{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:47:50Z","timestamp":1791528470640,"version":"4.3.4"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving \u03b2-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses\u2019 Health Study).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We created a fasting blood MRS for predicting 1-hour glucose (Pearson\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      =0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22\u20136.51) for T2D and 1.48 (95% CI, 1.04\u20132.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.327816","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:00:20Z","timestamp":1788253220000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Blood Metabolomic Signatures of 1-Hour Glucose Predict Cardiometabolic Risk"],"prefix":"10.1161","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0957-9309","authenticated-orcid":true,"given":"Yoriko","family":"Heianza","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Celia Scott Weatherhead School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA (Y.H., M.K., X.W., L.Q.)."},{"name":"Department of Nutrition (Y.H., Q.S., F.B.H., F.M.S., L.Q.), Harvard T.H. Chan School of Public Health, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3885-4103","authenticated-orcid":true,"given":"Minghao","family":"Kou","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Celia Scott Weatherhead School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA (Y.H., M.K., X.W., L.Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Celia Scott Weatherhead School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA (Y.H., M.K., X.W., L.Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8480-1563","authenticated-orcid":true,"given":"Qi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nutrition (Y.H., Q.S., F.B.H., F.M.S., L.Q.), Harvard T.H. Chan School of Public Health, Boston, MA."},{"name":"Department of Epidemiology (Q.S., F.B.H., J.E.M.), Harvard T.H. Chan School of Public Health, Boston, MA."},{"name":"Channing Division of Network Medicine, Department of Medicine (Q.S., F.B.H., L.Q.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-2987","authenticated-orcid":true,"given":"Jennifer","family":"Rood","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA (J.R., G.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9945-8772","authenticated-orcid":true,"given":"George A.","family":"Bray","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA (J.R., G.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-6823","authenticated-orcid":true,"given":"Lawrence J.","family":"Appel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (L.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8233-6274","authenticated-orcid":true,"given":"Frank B.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nutrition (Y.H., Q.S., F.B.H., F.M.S., L.Q.), Harvard T.H. Chan School of Public Health, Boston, MA."},{"name":"Department of Epidemiology (Q.S., F.B.H., J.E.M.), Harvard T.H. Chan School of Public Health, Boston, MA."},{"name":"Channing Division of Network Medicine, Department of Medicine (Q.S., F.B.H., L.Q.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-7595","authenticated-orcid":true,"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology (Q.S., F.B.H., J.E.M.), Harvard T.H. 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