Discordant high remnant cholesterol with LDL-C increases the metabolic dysfunction-associated steatotic liver disease risk in patients with type 2 diabetes mellitus

Introduction Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist in the same individual. Dyslipidemia plays a central role in the pathogenesis of MASLD. Remnant cholesterol (RC) is the cholesterol content carried in triglyceride-rich lipoproteins. We aimed to examine the association of RC, its discordance with low-density lipoprotein cholesterol (LDL-C) in terms of MASLD risk in patients with T2DM. Research design and methods A total of 26 302 T2DM patients who were hospitalized were cross-sectionally assessed. Logistic regression models were employed to assess the associations. We used three approaches to assess the effects of the discordance between RC and LDL-C on MASLD risk: clinical cut-off points, differences of >10 percentile points and residuals. Results The median age was 62.0 years, and 48.3% had MASLD. RC was more closely associated with MASLD than LDL-C. Furthermore, discordantly high RC was associated with higher MASLD risk than discordantly high LDL-C, regardless of which method of discordance analysis is used. For example, for the residual approach, in a regression model including LDL-C and RC residual, the latter, representing the portion of RC not explained by LDL-C, was more associated with MASLD risk than LDL-C (OR=1.26, 95% CI 1.22 to 1.30 for RC residual and OR=1.04, 95% CI 1.01 to 1.07 for LDL-C); in a regression model including RC and LDL-C residual, the latter representing the portion of LDL-C not explained by RC, RC was more associated with MASLD risk than LDL-C residual (OR=1.24, 95% CI 1.20 to 1.29 for RC and OR=1.09, 95% CI 1.06 to 1.12 for LDL-C residual). Conclusions Discordantly high RC was associated with higher MASLD risk than discordantly high LDL-C. Our findings suggest that RC may serve as a potential target for prevention and intervention for MASLD.