{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:04:46Z","timestamp":1790129086176,"version":"4.0.1"},"reference-count":38,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01-DK085476"],"award-info":[{"award-number":["U01-DK085476"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NU01-DK085505"],"award-info":[{"award-number":["NU01-DK085505"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK-093954"],"award-info":[{"award-number":["R01-DK-093954"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UC4-DK-127786"],"award-info":[{"award-number":["UC4-DK-127786"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21-DK119800"],"award-info":[{"award-number":["R21-DK119800"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK127308-01"],"award-info":[{"award-number":["R01DK127308-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30DK097512"],"award-info":[{"award-number":["P30DK097512"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CTSA program","award":["UL1-TR002494"],"award-info":[{"award-number":["UL1-TR002494"]}]},{"name":"VA Merit","award":["I01BX001733"],"award-info":[{"award-number":["I01BX001733"]}]},{"name":"JDRF Strategic Research Agreement"},{"name":"Institute for Pediatric Research"},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The oral minimal model is a widely accepted noninvasive tool to quantify both \u03b2-cell responsiveness and insulin sensitivity (SI) from glucose, C-peptide, and insulin concentrations during a 3-hour 9-point oral glucose tolerance test (OGTT).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Here, we aimed to validate a 2-hour 7-point protocol against the 3-hour OGTT and to test how variation in early sampling frequency impacts estimates of \u03b2-cell responsiveness and SI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a secondary analysis on 15 lean youth with stage 1 type 1 diabetes (T1D; \u2265 2 islet autoantibodies with no dysglycemia) who underwent a 3-hour 9-point OGTT. The oral minimal model was used to quantitate \u03b2-cell responsiveness (\u03c6total) and insulin sensitivity (SI), allowing assessment of \u03b2-cell function by the disposition index (DI = \u03c6total \u00d7 SI). Seven- and 5-point 2-hour OGTT protocols were tested against the 3-hour 9-point gold standard to determine agreement between estimates of \u03c6total and its dynamic and static components, SI, and DI across different sampling strategies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The 2-hour estimates for the disposition index exhibited a strong correlation with 3-hour measures (r = 0.975; P &amp;lt; .001) with similar results for \u03b2-cell responsiveness and SI (r = 0.997 and r = 0.982; P &amp;lt; .001, respectively). The agreement of the 3 estimates between the 7-point 2-hour and 9-point 3-hour protocols fell within the 95% CI on the Bland-Altman grid with a median difference of 16.9% (\u221235.3 to 32.5), 0.2% (\u22120.6 to 1.3), and 14.9% (\u22121.4 to 28.3) for DI, \u03c6total, and SI. Conversely, the 5-point protocol did not provide reliable estimates of \u03c6 dynamic and static components.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The 2-hour 7-point OGTT is reliable in individuals with stage 1 T1D for assessment of \u03b2-cell responsiveness, SI, and DI. Incorporation of these analyses into current 2-hour diabetes staging and monitoring OGTTs offers the potential to more accurately quantify risk of progression in the early stages of T1D.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgac740","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T10:16:07Z","timestamp":1671704167000},"page":"1376-1386","source":"Crossref","is-referenced-by-count":13,"title":["\u03b2-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-3056","authenticated-orcid":false,"given":"Alfonso","family":"Galderisi","sequence":"first","affiliation":[{"name":"Department of Woman and Child's Health, University of Padova , 35128 Padua , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-8663","authenticated-orcid":false,"given":"Carmella","family":"Evans-Molina","sequence":"additional","affiliation":[{"name":"Center for Diabetes and Metabolic Diseases, Indiana University , Indianapolis, Indiana 46202 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3091-9099","authenticated-orcid":false,"given":"Mariangela","family":"Martino","sequence":"additional","affiliation":[{"name":"Department of Woman and Child's Health, University of Padova , 35128 Padua , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7523-5053","authenticated-orcid":false,"given":"Sonia","family":"Caprio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University , New Haven, Connecticut 06520 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-6682","authenticated-orcid":false,"given":"Claudio","family":"Cobelli","sequence":"additional","affiliation":[{"name":"Department of Woman and Child's Health, University of Padova , 35128 Padua , Italy"}],"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, Minnesota 55454 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"issue":"10","key":"2023051701093153800_dgac740-B1","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.2337\/dc15-1419","article-title":"Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association","volume":"38","author":"Insel","year":"2015","journal-title":"Diabetes Care"},{"issue":"1","key":"2023051701093153800_dgac740-B2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1530\/EJE-14-0911","article-title":"Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis","volume":"173","author":"Donga","year":"2015","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"2023051701093153800_dgac740-B3","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.2337\/db13-1198","article-title":"The oral minimal model method","volume":"63","author":"Cobelli","year":"2014","journal-title":"Diabetes"},{"issue":"9","key":"2023051701093153800_dgac740-B4","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1210\/clinem\/dgab344","article-title":"Early