Abstract

To investigate the association between one-hour post-load plasma glucose (1h-PG) levels and metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic-associated steatohepatitis (MASH). Clinical data were collected from 538 obese participants who underwent oral glucose tolerance tests (OGTT) and liver biopsy in the Drum Tower Hospital affiliated with the Nanjing University Medical School. Participants were categorized into normal glucose tolerance (NGT), prediabetes (pre-DM), and type 2 diabetes (T2DM) groups, with further stratification of the NGT group into 1h-PG Low and 1h-PG High. The diagnosis of MASLD and MASH was performed using the NASH Clinical Research Network scoring system. Logistic regression analyses were performed to determine the association between each category and MASLD/ MASH. The prevalence of MASLD and MASH progressively increased across NGT 1h-PG Low, NGT 1h-PG High, pre-DM and T2DM groups. Compared to the NGT 1h-PG Low group, the NGT 1h-PG High group had a significantly higher risk of MASLD (OR 3.27 [95% CI 1.32;8.09]) and MASH (OR 3.08 [1.55;6.11]), which is similar to the pre-DM group. Additionally, elevated 1h-PG levels were associated with hepatic steatosis, lobular inflammation, and fibrosis. Mediation analysis indicated that Matsuda insulin sensitivity index and disposition index played a sequential mediating role between 1h-PG and hepatic steatosis, accounting for 14.23% of total effect (β 0.014 [95% CI 0.002;0.035]). Elevated 1h-PG levels increase the risk of MASLD and MASH in obese individuals. Early screening and management of MASLD are necessary, even in NGT individuals when 1h-PG levels are ≥8.6 mmol/l.

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