{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:30:17Z","timestamp":1788913817676,"version":"build-2803163510"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009745","name":"Emil and Wera Cornell Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009745","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tore Nilson Foundation"},{"name":"Erik & Lily Philipsons foundation"},{"name":"the Swedish state under the ALF agreement between the Swedish government and the county councils","award":["ALFGBG-720851"],"award-info":[{"award-number":["ALFGBG-720851"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Pregnancy induces significant physiological changes, particularly important in obesity (OB) and gestational diabetes (GDM). We aimed to determine metabolite changes and their relation to clinical variables of obesity and glucose metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum NMR metabolomics, clinical data, and body composition were determined in normoglycemic normal-weight (NW) (n\u2009=\u200932) and OB (n\u2009=\u200933) women at six time points spanning pregnancy and postpartum. Additionally, 31 GDM women (15 GDM-NW and 16 GDM-OB) were assessed during trimester 3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Profound shifts in the metabolome during pregnancy were exemplified by decreased branched chain amino acids (BCAAs) and tyrosine, and increased phenylalanine, succinate, lactate, and pyruvate. Comparison with clinical variables showed strong correlation between BCAAs\u2019 and bodyfat and insulin resistance mainly in the non-pregnant state. Conversely, pyruvate and lactate exhibited robust correlations with bodyfat, insulin resistance, and adipokines during pregnancy. Comparisons in late pregnancy showed higher levels of BCAAs, phenylalanine, lactate, and pyruvate in both obesity and GDM (GDM-NW and GDM-OB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BCAAs are elevated in obesity and GDM although may not be directly related to pregnancy-induced insulin resistance. Conversely, pyruvate and lactate appear connected to gestational changes of glucose metabolism where underlying obesity may contribute.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0335708","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:30:26Z","timestamp":1762540226000},"page":"e0335708","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomics and glucose tolerance in pregnancy and postpartum: The PONCH study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3722-3454","authenticated-orcid":true,"given":"Ulrika","family":"Andersson-Hall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders Bay","family":"Nord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8528-0141","authenticated-orcid":true,"given":"Daniel","family":"Malmodin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneta","family":"Holm\u00e4ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"pone.0335708.ref001","article-title":"Metabolic adaptations in pregnancy and their implications for the availability of substrates to the fetus","author":"E Herrera","year":"2000","journal-title":"Eur J Clin Nutr"},{"issue":"3","key":"pone.0335708.ref002","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1530\/REP-10-0088","article-title":"Obesity, insulin resistance, and pregnancy outcome","volume":"140","author":"PM Catalano","year":"2010","journal-title":"Reproduction"},{"issue":"9","key":"pone.0335708.ref003","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.3390\/nu13093080","article-title":"Longitudinal plasma metabolomics profile in pregnancy-A study in an ethnically diverse U.S. pregnancy cohort","volume":"13","author":"SD Mitro","year":"2021","journal-title":"Nutrients"},{"issue":"11","key":"pone.0335708.ref004","doi-asserted-by":"crossref","DOI":"10.1210\/clinem\/dgab475","article-title":"Longitudinal metabolic profiling of maternal obesity, gestational diabetes, and hypertensive pregnancy disorders","volume":"106","author":"J Kivel\u00e4","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"pone.0335708.ref005","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.3390\/ijms22115512","article-title":"Metabolomic biomarkers in gestational diabetes mellitus: a review of the evidence","volume":"22","author":"S Alesi","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pone.0335708.ref006","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41366-019-0452-7","article-title":"Longitudinal changes in adipokines and free leptin index during and after pregnancy in women with obesity","volume":"44","author":"U Andersson-Hall","year":"2020","journal-title":"Int J Obes (Lond)"},{"issue":"7","key":"pone.0335708.ref007","doi-asserted-by":"crossref","first-page":"626","DOI":"10.3109\/09513590.2013.777420","article-title":"Female obesity: short- and long-term consequences on the offspring","volume":"29","author":"D Galliano","year":"2013","journal-title":"Gynecol