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Preliminary studies suggest that a vaccine for tuberculosis might reduce the need for insulin in individuals with type 1 diabetes. However, this area of investigation has faced skepticism previously, and further evidence is required.(Image credit: Paul Kane / Stringer via Getty Images)Share this article 0Join the conversationFollow usAdd us as a preferred source on GoogleSubscribe to our newsletter
New findings from a clinical trial indicate that a tuberculosis vaccine, developed a century ago, has lessened insulin requirements in diabetic patients. The caveat: For years, the research surrounding this vaccine has been a point of contention within the diabetes research community.
The Bacillus Calmette-Guérin (BCG) vaccine comprises a weakened strain of the bacterium Mycobacterium bovis, the pathogen responsible for tuberculosis. Within the body, the vaccine stimulates a defensive reaction against this bacterium. It also holds approval for treating bladder cancer, where it functions as an immunotherapy, inciting an assault against tumors.
Dr. Denise Faustman of Massachusetts General Hospital, who spearheaded these trials, has been a focal point of debate. Early criticisms asserted that she had misleadingly generated optimism regarding her work’s potential to offer a remedy for individuals with long-standing type 1 diabetes.
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On June 5, Faustman and her associates unveiled findings from two recent clinical trials at the annual gathering of the American Diabetes Association in New Orleans. The outcomes suggest that the BCG vaccine might confer advantages to individuals with type 1 diabetes — not through a cure, but by potentially enhancing blood sugar regulation or mitigating disease advancement, contingent on the patient group. Here’s what is important to know.
Another tool in the arsenal?
Approximately 2 million Americans are affected by type 1 diabetes, an autoimmune condition where the body’s immune system attacks and destroys the insulin-producing cells within the pancreas. Sufferers must monitor their glucose levels and administer insulin multiple times daily, meticulously calculating each dose. An overdose of insulin can lead to a dangerous drop in blood sugar, resulting in symptoms like trembling, convulsions, or fainting; insufficient insulin leads to persistently elevated blood sugar, causing damage to the heart, kidneys, eyes, and nerves.
In the initial stages of the disease, individuals still possess some insulin-generating cells, but those with long-term diabetes have very few remaining. Reversing type 1 diabetes in individuals with advanced disease presents a significant challenge, necessitating the halting of the immune assault and the regeneration of sufficient insulin-producing cells to eliminate the reliance on external insulin injections.
The latest trial results do not demonstrate this degree of remission. Nevertheless, “the new data indicates that BCG could potentially reduce insulin resistance and decrease the quantity of insulin required by patients experiencing both late-onset and juvenile-onset type 1 diabetes,” stated Dr. Gillian Goddard, an endocrinologist certified by the board at NYU Langone Health, who was not affiliated with the research.
“These are phase 2 trials, so further investigations will be essential to thoroughly comprehend the advantages of BCG in Type 1 diabetes,” she conveyed to Live Science via email, “but it might serve as an additional resource in our efforts to enhance the quality of life for patients with type 1 diabetes.”
Others remain doubtful. Dr. John Buse, an endocrinologist at the University of North Carolina School of Medicine, cautioned that the observed enhancements in these limited trials might not be replicated in a more extensive study. The history of type 1 diabetes research, he noted, “is replete with failures and lacks any major breakthroughs,” he informed Live Science in an email.
Individuals with type 1 diabetes must diligently monitor their blood glucose levels and administer insulin to maintain equilibrium. Could BCG contribute to improved glycemic control?
(Image credit: BSIP / Contributor via Getty Images)Different trials, different benefits
In the conducted trials, researchers observed the impact of six BCG vaccine doses, administered over a five-year period, on two distinct groups of diabetes patients.
In one study, 34 adults diagnosed with childhood-onset type 1 received the BCG vaccine, while 24 were given a placebo. After a period of five years or more, the BCG group exhibited quantifiable improvements in blood sugar readings and a reduction in their insulin requirements compared to the placebo group.
