{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:33:28Z","timestamp":1790660008460,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T00:00:00Z","timestamp":1647648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK068001"],"award-info":[{"award-number":["R01 DK068001"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["T32DK07658"],"award-info":[{"award-number":["T32DK07658"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Colorado clinical and translational  science institute","award":["KL2-TR002534"],"award-info":[{"award-number":["KL2-TR002534"]}]},{"DOI":"10.13039\/100000071","name":"NICHD","doi-asserted-by":"publisher","award":["1K99HD108272-01"],"award-info":[{"award-number":["1K99HD108272-01"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Fetal overnutrition predisposes offspring to increased metabolic risk. The current study used metabolomics to assess sustained differences in serum metabolites across childhood and adolescence among youth exposed to three typologies of fetal overnutrition: maternal obesity only, gestational diabetes mellitus (GDM) only, and obesity + GDM. We included youth exposed in utero to obesity only (BMI \u2265 30; n = 66), GDM only (n = 56), obesity + GDM (n = 25), or unexposed (n = 297), with untargeted metabolomics measured at ages 10 and 16 years. We used linear mixed models to identify metabolites across both time-points associated with exposure to any overnutrition, using a false-discovery-rate correction (FDR) &lt;0.20. These metabolites were included in a principal component analysis (PCA) to generate profiles and assess metabolite profile differences with respect to overnutrition typology (adjusted for prenatal smoking, offspring age, sex, and race\/ethnicity). Fetal overnutrition was associated with 52 metabolites. PCA yielded four factors accounting for 17\u201327% of the variance, depending on age of measurement. We observed differences in three factor patterns with respect to overnutrition typology: sphingomyelin-mannose (8\u201313% variance), skeletal muscle metabolism (6\u201310% variance), and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF; 3\u20134% variance). The sphingomyelin-mannose factor score was higher among offspring exposed to obesity vs. GDM. Exposure to obesity + GDM (vs. GDM or obesity only) was associated with higher skeletal muscle metabolism and CMPF scores. Fetal overnutrition is associated with metabolic changes in the offspring, but differences between typologies of overnutrition account for a small amount of variation in the metabolome, suggesting there is likely greater pathophysiological overlap than difference.<\/jats:p>","DOI":"10.3390\/metabo12030265","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:34:27Z","timestamp":1647812067000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition"],"prefix":"10.3390","volume":"12","author":[{"given":"Ellen C.","family":"Francis","sequence":"first","affiliation":[{"name":"Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-5459","authenticated-orcid":false,"given":"Katerina","family":"Kechris","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8402-0118","authenticated-orcid":false,"given":"Catherine C.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Michelotti","sequence":"additional","affiliation":[{"name":"Metabolon, Inc., Morrisville, NC 27560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9514-8929","authenticated-orcid":false,"given":"Dana","family":"Dabelea","sequence":"additional","affiliation":[{"name":"Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8552-6850","authenticated-orcid":false,"given":"Wei","family":"Perng","sequence":"additional","affiliation":[{"name":"Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s00125-019-4914-1","article-title":"Developmental overnutrition and obesity and type 2 diabetes in offspring","volume":"62","author":"Perng","year":"2019","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.2105\/AJPH.2009.172890","article-title":"Percentage of gestational diabetes mellitus attributable to overweight and obesity","volume":"100","author":"Kim","year":"2010","journal-title":"Am. 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