Association Between Hepatic Steatosis and Deterioration of Metabolic Health in Obese Individuals: A 12-Year Follow-Up of the Tehran Lipid and Glucose Study Publisher Pubmed



Abiri B ; Nikoohemmat M ; Mahdavi M ; Ahmadi AR ; Valizadeh M ; Azizi F ; Hosseinpanah F
Source: Endocrinology, Diabetes and Metabolism Published:2026

Abstract

Background: Uncertainty surrounds the relationship between metabolic decline and fatty liver disease. The purpose of this study was to evaluate the effect of hepatic steatosis (HS) on the transition from metabolically healthy obesity (MHO) to metabolically unhealthy obesity (MUO) and to determine whether the Fatty Liver Index (FLI) can predict this progression. Methods: In this prospective cohort research, participants in the Tehran Lipid and Glucose Study (TLGS) comprised 593 MHO adults who were at least 40 years old at baseline. The subjects were followed up for a period of 12 years to see if the subjects' metabolically healthy obesity phenotype changed to an unhealthy one. The body mass index (BMI) of 30.0 kg/m2 was used to characterise obesity. The concept of metabolically healthy (less than two variables) or metabolically abnormal (two or more) was based on four metabolic parameters: low high density lipoprotein-cholesterol (HDL-c) concentration, hypertension, hypertriglyceridemia, and impaired fasting glucose. The technique used to construct the fatty liver index (FLI), which serves as an indication of HS, was based on waist circumference (WC), triglycerides, BMI, and gamma-glutamyl transferase. Results: During a median of 4.81 years of follow-up (interquartile range 1.75–10.74 years), 72.2% (n = 428) of MHO individuals transitioned to the MUO phenotype. Transitioning participants exhibited higher FLI scores, BMI, waist circumference, and unfavourable metabolic profiles compared to non-transitioning participants. Cox regression analysis revealed that hepatic steatosis (HR: 1.369; 95% CI: 1.014–1.848), lower physical activity (HR: 1.267; 95% CI: 1.035–1.551), and a higher TyG index (HR: 3.208; 95% CI: 1.546–6.657) were significant predictors of transition to MUO. Conclusion: Hepatic steatosis at baseline is an independent risk factor for progression from metabolically healthy status to metabolically abnormal phenotype in obese individuals. © 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.