{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:51:14Z","timestamp":1793829074016,"version":"4.6.1"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Gestational Diabetes Mellitus (GDM) is a metabolic disorder marked by Q10 hyperglycemia that can negatively affect both mothers and newborns. The increasing prevalence of GDM and the limitations associated with the standard diagnostic test highlight the urgent need for early screening strategies that promote timely interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study aims to investigate the metabolic profile associated with GDM through an untargeted metabolomic analysis using mass spectrometry (MS)- based omics. Serum samples were collected from 40 pregnant women at weeks 24\u201328 of gestation based on the 2-h 75-g oral glucose tolerance test (OGTT); 50% were diagnosed with GDM (n = 20), and the remaining were considered a control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>The results showed distinct metabolic differences between women with GDM and those without, with 222 significantly dysregulated metabolites, 120 up- and 102 downregulated in GDM compared to the control group. Key metabolic pathways, such as tryptophan, inositol phosphate, phenylalanine, and histidine metabolism, were notably dysregulated in GDM. The study also found that specific metabolites, like N-Acetylproline and Serylmethionine, with area under the curve (AUC) of 0.978 and 0.968, respectively, showed high accuracy in distinguishing between GDM and non-GDM women. This study would enhance our understanding of metabolic alterations in GDM and could contribute to early prediction and management strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmolb.2024.1485587","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T05:11:35Z","timestamp":1734930695000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Untargeted metabolomics profiling of gestational diabetes mellitus: insights into early diagnosis and metabolic pathway alterations"],"prefix":"10.3389","volume":"11","author":[{"given":"Shereen M.","family":"Aleidi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba","family":"Al Fahmawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem H.","family":"AlMalki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Al Mogren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Alwahsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Mujammami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Costanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas","family":"Abdel Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"111315","DOI":"10.1016\/j.biopha.2021.111315","article-title":"Adipose tissue and insulin resistance in obese","volume":"137","author":"Ahmed","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B2","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1080\/14789450.2023.2295866","article-title":"Metabolomics in diabetes mellitus: clinical insight","volume":"20","author":"Aleidi","year":"2023","journal-title":"Expert Rev. Proteomics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"628","DOI":"10.3390\/metabo11090628","article-title":"A distinctive human metabolomics alteration associated with osteopenic and osteoporotic patients","volume":"11","author":"Aleidi","year":"2021","journal-title":"Metabolites"},{"key":"B4","doi-asserted-by":"publisher","first-page":"5512","DOI":"10.3390\/ijms22115512","article-title":"Metabolomic biomarkers in gestational diabetes mellitus: a review of the evidence","volume":"22","author":"Alesi","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.2337\/db15-1720","article-title":"A predictive metabolic signature for the transition from gestational diabetes mellitus to type 2 diabetes","volume":"65","author":"Allalou","year":"2016","journal-title":"Diabetes"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4219","DOI":"10.3390\/ijms24044219","article-title":"E. coli secretome metabolically modulates MDA-MB-231 breast cancer cells' energy metabolism","volume":"24","author":"AlMalki","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"214","DOI":"10.5144\/0256-4947.2015.214","article-title":"N-acetyltransferase 1 and 2 polymorphisms and risk of diabetes mellitus type 2 in a Saudi population","volume":"35","author":"Al-Shaqha","year":"2015","journal-title":"Ann. Saudi Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e103217","DOI":"10.1371\/journal.pone.0103217","article-title":"Evidence that multiple defects in lipid regulation occur before hyperglycemia during the prodrome of type-2 diabetes","volume":"9","author":"Anderson","year":"2014","journal-title":"PLoS One"},{"key":"B9","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3390\/medsci9040059","article-title":"Early gestational diabetes mellitus: diagnostic strategies and clinical implications","volume":"9","author":"Bhattacharya","year":"2021","journal-title":"Med. