Nonlinear Association Between Estimated Glucose Disposal Rate and Incident Type 2 Diabetes: Mediation Role of Lipid Profiles

Objectives Estimated glucose disposition rate (eGDR) is a feasible alternative for evaluating insulin resistance (IR). The relationship and the intermediate mechanism between eGDR and type 2 diabetes mellitus (T2DM) still needs to be elucidated. Methods 15464 individuals from the NAGALA cohort were Included in the study, who was categorized into five groups by the eGDR. A Cox proportional hazard regression model was used to assess the association of eGDR with the incidents of T2DM. The Cox proportional hazards models incorporating threshold-saturation effects and restricted cubic splines were used in evaluating potential nonlinear associations. And mediation analysis is used to estimate the mediating mechanism of blood lipids in it. Results Over a median follow-up period of 1967.00 days, 373 (2.41%) participants devel oped T2DM. After adjusting for correction models, eGDR showed a negative correlation with T2DM, and there showed a non-linear relationship between eGDR and T2DM. The inflection point of eGDR was detected to be 9.82 mg/kg/min. When eGDR <9.82 mg/kg/min, higher eGDR levels were associated with increased risk for T2DM (HR: 1.16, 95%CI: 1.02 to 1.32, P = 0.0192). In the mediation analyses, eGDR has a substantial direct impact on the risk of T2DM, and the indirect effects mediated by HCL-C, TC and TG account for 28%, 7.7% and 18.7% of the total effects respectively. Conclusion Lipid profiles mediated in the nonlinear association between eGDR and incident type 2 diabetes.