{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:44:15Z","timestamp":1790066655367,"version":"4.0.1"},"reference-count":19,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Metabolic zones were developed to characterize heterogeneity of individuals with islet autoantibodies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Baseline 2-h oral glucose tolerance test data from 6,620 TrialNet Pathway to Prevention Study (TNPTP) autoantibody-positive participants (relatives of individuals with type 1 diabetes) were used to form 25 zones from five area under the curve glucose (AUCGLU) rows and five area under the curve C-peptide (AUCPEP) columns. Zone phenotypes were developed from demographic, metabolic, autoantibody, HLA, and risk data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>As AUCGLU increased, changes of glucose and C-peptide response curves (from mean glucose and mean C-peptide values at 30, 60, 90, and 120 min) were similar within the five AUCPEP columns. Among the zones, 5-year risk for type 1 diabetes was highly correlated with islet antigen 2 antibody prevalence (r = 0.96, P &amp;lt; 0.001). Disease risk decreased markedly in the highest AUCGLU row as AUCPEP increased (0.88\u20130.41; P &amp;lt; 0.001 from lowest AUCPEP column to highest AUCPEP column). AUCGLU correlated appreciably less with Index60 (an indicator of insulin secretion) in the highest AUCPEP column (r = 0.33) than in other columns (r \u2265 0.78). AUCGLU was positively related to \u201cfasting glucose \u00d7 fasting insulin\u201d and to \u201cfasting glucose \u00d7 fasting C-peptide\u201d (indicators of insulin resistance) before and after adjustments for Index60 (P &amp;lt; 0.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Phenotypes of 25 zones formed from AUCGLU and AUCPEP were used to gain insights into type 1 diabetes heterogeneity. Zones were used to examine GCRC changes with increasing AUCGLU, associations between risk and autoantibody prevalence, the dependence of glucose as a predictor of risk according to C-peptide, and glucose heterogeneity from contributions of insulin secretion and insulin resistance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc22-2236","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T17:28:41Z","timestamp":1680283721000},"page":"1098-1105","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":13,"title":["Phenotypes Associated With Zones Defined by Area Under the Curve Glucose and C-peptide in a Population With Islet Autoantibodies"],"prefix":"10.2337","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7204-8367","authenticated-orcid":false,"given":"Jay M.","family":"Sosenko","sequence":"first","affiliation":[{"name":"1Division of Endocrinology, Diabetes, and Metabolism, and Diabetes Research Institute, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-954X","authenticated-orcid":false,"given":"Emily K.","family":"Sims","sequence":"additional","affiliation":[{"name":"3Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, Indiana University, Indianapolis, IN"}],"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":"3Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, Indiana University, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6405-3994","authenticated-orcid":false,"given":"Brandon M.","family":"Nathan","sequence":"additional","affiliation":[{"name":"4Division of Pediatric Endocrinology, Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-7836","authenticated-orcid":false,"given":"Laura M.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"5Department of Pediatrics, College of Medicine, The University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8489-4782","authenticated-orcid":false,"given":"Mark A.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"5Department of Pediatrics, College of Medicine, The University of Florida, Gainesville, FL"},{"name":"6Department of Pathology, College of Medicine, The University of Florida, Gainesville, FL"}],"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":"7Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1534-6613","authenticated-orcid":false,"given":"Kevan C.","family":"Herold","sequence":"additional","affiliation":[{"name":"8Department of Immunobiology, Yale University School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-8110","authenticated-orcid":false,"given":"Jay S.","family":"Skyler","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes, and Metabolism, and Diabetes Research Institute, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-4645","authenticated-orcid":false,"given":"Maria J.","family":"Redondo","sequence":"additional","affiliation":[{"name":"9Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"TrialNet Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"2023042619072826100_B1","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.2337\/dc20-0701","article-title":"The pathological evolution of glucose response curves during the progression to type 1 diabetes in the TrialNet Pathway to Prevention Study","volume":"43","author":"Ismail","year":"2020","journal-title":"Diabetes 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