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0203799","DOI":"10.1371\/journal.pone.0203799","article-title":"Lipid profile changes in erythrocyte membranes of women with diagnosed GDM","volume":"13","author":"Bukowiecka-Matusiak","year":"2018","journal-title":"PLoS One"},{"key":"B11","doi-asserted-by":"publisher","first-page":"7811","DOI":"10.3390\/ijms21217811","article-title":"Associations of arginine with gestational diabetes mellitus in a follow-up study","volume":"21","author":"Burzynska-Pedziwiatr","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"5079","DOI":"10.3390\/molecules25215079","article-title":"Role of inositols and inositol phosphates in energy metabolism","volume":"25","author":"Chatree","year":"2020","journal-title":"Molecules"},{"key":"B13","doi-asserted-by":"publisher","first-page":"112183","DOI":"10.1016\/j.biopha.2021.112183","article-title":"Gestational diabetes mellitus - a metabolic and reproductive disorder","volume":"143","author":"Choudhury","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B14","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13578-024-01245-1","article-title":"Methylmalonic acidemia triggers lysosomal-autophagy dysfunctions","volume":"14","author":"Costanzo","year":"2024","journal-title":"Cell Biosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"705932","DOI":"10.3389\/fphar.2021.705932","article-title":"A metabolic pattern in healthy subjects given a single dose of metformin: a metabolomics approach","volume":"12","author":"Dahabiyeh","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"990","DOI":"10.3390\/metabo13090990","article-title":"Serum-based lipid panels for diagnosis of idiopathic Parkinson\u2019s disease","volume":"13","author":"Dahabiyeh","year":"2023","journal-title":"Metabolites"},{"key":"B17","doi-asserted-by":"publisher","first-page":"431","DOI":"10.3390\/cells12030431","article-title":"Diabetes and its cardiovascular complications: potential role of the acetyltransferase p300","volume":"12","author":"Di Pietrantonio","year":"2023","journal-title":"Cells"},{"key":"B18","doi-asserted-by":"publisher","first-page":"344","DOI":"10.3402\/ijch.v69i4.17669","article-title":"Individual saturated fatty acids are associated with different components of insulin resistance and glucose metabolism: the GOCADAN study","volume":"69","author":"Ebbesson","year":"2010","journal-title":"Int. J. Circumpolar Health"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2444","DOI":"10.3390\/nu14122444","article-title":"Role of beta cell function and insulin resistance in the development of gestational diabetes mellitus","volume":"14","author":"Ellerbrock","year":"2022","journal-title":"Nutrients"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4348","DOI":"10.1210\/jc.2015-2862","article-title":"Maternal early pregnancy serum metabolites and risk of gestational diabetes mellitus","volume":"100","author":"Enquobahrie","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B21","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/978-3-031-08014-2_64","article-title":"Metabolomic biomarkers, metabolite patterns, and gestational diabetes mellitus","volume-title":"Biomarkers in diabetes","author":"Francis","year":"2023"},{"key":"B22","doi-asserted-by":"publisher","first-page":"358","DOI":"10.2337\/db15-0659","article-title":"Skeletal muscle phospholipid metabolism regulates insulin sensitivity and contractile function","volume":"65","author":"Funai","year":"2016","journal-title":"Diabetes"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1096\/fj.201800724R","article-title":"The saturation degree of fatty acids and their derived acylcarnitines determines the direct effect of metabolically active thyroid hormones on insulin sensitivity in skeletal muscle cells","volume":"33","author":"Giacco","year":"2019","journal-title":"FASEB J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"609806","DOI":"10.3389\/fmolb.2020.609806","article-title":"Distinctive metabolomics patterns associated with insulin resistance and type 2 diabetes mellitus","volume":"7","author":"Gu","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"111425","DOI":"10.1016\/j.mce.2021.111425","article-title":"Mof acetyltransferase inhibition ameliorates glucose intolerance and islet dysfunction of type 2 diabetes via targeting pancreatic \u03b1-cells","volume":"537","author":"Guo","year":"2021","journal-title":"Mol. Cell Endocrinol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e000330","DOI":"10.1136\/bmjmed-2022-000330","article-title":"Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study","volume":"2","author":"Huhn","year":"2023","journal-title":"BMJ Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e0141","DOI":"10.1199\/tab.0141","article-title":"Histidine biosynthesis","volume":"9","author":"Ingle","year":"2011","journal-title":"Arab. BookAmerican Soc. Plant Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"384","DOI":"10.3390\/jcm11020384","article-title":"Serum C18:1-cer as a potential biomarker for early detection of gestational diabetes","volume":"11","author":"Juchnicka","year":"2022","journal-title":"J. Clin. