The role of remnant cholesterol beyond low-density lipoprotein cholesterol in diabetes mellitus

BACKGROUND: Previous research has linked elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) with diabetes mellitus (DM). The present study aims to estimate the RC-related DM risk beyond LDL-C, and to investigate the extent to which the association of RC and DM is mediated via insulin resistance and inflammation. METHODS: We enrolled 7308 individuals without previous history of DM into the present study from the China Health and Nutrition Survey. Fasting RC was calculated as total cholesterol minus LDL-C and high-density lipoprotein cholesterol. Subjects were divided into four groups according to their LDL-C (100 mg/dL) and RC (24 mg/dL) levels to evaluate the role of LDL-C vs. RC on DM. A logistic regression analysis was then employed to evaluate the relationships between the discordant/concordant LDL-C and RC and DM. A mediation analysis was undertaken to identify potential mediators. RESULTS: Of all the participants, a total of 625 (8.55%) patients were newly diagnosed with DM. Compared to the high LDL-C/low RC group, the low LDL-C/high RC group was more common in DM patients. After a multivariate adjustment, elevated LDL-C and RC were associated with DM. Moreover, the low LDL-C/high RC group and the high LDL-C/low RC group manifested a 4.04-fold (95% CI 2.93–5.56) and 1.61-fold (95% CI 1.21–2.15) higher risk of DM, relative to those with low LDL-C/low RC. The subgroup analysis indicated that low LDL-C/high RC was more likely to be related to DM in females. Similar results were also shown when the sensitivity analyses were performed with different clinical cut-points of LDL-C. Insulin resistance and inflammation partially mediated the association between RC and DM. CONCLUSIONS: Our findings provided evidence for RC beyond the LDL-C associations with DM that may be mediated via insulin resistance and the pro-inflammatory state. In addition, women are more susceptible to RC exposure-related DM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01554-0.