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In a longitudinal cohort, we examined T2DM risk, \u03b2-cell function, and the effects of genetic and lifestyle factors on high 1-h PG.Methods: We analyzed 7,464 participants without T2D at baseline from a community-based prospective cohort in Korea, who underwent biennial 2-h 75-g oral glucose tolerance tests over 14 years. Incident T2D risk were assessed across 1-h PG groups: &lt; 155, 155\u2013208, and \u2265 209 mg\/dL. In 6,588 participants with at least two 1-h PG measurements, we analyzed 1-h PG trajectories by T2D polygenic risk score (PRS; low, 1st quintile; intermediate, 2nd\u20134th quintiles; high, 5th quintile) and lifestyle, assessed using Life's Essential 8.Results: Compared to the &lt;155 mg\/dL group, hazard ratios for T2DM were 3.34 (95% confidence interval [CI], 2.99 to 3.74; &lt;i&gt;P&lt;\/i&gt;&lt;0.001) for 155\u2013208 mg\/dL, and 6.81 (95% CI, 5.81 to 7.98; &lt;i&gt;P&lt;\/i&gt;&lt;0.001) for \u2265209 mg\/dL. Both groups had lower baseline disposition index compared to the &lt;155 mg\/dL group (57.3% and 72.7%, respectively; both &lt;i&gt;P&lt;\/i&gt;&lt;0.001). Higher T2DM PRS was associated with elevated baseline 1-h PG (low: 131 mg\/dL, intermediate: 141 mg\/dL, high: 151 mg\/dL) and faster increase in 1-h PG (1.36 vs. 1.85 vs. 2.21 mg\/dL\/year; all &lt;i&gt;P&lt;\/i&gt;&lt;0.001). Importantly, healthy lifestyle attenuated the rate of increase across all PRS groups.Conclusion: High 1-h PG predicts T2DM risk and is associated with \u03b2-cell dysfunction. The 1-h PG level is influenced by genetic risk and can be modified with a healthy lifestyle.<\/jats:p>","DOI":"10.4093\/dmj.2025.0362","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:24:53Z","timestamp":1776831893000},"page":"1002-1013","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and Lifestyle Factors Influence High 1-Hour Plasma Glucose, a Predictor of Type 2 Diabetes Mellitus"],"prefix":"10.4093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3410-6375","authenticated-orcid":true,"given":"Soobin","family":"Cho","sequence":"first","affiliation":[{"name":"Kosin University College of Medicine, Busan, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-5868","authenticated-orcid":true,"given":"Hyunsuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea"},{"name":"Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea"},{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Howard University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonsoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Ho","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University 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