impairment of insulin sensitivity, \u03b2-cell responsiveness, and insulin clearance in youth with stage 1 type 1 diabetes","volume":"106","author":"Galderisi","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2023051701093153800_dgac740-B5","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/oby.2008.496","article-title":"Beta-cell function and insulin sensitivity in adolescents from an OGTT","volume":"17","author":"Sunehag","year":"2009","journal-title":"Obesity (Silver Spring)"},{"issue":"1","key":"2023051701093153800_dgac740-B6","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2337\/diabetes.50.1.150","article-title":"Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity","volume":"50","author":"Breda","year":"2001","journal-title":"Diabetes"},{"issue":"4","key":"2023051701093153800_dgac740-B7","doi-asserted-by":"crossref","first-page":"E637","DOI":"10.1152\/ajpendo.00319.2003","article-title":"Minimal model estimation of glucose absorption and insulin sensitivity from oral test: validation with a tracer method","volume":"287","author":"Dalla Man","year":"2004","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"6","key":"2023051701093153800_dgac740-B8","doi-asserted-by":"crossref","first-page":"E954","DOI":"10.1152\/ajpendo.00076.2005","article-title":"Insulin sensitivity by oral glucose minimal models: validation against clamp","volume":"289","author":"Dalla Man","year":"2005","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"2","key":"2023051701093153800_dgac740-B9","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/pedi.13149","article-title":"Adherence to oral glucose tolerance testing in children in stage 1 of type 1 diabetes: the TEDDY study","volume":"22","author":"Driscoll","year":"2021","journal-title":"Pediatr Diabetes"},{"issue":"11","key":"2023051701093153800_dgac740-B10","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.2337\/diabetes.54.11.3265","article-title":"Two-hour seven-sample oral glucose tolerance test and meal protocol: minimal model assessment of beta-cell responsivity and insulin sensitivity in nondiabetic individuals","volume":"54","author":"Dalla Man","year":"2005","journal-title":"Diabetes"},{"issue":"8","key":"2023051701093153800_dgac740-B11","doi-asserted-by":"crossref","first-page":"e3273","DOI":"10.1210\/clinem\/dgac285","article-title":"Oral glucose tolerance test measures of first-phase insulin response and their predictive ability for type 1 diabetes","volume":"107","author":"Baidal","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2023051701093153800_dgac740-B12","doi-asserted-by":"crossref","first-page":"456","DOI":"10.2337\/dc08-1274","article-title":"Primary defects in beta-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents","volume":"32","author":"Cali","year":"2009","journal-title":"Diabetes Care"},{"issue":"10","key":"2023051701093153800_dgac740-B13","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1109\/TBME.2011.2164918","article-title":"Multiscale modeling of insulin secretion","volume":"58","author":"Pedersen","year":"2011","journal-title":"IEEE Trans Bio-med Eng"},{"issue":"3","key":"2023051701093153800_dgac740-B14","doi-asserted-by":"crossref","first-page":"368","DOI":"10.2337\/diabetes.41.3.368","article-title":"Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance","volume":"41","author":"Van Cauter","year":"1992","journal-title":"Diabetes"},{"issue":"6","key":"2023051701093153800_dgac740-B15","doi-asserted-by":"crossref","first-page":"E1115","DOI":"10.1152\/ajpendo.00705.2009","article-title":"A model of GLP-1 action on insulin secretion in nondiabetic subjects","volume":"298","author":"Dalla Man","year":"2010","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"9","key":"2023051701093153800_dgac740-B16","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.2337\/dc20-0750","article-title":"The measurement of insulin clearance","volume":"43","author":"Piccinini","year":"2020","journal-title":"Diabetes Care"},{"issue":"5","key":"2023051701093153800_dgac740-B17","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/dom.13640","article-title":"One-hour post-load plasma glucose predicts progression to prediabetes in a multi-ethnic cohort of obese youths","volume":"21","author":"Trico","year":"2019","journal-title":"Diabetes Obes Metab"},{"issue":"2","key":"2023051701093153800_dgac740-B18","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1172\/JCI113338","article-title":"Quantitative study of insulin secretion and clearance in normal and obese subjects","volume":"81","author":"Polonsky","year":"1988","journal-title":"J Clin Invest"},{"issue":"4","key":"2023051701093153800_dgac740-B19","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1073\/pnas.040556697","article-title":"Early expression of antiinsulin autoantibodies of humans and the NOD mouse: evidence for early determination of subsequent diabetes","volume":"97","author":"Yu","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"2023051701093153800_dgac740-B20","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1210\/jc.2010-0293","article-title":"Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for National Institute of Diabetes and Digestive and Kidney Diseases Consortia","volume":"95","author":"Bonifacio","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2023051701093153800_dgac740-B21","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.2337\/dc11-2081","article-title":"Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies","volume":"35","author":"Yu","year":"2012","journal-title":"Diabetes Care"},{"issue":"2","key":"2023051701093153800_dgac740-B22","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0169-2607(86)90106-9","article-title":"MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test","volume":"23","author":"Pacini","year":"1986","journal-title":"Comput