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Using Bacillus Calmette-Guérin (BCG) vaccine restoration for a long period of time improves blood sugar to near-normal blood sugar levels. Three years after receiving two administrations of BCG vaccine for four weeks apart, all members of a group of adults with type 1 diabetes showed an improvement in HbA1c to near normal levels, improvement that persisted for the five years.
The study from a Massachusetts General Hospital (MGH) research team also reports that the effects of BCG vaccine on blood sugar control depend on a totally novel metabolic mechanism that increases cellular consumption of glucose. BCG vaccine doses can make permanent, beneficial changes to the immune system and lower blood sugars in type 1 diabetes.
BCG prevents tuberculosis, boosts production of a cytokine- tumor necrosis factor (TNF), which may be beneficial in autoimmune diseases by eliminating the autoreactive T cells that attack an individual’s tissues, in the case of type 1 diabetes, pancreatic islets and by inducing production of regulatory T cells (Tregs) that could prevent an autoimmune reaction.
Inducing TNF production could cure type 1 diabetes in mice, but since TNF dosing is toxic in humans, clinical trials have utilized BCG for its ability to elevate TNF levels safely. Two doses of BCG spaced for four weeks apart led to reductions in autoreactive T cells, an increase in Tregs and what turned out to be a transient increase in insulin production. But by the end of that short, 20-week trial, there was no reduction in HbA1c, the established measure of blood sugar levels over time.
An extension and expansion of that trial with long term follow-up, the current results are based on data from 282 human study participants—52 with type 1 diabetes who participated in the BCG clinical trials and 230 who contributed blood samples for mechanistic studies.
Regular monitoring of clinical trial participants found that HbA1c levels of those receiving BCG had dropped by more than 10 percent at three years after treatment and by more than 18 percent at four years. That reduction was maintained over the next four years, with treated participants having an average HbA1c of 6.65, close to the 6.5 considered the threshold for diabetes diagnosis, and with no reports of severe hypoglycemia.
Participants in the placebo group and in a comparison group of patients receiving no treatment experienced consistent HbA1c elevations over the same eight-year time period. In investigating how BCG administration produces its beneficial effects, the research team identified a mechanism never previously seen in humans in response to treatment with any drug, a shifting of the process of glucose metabolism from oxidative phosphorylation, the most common pathway by which cells convert glucose into energy, to aerobic glycolysis, a process that involves significantly greater glucose consumption by cells.
The researchers also found that BCG could reduce blood sugar elevations in mice that were caused by means other than autoimmune attack, raising the possibility that BCG vaccines could also be beneficial against type 2 diabetes. BCG vaccination induces epigenetic reprogramming at the chromatin architecture level and functional alterations indicative of a permanent change in immunity. The MGH trials and other, larger prevention and intervention trials underway around the globe may lead to a major shift in the prevention and treatment of infections and autoimmunity.
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