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Alfred Taubman Medical Research Institute","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008456","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006495","name":"Dr. Robert C. and Veronica Atkins Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100006495","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>As the incidence of obesity and type 2 diabetes (T2D) is occurring at a younger age, studying adolescent nutrient metabolism can provide insights on the development of T2D. Metabolic challenges, including an oral glucose tolerance test (OGTT) can assess the effects of perturbations in nutrient metabolism. Here, we present alterations in the global metabolome in response to an OGTT, classifying the influence of obesity and insulin resistance (IR) in adolescents that arrived at the clinic fasted and in a random-fed state. Participants were recruited as lean (n = 55, aged 8\u201317 years, BMI percentile 5\u201385%) and overweight and obese (OVOB, n = 228, aged 8\u201317 years, BMI percentile \u2265 85%). Untargeted metabolomics profiled 246 annotated metabolites in plasma at t0 and t60 min during the OGTT. Our results suggest that obesity and IR influence the switch from fatty acid (FA) to glucose oxidation in response to the OGTT. Obesity was associated with a blunted decline of acylcarnitines and fatty acid oxidation intermediates. In females, metabolites from the Fasted and Random-Fed OGTT were associated with HOMA-IR, including diacylglycerols, leucine\/isoleucine, acylcarnitines, and phosphocholines. Our results indicate that at an early age, obesity and IR may influence the metabolome dynamics in response to a glucose challenge.<\/jats:p>","DOI":"10.3390\/nu13103365","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T21:40:30Z","timestamp":1632778830000},"page":"3365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Comparing the Fasting and Random-Fed Metabolome Response to an Oral Glucose Tolerance Test in Children and Adolescents: Implications of Sex, Obesity, and Insulin Resistance"],"prefix":"10.3390","volume":"13","author":[{"given":"Jennifer L.","family":"LaBarre","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA"},{"name":"Department of Medicine, Dartmouth-Hitchcock Medical Center, Weight and Wellness Center, Lebanon, NH 03766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Hirschfeld","sequence":"additional","affiliation":[{"name":"Susan B Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanu","family":"Soni","sequence":"additional","affiliation":[{"name":"Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Kachman","sequence":"additional","affiliation":[{"name":"Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Wigginton","sequence":"additional","affiliation":[{"name":"Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Duren","sequence":"additional","affiliation":[{"name":"Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna Y.","family":"Fleischman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7388-8520","authenticated-orcid":false,"given":"Alla","family":"Karnovsky","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Burant","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA"},{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Susan B Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S2213-8587(17)30186-9","article-title":"Type 2 diabetes in adolescents and young adults","volume":"6","author":"Lascar","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/msb.2008.50","article-title":"Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity","volume":"4","author":"Shaham","year":"2008","journal-title":"Mol. 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