Hemoglobin glycation index and short-term mortality in sepsis: a retrospective cohort study with external validation

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Background The hemoglobin glycation index (HGI) reflects interindividual variability in hemoglobin glycation beyond average glycemic exposure. Although stress-related dysglycemia is common in sepsis, the prognostic relevance of HGI in critically ill patients with sepsis remains unclear. Methods We conducted a retrospective cohort study using the MIMIC-IV database ( n = 2,073) as the primary cohort. HGI was calculated as the difference between observed and predicted HbA1c based on admission glucose. The primary outcome was 28-day mortality. Findings were validated in an independent external cohort ( n = 166). Results In the primary cohort, the 28-, 60-, and 90-day mortality rates were 23.25, 27.69, and 30.00%, respectively. Non-survivors exhibited significantly lower HGI levels than survivors ( p < 0.001). Compared with the lowest HGI quartile (Q1), patients in the highest quartile (Q4) had a significantly lower risk of 28-day mortality (hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.52–0.94; p = 0.018) and 60-day mortality (HR 0.76, 95% CI 0.58–1.00; p = 0.050). A similar but non-significant trend was observed for 90-day mortality (HR 0.80, 95% CI 0.62–1.04; p = 0.101). In the external validation cohort, higher HGI was similarly associated with reduced 28-day mortality, supporting the robustness of the primary findings. Conclusion Higher HGI was associated with lower short-term mortality in this retrospective cohort of critically ill patients with sepsis, with the strongest evidence observed for 28-day mortality. These findings suggest that HGI may provide prognostic information during the early phase of sepsis. Prospective studies are needed to validate these findings and determine their clinical utility.