{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:05:59Z","timestamp":1790841959977,"version":"4.1.0"},"reference-count":40,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":93,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000098","name":"National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK24092"],"award-info":[{"award-number":["DK24092"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004462","name":"Consiglio Nazionale delle Ricerche","doi-asserted-by":"publisher","award":["DSB.AD003.061"],"award-info":[{"award-number":["DSB.AD003.061"]}],"id":[{"id":"10.13039\/501100004462","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:p>With the development of insulin resistance (IR), there is a compensatory increase in the plasma insulin response to offset the defect in insulin action to maintain normal glucose tolerance. The insulin response is the result of two factors: insulin secretion and metabolic clearance rate of insulin (MCRI). Subjects (104 with normal glucose tolerance [NGT], 57 with impaired glucose tolerance [IGT], and 207 with type 2 diabetes mellitus [T2DM]), divided in nonobese and obese groups, received a euglycemic insulin-clamp (40 mU\/m2 \u22c5 min) and an oral glucose tolerance test (OGTT) (75 g) on separate days. MCRI was calculated during the insulin-clamp performed with [3-3H]glucose and the OGTT and related to IR: peripheral (glucose uptake during the insulin clamp), hepatic (basal endogenous glucose production \u00d7 fasting plasma insulin [FPI]), and adipocyte (fasting free fatty acid \u00d7 FPI). MCRI during the insulin clamp was reduced in obese versus nonobese NGT (0.60 \u00b1 0.03 vs. 0.73 \u00b1 0.02 L\/min \u22c5 m2, P &amp;lt; 0.001), in nonobese IGT (0.62 \u00b1 0.02, P &amp;lt; 0.004), and in nonobese T2DM (0.68 \u00b1 0.02, P &amp;lt; 0.03). The MCRI during the insulin clamp was strongly and inversely correlated with IR (r = \u22120.52, P &amp;lt; 0.0001). During the OGTT, the MCRI was suppressed within 15\u201330 min in NGT and IGT subjects and remained suppressed. In contrast, suppression was minimal in T2DM. In conclusion, the development of IR in obese subjects is associated with a decline in MCRI that represents a compensatory response to maintain normal glucose tolerance but is impaired in individuals with T2DM.<\/jats:p>","DOI":"10.2337\/db19-1152","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T20:10:12Z","timestamp":1603138212000},"page":"377-385","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":77,"title":["Adaptation of Insulin Clearance to Metabolic Demand Is a Key Determinant of Glucose Tolerance"],"prefix":"10.2337","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-1651","authenticated-orcid":false,"given":"Amalia","family":"Gastaldelli","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Pisa, Italy"},{"name":"University of Texas Health Science Center, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4556-1787","authenticated-orcid":false,"given":"Muhammad","family":"Abdul Ghani","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-6273","authenticated-orcid":false,"given":"Ralph A.","family":"DeFronzo","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"2022031303035483100_B1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2337\/db09-9028","article-title":"Banting Lecture. 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