{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T20:29:33Z","timestamp":1774902573734,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01DK103946"],"award-info":[{"award-number":["R01DK103946"]}]},{"name":"National Institutes of Health","award":["K23DK110419"],"award-info":[{"award-number":["K23DK110419"]}]},{"name":"National Institutes of Health","award":["K24HD071843"],"award-info":[{"award-number":["K24HD071843"]}]},{"name":"National Institutes of Health","award":["K24DK109940"],"award-info":[{"award-number":["K24DK109940"]}]},{"name":"National Institutes of Health","award":["P30DK057521"],"award-info":[{"award-number":["P30DK057521"]}]},{"name":"National Institutes of Health","award":["1UL1TR002541-01"],"award-info":[{"award-number":["1UL1TR002541-01"]}]},{"name":"National Institutes of Health","award":["1UL1TR001102"],"award-info":[{"award-number":["1UL1TR001102"]}]},{"name":"National Institutes of Health","award":["1S10RR023405-01"],"award-info":[{"award-number":["1S10RR023405-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Adults with obesity have a reduction in branched-chain amino acid (BCAA) levels following metabolic and bariatric surgery (MBS), which is hypothesized to contribute to the metabolic advantages of MBS. We examined this relationship in 62 youth 13\u201324 years old with severe obesity (47 female) over 12 months. Thirty had sleeve gastrectomy (SG) and 32 were non-surgical controls (NS). We measured fasting insulin, glucose, glycated hemoglobin (HbA1c), isoleucine, leucine, and valine concentrations, and post-prandial insulin and glucose, following a mixed meal tolerance test. Twenty-four-hour food recalls were collected. At baseline, groups did not differ in the intake or the serum levels of BCAAs, HbA1C, HOMA-IR, Matsuda index, insulinogenic index, or oral Disposition index (oDI). Over 12 months, SG vs. NS had greater reductions in serum BCAAs, and SG had significant reductions in BCAA intake. SG vs. NS had greater reductions in HbA1c and HOMA-IR, with increases in the Matsuda index and oDI. In SG, baseline leucine and total BCAA concentrations were negatively correlated with the baseline Matsuda index. Reductions in serum leucine were positively associated with the reductions in HOMA-IR over 12 months. These associations suggest a potential role of BCAA in regulating metabolic health. Reducing dietary intake and serum BCAA concentrations may reduce insulin resistance.<\/jats:p>","DOI":"10.3390\/nu15173801","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T10:09:49Z","timestamp":1693390189000},"page":"3801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Changes in Branched-Chain Amino Acids One Year after Sleeve Gastrectomy in Youth with Obesity and Their Association with Changes in Insulin Resistance"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-7441","authenticated-orcid":false,"given":"Imen","family":"Becetti","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology, Mass General for Children and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan","family":"Lauze","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Lee","sequence":"additional","affiliation":[{"name":"Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5482-0440","authenticated-orcid":false,"given":"Miriam A.","family":"Bredella","sequence":"additional","affiliation":[{"name":"Department of Radiology, Musculoskeletal Imaging and Interventions, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhusmita","family":"Misra","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Mass General for Children and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-4433","authenticated-orcid":false,"given":"Vibha","family":"Singhal","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Mass General for Children and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Pediatric Program, MGH Weight Center, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","unstructured":"(2023, January 24). Products\u2014Health E Stats\u2014Prevalence of Overweight, Obesity, and Severe Obesity among Children and Adolescents Aged 2\u201319 Years: United States, 1963\u20131965 through 2017\u20132018, Available online: https:\/\/www.cdc.gov\/nchs\/data\/hestat\/obesity-child-17-18\/obesity-child.htm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.mayocp.2016.09.017","article-title":"Review of Childhood Obesity: From Epidemiology, Etiology and Comorbidities to Clinical Assessment and Treatment","volume":"92","author":"Kumar","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1001\/jama.2021.11165","article-title":"Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001\u20132017","volume":"326","author":"Lawrence","year":"2021","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41574-020-0334-z","article-title":"Young-onset type 2 diabetes mellitus\u2014Implications for morbidity and mortality","volume":"16","author":"Magliano","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108123","DOI":"10.1016\/j.jdiacomp.2021.108123","article-title":"Cardiovascular risk factor progression in adolescents and young adults with youth-onset type 2 diabetes","volume":"36","author":"Shah","year":"2022","journal-title":"J. Diabetes Its Complicat."