U-Shaped Association Between Preoperative Fasting Blood Glucose and Postoperative Delirium in Elderly Diabetic Patients: A Multicentre Retrospective Cohort Study

Abstract Objective: The heightened susceptibility of the aging brain to dysglycemia establishes blood glucose as a pivotal risk factor for postoperative delirium (POD) in elderly diabetic patients. This study investigated the association between preoperative fasting blood glucose (FBG) and POD risk in this population to define the optimal FBG range for POD. Methods: This study included 2,157 elderly diabetic patients undergoing non-cardiac surgery between April 2020 and April 2022 in 20 hospitals across China. The POD incidence was prospectively assessed using the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) within 7 postoperative days. The FBG-POD relationship was retrospectively analysed using restricted cubic splines within Cox proportional hazards model. Thresholds were validated with the machine learning-guided optimal cut-point analysis. A multivariable linear regression model was plotted to compare the distribution of time to POD onset and subgroup analyses were performed based on specific populations. Results: A significant U-shaped relationship was observed between preoperative FBG and POD risk (P for nonlinearity=0.03). The hazard ratio identified the risk nadir of FBG at 8.43 mmol L-1. Optimal cut-point analysis defined three risk strata: a hypoglycemic-risk group (FBG ≤5.92 mmol L-1; 13.3% POD), an optimal-glycemic group (FBG 5.92-9.75 mmol L-1; 9.7% POD), and a hyperglycemic-risk group (FBG >9.75 mmol L-1; 18.5% POD). Compared with the optimal-glycemic group, both the hypoglycemic-risk group (HR=1.65, P<0.001) and the hyperglycemic-risk group (HR=1.51, P=0.03) showed significantly increased risk. Interpretation: Preoperative FBG has a U-shaped association with POD risk in elderly diabetic patients with an optimal lowest-risk range as 5.92-9.75 mmol L-1. Keywords: Diabetes Mellitus; Elderly; Fasting Blood Glucose; Postoperative Delirium; Risk Stratification; Threshold Analysis.