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1111\/jdi.13219","article-title":"N\u2010acetyl\u2010seryl\u2010aspartyl\u2010lysyl\u2010proline is a valuable endogenous antifibrotic peptide for kidney fibrosis in diabetes: an update and translational aspects","volume":"11","author":"Kanasaki","year":"2020","journal-title":"J. Diabetes Investig."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1111\/dme.14292","article-title":"Barriers to completing oral glucose tolerance testing in women at risk of gestational diabetes","volume":"37","author":"Lachmann","year":"2020","journal-title":"Diabet. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12916-023-02819-5","article-title":"Exploring preconception signatures of metabolites in mothers with gestational diabetes mellitus using a non-targeted approach","volume":"21","author":"Li","year":"2023","journal-title":"BMC Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4863","DOI":"10.1016\/j.clnu.2021.07.008","article-title":"A longitudinal study of plasma acylcarnitines throughout pregnancy and associations with risk of gestational diabetes mellitus","volume":"40","author":"Lin","year":"2021","journal-title":"Clin. Nutr."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3283","DOI":"10.1210\/clinem\/dgab513","article-title":"Maternal metabolites associated with gestational diabetes mellitus and a postpartum disorder of glucose metabolism","volume":"106","author":"Liu","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.2337\/dc16-0863","article-title":"An unbiased lipidomics approach identifies early second trimester lipids predictive of maternal glycemic traits and gestational diabetes mellitus","volume":"39","author":"Lu","year":"2016","journal-title":"Diabetes Care"},{"key":"B35","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12986-021-00606-8","article-title":"Discovery of metabolic biomarkers for gestational diabetes mellitus in a Chinese population","volume":"18","author":"Lu","year":"2021","journal-title":"Nutr. Metab."},{"key":"B36","doi-asserted-by":"publisher","first-page":"6689414","DOI":"10.1155\/2021\/6689414","article-title":"Unique biomarker characteristics in gestational diabetes mellitus identified by LC\u2010MS\u2010based metabolic profiling","volume":"2021","author":"Meng","year":"2021","journal-title":"J. Diabetes Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00125-003-1275-5","article-title":"Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes","volume":"47","author":"Min","year":"2004","journal-title":"Diabetologia"},{"key":"B38","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/jn\/nxz220","article-title":"Distinct metabolic profile in early pregnancy of overweight and obese women developing gestational diabetes","volume":"150","author":"Mokkala","year":"2020","journal-title":"J. Nutr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.cmet.2012.01.024","article-title":"Interplay between lipids and branched-chain amino acids in development of insulin resistance","volume":"15","author":"Newgard","year":"2012","journal-title":"Cell Metab."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1152\/japplphysiol.00664.2015","article-title":"Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans","volume":"120","author":"Newsom","year":"2016","journal-title":"J. Appl. Physiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e1000229","DOI":"10.1371\/journal.pbio.1000229","article-title":"Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation","volume":"7","author":"Paulmann","year":"2009","journal-title":"PLoS Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.biochi.2005.04.002","article-title":"Catabolism of intracellular N-terminal acetylated proteins: involvement of acylpeptide hydrolase and acylase","volume":"87","author":"Perrier","year":"2005","journal-title":"Biochimie"},{"key":"B44","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1097\/MED.0000000000000170","article-title":"Obesity, insulin resistance, and type 1 diabetes mellitus","volume":"22","author":"Polsky","year":"2015","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e001551","DOI":"10.1136\/bmjdrc-2020-001551","article-title":"Plasma lipidomics profile in pregnancy and gestational diabetes risk: a prospective study in a multiracial\/ethnic cohort","volume":"9","author":"Rahman","year":"2021","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"B46","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s13098-023-01098-7","article-title":"An early prediction model for gestational diabetes mellitus based on metabolomic biomarkers","volume":"15","author":"Razo-Azamar","year":"2023","journal-title":"Diabetol. Metab. Syndr."