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"TODAY Study Group (2021). Long-Term Complications in Youth-Onset Type 2 Diabetes. N. Engl. J. Med., 385, 416\u2013426.","DOI":"10.1056\/NEJMoa2100165"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1001\/jamapediatrics.2018.3030","article-title":"National Trends in the Use of Metabolic and Bariatric Surgery Among Pediatric Patients with Severe Obesity","volume":"172","author":"Griggs","year":"2018","journal-title":"JAMA Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1056\/NEJMoa1813909","article-title":"Five-Year Outcomes of Gastric Bypass in Adolescents as Compared with Adults","volume":"380","author":"Inge","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e20191399","DOI":"10.1542\/peds.2019-1399","article-title":"Musculoskeletal Pain, Physical Function, and Quality of Life After Bariatric Surgery","volume":"144","author":"Gupta","year":"2019","journal-title":"Pediatrics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJMoa1506699","article-title":"Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents","volume":"374","author":"Inge","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","article-title":"A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance","volume":"9","author":"Newgard","year":"2009","journal-title":"Cell Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.2337\/dc08-2075","article-title":"Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women","volume":"32","author":"Huffman","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1002\/oby.20901","article-title":"Metabolomic profiles and childhood obesity","volume":"22","author":"Perng","year":"2014","journal-title":"Obesity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00125-009-1637-8","article-title":"Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men","volume":"53","author":"Tai","year":"2010","journal-title":"Diabetologia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e1827","DOI":"10.1210\/clinem\/dgaa751","article-title":"Elevated Plasma Branched-Chain Amino Acid Levels Correlate with Type 2 Diabetes\u2013Related Metabolic Disturbances","volume":"106","author":"Vanweert","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.2047-6310.2012.00087.x","article-title":"Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents","volume":"8","author":"McCormack","year":"2013","journal-title":"Pediatr. Obes."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nm.2307","article-title":"Metabolite profiles and the risk of developing diabetes","volume":"17","author":"Wang","year":"2011","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"833","DOI":"10.2337\/dc15-2251","article-title":"Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis","volume":"39","author":"Hruby","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"648","DOI":"10.2337\/dc12-0895","article-title":"Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults","volume":"36","author":"Soininen","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s00125-011-2356-5","article-title":"Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss","volume":"55","author":"Shah","year":"2012","journal-title":"Diabetologia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/1753-0407.12645","article-title":"Diabetes and branched-chain amino acids: What is the link?","volume":"10","author":"Bloomgarden","year":"2018","journal-title":"J. Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101261","DOI":"10.1016\/j.molmet.2021.101261","article-title":"Insulin action, type 2 diabetes, and branched-chain amino acids: A two-way street","volume":"52","author":"White","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrendo.2014.171","article-title":"Branched-chain amino acids in metabolic signalling and insulin resistance","volume":"10","author":"Lynch","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.cmet.2021.03.025","article-title":"The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine","volume":"33","author":"Yu","year":"2021","journal-title":"Cell Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nm.4057","article-title":"A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance","volume":"22","author":"Jang","year":"2016","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41387-022-00213-3","article-title":"Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances BCAA metabolism in type 2 diabetes","volume":"12","author":"Vanweert","year":"2022","journal-title":"Nutr. Diabetes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.1093\/jn\/nxaa298","article-title":"Branched-Chain Amino Acid Oxidation Is Elevated in Adults with Morbid Obesity and Decreases Significantly after Sleeve Gastrectomy","volume":"150","author":"Tan","year":"2020","journal-title":"J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.2337\/dc14-0195","article-title":"Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes","volume":"37","author":"Lips","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.2337\/db13-0185","article-title":"Effect of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding on branched-chain amino acid metabolism","volume":"62","author":"Magkos","year":"2013","journal-title":"Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.nutres.2020.10.008","article-title":"Bariatric surgery reduces branched-chain amino acids\u2019 levels: A systematic review and meta-analysis","volume":"87","author":"Esmaeilinezhad","year":"2021","journal-title":"Nutr. