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.