{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T14:08:40Z","timestamp":1776866920017,"version":"3.51.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"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. Nutr."],"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>We aimed to provide a comprehensive understanding of the associations between Trimethylamine-N-oxide (TMAO), its precursor and gestational diabetes mellitus (GDM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective study, 940 women were included in a Chinese single -center pregnant cohort. First trimester plasma concentrations of TMAO and its precursors (betaine, choline, L-carnitine, and trimethylamine) were measured using UPLC-ESI-MS\/MS. GDM and specific abnormal glucose levels (fasting glucose; one-hour post-load glucose, 1-h PG; two-hour post load glucose, 2-h PG; and 1-h PG\u202f\u2265\u202f8.6\u202fmmol\/L) were assessed through oral glucose tolerance tests. First-trimester plasma concentrations of TMAO and its precursors were divided into quartile groups (bottom, Q1; middle, Q2 and Q3; top, Q4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the subjects, 167 (17.8%) were found to have GDM. After adjusting for potential covariates, the lower groups (Q1) of L-carnitine were associated with a higher risk of GDM compared to the reference group (middle quartiles). The OR (95% CI, p) was1.56 (1.04, 2.35, <jats:italic>p<\/jats:italic>\u202f=\u202f0.032) for L-carnitine. Specifically, the associations were mainly derived from L-carnitine and abnormal 1-h PG. The ORs (95% CI, p) were 2.00 (1.24, 3.24, <jats:italic>p<\/jats:italic>\u202f=\u202f0.005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Low plasma levels (bottom vs. middle quartiles) of L-carnitine the first-trimester pregnancy were associated with a higher risk of GDM and abnormal 1-h PG in Chinese pregnant women.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1587863","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T04:10:59Z","timestamp":1750047059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Associations of first-trimester TMAO and its precursors with gestational diabetes mellitus: a pilot prospective cohort study"],"prefix":"10.3389","volume":"12","author":[{"given":"Geng-Dong","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting-Ting","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng-Sheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao-Xin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Yan","family":"Gou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Xin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-Zhi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu-Sha","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Juan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-Xing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e067946","DOI":"10.1136\/bmj-2021-067946","article-title":"Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis","volume":"377","author":"Ye","year":"2022","journal-title":"BMJ"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.2337\/dc24-0108","article-title":"Long-term neurobehavioral and metabolic outcomes in offspring of mothers with diabetes during pregnancy: a large, population-based cohort study in Ontario, Canada","volume":"47","author":"Feig","year":"2024","journal-title":"Diabetes Care"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e250142","DOI":"10.1001\/jamanetworkopen.2025.0142","article-title":"Sleep characteristics and long-term risk of type 2 diabetes among women with gestational diabetes","volume":"8","author":"Yin","year":"2025","journal-title":"JAMA Netw Open"},{"key":"ref4","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":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/jdi.12854","article-title":"Prevalence of gestational diabetes mellitus in mainland China: a systematic review and meta-analysis","volume":"10","author":"Gao","year":"2019","journal-title":"J Diabetes Investig"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1136\/gutjnl-2020-322473","article-title":"Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men","volume":"71","author":"Li","year":"2022","journal-title":"Gut"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1093\/jn\/nxab367","article-title":"Assessment of dietary choline intake, contributing food items, and associations with one-carbon and lipid metabolites in middle-aged and elderly adults: the Hordaland health study","volume":"152","author":"Van Parys","year":"2022","journal-title":"J Nutr"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1093\/ajcn\/nqab108","article-title":"Trimethylamine N-oxide variation in humans: the product of a diet-microbiota interaction?","volume":"113","author":"Tilves","year":"2021","journal-title":"Am J Clin Nutr"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1093\/ajcn\/nqaa225","article-title":"Association of diet with circulating trimethylamine-N-oxide