Association between Glycemic Traits and Delayed Cerebral Infarction among Non-Diabetic Patients with Aneurysmal Subarachnoid Hemorrhage: A Nested Case-Control Study

ABSTRACT Objective Delayed cerebral infarction (DCIn) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH). Previous studies suggest that glycemic variability is associated with DCIn. However, whether diabetes status modifies the relationship between glycemic traits and DCIn remains unknown. Methods Clinical data were collected from aSAH patients admitted to the First Affiliated Hospital of Shantou University Medical College between January 2015 and April 2025. The collected data included demographic characteristics, clinical variables, and glycemic traits. Glycemic traits included mean blood glucose (GLU-M), standard deviation of blood glucose (GLU-SD), coefficient of variation of blood glucose (GLU-CV), variance of blood glucose (GLU-Var), range of blood glucose (GLU-R), average real variability of blood glucose (GLU-ARV), and variability independent of the mean (GLU-VIM). After 1:2 case-control matching, conditional logistic regression models were used to evaluate the associations between glycemic traits and DCIn risk, with stratified analyses performed according to diabetes status. Multiplicative interaction terms were additionally included to assess the potential modifying effect of diabetes status. Results A total of 306 patients with aSAH were included. Among them, 102 developed DCIn cases. For each of these 102 cases, two controls were matched by age ({+/-}5 years), sex and year of admission ({+/-}5 years). In the overall population, higher GLU-M and GLU-ARV were associated with increased DCIn risk, with odds ratios (ORs) per 1-SD increase of 1.62 (95% CI, 1.25-2.11) and 1.63 (95% CI, 1.25-2.11), respectively. Among patients without diabetes (n=266), the associations with DCIn per 1-SD were observed for GLU-M (OR, 2.23; 95% CI, 1.56-3.19), GLU-SD (OR, 1.53; 95% CI, 1.13-2.06), GLU-Var (OR, 1.48; 95% CI, 1.04-2.10), and GLU-ARV (OR, 1.88; 95% CI, 1.38-2.55). No significant associations were observed among patients with diabetes. Significant interactions were observed between diabetes status and GLU-SD and GLU-Var, with P for interaction values of 0.033 and 0.032, respectively. Conclusion Higher mean blood glucose and greater glycemic variability are associated with an increased risk of DCIn in aSAH patients, especially in those without diabetes.