Potential mechanism by which BCG vaccine lowers blood sugar levels to near normal in type 1 diabetes discovered

October 3, 2018, Diabetologia

Previous research has shown that the bacillus Calmette-Guerin (BCG) vaccine, used to prevent tuberculosis, can reduce blood sugar levels in people with advanced type 1 diabetes in the long term. New research being presented at this year's European Association for the Study of Diabetes (EASD) Annual Meeting in Berlin, Germany (1-5 October) reveals the mechanism through which the vaccine can make durable, beneficial changes to the immune system and lower blood sugars.

The new findings suggest that the immune-metabolic imbalance in type 1 could stem from too few microbial (ie, germ) exposures that have been eliminated in today's more sterile environments, and that reintroduction of a bacterium (BCG) might reset abnormal metabolic functions boosting the immune system to consume and reduce blood glucose levels over time.

"It has long been believed that the move to cleaner and more urban environments is involved in not only how type 1 diabetes develops, but increased incidence of the disease", explains Dr. Faustman, Director of the Massachusetts General Hospital Immunobiology Laboratory, who led the study. "In particular, reduced exposures to certain microbes, the consequence of better sanitation, greater use of antibiotics, smaller family sizes, cleaner houses, less daily exposures to the soil, and less exposure to domesticated animals, appears to have changed the modern metabolic function."

The BCG vaccine, based on a harmless strain of bacteria related to the one that causes tuberculosis, appears to have the effect of safely mimicking the microbial exposures modern societies have lost.

In an earlier phase 1 randomised trial, two injections of the BCG vaccine 2 weeks apart reduced average blood sugar to near normal levels by the 3-year mark in people with advanced type 1 diabetes, an improvement that was sustained for 5 more years. [1] Faustman and colleagues from Massachusetts General Hospital in the USA also identified that the BCG vaccine uses a novel mechanism to change the way the body consumes glucose—from oxidative phosphorylation (the most common pathway by which cells convert glucose to energy) to aerobic glycolysis, a state that speeds up the rate cells turn glucose into energy, leading to reduced over time.

These new findings show that type 1 diabetics have metabolism consistent with less microbial exposure. As a result, type 1 diabetic patients have that use minimal blood sugar compared to non-diabetics control subjects. Exposing the patients to microbes in the BCG vaccine seems to result in the white blood cells using more blood sugar by increasing aerobic glycolysis.

"BCG is an organism that needs a lot of energy sources. It lives inside white cells and elevates the sugar utilisation", explains Dr. Faustman.

The findings support the hygiene hypothesis which suggests that early life exposure to microbes that promote is actually beneficial to the development of the immune system and is an important determinant of sensitivity to autoimmune diseases such as type 1 diabetes.

"The BGC vaccinations like tuberculosis itself, convert a depressed lymphatic system deficient in sugar utilisation into a highly efficient process, a restoration similar to normal subjects without diabetes", says Dr. Faustman.

"Our discovery that type 1 diabetic patients have too little lymphoid sugar utilisation opens the door for more clinical trials using the BCG vaccine, even in advanced type 1 diabetes, to permanently lower with the potential to reduce the substantial illness and mortality associated with this disease."

The authors note some limitations including that this is an early, small study, and a large 5-year phase 2 trial of 150 type 1 diabetic subjects approved by the US Food and Drug Administration is currently underway to test whether repeat BCG can clinically improve type 1 diabetes in adults with existing disease.

Explore further: BCG vaccine leads to long-term blood sugar improvement in type 1 diabetes patients

More information: [1] The June 2018 Nature study of 282 participants—52 with type 1 diabetes and 230 who contributed blood samples for mechanistic studies (211 with type 1 diabetes and 71 non-diabetic controls) showed that 3 years after BCG vaccination, blood sugar levels had dropped on average by more than 10%, and by over 18% after 4 years. This reduction was maintained after 8 years in the BCG treated six participants, who had an average HbA1c score of 6.65—close to the 6.5 threshold for diabetes diagnosis, and with no reports of hypoglycemia (low blood sugar). BCG-treated patients were also able to reduce their insulin intake. In contrast, average blood sugar levels of participants in the placebo group continued to rise over the study period.

Related Stories

BCG vaccine leads to long-term blood sugar improvement in type 1 diabetes patients

June 21, 2018
Long-term follow-up of participants in clinical trials of a generic vaccine to reverse advanced type 1 diabetes finds significant clinical benefits, including restoration of near-normal blood sugar levels. Three years after ...

Diabetes, dementia can be deadly combination

October 2, 2018
(HealthDay)—The risk of death from dangerously low blood sugar is much higher among seniors who have both diabetes and dementia than those with diabetes alone, a new study finds.

Retooled vaccine raises hopes as a lower-cost treatment for Type 1 diabetes

July 17, 2018
For Hodalis Gaytan, 20, living with Type 1 diabetes means depending on an assortment of expensive medicines and devices to stay healthy. Test strips. Needles. A glucose meter. Insulin.

Artificial pancreas helps hospitalized type 2 diabetics

June 26, 2018
(HealthDay)—Using an artificial pancreas can help hospitalized patients with type 2 diabetes maintain good blood sugar control, a new study suggests.

Brain scans show why some type 1 diabetics miss low blood sugar cues

February 2, 2018
The brains of people with type 1 diabetes react differently to low blood sugar compared with healthy adults, say Yale researchers.

Study finds potential mechanism for BCG vaccine reversal of type 1 diabetes

June 10, 2017
Interim results from a FDA-approved clinical trial testing the generic vaccine bacillus Calmette-Guérin (BCG) to reverse advanced type 1 diabetes are being presented at the 75th Scientific Sessions of the American Diabetes ...

Recommended for you

Does diabetes damage brain health?

December 14, 2018
(HealthDay)—Diabetes has been tied to a number of complications such as kidney disease, but new research has found that older people with type 2 diabetes can also have more difficulties with thinking and memory.

Researchers study abnormal blood glucose levels of discharged patients

December 14, 2018
University of Minnesota Medical School researchers decided to delve into an area where little data currently exists. They wanted to know what happens after these patients with abnormal blood glucose measurements are discharged? ...

Researchers zero in on potential therapeutic target for diabetes, associated diseases

December 14, 2018
A recent study led by researchers in Texas A&M University's department of nutrition and food science shows how a novel regulatory mechanism serves as an important biomarker for the development of diabetes, as well as a potential ...

Researchers have found that incidence of heart failure was around two-fold higher in people with diabetes

December 11, 2018
Researchers have found that incidence of heart failure was around two-fold higher in people with diabetes.

Millions of low-risk people with diabetes may be testing their blood sugar too often

December 10, 2018
For people with Type 2 diabetes, the task of testing their blood sugar with a fingertip prick and a drop of blood on a special strip of paper becomes part of everyday life.

Very low calorie diets trialled by NHS to tackle diabetes

December 7, 2018
Hundreds of thousands of people will receive NHS help to battle obesity and type 2 diabetes under radical action set out by Simon Stevens, Chief Executive of NHS England.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.