Differential prognostic value of glycemic dysregulation markers in critically ill individuals with ischemic stroke, with and without diabetes

Glycemic dysregulation is common in critically ill patients with ischemic stroke and is strongly associated with adverse outcomes. However, the prognostic implications of hyperglycemia may differ substantially between patients with diabetes and without diabetes, reflecting divergent metabolic responses to acute stress. Traditional glucose metrics often fail to capture this complexity. Novel glycemic markers—hemoglobin glycation index (HGI), stress hyperglycemia ratio (SHR), and glycemic variability (GV)—may better characterize both acute and chronic glycemic disturbances. Understanding whether these markers have differential prognostic value based on diabetes status is critical for advancing individualized glycemic management strategies in the ICU setting. The cohort included 1,293 critically ill individuals with ischemic stroke, with a mean age of 68 ± 12 years, and 67% were male. Of these, 640 (49.5%) had diabetes and 653 (50.5%) did not. Three glycemic markers—HGI, SHR, and GV—were calculated from admission glucose and HbA1c values. The primary outcome was all-cause mortality at 30, 180, and 360 days. Multivariable Cox regression, Kaplan–Meier analysis, restricted cubic spline modeling, and time-dependent ROC curves were used to evaluate associations. To investigate potential heterogeneity, we subsequently performed subgroup analyses stratified by diabetes status, including recalibration of the HGI estimation models for patients with diabetes and without diabetes. All three glycemic markers were independently associated with mortality, though their prognostic value varied by diabetes status. Among patients without diabetes, moderate HGI was associated with significantly lower 180-day (HR = 0.64, p = 0.049) and 360-day mortality (HR = 0.65, p = 0.023). SHR was a stronger predictor in patients without diabetes at 30 days (HR = 1.52, 95% CI: 1.11–2.08, p = 0.009), while GV was associated with increased 360-day mortality (HR = 1.50, p = 0.015). In contrast, for patients with diabetes, only SHR showed consistent association with 180-day mortality (HR = 1.46, p = 0.028). HGI, SHR, and GV are independently associated with mortality in individuals with ischemic stroke who are critically ill, but their prognostic value differs by diabetes status. Patients without diabetes appear more vulnerable to glycemic stress, underscoring the need for diabetes-stratified approaches in glycemic risk assessment and ICU management.