Increased mortality associated with uncontrolled diabetes mellitus in patients with pulmonary cryptococcosis: a single US cohort study

Background: Diabetes mellitus is an established risk factor for bacterial infections, but its role in cryptococcosis is unclear. The study aimed to determine whether uncontrolled diabetes (HbA1c >7%) was an independent risk factor for mortality in cryptococcosis. Methods: A retrospective case-control study partially matched by age and gender was performed in patients tested for Cryptococcus infection at the University of Colorado Hospital from 2000 to 2019. A multivariable logistic regression model was used to identify mortality predictors. Cox proportional hazard model was used for survival analysis. Results: We identified 96 cases of cryptococcosis and 125 controls. Among cases, cryptococcal meningitis (49.0%1 and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis with uncontrolled diabetes had a higher mortality at 10weeks (50% versus 7%, p=0.0061 and 1 year (66.7% versus 13.8%, p= 0.0051 compared to pulmonary cases with controlled or no diabetes. Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10 weeks [hazard ratio 8.4, confidence interval (CI): 1.4-50.8, p=0.02] and 1 year (hazard ratio 7.0, CI: 1.7-28.4, p=0.007) among pulmonary cryptococcosis cases. Multivariable analysis showed a significantly increased odds of 10 weeks [odds ratio (OR)=4.3, CI: 1.1-16.5, p=0.035] and 1 year (OR= 5.0, CI: 1.4-18.3, p=0.014) mortality for uncontrolled diabetes among pulmonary cryptococcosis cases. After adjustment for gender, age, and case/control, for every 1% increase in HbA1c levels, the odds of pulmonary cryptococcosis mortality at 1 year increased by 11% (OR=1.6, CI 95%: 1.1-2.3, p= 0.006). Conclusion: Uncontrolled diabetes is associated with worse outcomes in pulmonary cryptococcosis, including a 4-fold and 6-fold increased odds of death at 10 weeks and 1 year, respectively. Glucose control interventions should be explored to improve clinical outcomes in patients with pulmonary cryptococcosis.