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1007\/s11695-015-2023-x","article-title":"The Effects of Sleeve Gastrectomy and Gastric Bypass on Branched-Chain Amino Acid Metabolism 1 Year after Bariatric Surgery","volume":"26","author":"Tan","year":"2016","journal-title":"Obes. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108239","DOI":"10.1016\/j.celrep.2020.108239","article-title":"The Role of Elevated Branched-Chain Amino Acids in the Effects of Vertical Sleeve Gastrectomy to Reduce Weight and Improve Glucose Regulation","volume":"33","author":"Kramer","year":"2020","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/ijo.2013.142","article-title":"Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents","volume":"38","author":"Liang","year":"2014","journal-title":"Int. J. Obes."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.2337\/diacare.25.11.2081","article-title":"Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children","volume":"25","author":"Uwaifo","year":"2002","journal-title":"Diabetes Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"335","DOI":"10.2337\/dc08-1478","article-title":"Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels","volume":"32","author":"Utzschneider","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jpeds.2011.12.050","article-title":"Oral disposition index in obese youth from normal to prediabetes to diabetes: Relationship to clamp disposition index","volume":"161","author":"Sjaarda","year":"2012","journal-title":"J. Pediatr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1210\/jc.2014-2299","article-title":"Fasting and OGTT-derived measures of insulin resistance as compared with the euglycemic-hyperinsulinemic clamp in nondiabetic finnish offspring of type 2 diabetic individuals","volume":"100","author":"Lorenzo","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/CIRCULATIONAHA.117.029468","article-title":"Metabolic Predictors of Incident Coronary Heart Disease in Women","volume":"137","author":"Paynter","year":"2018","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"155346","DOI":"10.1016\/j.metabol.2022.155346","article-title":"Early metabolomic, lipid and lipoprotein changes in response to medical and surgical therapeutic approaches to obesity","volume":"138","author":"Angelidi","year":"2023","journal-title":"Metabolism"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E1552","DOI":"10.1152\/ajpendo.00134.2007","article-title":"Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism","volume":"293","author":"She","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14841","DOI":"10.1038\/srep14841","article-title":"Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue","volume":"5","author":"Mardinoglu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E1175","DOI":"10.1152\/ajpendo.00630.2012","article-title":"Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity","volume":"304","author":"Lackey","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1021\/pr500416v","article-title":"Serum and adipose tissue amino acid homeostasis in the metabolically healthy obese","volume":"13","author":"Badoud","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13850","DOI":"10.1038\/s41598-017-14120-6","article-title":"Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism","volume":"7","author":"Berdasco","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.2337\/diabetes.54.9.2674","article-title":"Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability","volume":"54","author":"Tremblay","year":"2005","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2337\/diabetes.51.3.599","article-title":"Mechanism of amino acid-induced skeletal muscle insulin resistance in humans","volume":"51","author":"Krebs","year":"2002","journal-title":"Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s00125-003-1129-1","article-title":"Direct and indirect effects of amino acids on hepatic glucose metabolism in humans","volume":"46","author":"Krebs","year":"2003","journal-title":"Diabetologia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.molmet.2016.08.001","article-title":"Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism","volume":"5","author":"Lerin","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.2337\/db16-1475","article-title":"Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated with Protein Ingestion\u2013Induced Insulin Resistance","volume":"66","author":"Harris","year":"2017","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s00125-017-4222-6","article-title":"Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels","volume":"60","author":"Mahendran","year":"2017","journal-title":"Diabetologia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.2337\/dc17-1642","article-title":"Genetic Support for a Causal Role of Insulin Resistance on Circulating Branched-Chain Amino Acids and Inflammation","volume":"40","author":"Wang","year":"2017","journal-title":"Diabetes Care"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/17\/3801\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:43:20Z","timestamp":1760129000000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/17\/3801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,30]]},"references-count":53,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["nu15173801"],"URL":"https:\/\/doi.org\/10.3390\/nu15173801","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,30]]}}}