concentration","volume":"112","author":"Hamaya","year":"2020","journal-title":"Am J Clin Nutr"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11883-021-00910-x","article-title":"Trimethylamine N-oxide (TMAO), diet and cardiovascular disease","volume":"23","author":"Thomas","year":"2021","journal-title":"Curr Atheroscler Rep"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1111\/obr.12843","article-title":"Gut microbe-generated metabolite trimethylamine N-oxide and the risk of diabetes: a systematic review and dose-response meta-analysis","volume":"20","author":"Zhuang","year":"2019","journal-title":"Obes Rev"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1093\/eurheartj\/ehad089","article-title":"Trimethylamine N-oxide is associated with long-term mortality risk: the multi-ethnic study of atherosclerosis","volume":"44","author":"Wang","year":"2023","journal-title":"Eur Heart J"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"547","DOI":"10.2147\/DMSO.S398008","article-title":"Trimethylamine N-oxide and related metabolites in the serum and risk of type 2 diabetes in the Chinese population: a case-control study","volume":"16","author":"Qi","year":"2023","journal-title":"Diabetes Metab Syndr Obes."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.3390\/jcm8111813","article-title":"High betaine, a trimethylamine N-oxide related metabolite, is prospectively associated with low future risk of type 2 diabetes mellitus in the PREVEND study","volume":"8","author":"Garcia","year":"2019","journal-title":"J Clin Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1002\/ijgo.15288","article-title":"Investigation of serum trimethylamine-N-oxide levels in missed abortion: a prospective study","volume":"165","author":"Sarikaya","year":"2024","journal-title":"Int J Gynaecol Obstet"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"nzac108","DOI":"10.1093\/cdn\/nzac108","article-title":"Trimethylamine N-oxide and its precursors are associated with gestational diabetes mellitus and pre-eclampsia in the Boston birth cohort","volume":"6","author":"McArthur","year":"2022","journal-title":"Curr Dev Nutr"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41430-024-01502-z","article-title":"Association of maternal gut microbial metabolites with gestational diabetes mellitus: evidence from an original case-control study, meta-analysis, and Mendelian randomization","volume":"79","author":"Yao","year":"2025","journal-title":"Eur J Clin Nutr"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1007\/s12020-024-03732-4","article-title":"Serum betaine and dimethylglycine in mid-pregnancy and the risk of gestational diabetes mellitus: a case-control study","volume":"85","author":"Zhou","year":"2024","journal-title":"Endocrine"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1017\/S0007114524001995","article-title":"Choline and betaine intakes during pregnancy in relation to risk of gestational diabetes mellitus among Chinese women","volume":"132","author":"Lamkin","year":"2024","journal-title":"Br J Nutr"},{"key":"ref20","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":"ref21","doi-asserted-by":"publisher","first-page":"e24333","DOI":"10.1002\/jcla.24333","article-title":"Alterations of gut microbiota-derived metabolites in gestational diabetes mellitus and clinical significance","volume":"36","author":"Gao","year":"2022","journal-title":"J Clin Lab Anal"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.2147\/DMSO.S312334","article-title":"Maternal plasma betaine in middle pregnancy was associated with decreased risk of GDM in twin pregnancy: a cohort study","volume":"14","author":"Gong","year":"2021","journal-title":"Diabetes Metab Syndr Obes"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"5529","DOI":"10.1210\/jc.2019-00710","article-title":"Trimethylamine N-oxide metabolites in early pregnancy and risk of gestational diabetes: a nested case-control study","volume":"104","author":"Huo","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1093\/ajcn\/nqy116","article-title":"Plasma concentration of trimethylamine-N-oxide and risk of gestational diabetes mellitus","volume":"108","author":"Li","year":"2018","journal-title":"Am J Clin Nutr"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.nutres.2018.04.010","article-title":"Fetal one-carbon nutrient concentrations may be affected by gestational diabetes","volume":"55","author":"Barzilay","year":"2018","journal-title":"Nutr Res"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.2337\/db19-0153","article-title":"Assessment of causal direction between gut microbiota-dependent metabolites and Cardiometabolic health: a bidirectional Mendelian randomization analysis","volume":"68","author":"Jia","year":"2019","journal-title":"Diabetes"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"111589","DOI":"10.1016\/j.diabres.2024.111589","article-title":"International diabetes federation position statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes","volume":"209","author":"Bergman","year":"2024","journal-title":"Diabetes