New research by Denise Faustman and colleagues demonstrates that the Bacillus Calmette–Guérin (BCG) vaccine, developed to protect against tuberculosis, can lower blood levels of glucose to a range that is near normal (<6%) in patients with established type 1 diabetes mellitus (T1DM), a change that was sustained long-term.

The authors previously conducted a short phase I trial that included six patients with T1DM who received standard care plus either two doses of BCG vaccine or placebo. After 20 weeks, those treated with BCG vaccine showed increased numbers of regulatory T (Treg) cells, which are important for immune balance; however, there was no overall clinical response. “Owing to the increasing amount of data on the BCG vaccine working in other autoimmune diseases, we re-opened this study and started following-up the participants from the original phase I trial and enrolled additional patients with T1DM who had received the BCG vaccine,” explains Faustman.

In the current study, 52 participants with T1DM received standard care or standard care with either BCG vaccine or placebo. The original phase I trial participants were followed-up for 8 years and the second group were followed-up for 5 years. The initial serum levels of HbA1c in the BCG group were 7.36% and dropped to 6.18% after 5 years, while the placebo and standard-care-only groups showed no decrease. At 8 years, serum levels of HbA1c held steady at ~6.65% in the BCG group.

The researchers showed that BCG vaccination demethylated Treg genes and increased their expression. Additionally, the authors demonstrated that BCG vaccination improved glucose metabolism by systemically switching from oxidative phosphorylation to aerobic glycolysis (a high glucose consumption state) in diabetic mouse models. “These data reveal a new mechanism for BCG-induced lowering of blood sugars,” concludes Faustman.