LIVER FIBROSIS in people with prediabetes was concentrated among those with obesity and substantial insulin resistance, a study of adults attending primary care and diabetes clinics has found.
The findings suggest that the metabolic effects of excess weight may help distinguish people with a higher prevalence of significant liver scarring, beyond their blood glucose category alone.
Researchers assessed 1,446 adults recruited from University of Florida-affiliated clinics in a prospectively recruited, cross-sectional study spanning normoglycaemia, prediabetes and Type 2 diabetes.
Transient elastography was used to assess liver fat and stiffness. Where significant fibrosis was suspected, magnetic resonance imaging or liver biopsy was used to refine staging when available. Clinically significant fibrosis was defined as stage F2 or above.
The team also assessed insulin resistance using HOMA-IR and an adipose tissue insulin resistance index, Adipo-IR, to explore how metabolic dysfunction related to liver disease across BMI and glycaemic categories.
Metabolic dysfunction-associated steatotic liver disease (MASLD) was present in 39% of participants with normoglycaemia, 55% with prediabetes and 68% with Type 2 diabetes. Significant fibrosis affected 1%, 6% and 12% of these groups, respectively.
However, liver scarring did not follow the same consistent pattern across BMI categories as liver fat.
Among participants with prediabetes, significant fibrosis was uncommon in those who were lean or overweight, but its prevalence rose from approximately 2% with overweight to 9% with obesity.
Participants with both obesity and Type 2 diabetes had the highest prevalence of significant fibrosis, at 16%. Across glycaemic groups, most participants with significant fibrosis were in the two highest quintiles of HOMA-IR or Adipo-IR, indicating more severe insulin resistance.
The authors suggest that measuring metabolic dysfunction could help refine MASLD risk assessment, particularly in people with prediabetes and obesity. They identify HOMA-IR as a potentially practical measure for further evaluation alongside existing approaches.
However, HOMA-IR is a surrogate measure that requires assay standardisation and appropriate reference ranges. It cannot be used to assess insulin resistance in people receiving insulin therapy, and interpretation is also limited by severe pancreatic beta cell dysfunction.
The cross-sectional design cannot establish whether insulin resistance caused fibrosis or identify which participants will experience faster progression. Some participants also did not undergo confirmatory imaging or biopsy.
The findings do however support further investigation of metabolic measures within liver risk assessment, rather than establishing a new screening threshold or replacing existing clinical pathways.
Reference
Godinez Leiva E et al. Prediabetes and diabetes as drivers of fibrosis in MASLD: roles of obesity, adipose tissue dysfunction and insulin resistance. Diabetologia. 2026. https://doi.org/10.1007/s00125-026-06904-1
Featured image: Vadym Huzhva on AdobeStock
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