{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T22:58:33Z","timestamp":1772578713007,"version":"3.50.1"},"reference-count":31,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:sec>\n                  <jats:title>Context:<\/jats:title>\n                  <jats:p>Prediabetes is a heterogeneous disorder classified on the basis of fasting glucose concentrations and 2-hour glucose tolerance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>We sought to determine the relative contributions of insulin secretion and action to the pathogenesis of isolated impaired glucose tolerance (IGT).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design:<\/jats:title>\n                  <jats:p>The study consisted of an oral glucose tolerance test and a euglycemic clamp performed in two cohorts matched for anthropometric characteristics and fasting glucose but discordant for glucose tolerance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting:<\/jats:title>\n                  <jats:p>An inpatient clinical research unit at an academic medical center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients or Other Participants:<\/jats:title>\n                  <jats:p>Twenty-five subjects who had normal fasting glucose (NFG) and normal glucose tolerance (NGT) and 19 NFG\/IGT subjects participated in this study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention(s):<\/jats:title>\n                  <jats:p>Subjects underwent a seven-sample oral glucose tolerance test and a 4-hour euglycemic, hyperinsulinemic clamp on separate occasions. Glucose turnover during the clamp was measured using tracers, and endogenous hormone secretion was inhibited by somatostatin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures:<\/jats:title>\n                  <jats:p>We sought to determine whether hepatic glucose metabolism, specifically the contribution of gluconeogenesis to endogenous glucose production, differed between subjects with NFG\/NGT and those with NFG\/IGT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Endogenous glucose production did not differ between groups before or during the clamp. Insulin-stimulated glucose disappearance was lower in NFG\/IGT (24.6 \u00b1 2.2 vs 35.0 \u00b1 3.6 \u03bcmol\/kg\/min; P = .03). The disposition index was decreased in NFG\/IGT (681 \u00b1 102 vs 2231 \u00b1 413 \u00d7 10\u221214 dL\/kg\/min2 per pmol\/L; P &amp;lt; .001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>We conclude that innate defects in the regulation of glycogenolysis and gluconeogenesis do not contribute to NFG\/IGT. However, insulin-stimulated glucose disposal is impaired, exacerbating defects in \u03b2-cell function.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2016-1998","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T17:01:14Z","timestamp":1473267674000},"page":"4816-4824","source":"Crossref","is-referenced-by-count":15,"title":["Mechanisms Underlying the Pathogenesis of Isolated Impaired Glucose Tolerance in Humans"],"prefix":"10.1210","volume":"101","author":[{"given":"Ron T.","family":"Varghese","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism (R.T.V., A.S., M.S., J.M.M., R.A.R., A.V.) 1250-203 Lisbon, Portugal"}]},{"given":"Chiara","family":"Dalla Man","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine, Rochester, Minnesota 55905; Department of Information Engineering (C.D.M., C.C.) 1250-203 Lisbon, Portugal"}]},{"given":"Anu","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism (R.T.V., A.S., M.S., J.M.M., R.A.R., A.V.) 1250-203 Lisbon, Portugal"}]},{"given":"Ivan","family":"Viegas","sequence":"additional","affiliation":[{"name":"Universit\u00e1 di Padova, 35122 Padova, Italy; Center for Neurosciences and Cell Biology (I.V., C.B., C.M., J.G.J.) 1250-203 Lisbon, Portugal"}]},{"given":"Cristina","family":"Barosa","sequence":"additional","affiliation":[{"name":"Universit\u00e1 di Padova, 35122 Padova, Italy; Center for Neurosciences and Cell Biology (I.V., C.B., C.M., J.G.J.) 1250-203 Lisbon, Portugal"}]},{"given":"Catia","family":"Marques","sequence":"additional","affiliation":[{"name":"Universit\u00e1 di Padova, 35122 Padova, Italy; Center for Neurosciences and Cell Biology (I.V., C.B., C.M., J.G.J.) 1250-203 Lisbon, Portugal"}]},{"given":"Meera","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism (R.T.V., A.S., M.S., J.M.M., R.A.R., A.V.) 1250-203 Lisbon, Portugal"}]},{"given":"John M.","family":"Miles","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism (R.T.V., A.S., M.S., J.M.M., R.A.R., A.V.) 1250-203 Lisbon, Portugal"}]},{"given":"Robert A.","family":"Rizza","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism (R.T.V., A.S., M.S., J.M.M., R.A.R., A.V.) 1250-203 Lisbon, Portugal"}]},{"given":"John G.","family":"Jones","sequence":"additional","affiliation":[{"name":"Universit\u00e1 di Padova, 35122 Padova, Italy; Center for Neurosciences and Cell Biology (I.V., C.B., C.M., J.G.J.) 1250-203 Lisbon, Portugal"},{"name":"University of Coimbra, 3000-370 Coimbra, Portugal; and APDP-Portuguese Diabetes Association (J.G.J.), 1250-203 Lisbon, Portugal"}]},{"given":"Claudio","family":"Cobelli","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine, Rochester, Minnesota 55905; Department of Information Engineering (C.D.M., C.C.) 1250-203 Lisbon, Portugal"}]},{"given":"Adrian","family":"Vella","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism (R.T.V., A.S., M.S., J.M.M., R.A.R., A.V.) 1250-203 Lisbon, Portugal"}]}],"member":"80","published-online":{"date-parts":[[2016,9,7]]},"reference":[{"key":"2020071616570592500_B1","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1056\/NEJMra0906948","article-title":"Genomics, type 2 diabetes, and obesity","volume":"363","author":"McCarthy","year":"2010","journal-title":"N Engl J Med"},{"key":"2020071616570592500_B2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jpeds.2011.12.050","article-title":"Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship 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