{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:35:51Z","timestamp":1785857751222,"version":"3.56.0"},"reference-count":69,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK117067"],"award-info":[{"award-number":["DK117067"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018268","name":"Children's Miracle Network Hospitals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Duke Children's"},{"name":"Derfner Foundation Research Grant"},{"name":"Duke University Pediatric Departmental Support"},{"name":"Duke Strong Start Award Program","award":["P30DK124723"],"award-info":[{"award-number":["P30DK124723"]}]},{"name":"Duke Strong Start Award Program","award":["DK121710"],"award-info":[{"award-number":["DK121710"]}]},{"name":"Duke Strong Start Award Program","award":["5R01DK117491"],"award-info":[{"award-number":["5R01DK117491"]}]},{"name":"Duke Strong Start Award Program","award":["1U24DK129557"],"award-info":[{"award-number":["1U24DK129557"]}]},{"name":"Duke Strong Start Award Program","award":["2P30AG027816"],"award-info":[{"award-number":["2P30AG027816"]}]},{"name":"Clinical Trials Unit","award":["U54 GM104940"],"award-info":[{"award-number":["U54 GM104940"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018106","name":"Louisiana Clinical and Translational Science Center","doi-asserted-by":"publisher","award":["#P30DK072476"],"award-info":[{"award-number":["#P30DK072476"]}],"id":[{"id":"10.13039\/100018106","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Insulin resistance is associated with elevations in plasma branched-chain amino acids (BCAAs). BCAAs compete with aromatic amino acids including tryptophan for uptake into \u03b2 cells. To explore relationships between BCAAs and tryptophan metabolism, adiposity, and glucose tolerance, we compared urine metabolites in overweight\/obese youth with type 2 diabetes (T2D) with those in nondiabetic overweight\/obese and lean youth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Metabolites were measured in 24-hour and first-morning urine samples of 56 nondiabetic adolescents with overweight\/obesity, 42 adolescents with T2D, and 43 lean controls, aged 12 to 21 years. Group differences were assessed by Kruskal Wallis or ANOVA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Groups were comparable for age, pubertal status, and ethnicity. Youth with T2D were predominantly female and had highest percent body fat. BCAAs, branched-chain ketoacids (BCKAs), tryptophan, and kynurenine were higher in urine of subjects with T2D. There were no differences between lean controls and nondiabetic youth with overweight\/obesity. T2D was associated with diversion of tryptophan from the serotonin to the kynurenine pathway, with higher urinary kynurenine\/serotonin ratio and lower serotonin\/tryptophan and 5-HIAA\/kynurenine ratios. Urinary BCAAs, BCKAs, tryptophan, and ratios reflecting diversion to the kynurenine pathway correlated positively with metrics of body fat and hemoglobin A1c. Increases in these metabolites in the obese T2D group were more pronounced and statistically significant only in adolescent girls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Increases in urinary BCAAs and BCKAs in adolescent females with T2D are accompanied by diversion of tryptophan metabolism from the serotonin to the kynurenine pathway. These adaptations associate with higher risks of T2D in obese adolescent females than adolescent males.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad708","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T16:54:58Z","timestamp":1701968098000},"page":"e1345-e1358","source":"Crossref","is-referenced-by-count":12,"title":["Sex Differences in Branched-chain Amino Acid and Tryptophan Metabolism and Pathogenesis of Youth-onset Type 2 Diabetes"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9491-5891","authenticated-orcid":false,"given":"Natalie","family":"Hernandez","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliya","family":"Lokhnygina","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Duke University School of Medicine , Durham, NC 27710 , USA"},{"name":"Duke Clinical Research Institute, Duke University Medical Center , Durham, NC 27701 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan Elizabeth","family":"Ramaker","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute (DMPI), Duke University Medical Center , Durham, NC 27701 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Ilkayeva","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute (DMPI), Duke University Medical Center , Durham, NC 27701 , USA"},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center , Durham, NC 27705 , USA"},{"name":"Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Muehlbauer","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute (DMPI), Duke University Medical Center , Durham, NC 27701 , USA"},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center , Durham, NC 27705 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Research and Development, LabCorp , Burlington, NC 27215 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Research and Development, LabCorp , Burlington, NC 27215 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S","family":"Hsia","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, Pennington Biomedical Research Center , Baton Rouge, LA 70808 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Jain","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, University of North Carolina , Chapel Hill, NC 27514 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Bain","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute (DMPI), Duke University Medical Center , Durham, NC 27701 , USA"},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center , Durham, NC 27705 , USA"},{"name":"Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University Medical Center , Durham, NC 27701 , USA"},{"name":"Division of General Pediatrics and Adolescent Health, Duke University Medical Center , Durham, NC 27710 , USA"},{"name":"Department of Family Medicine and Community Health, Duke University Medical Center , Durham, NC 27710 , USA"},{"name":"Department of Population Health Sciences, Duke University Medical Center , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B","family":"Newgard","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute (DMPI), Duke University Medical Center , Durham, NC 27701 , USA"},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center , Durham, NC 27705 , USA"},{"name":"Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center , Durham, NC 27710 , USA"},{"name":"Department of Pharmacology and Cancer Biology, Duke University Medical Center , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Freemark","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center , Durham, NC 27710 , USA"},{"name":"Duke Molecular Physiology Institute (DMPI), Duke University Medical Center , Durham, NC 27701 , USA"},{"name":"Sarah W. 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