Why the study?
Prior studies suggested incretins predict adverse outcomes in critical illness, motivating an investigation into whether GLP-1 and GIP indicate disease severity and outcomes in acute respiratory failure.
Higher circulating levels of GLP-1, but not GIP, are associated with increased systemic inflammation and 90-day mortality in critically ill patients with acute respiratory failure.
May aid ICU risk stratification in respiratory failure; hypothesis-generating and should not yet change practice.
OBJECTIVES: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have therapeutic effects in diabetes mellitus. Prior clinical studies suggest incretins are prognostic of adverse outcomes in critical illness. We investigated whether incretin levels indicate disease severity and clinical outcomes in patients with acute respiratory failure, a common cause of critical illness. DESIGN: Retrospective cohort study. SETTING: ICUs in UPMC Health Systems hospitals within Western Pennsylvania. PATIENTS: Two hundred ninety-seven critically ill adults with acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured GLP-1 and GIP levels in baseline samples collected at the time of study enrollment. We compared incretin levels across subgroups differing by severity of illness and investigated associations between incretins and markers of systemic host responses and intestinal permeability. In our primary analysis, we tested the association of each incretin level with 90-day mortality by logistic regression in unadjusted analyses and in analyses adjusted for age, Sequential Organ Failure Assessment score, and circulating interleukin-6 levels. GLP-1 levels were higher in nonsurvivors and patients with or at-risk for acute respiratory distress syndrome compared to those intubated for airway protection. GLP-1 levels also positively correlated with systemic immune response biomarkers but not with markers of intestinal permeability. GLP-1 levels positively correlated with mortality in unadjusted (odds ratio, 1.99 [1.55-2.56]; p < 0.01) and adjusted (2.02 [1.23-3.31]; p < 0.01) analyses. GIP levels were not associated with mortality or with host response biomarkers. CONCLUSIONS: GLP-1 but not GIP levels were positively associated with systemic inflammation and mortality in critically ill patients with acute respiratory failure. Increased circulating GLP-1 levels may serve as prognostic biomarkers to identify patients who are likely to have worse outcomes.
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Aneis et al. (2025) studied this question.
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