Comparisons of Post-Load Glucose at Different Time Points for Identifying High Risks of MASLD Progression

<b>Background</b>: The 1-h post-load plasma glucose was proposed to replace the current OGTT criteria for diagnosing prediabetes/diabetes. However, it remains unclear whether it is superior in identifying progressive metabolic dysfunction-associated steatotic liver disease (MASLD), and thus we aimed to clarify this issue. <b>Methods</b>: Consecutive Asian participants (non-MASLD, <i>n</i> = 1049; MASLD, <i>n</i> = 1165) were retrospectively enrolled between June 2012 and June 2024. CT was used to quantify liver steatosis, while the serum liver fibrotic marker was used to evaluate liver fibrosis. <b>Results</b>: Compared with those with normal levels of both 1-h post-glucose (1hPG) and 2-h post-glucose (2hPG), patients with MASLD showed a significant positive association between elevated 1hPG levels and moderate to severe liver steatosis (odds ratio [OR] = 2.19, 95% confidence interval [CI]: 1.13-4.25, <i>p</i> = 0.02]. Elevated levels of both 1hPG and 2hPG were associated with an increased risk of liver injury (OR = 2.03, 95% CI: 1.44-2.86, <i>p</i> < 0.001). Elevated 2hPG levels with or without elevated 1hPG levels were associated with liver fibrosis (OR = 1.99, 95% CI: 1.15-3.45, <i>p</i> < 0.001; OR = 2.72, 95% CI: 1.79-4.11, <i>p</i> < 0.001, respectively). Additionally, either 1hPG or 2hPG levels were associated with atherosclerosis, revealing significant dose-dependent associations between glucose status and atherosclerosis risk (OR = 2.77, 95% CI: 1.55-4.96, <i>p</i> < 0.001 for elevated 1hPG; OR = 2.98, 95% CI = 1.54-5.78, <i>p</i> = 0.001 for elevated 2hPG; OR = 2.41, 95% CI = 1.38-4.21, <i>p</i> = 0.001 for elevated levels of both 1hPG and 2hPG). The areas under the ROC for predicting steatosis, liver injury, liver fibrosis, and atherosclerosis were 0.64, 0.58, 0.58, and 0.64 for elevated 1hPG (all <i>p</i> < 0.05) and 0.50, 0.60, 0.56, and 0.62 for elevated 2hPG (all <i>p</i> < 0.05), respectively. <b>Conclusions</b>: These findings underscore the necessity for clinicians to acknowledge that the screening and management of MALSD requires the monitoring of 1hPG levels.