Genetic and Lifestyle Factors Influence High 1-Hour Plasma Glucose, a Predictor of Type 2 Diabetes Mellitus

Background: High 1-hour plasma glucose (1-h PG) level has been proposed by the International Diabetes Federation to identify high-risk individuals and diagnose type 2 diabetes mellitus (T2DM). In a longitudinal cohort, we examined T2DM risk, β-cell function, and the genetic and lifestyle effects associated with the high 1-h PG. Methods: We analyzed 6,588 participants without baseline T2DM from a community-based prospective cohort in Korea. Participants underwent biennial 2-hour 75-g oral glucose tolerance tests over 14 years. We assessed incident T2DM risk across 1-h PG groups: <155, 155-208, and ≥209 mg/dL. T2DM polygenic risk scores (PRS) were stratified into low (1st quintile), intermediate (2nd-4th quintiles), and high (5th quintile). Lifestyle was evaluated using Life's Essential 8. Results: Compared to the <155 mg/dL group, hazard ratios for T2DM were 3.34 (95% confidence interval [CI], 2.99 to 3.74; P<0.001) for 155-208 mg/dL, and 6.81 (95% CI, 5.81 to 7.98; P<0.001) for ≥209 mg/dL. Both groups had lower baseline disposition index compared to the <155 mg/dL group (57.3% and 72.7%, respectively; both P<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 P<0.001). Importantly, healthy lifestyle attenuated the increase in rate across all PRS groups. Conclusion: High 1-h PG predicts T2DM risk and is associated with β-cell dysfunction. The 1-h PG level is influenced by genetic risk and can be modified with a healthy lifestyle.