},{"key":"B47","doi-asserted-by":"publisher","first-page":"16913","DOI":"10.3390\/ijms242316913","article-title":"Proteomics and metabolomics in biomedicine","volume":"24","author":"Santorelli","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"106462","DOI":"10.1016\/j.bpc.2020.106462","article-title":"Metabolomics: an emerging potential approach to decipher critical illnesses","volume":"267","author":"Siddiqui","year":"2020","journal-title":"Biophys. Chem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2881","DOI":"10.3390\/diagnostics12112881","article-title":"A study of the metabolic pathways affected by gestational diabetes mellitus: comparison with type 2 diabetes","volume":"12","author":"Spanou","year":"2022","journal-title":"Diagnostics"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e0135657","DOI":"10.1371\/journal.pone.0135657","article-title":"An enlarged profile of uremic solutes","volume":"10","author":"Tanaka","year":"2015","journal-title":"PloS One"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e23251","DOI":"10.1096\/fj.202301122RR","article-title":"Targeting phospholipid remodeling pathway improves insulin resistance in diabetic mouse models","volume":"37","author":"Tian","year":"2023","journal-title":"FASEB J."},{"key":"B52","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1038\/hr.2010.113","article-title":"Metabolomic profiling of uremic solutes in CKD patients","volume":"33","author":"Toyohara","year":"2010","journal-title":"Hypertens. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/00005176-198201010-00019","article-title":"Postnatal development of peptidase enzymes in rat small intestine","volume":"1","author":"Vaeth","year":"1982","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"B54","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1681\/ASN.2007121377","article-title":"A bench to bedside view of uremic toxins","volume":"19","author":"Vanholder","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"109050","DOI":"10.1016\/j.diabres.2021.109050","article-title":"IDF diabetes atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by international association of diabetes in pregnancy study group\u2019s criteria","volume":"183","author":"Wang","year":"","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.4239\/wjd.v12.i8.1164","article-title":"Current progress in metabolomics of gestational diabetes mellitus","volume":"12","author":"Wang","year":"2021","journal-title":"World J. Diabetes"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1000296","DOI":"10.3389\/fendo.2022.1000296","article-title":"Dynamic changes and early predictive value of branched-chain amino acids in gestational diabetes mellitus during pregnancy","volume":"13","author":"Wang","year":"","journal-title":"Front. Endocrinol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"333","DOI":"10.4093\/dmj.2022.0348","article-title":"Gestational diabetes mellitus and its implications across the life span","volume":"47","author":"Wicklow","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"B59","doi-asserted-by":"publisher","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: the human metabolome database for 2022","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"92","DOI":"10.2174\/2213235X11301010092","article-title":"Multivariate analysis in metabolomics","volume":"1","author":"Worley","year":"2013","journal-title":"Curr. Metabolomics"},{"key":"B61","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1007\/s00404-023-07131-4","article-title":"Prediction of gestational diabetes mellitus at the first trimester: machine-learning algorithms","volume":"309","author":"Xin","year":"2024","journal-title":"Arch. Gynecol. Obstet."},{"key":"B62","doi-asserted-by":"publisher","first-page":"e85413","DOI":"10.5812\/ijem.85413","article-title":"Association of circulating branched-chain amino acids with gestational diabetes mellitus: a meta-analysis","volume":"17","author":"Zhao","year":"2019","journal-title":"Int. J. Endocrinol. Metab."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1093\/ajcn\/nqy051","article-title":"A prospective and longitudinal study of plasma phospholipid saturated fatty acid profile in relation to cardiometabolic biomarkers and the risk of gestational diabetes","volume":"107","author":"Zhu","year":"2018","journal-title":"Am. J. Clin. Nutr."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2024.1485587\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T05:11:39Z","timestamp":1734930699000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2024.1485587\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":63,"alternative-id":["10.3389\/fmolb.2024.1485587"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2024.1485587","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,23]]},"article-number":"1485587"}}