{"doi":"10.1001/jamanetworkopen.2024.0447","title":"Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes","abstract":"Importance: 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. Objective: To identify associations of growth hormone mediators with glycemic failure, beta cell function, and insulin sensitivity in youth-onset T2D. Design, Setting, and Participants: 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. Exposure: Plasma insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and insulin-like growth factor binding protein 1 (IGFBP-1). Main Outcomes and Measures: Main outcomes were (1) loss of glycemic control during the TODAY study, defined as hemoglobin A1c (HbA1c) 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, HbA1c), insulin sensitivity (1/fasting C-peptide), high-molecular-weight adiponectin, and beta cell function (C-peptide index, C-peptide oral disposition index). Results: 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]; P < .001) and higher C-peptide index per 100-ng/mL increase in IGF-1 (β [SE], 0.015 [0.003]; P < .001). A greater increase in log2 GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75 [95% CI, 1.05-2.99]; P = .04) and lower C-peptide index (β [SE], -0.02 [0.006]; P < .001). A greater increase in log2 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]; P = .007) and higher high-molecular-weight adiponectin (β [SE], 431 [156]; P = .007). Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT00081328.","journal":"JAMA Network Open","year":2024,"id":453389,"datarank":0.4965272724479326,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.1669435858474996,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.1669435858474996,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":7,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00081328"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":324755,"name":"Danielle Wolfs","orcid":null,"position":1,"is_corresponding":false},{"id":524295,"name":"Laure El ghormli","orcid":"0000-0003-4223-8407","position":2,"is_corresponding":false},{"id":671016,"name":"Lynne L. Levitsky","orcid":"0000-0002-3898-3933","position":3,"is_corresponding":false},{"id":365442,"name":"Lorraine E. Levitt Katz","orcid":null,"position":4,"is_corresponding":false},{"id":280970,"name":"Lori M. Laffel","orcid":"0000-0002-9675-3001","position":5,"is_corresponding":false},{"id":53898,"name":"Mary‐Elizabeth Patti","orcid":"0000-0002-8163-3429","position":6,"is_corresponding":false},{"id":323528,"name":"Elvira Isganaitis","orcid":"0000-0003-3477-0305","position":7,"is_corresponding":false},{"id":1275920,"name":"Chang Lu","orcid":"0009-0008-6107-6099","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:02:58.784290Z","pmid":"38421647","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}