BCG may play role in type 1 diabetes prevention but not type 2 diabetes

"Our ecological analysis of global data indicates a role for neonatal BCG in T1D prevention and T2D to a lesser extent," Hans F. Dias and colleagues from the USA wrote in their study. "Randomized clinical trials are required to confirm these findings."

Diabetes is a common disease characterized by high blood sugar. An earlier clinical trial in patients with type 1 diabetes reported that repeat BCG vaccination lowered HbA1c values over a multi-year course. In the study, the research team seek to investigate whether BCG therapy for bladder cancer improves blood sugar levels in patients with comorbid type 1 and type 2 diabetes. They also investigated whether BCG exposure may reduce T1D and T2D onset by examining the country-by-country impact of BCG childhood vaccination policies concerning disease incidence.

For this purpose, the researchers first analyzed large datasets of US patients (Optum Labs data comprising 45 million adults, Quest Diagnostics comprising 263 million adults and Massachusetts General Brigham comprising 6.5 million adults). Subjects with documented type 1 diabetes (N = 19) or type 2 diabetes (N = 106) undergoing BCG therapy for bladder cancer were sorted out and then analyzed by retrospective assessment of BCG's subsequent year-by-year impact on blood sugar trends.

An ecological analysis of global data was also performed to examine the country-by-country associations between requisite neonatal BCG vaccination programs and type 1 diabetes and type 2 diabetes incidence.

The researchers reported the following findings:

· In adults with comorbid bladder cancer and diabetes, multi-dose BCG therapy was associated with multi-year and stable HbA1c lowering in T1Ds, but not in T2Ds.

· The lack of a similar benefit in type 2 diabetes may be due to the concurrent administration of metformin, a diabetes drug, which inhibits BCG's beneficial effect on glycolysis pathways.

· Countries with requisite neonatal BCG vaccination policies had a lower T1D incidence in two international databases and a lower T2D incidence in one of the databases.

Three different patient datasets demonstrated decreased HbA1c post-intravesical instillation of BCG for bladder cancer, even though the patients with type 1 diabetes were elderly and had the longstanding disease.

"The data indicate that BCG helps regulate blood sugar in T1D patients," the researchers wrote. "We observed that BCG's multi-dosing elicited a beneficial response."

"More thorough investigations should also be conducted into the possibility of T1D and T2D prevention based on observed associations between neonatal BCG vaccinations programs and diabetes incidence," they stated. "Further research is warranted to validate the potential beneficial effects of BCG on diabetes, including the requirement for multiple doses or a particular strain."

Reference:

Dias, H. F., Mochizuki, Y., Kühtreiber, W. M., Takahashi, H., Zheng, H., & Faustman, D. L. (2023). Bacille Calmette Guerin (BCG) and prevention of types 1 and 2 diabetes: Results of two observational studies. PLOS ONE, 18(1), e0276423. https://doi.org/10.1371/journal.pone.0276423