BackgroundThe atherogenic index of plasma (AIP) and systematic inflammation, as measured by high-sensitivity C-reactive protein (hsCRP), are predictors of diabetes, but their combined impacts on incident diabetes are poorly understood. Using a nationally representative cohort in China, we aimed to investigate the association of AIP and hsCRP with incident diabetes among middle-aged and elderly adults.MethodsThis cohort comprised 9,112 participants aged at least 45 years from 125 cities in the China Health and Retirement Longitudinal Study who were free of diabetes at baseline in 2011. Of these, 5,048 participants were followed up until 2015. The AIP was calculated as Log10[TG (mg/dL)/HDL-C(mg/dL)]. Multivariate logistic regression and linear mixed-effect (LME) models were performed to evaluate the associations of AIP, hsCRP, and incident diabetes as well as glycemic biomarkers. Receiver operating characteristic (ROC) curves were used to evaluate their diagnostic values. We conducted a mediation analysis to assess the direct and indirect associations between AIP and hsCRP with diabetes.Results489 (9.7%) cases developed diabetes during four years. Higher levels of AIP and hsCRP were independently associated with diabetes. Compared to the lowest quartile of AIP or hsCRP, the highest quartile of AIP (adjusted odds ratio, aOR 2.53, 95% CI: 1.90-3.38) and hsCRP (aOR 2.38, 1.79-3.16) was significantly associated with incident diabetes. The joint effects showed that participants with higher levels of AIP and hsCRP had significantly higher aOR of 2.76 (2.13-3.57). The LME models showed AIP and hsCRP were related to an increased level of fasting blood glucose and glycated hemoglobin. The combination of AIP and hsCRP has better predictive efficacy (area under the curve, AUC: 0.628, 0.601-0.654) for incident diabetes than alone. Mediation analyses showed that high AIP significantly mediated 25.4% of the association between hsCRP and diabetes, and hsCRP simultaneously mediated 5.7% of the association between AIP and diabetes.ConclusionsThis cohort suggests combined effects and mutual mediation between the AIP and hsCRP on incident diabetes in China. Our findings provide clinical implications for monitoring and managing AIP and hsCRP levels to mitigate the development of diabetes.