Effects of combined high-sensitivity C-reactive protein and residual cholesterol levels on new-onset diabetes: evidence from two prospective cohort studies

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) and residual cholesterol (RC) have been pinpointed as potential diabetes risk factors. Nonetheless, the combined impact of these biomarkers on the incidence of diabetes is still unclear. The objective of this analysis is to explore the joint effects of RC and hsCRP on the incidence of new diabetes. METHODS: We analyzed 9,309 individuals in the China Health and Retirement Longitudinal Study (CHARLS) and 4,743 participants in the English Longitudinal Study of Ageing (ELSA), all of whom had no history of diabetes at baseline. To examine the joint effect of RC and hsCRP on diabetes risk, individuals were sorted into four groups based on median RC levels and an hsCRP threshold of 1 mg/L. To comprehensively assess the effects of RC and hsCRP on diabetes, a Residual Cholesterol-Inflammation Index (RCII) was established. Cox proportional hazards regression analysis and mediation analysis were conducted. RESULTS: Following comprehensive adjustments, individuals with elevated hsCRP alone, elevated RC alone, and both elevated hsCRP and RC demonstrated progressively increased risks of diabetes relative to those with low levels of hsCRP and RC across two databases. Multivariate analyses demonstrated that subjects in the highest quartile of RCII experienced a 79% increased likelihood of diabetes in CHARLS and a 99% increase in ELSA, relative to those in the lowest quartile of RCII. In the relationship between RC and diabetes, hsCRP acts as a mediator, accounting for 4.8% of the effect in CHARLS and 5.1% in ELSA. Conversely, in the relationship between hsCRP and diabetes, RC mediates 12.7% of the impact in CHARLS and 10.5% in ELSA. CONCLUSION: Our findings demonstrate the joint and mediating impacts of RC and hsCRP in diabetes risk assessment. Consequently, we recommend assessing both RC and hsCRP levels together and taking further steps to reduce the risk of diabetes.