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

**Authors:** Behnaz Abiri, Mohammad Nikoohemmat, Maryam Mahdavi, Amirhossein Ramezani Ahmadi, Majid Valizadeh, Fereidoun Azizi, Farhad Hosseinpanah

PMC · DOI: 10.1002/edm2.70156 · Endocrinology, Diabetes & Metabolism · 2026-02-09

## TL;DR

This 12-year study shows that fatty liver disease increases the risk of metabolically healthy obese individuals becoming metabolically unhealthy.

## Contribution

The study demonstrates that hepatic steatosis is an independent predictor of metabolic health deterioration in obese individuals.

## Key findings

- 72.2% of metabolically healthy obese individuals transitioned to metabolically unhealthy obesity over 12 years.
- Higher Fatty Liver Index scores were associated with a greater risk of transitioning to metabolically unhealthy obesity.
- Hepatic steatosis, low physical activity, and a higher TyG index were significant predictors of metabolic deterioration.

## Abstract

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.

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.

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.

Hepatic steatosis at baseline is an independent risk factor for progression from metabolically healthy status to metabolically abnormal phenotype in obese individuals.

This 12‐year study reveals that hepatic steatosis significantly predicts the transition from metabolically healthy obesity (MHO) to an unhealthy phenotype in obese individuals, underscoring the clinical importance of early detection and intervention to prevent metabolic deterioration.

## Linked entities

- **Diseases:** obesity (MONDO:0011122), hypertriglyceridemia (MONDO:0005347)

## Full-text entities

- **Genes:** GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}
- **Diseases:** hypertriglyceridemia (MESH:D015228), MHO (MESH:D000067329), of Metabolic Health (MESH:D008659), Fatty Liver (MESH:D005234), Obese (MESH:D009765), hypertension (MESH:D006973)
- **Chemicals:** triglycerides (MESH:D014280), Lipid (MESH:D008055), Glucose (MESH:D005947)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12885240/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12885240/full.md

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Source: https://tomesphere.com/paper/PMC12885240