Endocrinol"},{"issue":"3","key":"pone.0335708.ref008","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/dme.12381","article-title":"Trying to understand gestational diabetes","volume":"31","author":"PM Catalano","year":"2014","journal-title":"Diabet Med"},{"key":"pone.0335708.ref009","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.metabol.2016.12.018","article-title":"Pregnancy to postpartum transition of serum metabolites in women with gestational diabetes","volume":"72","author":"E Chorell","year":"2017","journal-title":"Metabolism"},{"issue":"7","key":"pone.0335708.ref010","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.05.002","article-title":"Metabolic dynamics and prediction of gestational age and time to delivery in pregnant women","volume":"181","author":"L Liang","year":"2020","journal-title":"Cell"},{"issue":"2","key":"pone.0335708.ref011","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1021\/pr5011982","article-title":"Following healthy pregnancy by NMR metabolomics of plasma and correlation to urine","volume":"14","author":"J Pinto","year":"2015","journal-title":"J Proteome Res"},{"issue":"1","key":"pone.0335708.ref012","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s12916-016-0733-0","article-title":"Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence","volume":"14","author":"Q Wang","year":"2016","journal-title":"BMC Med"},{"issue":"12","key":"pone.0335708.ref013","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0145794","article-title":"Longitudinal metabolomic profiling of amino acids and lipids across healthy pregnancy","volume":"10","author":"KL Lindsay","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"pone.0335708.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0152740","article-title":"Metabolomics of human amniotic fluid and maternal plasma during normal pregnancy","volume":"11","author":"M Orczyk-Pawilowicz","year":"2016","journal-title":"PLoS One"},{"issue":"9","key":"pone.0335708.ref015","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3390\/metabo10090350","article-title":"Diabetes leads to alterations in normal metabolic transitions of pregnancy as revealed by time-course metabolomics","volume":"10","author":"JM Walejko","year":"2020","journal-title":"Metabolites"},{"issue":"3","key":"pone.0335708.ref016","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41390-018-0248-9","article-title":"Maternal obesity and gestational diabetes mellitus affect body composition through infancy: the PONCH study","volume":"85","author":"UK Andersson-Hall","year":"2019","journal-title":"Pediatr Res"},{"issue":"6","key":"pone.0335708.ref017","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2337\/diacare.27.6.1487","article-title":"Use and abuse of HOMA modeling","volume":"27","author":"TM Wallace","year":"2004","journal-title":"Diabetes Care"},{"issue":"19","key":"pone.0335708.ref018","doi-asserted-by":"crossref","first-page":"9887","DOI":"10.1021\/ac5025039","article-title":"Precision high-throughput proton NMR spectroscopy of human urine, serum, and plasma for large-scale metabolic phenotyping","volume":"86","author":"AC Dona","year":"2014","journal-title":"Anal Chem"},{"issue":"8","key":"pone.0335708.ref019","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1021\/ja055336t","article-title":"Measuring protein concentrations by NMR spectroscopy","volume":"128","author":"G Wider","year":"2006","journal-title":"J Am Chem Soc"},{"issue":"2","key":"pone.0335708.ref020","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.clnu.2013.04.013","article-title":"Increased consumption of salmon during pregnancy partly prevents the decline of some plasma essential amino acid concentrations in pregnant women","volume":"33","author":"A Rossary","year":"2014","journal-title":"Clin Nutr"},{"issue":"1","key":"pone.0335708.ref021","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12916-018-1248-7","article-title":"The effect of a lifestyle intervention in obese pregnant women on gestational metabolic profiles: findings from the UK pregnancies better eating and activity trial (UPBEAT) randomised controlled trial","volume":"17","author":"HL Mills","year":"2019","journal-title":"BMC Med"},{"issue":"1","key":"pone.0335708.ref022","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.diabres.2007.12.012","article-title":"Adipokines and insulin resistance during pregnancy","volume":"80","author":"AB Zavalza-G\u00f3mez","year":"2008","journal-title":"Diabetes Res Clin Pract"},{"issue":"1","key":"pone.0335708.ref023","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1017\/S0007114509991371","article-title":"Body fat, insulin resistance, energy expenditure and serum concentrations of leptin, adiponectin and resistin before, during and after pregnancy in healthy Swedish women","volume":"103","author":"B Eriksson","year":"2010","journal-title":"Br J Nutr"},{"key":"pone.0335708.ref024","article-title":"Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes","volume":"264","author":"PM