Association between hemoglobin glycation index and mortality in critically ill patients with chronic obstructive pulmonary disease: a retrospective cohort study

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a critical illness with high intensive care unit (ICU) mortality. Traditional glycemic markers like hemoglobin A1c (HbA1c) poorly reflect individual glucose metabolism variability. The hemoglobin glycation index (HGI), derived from the discrepancy between measured HbA1c and values predicted by fasting plasma glucose (FPG), assesses glycometabolic variability but remains unstudied in critically ill COPD patients. METHODS: This retrospective cohort enrolled 1,125 critically ill COPD patients admitted to the ICU, with data derived from the MIMIC-IV database. HGI was calculated as measured HbA1c minus predicted HbA1c (model: HbA1c = - 0.0095 × FPG + 5.02) and divided into tertiles. Cox regression models, adjusted for demographics, comorbidities, and clinical parameters, evaluated HGI tertile associations with 30-day, 90-day, and 365-day all-cause mortality. Restricted cubic splines (RCS) and threshold analysis explored nonlinear relationships. RESULTS: Among 1,125 patients, higher HGI tertiles were independently associated with lower mortality at all timepoints. In multivariable-adjusted Model II (age, sex, ethnicity, hematocrit, hemoglobin, SOFA score, SAPS II score, corticosteroid use, sepsis, and mechanical ventilation, diabetes), compared to the lowest tertile (T1), T2 and T3 showed significantly reduced mortality. For the 30-day mortality, the hazard ratios (HRs) were 0.54 (95% confidence interval [CI] 0.36-0.77, P = 0.0012) for T2 and 0.69 (95% CI 0.46-0.98, P = 0.0396) for T3; for the 90-day mortality, the HRs were 0.59 (95% CI 0.42-0.80, P = 0.0015) for T2 and 0.68 (95% CI 0.50-0.96, P = 0.0274) for T3; and for the 365-day mortality, the HRs were 0.67 (95% CI 0.51-0.87, P = 0.0108) for T2 and 0.73 (95% CI 0.57-0.96, P = 0.0277) for T3, all of which showed significant decreasing trends (all P for trend < 0.05). RCS analysis identified a nonlinear relationship between HGI and 30-day mortality (threshold: HGI = 0.865), with HGI increases below this threshold reducing mortality, and no association above it. Subgroup analyses showed no significant interactions. CONCLUSIONS: Lower HGI levels are independently associated with higher short- and long-term mortality in critically ill COPD patients, with a nonlinear threshold effect. HGI may serve as a novel prognostic biomarker, highlighting the need for personalized glycometabolic management.