Diabetes Mellitus Type 2 as a Risk Factor and Outcome Modifier for Cryptococcosis in HIV negative, non-transplant Patients, a Propensity Score Match Analysis

Abstract

Cryptococcosis is an opportunistic fungal infection of worldwide distribution with significant associated morbidity and mortality. HIV, organ transplantation, malignancy, cirrhosis, sarcoidosis, and immunosuppressive medications, are established risk factors for cryptococcosis. Type 2 diabetes mellitus (DM2) has been hypothesized as a risk factor and an outcome modifier for cryptococcosis. We aimed to compare outcomes among HIV-negative, non-transplant (NHNT) patients with and without DM2. We also characterized a cohort of patients with cryptococcosis and DM2 as the only identifiable risk factor. We queried a global research network to identify NHNT patients (n = 3,280). We performed a propensity score-matched (PSM) analysis comparing clinical outcomes among cryptococcosis patients with DM2 (n = 995) versus those without DM2 (n = 2,285). We also characterize adults with cryptococcosis and DM2 as the only risk factor. After PSM, NHNT patients with DM2 were more likely to develop cognitive dysfunction [9% vs. 6%, OR = 1.6; 95% CI (1.1–2.3); p = 0.01] but had similar mortality, hospitalization, ICU, and stroke risk after acquiring cryptococcosis when compared to NHNT patients without DM2. We identified 44 patients with cryptococcosis who had DM2 as the only identifiable risk factor for infection. Patients with cryptococcosis and isolated DM2 commonly had chronic kidney and end-stage renal disease. The most common anatomic site of cryptococcal infection was pulmonary. The annual incidence of cryptococcosis in patients with DM2 as their only identifiable risk factor was only 0.001%, and the prevalence was 0.002%. DM2 is associated with increased cognitive dysfunction risk in NHNT patients with cryptococcosis. It is rare for DM2 to be the only identified risk factor for developing cryptococcosis. Kidney disease, hyperglycemia, and immune dysfunction can increase risk in this setting.