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nonrelated peers during a 3-hour oral glucose tolerance test (OGTT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-eight lean youth, 14 with \u22652 islet autoantibodies (cases) and 14 healthy controls underwent a 3-hour 9-point OGTT with measurement of glucose, C-peptide, and insulin. 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\u00d7SI). Fasting insulin clearance (CL0) was calculated as the ratio between the fasting insulin secretion rate (ISR) and plasma insulin levels (ISR0\/I0), while postload clearance (CL180) was estimated by the ratio of AUC of ISR over the plasma insulin AUC for the 3-hour OGTT (ISRAUC\/IAUC). Participants with impaired fasting glucose, impaired glucose tolerance, or any OGTT glucose concentration \u2265200 mg\/dL were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cases (10.5 years [8, 15]) exhibited reduced DI (P &amp;lt; .001) due to a simultaneous reduction in both \u03c6total (P &amp;lt; 0.001) and SI (P = .008) compared with controls (11.5 years [10.4, 14.9]). CL0 and CL180 were lower in cases than in controls (P = .005 and P = .019).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Presymptomatic Stage 1 T1D in youth is associated with reduced insulin sensitivity and lower \u03b2-cell responsiveness, and the presence of blunted insulin clearance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgab344","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T16:39:03Z","timestamp":1621269543000},"page":"2660-2669","source":"Crossref","is-referenced-by-count":25,"title":["Early Impairment of Insulin Sensitivity, \u03b2-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes"],"prefix":"10.1210","volume":"106","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\u2019s Health, University of Padova, Padova, Italy"},{"name":"Department of Pediatrics, Yale University, New Haven, CT, 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, MN, USA"}],"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, Bloomington, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Martino","sequence":"additional","affiliation":[{"name":"Department of Woman and Child\u2019s Health, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-4173","authenticated-orcid":false,"given":"Nicola","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University, New Haven, CT, USA"},{"name":"Department of Medicine and Health Sciences \u201cV. 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