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DK117009"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001067","name":"JDRF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001067","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Staging preclinical type 1 diabetes (T1D) and monitoring the response to disease-modifying treatments rely on the oral glucose tolerance test (OGTT). However, it is unknown whether OGTT-derived measures of beta cell function can detect subtle changes in metabolic phenotype, thus limiting their usability as endpoints in prevention trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To describe the metabolic phenotype of people with Stage 1 and Stage 2 T1D using metabolic modelling of \u03b2 cell function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We characterized the metabolic phenotype of individuals with islet autoimmunity in the absence (Stage 1) or presence (Stage 2) of dysglycemia. Participants were screened at a TrialNet site and underwent a 5-point, 2-hour OGTT. Standard measures of insulin secretion (area under the curve, C-peptide, Homeostatic Model Assessment [HOMA] 2-B) and sensitivity (HOMA Insulin Resistance, HOMA2-S, Matsuda Index) and oral minimal model\u2013derived insulin secretion (\u03c6 total), sensitivity (sensitivity index), and clearance were adopted to characterize the cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty participants with Stage 1 and 27 with Stage 2T1D were selected. Standard metrics of insulin secretion and sensitivity did not differ between Stage 1 and Stage 2 T1D, while the oral minimal model revealed lower insulin secretion (P &amp;lt; .001) and sensitivity (P = .034) in those with Stage 2 T1D, as well as increased insulin clearance (P = .006). A higher baseline \u03c6 total was associated with reduced odds of disease progression, independent of stage (OR 0.92 [0.86, 0.98], P = .016).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The oral minimal model describes the differential metabolic phenotype of Stage 1 and Stage 2 T1D and identifies the \u03c6 total as a progression predictor. This supports its use as a sensitive tool and endpoint for T1D prevention trials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf086","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T15:19:54Z","timestamp":1739546394000},"page":"3168-3178","source":"Crossref","is-referenced-by-count":9,"title":["Metabolic Phenotype of Stage 1 and Stage 2 Type 1 Diabetes Using Modeling of \u03b2 Cell Function"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-3056","authenticated-orcid":false,"given":"Alfonso","family":"Galderisi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Yale University , New Haven, 06510 CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Bonet","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, University of Padova , 35131 Padova ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-0030","authenticated-orcid":false,"given":"Heba M","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine , Indianapolis, 46202 IN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2694-5147","authenticated-orcid":false,"given":"Antoinette","family":"Moran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota , Minneapolis, 55455 MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fiorina","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan , Milan 20122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Bosi","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, IRCCS Ospedale San Raffaele , Milan 20132 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5639-9415","authenticated-orcid":false,"given":"Alessandra","family":"Petrelli","sequence":"additional","affiliation":[{"name":"Cardiac-Thoracic-Metabolic Unit, Pio Albergo Trivulzio , Milan 20146 ,","place":["Italy"]},{"name":"Department of Clinical Sciences and Community Health, University of Milan , Milan 20122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"issue":"10","key":"2025101519583194700_dgaf086-B1","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.2337\/dc15-1419","article-title":"Staging presymptomatic type 1 diabetes: a 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