Bacillus Calmette-Guerin 's beneficial impact on glucose metabolism: evidence for broad based applications

Shpilsky, Gabriella F.; Takahashi, Hiroyuki; Aristarkhova, Anna; Weil, Michele; Ng, Nathan; Nelson, Kacie J.; Lee, Amanda; Zheng, Hui; Kühtreiber, Willem M.; Faustman, Denise L.

Bacillus Calmette-Guerin (BCG) vaccinations improve glycemic control in juvenile-onset Type I diabetes (T1D), an effect driven by restored sugar transport through aerobic glycolysis. In a pilot clinical trial, T1D, but not latent autoimmune diabetes of adults (LADA), exhibited lower blood sugars after multidose BCG. Using a glucose transport assay, monocytes from T1D subjects showed a large stimulation index with BCG exposures; LADA subjects showed minimal BCG-induced sugar responsiveness. Monocytes from T1D, type 2 diabetes (T2D), and non-diabetic controls (NDC) were all responsive in vitro to BCG by augmented sugar utilization. Adults with prior neonatal BCG vaccination show accelerated glucose transport decades later. Finally, in vivo experiments with the NOD mouse (a T1D model) and obese db/db mice (a T2D model) confirm BCG's blood-sugar-lowering and accelerated glucose metabolism with sufficient dosing. Our results suggest that BCG's benefits for glucose metabolism may be broadly applicable to T1D and T2D, but less to LADA.