{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:37:41Z","timestamp":1791499061585,"version":"4.3.4"},"reference-count":53,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":74,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK-24092-36"],"award-info":[{"award-number":["DK-24092-36"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:p>The aim of the current study was to evaluate the effect of sustained physiologic increase of \u223c50 mg\/dL in plasma glucose concentration on insulin secretion in normal glucose-tolerant (NGT) subjects. Twelve NGT subjects without family history of type 2 diabetes mellitus (T2DM; FH\u2212) and 8 NGT with family history of T2DM (FH+) received an oral glucose tolerance test and two-step hyperglycemic clamp (100 and 300 mg\/dL) followed by intravenous arginine bolus before and after 72-h glucose infusion. Fasting plasma glucose increased from 94 \u00b1 2 to 142 \u00b1 4 mg\/dL for 72 h. First-phase insulin secretion (0\u201310 min) increased by 70%, while second-phase insulin secretion during the first (10\u201380 min) and second (90\u2013160 min) hyperglycemic clamp steps increased by 3.8-fold and 1.9-fold, respectively, following 72 h of physiologic hyperglycemia. Insulin sensitivity during hyperglycemic clamp declined by \u223c30% and \u223c55% (both P &amp;lt; 0.05), respectively, during the first and second hyperglycemic clamp steps. Insulin secretion\/insulin resistance (disposition) index declined by 60% (second clamp step) and by 62% following arginine (both P &amp;lt; 0.005) following 72-h glucose infusion. The effect of 72-h glucose infusion on insulin secretion and insulin sensitivity was similar in subjects with and without FH of T2DM. Following 72 h of physiologic hyperglycemia, metabolic clearance rate of insulin was markedly reduced (P &amp;lt; 0.01). These results demonstrate that sustained physiologic hyperglycemia for 72 h 1) increases absolute insulin secretion but impairs \u03b2-cell function, 2) causes insulin resistance, and 3) reduces metabolic clearance rate of insulin.<\/jats:p>","DOI":"10.2337\/db20-0039","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T03:10:26Z","timestamp":1602213026000},"page":"204-213","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":38,"title":["Effect of Mild Physiologic Hyperglycemia on Insulin Secretion, Insulin Clearance, and Insulin Sensitivity in Healthy Glucose-Tolerant Subjects"],"prefix":"10.2337","volume":"70","author":[{"given":"Aurora","family":"Merovci","sequence":"first","affiliation":[{"name":"Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devjit","family":"Tripathy","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX"},{"name":"Audie L. 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