Objective:

To clarify the differences in NAFLD risk among different prediabetes phenotypes and explore their underlying associations, emphasizing the significance of these differences for clinical outcomes.

Key Findings:

• Four distinct prediabetes phenotypes were identified, each with significant differences in NAFLD probability.
• Class 1 had the highest NAFLD prevalence (87.93%), characterized by young individuals with severe insulin resistance and obesity, with hepatocellular damage strongly associated with NAFLD.
• Class 2 had the lowest prevalence (18.39%), consisting of middle-aged individuals with mild insulin resistance and normal weight.
• Neutrophilic inflammation was the most relevant factor for middle-aged individuals with moderate insulin resistance and overweight, highlighting the metabolism-immunity-inflammation axis.

Interpretation:

The study characterizes novel prediabetes phenotypes and their pathogenic associations with NAFLD, providing insights for targeted prevention and management, which could improve clinical outcomes.

Limitations:

• The study is retrospective and relies on electronic health records, which may introduce biases.
• Informed consent was waived, which may limit participant engagement and affect the generalizability of the findings.

Conclusion:

This research contributes to understanding the variability in NAFLD risk among prediabetic phenotypes, aiming to improve endocrine disease management and support targeted prevention strategies.