Association Between the Hepatic Steatosis Index and Risk of Incident Type 2 Diabetes Mellitus in the Normoglycemic Population:A Longitudinal Prospective Study in Japan

Rite Si,1,2,* Jingyi Xiao,2,* Keyang Zheng,3 Yuzhe Yin,2 Yamin Li1 1Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Sixth Clinical Medical School, Capital Medical University, Beijing, People’s Republic of China; 3Center of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yamin Li, Email lymdoctor@126.comPurpose: The Hepatic Steatosis Index (HSI) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD), which can increase the risk of type 2 diabetes mellitus (T2DM). However, limited research has directly predicted HSI’s association with T2DM occurrence at normal blood glucose levels. Hence, this study aimed to assess the link between baseline HSI and T2DM development under euglycemic conditions while also exploring potential sex differences.Methods: Using data from the NAGALA cohort study, a Cox regression model analyzed the relationship between HSI and T2DM risk, calculating hazard ratios (HR) and 95% confidence intervals (CI). Subgroup analyses were conducted to investigate factors influencing HSI’s prediction of incident T2DM.Results: During a mean 6.1-year follow-up, 238 individuals (1.65% of participants) developed T2DM. After adjusting for age, ethanol consumption, smoking status, SBP, DBP, TG, and TC, HSI showed a significant association with incident T2DM in individuals with normal glucose levels, consistent across sexes. Compared to the lowest quartile group (Q1), the HR and 95% CI for Q2, Q3, and Q4 were 1.09 (0.61, 1.93), 1.16 (0.68, 1.98), and 3.30 (2.04, 5.33), respectively (P for trend < 0.001). Subgroup analysis indicated that elevated HSI significantly increased the risk of incident T2DM in individuals with normal TG levels (P for interaction = 0.0170).Conclusion: This study highlights the significant association between elevated HSI levels and the likelihood of developing incident T2DM in individuals with normal glucose levels. Furthermore, it offers a simple and valuable screening tool for predicting T2DM.Keywords: Type 2 Diabetes Mellitus, hepatic steatosis index, Non-alcoholic fatty liver disease, risk prediction, longitudinal study