Controlled attenuation parameter (CAP) shows a more robust association with insulin clearance index than liver stiffness measurement (LSM) in type 2 diabetes mellitus: a retrospective cross-sectional study

Obesity, hepatic steatosis, and altered insulin metabolism frequently coexist in patients with type 2 diabetes mellitus (T2DM). Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) are widely used non-invasive measures for assessing hepatic steatosis and liver stiffness, respectively. Although the liver is a major site of endogenous insulin clearance, whether these measures show differential associations with insulin clearance remains unclear. We therefore compared their associations with insulin clearance and explored their potential roles in the relationship between body mass index (BMI) and insulin clearance in patients with T2DM. This retrospective cross-sectional study included 605 hospitalized patients with T2DM. Participants were categorized into three BMI groups (< 24, 24–<28, and ≥ 28 kg/m²) and four median-based CAP-LSM phenotypes. CAP and LSM were assessed by FibroScan, and a surrogate insulin clearance index was calculated as C-peptide AUC 0–120 /insulin AUC 0–120 during a standardized meal test. Associations were examined using correlation and hierarchical multivariable regression analyses; mediation analysis evaluated indirect effects through CAP and LSM. Higher BMI was associated with higher CAP and LSM, greater insulin resistance, lower insulin sensitivity, and reduced insulin clearance index. Among the four median-based CAP-LSM phenotypes, the High CAP-High LSM group had the lowest insulin clearance index. Adding CAP to a model including sex, age, diabetes duration, and BMI increased the explained variance in insulin clearance index (ΔR 2 = 0.032, P < 0.001). In the full model, CAP remained inversely associated with insulin clearance index (standardized β = −0.194, P < 0.001), whereas adding LSM after CAP did not improve the model. Mediation analysis adjusted for age, sex, and diabetes duration identified a significant indirect effect through CAP, accounting for 40.4% of the total association between BMI and insulin clearance index; the indirect effect through LSM was not significant. In patients with T2DM, CAP showed a more robust and consistent inverse association with insulin clearance index than LSM. The significant statistical indirect effect through CAP suggests that a steatosis-related liver phenotype may partly account for the association between greater adiposity and reduced insulin clearance.