Res Clin Pract"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.2337\/db21-0227","article-title":"Profiles of glucose metabolism in different prediabetes phenotypes, classified by fasting Glycemia, 2-hour OGTT, glycated hemoglobin, and 1-hour OGTT: an IMI DIRECT study","volume":"70","author":"Tura","year":"2021","journal-title":"Diabetes"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"127514","DOI":"10.1016\/j.jtemb.2024.127514","article-title":"Associations of maternal serum concentration of iron-related indicators with gestational diabetes mellitus in Chinese: a pilot prospective cohort study","volume":"86","author":"Chen","year":"2024","journal-title":"J Trace Elem Med Biol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13052-024-01621-0","article-title":"Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study","volume":"50","author":"Chen","year":"2024","journal-title":"Ital J Pediatr"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.3945\/jn.115.211136","article-title":"Maternal choline status, but not fetal genotype, influences cord plasma choline metabolite concentrations","volume":"145","author":"Visentin","year":"2015","journal-title":"J Nutr"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1124\/dmd.119.086439","article-title":"Maternal plasma l-carnitine reduction during pregnancy is mainly attributed to OCTN2-mediated placental uptake and does not result in maternal hepatic fatty acid \u03b2-oxidation decline","volume":"47","author":"Bai","year":"2019","journal-title":"Drug Metab Dispos"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e0145794","DOI":"10.1371\/journal.pone.0145794","article-title":"Longitudinal Metabolomic profiling of amino acids and lipids across healthy pregnancy","volume":"10","author":"Lindsay","year":"2015","journal-title":"PLoS One"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.clinthera.2024.03.002","article-title":"The effects of L-carnitine supplementation on weight loss, glycemic control, and cardiovascular risk factors in patients with type 2 diabetes: a systematic review and dose-response Meta-analysis of randomized controlled trials","volume":"46","author":"Mirrafiei","year":"2024","journal-title":"Clin Ther"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1082097","DOI":"10.3389\/fnut.2022.1082097","article-title":"The effects of L-carnitine supplementation on glycemic markers in adults: a systematic review and dose-response meta-analysis","volume":"9","author":"Zamani","year":"2022","journal-title":"Front Nutr"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2864","DOI":"10.1111\/dom.16298","article-title":"Carnitine supplementation improves insulin sensitivity and skeletal muscle acetylcarnitine formation in patients with type 2 diabetes","volume":"27","author":"Op den Kamp-Bruls","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.metabol.2017.09.005","article-title":"Carnitine induces autophagy and restores high-fat diet-induced mitochondrial dysfunction","volume":"78","author":"Choi","year":"2018","journal-title":"Metabolism"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.3390\/ijms23052717","article-title":"The role of l-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation","volume":"23","author":"Virmani","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.phrs.2015.11.014","article-title":"Decreased acylcarnitine content improves insulin sensitivity in experimental mice models of insulin resistance","volume":"113","author":"Liepinsh","year":"2016","journal-title":"Pharmacol Res"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"771940","DOI":"10.3389\/fphar.2021.771940","article-title":"Enhancing fatty acids oxidation via L-carnitine attenuates obesity-related atrial fibrillation and structural remodeling by activating AMPK signaling and alleviating cardiac lipotoxicity","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Pharmacol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"933","DOI":"10.4093\/dmj.2020.0223","article-title":"Carnitine Orotate complex ameliorates insulin resistance and hepatic steatosis through carnitine acetyltransferase pathway","volume":"45","author":"Hong","year":"2021","journal-title":"Diabetes Metab J"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1093\/eurheartj\/ehad336","article-title":"Red meat consumption, cardiovascular diseases, and diabetes: a systematic review and meta-analysis","volume":"44","author":"Shi","year":"2023","journal-title":"Eur Heart J"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1587863\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T04:10:59Z","timestamp":1750047059000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1587863\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,16]]},"references-count":42,"alternative-id":["10.3389\/fnut.2025.1587863"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1587863","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,16]]},"article-number":"1587863"}}