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A hyperinsulinemic-euglycemic and a hyperglycemic clamp were performed in 110 youths to quantify hepatic and peripheral clearance, insulin sensitivity, and \u03b2-cell function (disposition index, DIh-clamp). Participants underwent an oral glucose tolerance test at baseline and after 2 years to assess glucose tolerance and oral \u03b2-cell function (oDIcpep) and were sorted into four groups (lean and obese normal glucose tolerance, insulin sensitive, insulin resistant, and impaired glucose tolerance). Insulin sensitivity was defined based on the median of insulin stimulated glucose disposal (M) measured during the hyperinsulinemic-euglycemic clamp. Lean and obese insulin-sensitive participants did not differ with respect to hepatic and peripheral clearance or for insulin sensitivity. Insulin sensitivity was linearly correlated with whole-body insulin clearance. Hepatic insulin extraction at baseline acted as an independent determinant of \u03b2-cell function at follow-up. The decline in insulin sensitivity, even in the absence of an impairment of glucose tolerance, is associated with lowering of hepatic insulin clearance in obese youth, which in turn may contribute to the decline in \u03b2-cell function over time.<\/jats:p>","DOI":"10.2337\/db19-0120","type":"journal-article","created":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T02:35:14Z","timestamp":1565404514000},"page":"2074-2084","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":43,"title":["Lower Insulin Clearance Parallels a Reduced Insulin Sensitivity in Obese Youths and Is Associated With a Decline in \u03b2-Cell Function Over Time"],"prefix":"10.2337","volume":"68","clinical-trial-number":[{"clinical-trial-number":"nct01967849","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-3056","authenticated-orcid":false,"given":"Alfonso","family":"Galderisi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Pediatric Endocrinology and Diabetes Section, Yale School of Medicine, New Haven, CT"},{"name":"Department of Woman and Child\u2019s Health, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Polidori","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5663-8105","authenticated-orcid":false,"given":"Ram","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ospedale \u201cSS Annunziata,\u201d Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo","family":"Giannini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Endocrinology and Diabetes Section, Yale School of Medicine, New Haven, CT"},{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Pierpont","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Endocrinology and Diabetes Section, Yale School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-1346","authenticated-orcid":false,"given":"Domenico","family":"Tric\u00f2","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Sant\u2019Anna School of Advanced Studies, Pisa, Italy"},{"name":"Department of Pediatrics, Ruth Rappaport Children\u2019s Hospital, Rambam Medical Center, Haifa, Israel"}],"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, Pediatric Endocrinology and Diabetes Section, Yale School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2019,8,9]]},"reference":[{"key":"2022031303425938600_B1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1056\/NEJM198607243150402","article-title":"Impaired insulin action in puberty. 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