Liver MRI–derived Proton Density Fat Fraction Predicts Diabetes Risk in Patients with Obesity: A Dose-Response Study

Background Metabolic dysfunction-associated steatotic liver disease is linked to type 2 diabetes mellitus, but its relationship with a risk of prediabetes or type 2 diabetes in patients with obesity remains unclear. MRI-derived proton density fat fraction (PDFF) can accurately quantify liver fat. Purpose To define the precise dose-response relationship between liver MRI-derived PDFF and risk of prediabetes or type 2 diabetes in patients with obesity, and to explore the mediating role of liver enzymes. Materials and Methods This retrospective study included adult patients with obesity who underwent MRI to determine PDFF and who were administered a 75-g oral glucose tolerance test between September 2020 and December 2023. Based on oral glucose tolerance test results, patients were classified as having normal glucose tolerance, prediabetes, or type 2 diabetes. Steatosis severity was categorized by PDFF (<5%, 5% to <15%, 15% to <25%, or ≥25%). Multinomial logistic regression assessed the association between liver PDFF and prediabetes or type 2 diabetes. Mediation analysis evaluated the levels of alanine aminotransferase and aspartate aminotransferase. The findings were validated in an independent cohort. Results A dose-response relationship was found between liver PDFF and abnormal glucose metabolism in 683 patients (mean age, 33 years ± 6.5 [SD]; 121 male patients). Each 1% increase in PDFF was associated with higher odds of both prediabetes and type 2 diabetes (odds ratio [OR], 1.04; 95% CI: 1.02, 1.07; P < .001). Severe steatosis (PDFF ≥ 25%) was associated with higher odds of prediabetes (OR, 3.49; 95% CI: 1.35, 9.02; P = .01) and type 2 diabetes (OR, 3.45; 95% CI: 1.30, 9.13; P = .01). The association was partially mediated by aspartate aminotransferase (mediation proportion, 27.3%) and alanine aminotransferase (mediation proportion, 38.8%) (P < .001 for both). These findings were validated because patients with dysglycemia had higher mean liver PDFF than did patients with normoglycemia (19.7% vs 12.9%, respectively; P < .001). Conclusion In patients with obesity, the liver MRI-derived PDFF was strongly associated with the odds of prediabetes and type 2 diabetes, showing a dose-response relationship partially mediated by liver enzymes. © The Authors 2025. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Reeder and Starekova in this issue.