This determination was based on hemoglobin A1C (HbA1c) assessments, which gauge an individual’s average blood sugar concentration over the preceding two to three months. The cohort that received the vaccination transitioned from an average of 7.84% at the trial’s commencement to 7.30% five years later. Historically, a decrease of 0.5% has been deemed significant enough to warrant consideration for therapy approval.
The vaccinated participants also spent a greater proportion of time within a healthy blood sugar range, experiencing this up to 183% more frequently than they did at the outset of the trial. They did not encounter a higher incidence of dangerously low blood sugar episodes compared to the unvaccinated cohort.
A comprehensive program would be necessary to establish definitive proof, which is likely the most significant hurdle in determining its actual utility.
Dr. John Buse, an endocrinologist at the University of North Carolina School of Medicine
The second trial focused on latent autoimmune diabetes (LADA). This is an adult-onset variant of diabetes also referred to as “type 1.5.” It is distinct from type 2 diabetes, which is not characterized by autoimmunity.
Sixty-eight adults with LADA were administered the BCG vaccine, while 27 received a placebo. The vaccine did not lead to a reduction in blood sugar readings; however, it appeared to decelerate the progression of the disease. Vaccinated patients demonstrated preserved, and in some instances, partially restored, insulin production over a five-year span, as indicated by levels of C-peptide, a protein co-released by the pancreas with insulin.
Over five years, vaccinated patients required less insulin, whereas those who received the placebo needed 22% more insulin at the five-year mark than they did at the trial’s commencement.
“The outcomes surpassed my expectations,” Faustman communicated to Live Science via email.
How does it work?
Within the LADA trial, the blood samples from the vaccinated group exhibited diminished levels of two critical antibodies implicated in the autoimmune attack on insulin-producing cells. This suggests that the BCG vaccine may offer protection to an individual’s existing insulin-producing cells from the immune system, according to the researchers’ hypothesis.
Faustman and her colleagues propose that a different mechanism — one they outlined in a 2018 publication — is operative in cases of childhood-onset diabetes, where participants had minimal or no residual insulin production capacity in their pancreas at the trial’s inception.
Uncontrolled diabetes compels cells to utilize fat for energy, hindering their ability to efficiently alternate between burning fat and sugar. Based on their 2018 research, the investigators concluded that BCG inoculations specifically facilitate a shift in immune cells, known as regulatory T cells, from a fat-utilizing state to a sugar-utilizing state. These immune cells then extract glucose from the bloodstream but cease their activity once blood sugar levels normalize, thereby preventing dangerous hypoglycemic episodes, Faustman elucidated.
Buse indicated that he cannot personally ascertain the validity of these proposed mechanisms underlying the vaccine’s effects. However, he does surmise that BCG might be more effective for certain diabetes patients than others, suggesting the possibility of responders and non-responders.
The presented evidence “suggests that a benefit may exist,” he commented, but the current dataset is likely insufficient to assert this definitively. “A substantial initiative would be required to amass proof, and that likely represents the foremost obstacle in ascertaining its actual efficacy,” he stated.
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The sole medication approved by the Food and Drug Administration for delaying insulin dependence is teplizumab, which is administered early in the disease course, prior to the necessity of insulin. In contrast, BCG might offer advantages even to patients who have been using insulin for several years, Goddard observed.
Faustman’s research group has now examined over 350 adults, tracking individual participants for up to eight years, and another trial involving 250 children is presently ongoing. “This represents the subsequent phase to confirm that this secure, economical, and lasting medication can be effective across all stages of T1D,” she stated.
Irrespective of whether BCG enhances glycemic control in type 1 diabetes, the “future trajectory” involves employing integrated strategies that address the disease from multiple angles concurrently, Buse opined. Whether BCG will be incorporated into such a regimen remains uncertain, he added.
“It appears prudent to advance further [with research],” he remarked, “but funding bodies will need to interpret the signs to determine where to allocate their resources amidst numerous possibilities.”
