Effects of Body-Weight Changes on the Risk of New-Onset Diabetes in Individuals With Non-Diabetic Metabolic Dysfunction-Associated Steatotic Liver Disease

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of hepatic and extrahepatic complications.Although weight reduction is the primary recommended intervention, its impact on extrahepatic outcomes remains uncertain.We investigated the association between body-weight change and new-onset diabetes in individuals with non-diabetic MASLD.Methods: This study included 14,496 adults with MASLD and no diabetes at baseline.MASLD was diagnosed using ultrasonography.Body-weight change was calculated as the percentage difference from baseline until diabetes onset or the last follow-up.Results: Over a follow-up of 78,680 person-years (mean, 5.4 years), 2,386 participants developed diabetes.When compared to participants who experienced no significant change in body weight (-4.9% to 4.9%), the adjusted hazard ratios (aHRs) for developing diabetes were 0.53 (95% confidence interval, 0.46-0.62)for those with a weight reduction of 5.0-9.9% and 0.44 (0.34-0.58) for those with a reduction of ≥ 10.0%.Conversely, the aHRs were 1.19 (1.03-1.36)and 1.30 (0.99-1.71) for weight gains of 5.0-9.9% and ≥ 10.0%, respectively.Spline regression models demonstrated a dose-response relationship between weight change and diabetes risk.This association was generally consistent across cardiometabolic subgroups, with the inverse relationship more pronounced in participants with overweight or obesity.Conclusion: In individuals with non-diabetic MASLD, weight reduction was strongly associated with a lower risk of diabetes, whereas weight gain increased the risk in a dosedependent manner.These findings underscore that both promoting weight reduction and preventing weight gain remain central to the clinical management of MASLD.