{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:32:07Z","timestamp":1740144727169,"version":"3.37.3"},"reference-count":20,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001873"],"award-info":[{"award-number":["UL1TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Columbia University Department of Medicine","award":["Career startup package"],"award-info":[{"award-number":["Career startup package"]}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["P30DK063608"],"award-info":[{"award-number":["P30DK063608"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>Our objective was to test a single dose of the phosphatidylinositol 3-kinase (PI3K) inhibitor alpelisib as a tool for acute modeling of insulin resistance in healthy volunteers. This single-center double-blind phase 1 clinical trial randomly assigned healthy adults to a single oral dose of 300 mg alpelisib (n = 5) or placebo (n = 6) at bedtime, followed by measurement of glucose, insulin, and C-peptide levels after an overnight fast and during a 3-h 75-g oral glucose tolerance test (OGTT). Fasting plasma glucose trended higher with alpelisib (mean \u00b1 SD 93 \u00b1 11 mg\/dL) versus placebo (84 \u00b1 5 mg\/dL); mean fasting serum insulin increased nearly fivefold (23 \u00b1 12 vs. 5 \u00b1 3 \u03bcU\/mL, respectively), and HOMA of insulin resistance (IR) scores were 5.4 \u00b1 3.1 for alpelisib and 1.1 \u00b1 0.6 for placebo. During OGTT, incremental area under the curve (AUC) for insulin was more than fourfold greater with alpelisib (22 \u00b1 15 mU\/mL \u00d7 min) than with placebo (5 \u00b1 2 mU\/mL \u00d7 min); glucose AUC trended higher with alpelisib. Single-dose alpelisib was well tolerated and produced metabolic alterations consistent with acute induction of IR, validating its use for mechanistic study of insulin action in humans.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n               <\/jats:sec>","DOI":"10.2337\/db24-0402","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T16:33:21Z","timestamp":1726158801000},"page":"2003-2008","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Single Dose of Phosphatidylinositol 3-Kinase Inhibitor Alpelisib Induces Insulin Resistance in Healthy Adults: A Randomized Feasibility Study"],"prefix":"10.2337","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6004-0504","authenticated-orcid":false,"given":"Joshua R.","family":"Cook","sequence":"first","affiliation":[{"name":"1Diabetes and 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