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

Area of Science:

• Radiology
• Metabolic Disease
• Hepatology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with type 2 diabetes mellitus.
• The precise relationship between liver fat and prediabetes or type 2 diabetes risk in individuals with obesity is not fully understood.
• Magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) offers accurate liver fat quantification.

Purpose of the Study:

• To establish the dose-response relationship between liver MRI-PDFF and the risk of prediabetes or type 2 diabetes in obese patients.
• To investigate the potential mediating role of liver enzymes in this association.

Main Methods:

• Retrospective study of obese adults who underwent MRI for PDFF measurement and an oral glucose tolerance test.
• Classification of glucose tolerance status: normal, prediabetes, or type 2 diabetes.
• Multinomial logistic regression and mediation analysis to assess associations and enzyme roles, with validation in an independent cohort.

Main Results:

• A significant dose-response relationship was observed between liver PDFF and abnormal glucose metabolism in 683 patients.
• Each 1% increase in PDFF correlated with increased odds of prediabetes and type 2 diabetes (OR, 1.04).
• Severe steatosis (PDFF ≥ 25%) significantly increased odds for prediabetes and type 2 diabetes, with mediation by aspartate aminotransferase (27.3%) and alanine aminotransferase (38.8%).

Conclusions:

• Liver MRI-PDFF is a strong predictor of prediabetes and type 2 diabetes risk in obese individuals.
• A clear dose-response relationship exists, indicating that greater liver fat increases diabetes risk.
• Liver enzymes partially mediate this association, highlighting their role in metabolic dysfunction.