{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:25:40Z","timestamp":1791530740550,"version":"4.3.4"},"reference-count":40,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":2873,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:p>We examined the metabolic characteristics that attend the development of type 2 diabetes (T2DM) in 441 impaired glucose tolerance (IGT) subjects who participated in the ACT NOW Study and had complete end-of-study metabolic measurements. Subjects were randomized to receive pioglitazone (PGZ; 45 mg\/day) or placebo and were observed for a median of 2.4 years. Indices of insulin sensitivity (Matsuda index [MI]), insulin secretion (IS)\/insulin resistance (IR; \u0394I0\u2013120\/\u0394G0\u2013120, \u0394IS rate [ISR]0\u2013120\/\u0394G0\u2013120), and \u03b2-cell function (\u0394I\/\u0394G \u00d7 MI and \u0394ISR\/\u0394G \u00d7 MI) were calculated from plasma glucose, insulin, and C-peptide concentrations during oral glucose tolerance tests at baseline and study end. Diabetes developed in 45 placebo-treated vs. 15 PGZ-treated subjects (odds ratio [OR] 0.28 [95% CI 0.15\u20130.49]; P &amp;lt; 0.0001); 48% of PGZ-treated subjects reverted to normal glucose tolerance (NGT) versus 28% of placebo-treated subjects (P &amp;lt; 0.005). Higher final glucose tolerance status (NGT &amp;gt; IGT &amp;gt; T2DM) was associated with improvements in insulin sensitivity (OR 0.61 [95% CI 0.54\u20130.80]), IS (OR 0.61 [95% CI 0.50\u20130.75]), and \u03b2-cell function (ln IS\/IR index and ln ISR\/IR index) (OR 0.26 [95% CI 0.19\u20130.37]; all P &amp;lt; 0.0001). Of the factors measured, improved \u03b2-cell function was most closely associated with final glucose tolerance status.<\/jats:p>","DOI":"10.2337\/db13-0265","type":"journal-article","created":{"date-parts":[[2013,7,18]],"date-time":"2013-07-18T00:26:04Z","timestamp":1374107164000},"page":"3920-3926","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":97,"title":["Prevention of Diabetes With Pioglitazone in ACT NOW"],"prefix":"10.2337","volume":"62","author":[{"given":"Ralph A.","family":"DeFronzo","sequence":"first","affiliation":[{"name":"Texas Diabetes Institute, San Antonio, Texas"},{"name":"University of Texas Health Science Center, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devjit","family":"Tripathy","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute, San Antonio, Texas"},{"name":"University of Texas Health Science Center, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn C.","family":"Schwenke","sequence":"additional","affiliation":[{"name":"Phoenix VA Health Care System, Phoenix, Arizona"},{"name":"College of Nursing & Health Innovation, Arizona State University, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MaryAnn","family":"Banerji","sequence":"additional","affiliation":[{"name":"State University of New York Health Science Center at Brooklyn, Brooklyn, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Bray","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Clement","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Georgetown University, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center, San Antonio, Texas"},{"name":"Cardiometabolic Risk Unit, Institute of Clinical Physiology, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Henry","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System, San Diego, California"},{"name":"University of California at San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas E.","family":"Kitabchi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Tennessee, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunder","family":"Mudaliar","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System, San Diego, California"},{"name":"University of California at San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Ratner","sequence":"additional","affiliation":[{"name":"Medstar Research Institute, Hyattsville, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frankie B.","family":"Stentz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Tennessee, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Musi","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute, San Antonio, Texas"},{"name":"University of Texas Health Science Center, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Reaven","sequence":"additional","affiliation":[{"name":"Phoenix VA Health Care System, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the ACT NOW Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2013,10,18]]},"reference":[{"key":"2022031223085019000_B1","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.2337\/dc06-0062","article-title":"Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999-2002","volume":"29","author":"Cowie","year":"2006","journal-title":"Diabetes Care"},{"key":"2022031223085019000_B2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1001\/jama.2012.39","article-title":"Prevalence of obesity and trends in the distribution of body mass 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