{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:58:40Z","timestamp":1770973120016,"version":"3.50.1"},"reference-count":49,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Youth-onset type 2 diabetes (T2D) has a more aggressive phenotype than adult-onset T2D, including rapid loss of glycemic control and increased complication risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify associations of growth hormone mediators with glycemic failure, beta cell function, and insulin sensitivity in youth-onset T2D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This post hoc secondary analysis of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomized clinical trial, which enrolled participants from July 2004 to February 2009, included 398 participants from 15 university-affiliated medical centers with available plasma samples from baseline and 36 months. Participants were youths aged 10 to 17 years with a duration of T2D of less than 2 years who were randomized to metformin, metformin plus lifestyle intervention, or metformin plus rosiglitazone. Participants were followed up for a mean (SD) of 3.9 (1.5) years during the trial, ending in 2011. Statistical analysis was performed from August 2022 to November 2023.<\/jats:p><\/jats:sec><jats:sec><jats:title>Exposure<\/jats:title><jats:p>Plasma insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and insulin-like growth factor binding protein 1 (IGFBP-1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Main outcomes were (1) loss of glycemic control during the TODAY study, defined as hemoglobin A<jats:sub>1c<\/jats:sub> (HbA<jats:sub>1c<\/jats:sub>) level of 8% or more for 6 months or inability to wean from insulin therapy, and (2) baseline and 36-month measures of glycemia (fasting glucose, HbA<jats:sub>1c<\/jats:sub>), insulin sensitivity (1\/fasting C-peptide), high-molecular-weight adiponectin, and beta cell function (C-peptide index, C-peptide oral disposition index).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This analysis included 398 participants (mean [SD] age, 13.9 [2.0] years; 248 girls [62%]; 166 Hispanic participants [42%]; 134 non-Hispanic Black participants [34%], and 84 non-Hispanic White participants [21%]). A greater increase in IGF-1 level between baseline and 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995 [95% CI, 0.991-0.997]; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) and higher C-peptide index per 100-ng\/mL increase in IGF-1 (\u03b2 [SE], 0.015 [0.003]; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001). A greater increase in log<jats:sub>2<\/jats:sub> GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75 [95% CI, 1.05-2.99]; <jats:italic>P<\/jats:italic>\u2009=\u2009.04) and lower C-peptide index (\u03b2 [SE], \u22120.02 [0.006]; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001). A greater increase in log<jats:sub>2<\/jats:sub> IGFBP-1 level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.37 [95% CI, 1.09-1.74]; <jats:italic>P<\/jats:italic>\u2009=\u2009.007) and higher high-molecular-weight adiponectin (\u03b2 [SE], 431 [156]; <jats:italic>P<\/jats:italic>\u2009=\u2009.007).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This study suggests that changes in plasma growth hormone mediators are associated with loss of glycemic control in youth-onset T2D, with IGF-1 associated with lower risk and GHR and IGFBP-1 associated with increased risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT00081328\">NCT00081328<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.0447","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T16:01:00Z","timestamp":1709222460000},"page":"e240447","source":"Crossref","is-referenced-by-count":8,"title":["Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes"],"prefix":"10.1001","volume":"7","author":[{"given":"Chang","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Wolfs","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laure","family":"El ghormli","sequence":"additional","affiliation":[{"name":"The Biostatistics Center, George Washington University, Washington, DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynne L.","family":"Levitsky","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetes, Massachusetts General Hospital, Harvard Medical School, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorraine E.","family":"Levitt Katz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori M.","family":"Laffel","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Boston Children\u2019s Hospital, 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