Increased mortality associated with uncontrolled diabetes mellitus in patients with Pulmonary Cryptococcosis- a single U.S. 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 2000-2019. 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%) and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis had a higher mortality at 10 weeks (50% vs 7%, p=0.006) and one year (66.7% vs 13.8%, p=0.005). Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10-weeks (hazard ratio 8.4, 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 (OR=4.3, CI: 1.1-16.5, p=0.035) and one-year (OR=5.9, CI: 2.2-15.8, 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 one-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.