Methods Programs Biomed"},{"issue":"2","key":"2023051701093153800_dgac740-B23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2337\/dc21-0944","article-title":"Index60 identifies individuals at appreciable risk for stage 3 among an autoantibody-positive population with normal 2-hour glucose levels: implications for current staging criteria of type 1 diabetes","volume":"45","author":"Nathan","year":"2022","journal-title":"Diabetes Care"},{"issue":"23","key":"2023051701093153800_dgac740-B24","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1001\/jama.2013.6285","article-title":"Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children","volume":"309","author":"Ziegler","year":"2013","journal-title":"JAMA"},{"issue":"2","key":"2023051701093153800_dgac740-B25","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1210\/clinem\/dgz207","article-title":"Metabolic and genetic determinants of glucose shape after oral challenge in obese youths: a longitudinal study","volume":"105","author":"Galderisi","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2023051701093153800_dgac740-B26","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.2337\/dc17-0290","article-title":"The rs7903146 variant in the TCF7L2 gene increases the risk of prediabetes\/type 2 diabetes in obese adolescents by impairing \u03b2-cell function and hepatic insulin sensitivity","volume":"40","author":"Cropano","year":"2017","journal-title":"Diabetes Care"},{"issue":"3","key":"2023051701093153800_dgac740-B27","doi-asserted-by":"crossref","first-page":"606","DOI":"10.2337\/db11-1111","article-title":"Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study","volume":"61","author":"Giannini","year":"2012","journal-title":"Diabetes"},{"issue":"2","key":"2023051701093153800_dgac740-B28","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1399-543X.2005.00097.x","article-title":"Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates","volume":"6","author":"Saad","year":"2005","journal-title":"Pediatr Diabetes"},{"issue":"11","key":"2023051701093153800_dgac740-B29","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.2337\/db13-1951","article-title":"\u03b2-Cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes","volume":"63","author":"Michaliszyn","year":"2014","journal-title":"Diabetes"},{"issue":"3","key":"2023051701093153800_dgac740-B30","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/S0022-3476(96)70078-1","article-title":"Differences in the in vivo insulin secretion and sensitivity of healthy black versus white adolescents","volume":"129","author":"Arslanian","year":"1996","journal-title":"J Pediatr"},{"issue":"8","key":"2023051701093153800_dgac740-B31","doi-asserted-by":"crossref","first-page":"E819","DOI":"10.1152\/ajpendo.00482.2012","article-title":"Modeling hepatic insulin sensitivity during a meal: validation against the euglycemic hyperinsulinemic clamp","volume":"304","author":"Dalla Man","year":"2013","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"5","key":"2023051701093153800_dgac740-B32","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1111\/dom.14646","article-title":"Inhibition of 11\u03b2-hydroxysteroid dehydrogenase-1 with AZD4017 in patients with nonalcoholic steatohepatitis or nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled, phase II study","volume":"24","author":"Yadav","year":"2022","journal-title":"Diabetes Obes Metab"},{"issue":"8","key":"2023051701093153800_dgac740-B33","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.2337\/dc19-2288","article-title":"C-peptide levels in subjects followed longitudinally before and after type 1 diabetes diagnosis in TrialNet","volume":"43","author":"Bogun","year":"2020","journal-title":"Diabetes Care"},{"issue":"7","key":"2023051701093153800_dgac740-B34","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1056\/NEJMoa1902226","article-title":"An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes","volume":"381","author":"Herold","year":"2019","journal-title":"N Engl J Med"},{"issue":"11","key":"2023051701093153800_dgac740-B35","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.2337\/dc17-0916","article-title":"Dysglycemia and Index60 as prediagnostic end points for type 1 diabetes prevention trials","volume":"40","author":"Nathan","year":"2017","journal-title":"Diabetes Care"},{"issue":"6","key":"2023051701093153800_dgac740-B36","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.2337\/db11-1660","article-title":"The metabolic progression to type 1 diabetes as indicated by serial oral glucose tolerance testing in the Diabetes Prevention Trial\u2013Type 1","volume":"61","author":"Sosenko","year":"2012","journal-title":"Diabetes"},{"issue":"6","key":"2023051701093153800_dgac740-B37","first-page":"E667","article-title":"Quantitative estimation of insulin sensitivity","volume":"236","author":"Bergman","year":"1979","journal-title":"Am J Physiol"},{"issue":"12","key":"2023051701093153800_dgac740-B38","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1109\/TBME.2006.883792","article-title":"A system model of oral glucose absorption: validation on gold standard data","volume":"53","author":"Dalla Man","year":"2006","journal-title":"IEEE Trans Biomed Eng"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgac740\/50094906\/dgac740.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/6\/1376\/50355217\/dgac740.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/6\/1376\/50355217\/dgac740.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T01:12:44Z","timestamp":1684285964000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/108\/6\/1376\/6955789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,21]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,12,21]]},"published-print":{"date-parts":[[2023,5,17]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgac740","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6]]},"published":{"date-parts":[[2022,12,21]]}}}