{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:31:53Z","timestamp":1793835113308,"version":"4.6.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the associations between pre-pregnancy BMI, amino acid metabolism in early pregnancy, and glucose levels\/gestational diabetes mellitus (GDM) in later pregnancy. We also examined the mediating effects of amino acids on BMI and glucose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cohort study examined the association between BMI, first-trimester amino acids, and glucose\/GDM among 1074 pregnant women. Regression analyses detected changes in amino acid levels and glucose measurements from oral glucose tolerance test (OGTT) at the 10th, 50th, and 90th percentiles. A mediation analysis was conducted to determine if amino acids mediated the relationship between BMI and glucose\/GDM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four essential amino acid concentrations (leucine, phenylalanine, threonine, and valine) increased significantly with increasing BMI (P &amp;lt; 0.05). Additionally, overweight women exhibited higher levels of non-essential amino acids (alanine, arginine, asparagine, aspartate, proline, tyrosine) and ornithine than underweight and normal-weight women. Women with GDM demonstrated higher levels of leucine, valine, alanine, asparagine, proline, and tyrosine compared to those without (P &amp;lt; 0.05). Fasting blood glucose (OGTT0) increased by 0.07 mmol\/L when alanine levels increased by 50%. Similarly, increasing asparagine and leucine levels by 50% led to a 0.24 mmol\/L increase in 1-hour postprandial blood glucose (OGTT1). A 50% rise in alanine, asparagine, and leucine levels led to average increases of 0.31, 0.19, and 0.21 mmol\/L in mean 2-h postprandial blood glucose (OGTT2). These associations were statistically significant at the upper 90th percentile of the OGTT2 distribution. 50% increase in valine was correlated with a 0.22 mmol\/L increase in mean OGTT2. The levels of alanine accounted for 11.76%, 8.08%, and 11.38% of the associations between BMI and GDM, OGTT0, and OGTT2, respectively. Additionally, the indirect effect of BMI-associated OGTT2 on leucine levels was estimated to be 5.39 percent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Amino acid metabolism is correlated with BMI, GDM, and glucose levels. Notably, BMI and GDM\/glucose intolerance are significantly mediated by alanine and leucine levels. This suggests a new way to study why overweight or obese mothers are more likely to develop GDM and glucose intolerance.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1502678","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T09:23:47Z","timestamp":1747733027000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring the mediating effects of amino acids on BMI and gestational diabetes mellitus: a longitudinal population-based cohort 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