Catalano","year":"1993","journal-title":"Am J Physiol"},{"key":"pone.0335708.ref025","doi-asserted-by":"crossref","first-page":"4207067","DOI":"10.1155\/2018\/4207067","article-title":"Higher Concentrations of BCAAs and 3-HIB are associated with insulin resistance in the transition from gestational diabetes to type 2 diabetes","volume":"2018","author":"U Andersson-Hall","year":"2018","journal-title":"J Diabetes Res"},{"issue":"12","key":"pone.0335708.ref026","doi-asserted-by":"crossref","DOI":"10.1172\/JCI173214","article-title":"SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes","volume":"134","author":"J Sabadell-Basallote","year":"2024","journal-title":"J Clin Invest"},{"issue":"7","key":"pone.0335708.ref027","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1007\/s00125-017-4261-z","article-title":"SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes","volume":"60","author":"JA van Diepen","year":"2017","journal-title":"Diabetologia"},{"issue":"21","key":"pone.0335708.ref028","doi-asserted-by":"crossref","first-page":"12048","DOI":"10.3390\/ijms222112048","article-title":"SUCNR1 is expressed in human placenta and mediates angiogenesis: significance in gestational diabetes","volume":"22","author":"R Atallah","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0335708.ref029","article-title":"Lactate induces insulin resistance in skeletal muscle by suppressing glycolysis and impairing insulin signaling","volume":"283","author":"CS Choi","year":"2002","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"4","key":"pone.0335708.ref030","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.2337\/dc21-1705","article-title":"Metabolomics and type 2 diabetes risk: an updated systematic review and meta-analysis of prospective cohort studies","volume":"45","author":"J Morze","year":"2022","journal-title":"Diabetes Care"},{"issue":"7","key":"pone.0335708.ref031","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1038\/s41396-018-0068-2","article-title":"Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota","volume":"12","author":"C Serena","year":"2018","journal-title":"ISME J"},{"issue":"3","key":"pone.0335708.ref032","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1111\/febs.16306","article-title":"Pathophysiology of type 2 diabetes and the impact of altered metabolic interorgan crosstalk","volume":"290","author":"JM Sanches","year":"2023","journal-title":"FEBS J"},{"issue":"18","key":"pone.0335708.ref033","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1002\/1873-3468.14441","article-title":"Nutritional and metabolic signalling through GPCRs","volume":"596","author":"E Pardella","year":"2022","journal-title":"FEBS Lett"},{"issue":"5","key":"pone.0335708.ref034","doi-asserted-by":"crossref","first-page":"351","DOI":"10.7555\/JBR.35.20200191","article-title":"Differentiation of gestational diabetes mellitus by nuclear magnetic resonance-based metabolic plasma analysis","volume":"35","author":"L Liu","year":"2021","journal-title":"J Biomed Res"},{"issue":"1","key":"pone.0335708.ref035","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":"F Vanweert","year":"2022","journal-title":"Nutr Diabetes"},{"issue":"7","key":"pone.0335708.ref036","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1038\/s41390-020-01115-9","article-title":"Infant body composition relationship to maternal adipokines and fat mass: the PONCH study","volume":"89","author":"UK Andersson-Hall","year":"2021","journal-title":"Pediatr Res"},{"issue":"2","key":"pone.0335708.ref037","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s10995-011-0775-z","article-title":"Association between gestational weight gain according to body mass index and postpartum weight in a large cohort of Danish women","volume":"16","author":"L Rode","year":"2012","journal-title":"Matern Child Health J"},{"issue":"5","key":"pone.0335708.ref038","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1080\/00016340802012288","article-title":"Effects of pre-pregnancy physical activity and maternal BMI on gestational weight gain and birth weight","volume":"87","author":"M L\u00f6f","year":"2008","journal-title":"Acta Obstet Gynecol Scand"},{"issue":"9","key":"pone.0335708.ref039","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1111\/aogs.12910","article-title":"Effects on postpartum weight retention after antenatal lifestyle intervention - a secondary analysis of a randomized controlled trial","volume":"95","author":"A Ronnberg","year":"2016","journal-title":"Acta Obstet Gynecol Scand"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:30:32Z","timestamp":1762540232000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335708"}},"subtitle":[],"editor":[{"given":"Hui-Qi","family":"Qu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,7]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0335708","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,7]]}}}