Bacillus Calmette-Guerin Vaccination Lowers HbA1c in Type 1 Diabetes

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Originally developed for tuberculosis, the bacillus Calmette-Guerin vaccine is now involved in global trials for new immune indications.
Originally developed for tuberculosis, the bacillus Calmette-Guerin vaccine is now involved in global trials for new immune indications.

The bacillus Calmette-Guerin vaccine provides a stable and long-term reduction of hemoglobin (Hb) A1c in patients with type 1 diabetes (T1D), according to a phase 1 study presented at the European Association for the Study of Diabetes 54th Annual Meeting in Berlin, Germany.

Originally developed for tuberculosis, the bacillus Calmette-Guerin vaccine is now involved in global trials for new immune indications. A randomized, placebo-controlled study of the effects of bacillus Calmette-Guerin vaccination in T1D involved an 8-year follow-up for original study participants and a 5-year follow-up for new study participants. The vaccine was administered twice at 4 weeks apart, after which blood analysis was completed. Mechanistic in vitro analyses (n = 230) of RNA sequencing, metabolomics, and epigenetics were performed to observe the vaccine's systemic and mechanistic effects on glycemic control.

After year 3, participants who were vaccinated had lower HbA1c levels (6.18 ± 0.34) when compared with the placebo group (7.07 ± 0.41). In the longer-term follow-up, lower HbA1c levels were maintained by the vaccinated group through year 8 when compared with the placebo group (6.65 ± 0.26 vs 7.22 ± 0.38, respectively; P =.0002). The stable reduction in HbA1c was not associated with hypoglycemia and appeared to be the result of a shift in glucose metabolism and regulatory T cell tolerance in the immune system.

The researchers concluded that repeat bacillus Calmette-Guerin vaccination impacted blood sugar levels in patients with T1D by causing “a systemic shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis.” This “novel mechanism for significant blood sugar lowering with [bacillus Calmette-Guerin] opens the door for future trials in both type 1 and 2 diabetes with a safe, novel, and affordable approach,” they added.

Reference

Faustman D, Kühtreiber WM, Tran L, et al. Repeat BCG vaccination creates lasting HbA1c reductions in adult subjects with longstanding type 1 diabetes. Presented at: European Association for the Study of Diabetes Annual Meeting; October 1-5, 2018; Berlin, Germany. Abstract 426.

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