Preexisting Diabetes Mellitus and All-Cause Mortality in Adult Patients With Sepsis: A Population-Based Cohort Study

Objectives: We assessed the association of preexisting diabetes mellitus with all-cause mortality and organ support receipt in adult patients with sepsis.

Design: Population-based cohort study.

Setting: Ontario, Canada (2008-2019).

Population: Adult patients (18 yr old or older) with a first sepsis-related hospitalization episode.

Interventions: None.

Measurements and main results: The main exposure of interest was preexisting diabetes (either type 1 or 2). The primary outcome was all-cause mortality by 90 days; secondary outcomes included receipt of invasive mechanical ventilation and new renal replacement therapy. We report adjusted (for baseline characteristics using standardization) risk ratios (RRs) alongside 95% CIs. A main secondary analysis evaluated the potential mediation by prior metformin use of the association between preexisting diabetes and all-cause mortality following sepsis. Overall, 503,455 adults with a first sepsis-related hospitalization episode were included; 36% had preexisting diabetes. Mean age was 73 years, and 54% of the cohort were females. Preexisting diabetes was associated with a lower adjusted risk of all-cause mortality at 90 days (RR, 0.81; 95% CI, 0.80-0.82). Preexisting diabetes was associated with an increased risk of new renal replacement therapy (RR, 1.53; 95% CI, 1.46-1.60) but not invasive mechanical ventilation (RR, 1.03; 95% CI, 1.00-1.05). Overall, 21% (95% CI, 19-28) of the association between preexisting diabetes and reduced risk of all-cause mortality was mediated by prior metformin use.

Conclusions: Preexisting diabetes is associated with a lower risk of all-cause mortality and higher risk of new renal replacement therapy among adult patients with sepsis. Future studies should evaluate the underlying mechanisms of these associations.