In clinical trials, type 1 diabetes patients had significant benefits, including near-normal blood sugar levels, with a generic vaccine. Patients currently control their blood sugar with insulin. Photo by stevepb/pixabay

June 21 (UPI) -- A generic vaccine offered type 1 diabetes patients with significant benefits, including near-normal blood sugar levels, according to Phase 1 clinical trials.

Three years after receiving two doses of the bacillus Calmette-Guerin vaccine four weeks apart, all tested participants with longstanding type 1 diabetes showed an improvement in HbA1c to near normal levels. This improvement continued for the next five years.


A Massachusetts General Hospital research team, which published the study Thursday in npj Vaccines, said the vaccine's effect apparently depends on a metabolic mechanism that helps cells consume glucose. The study will be presented Saturday at the 78th Scientific Sessions of the American Diabetes Association in Orlando, Fla.

"This is clinical validation of the potential to stably lower blood sugars to near normal levels with a safe vaccine, even in patients with longstanding disease," principal investigator Dr. Denise Faustman, director of the Massachusetts General Hospital's immunobiology laboratory, said in a press release. "In addition to the clinical outcomes, we now have a clear understanding of the mechanisms through which limited BCG vaccine doses can make permanent, beneficial changes to the immune system and lower blood sugars in type 1 diabetes."

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Higher HbA1c has been correlated with greater risks of developing diabetes-related complications such as blindness, heart attacks, strokes and renal failure.

In type 1 diabetes, insulin delivery will lower blood sugars, but it alone can continue to lower blood sugars to ranges below normal, risking potentially lethal hypoglycemia. Continuous glucose monitors and insulin pumps help maintain this balance but they are expensive devices that need to be attached to the body and require continuous monitoring.

The vaccine has been administered worldwide for 100 years against tuberculosis.

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And for more than 30 years, the vaccine was known to boost production of a cytokine -- tumor necrosis factor -- to benefit autoimmune diseases by eliminating the autoreactive T cells that attack an individual's tissues and by inducing production of regulatory T cells.

In 2001, Faustman's team first reported that inducing TNF production could cure type 1 diabetes in mice. But it is toxic in humans.

But the dose levels were adjusted. In initial clinical trial results, published in 2012, two doses of BCG spaced four weeks apart safely led to reductions in autoreactive T cells, an increase in Tregs and a transient increase in insulin production.

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After the 20-week trial, HbA1c wasn't reduced. But the trial was extended and expanded. The study included 282 human participants -- 52 with type 1 diabetes who participated in the BCG clinical trials and 230 who contributed blood samples for mechanistic studies.

In this study, 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. And it was maintained over another four years.

BCG-treated participants' HbA1c averaged 6.1 at five years and 6.6 after eight years, values close to the normal range of 6.5 considered the threshold for diabetes diagnosis. Also there were no reports of severe hypoglycemia.

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During the study, the research team found a mechanism never previously seen in humans in response to treatment with any drug: the process of glucose metabolism shifted from a process in which cells convert glucose into energy to one that involves significantly greater glucose consumption by cells.

In addition, researchers also found that vaccine could reduce blood sugar elevations in mice not caused by an autoimmune attack. This raises the possibility that the vaccines could be used to treat type 2 diabetes, the researchers said.

"The clinical effects and the proposed mechanism demonstrated are exciting and add to the emerging consensus that the BCG vaccine can have a lasting and valuable impact on the immune system," said Dr. Mihai G. Netea, a professor at Radboud University Medical Center in the Netherlands, who was not involved in the study. "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."

Eight clinical trials are underway and planned are ones involving children and other autoimmune diseases. Potential participants can register at {link:http://www.faustmanlab.org : "https://www.faustmanlab.org/" target="_blank"}