Nonlinear association of residual cholesterol to high-density lipoprotein cholesterol ratio with diabetes mellitus: a retrospective cohort study

Diabetes mellitus is a major public health challenge in the world, and the role of lipid metabolism disorder in its pathogenesis has attracted much attention. The ratio of residual cholesterol to high-density lipoprotein cholesterol (RC/HDL-C), as a comprehensive index of atherosclerosis and anti-atherosclerotic lipid load, has shown predictive value in cardiovascular diseases, but its relationship with diabetes mellitus has not been clear. Therefore, we conducted a retrospective cohort study to investigate the relationship between RC/HDL-C and the risk of diabetes mellitus. This study was based on open data from the Murakami Memorial Hospital Health Screening Cohort in Japan. A total of 15,216 subjects without diabetes mellitus at baseline were included. The association between RC/HDL-C and diabetes mellitus risk was assessed by Cox proportional risk regression modeling. Restricted cubic spline (RCS) and smoothed curve fitting were used to explore the nonlinear association of RC/HDL-C with diabetes mellitus. Sensitivity analyses (excluding people of advanced age, obesity and hypertension) and subgroup analyses were performed to verify the robustness of the results. During median follow-up, 340 (2.23%) new cases of diabetes mellitus developed. After correcting for confounders, each 1-unit increase in RC/HDL-C was associated with a 5.21-fold increase in the risk of diabetes mellitus (HR 5.21, 95% CI 2.59-10.52; P < 0.001). The RCS model revealed a nonlinear association between RC/HDL-C and diabetes mellitus risk with a threshold point of 0.41. When RC/HDL-C ≤ 0.41, RC/HDL-C was significantly and positively associated with the risk of diabetes mellitus (HR 50.6, 95% CI 6.4-403.4; P < 0.001). In contrast, when RC/HDL-C > 0.41, RC/HDL-C was not associated with an increased risk of diabetes mellitus (HR 2.5, 95% CI 1.0-6.5; P = 0.053). Sensitivity and subgroup analyses showed that the positive association between RC/HDL-C and risk of diabetes mellitus was stable and consistent in the general population. This study revealed a nonlinear association between RC/HDL-C and the risk of developing diabetes mellitus through large-scale cohort data. This finding not only provides a new biomarker for early risk prediction of diabetes mellitus, but also deepens the understanding of lipid metabolic imbalance in the pathogenesis of diabetes mellitus. This study provides new ideas for early risk stratification and individualized lipid management in diabetes mellitus.