Introduction & Objective: In randomized clinical trials in patients with type 1 diabetes (T1D), bacillus Calmette-Guérin (BCG) vaccinations gradually lower blood sugar to near-normal levels, which appears to be driven by a BCG-induced shift in lymphoid cells’ glucose metabolism from oxidative phosphorylation to aerobic glycolysis. Here we investigated whether the BCG bacterium establishes residence in organs and alters their glucose metabolism.
Methods: In an open-label clinical trial in patients with longstanding T1D (n=6; T1D duration >13 years at time of baseline BCG injection), we used positron emission tomography (PET) and x-ray computed tomography (CT) to map organs with increased uptake of the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) after BCG vaccinations (Tokyo 172 BCG strain, Japan BCG Laboratory, Tokyo, Japan). Patients received a total of 6 BCG doses over a 2-year period. The first PET/CT scan was performed prior to receipt of BCG; each patient’s subsequent scans were compared to their baseline scan. We also injected BALB/c mice with BCG to test for BCG’s presence in various organs.
Results: The human and murine studies identified the spleen as the dominant site for glucose uptake and BCG residence after vaccination. Overall, the spleen showed a 47% increase in glucose uptake compared to baseline (p-value=0.03; mixed linear effects model statistics), which correlated in time with a systemic drop in blood sugar. The spleen’s activity steadily and significantly increased over the course of 2-years of 18F-FDG mapping, and the microbe persisted there over a 20-week period in the mice.
Conclusion: These findings suggest that the spleen, triggered by BCG vaccinations, assumes a critical role in systemic glucose regulation in the absence of a functional pancreas. This data fits with surgical data wherein splenectomy can cause diabetes in patients due to glucose dysregulation.
H.F. Dias: None. J. Fu: None. H. Zheng: None. W. Kuhtreiber: None. J. Price: None. C. Catana: None. D.L. Faustman: None.
