400226000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/19322968241266825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,30]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1177\/19322968241266825"],"URL":"https:\/\/doi.org\/10.1177\/19322968241266825","relation":{},"ISSN":["1932-2968","1932-2968"],"issn-type":[{"value":"1932-2968","type":"print"},{"value":"1932-2968","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,30]]}}}