Type 1 diabetes mellitus (previously termed juvenile onset diabetes) is a form of diabetes that results from autoimmune destruction of insulin secreting beta islet cells of the pancreas. This disease has all the hallmarks of the more common type 2 diabetes as well as the increased risk of vascular disease, heart disease, stroke, renal failure, and dementia. Of all cases of diabetes, it is estimated that 10% are type 1 diabetes. There are approximately 20 million people with type 1 diabetes worldwide. Since type 1 diabetes is an autoimmune disorder, research has focused on suppressing the immune cells that attack the insulin secreting beta islet cells of the pancreas.
Researchers, lead by Dr. Denise Faustman from Harvard Medical School, have found that administration of the Bacillus-Calmette-Guerin (BCG) vaccine suppresses disease causing autoimmune T cells and restores insulin secretion by beta islet cells in type 1 diabetic patients. The results of their study were reported online in the journal PLoS ONE. The mechanism is thought to be stimulation of innate immunity by the BCG vaccine and production of tumor necrosis factor (TNF), which is known to suppress autoimmunity in type 1 diabetes.
For their study, the investigators used a placebo controlled double blind clinical trial involving six type 1 diabetics. Three study participants received two doses of the BCG vaccine four weeks apart. The other three study participants received saline injections as a control. Additional controls were used, and included healthy individuals and other type 1 diabetics. The investigators measured levels of disease causing autoimmune T cells, regulatory T cells, and C-peptide (a marker for insulin secretion) after vaccine administration. It was found that there was an increase in the level of insulin secretion and decreased numbers of disease causing autoimmune T cells. Incidentally, one of the control study participants became infected with the Epstein Barr virus and also showed an improvement. The investigators postulate that Epstein Barr virus stimulated the production of TNF similarly to BCG vaccine.
The authors wrote, “We also found that BCG vaccination and an unexpected EBV infection in a placebo-treated diabetic subject, both known triggers of innate immunity, caused rapid increases in circulating insulin-autoreactive T cells that were mostly dead. The rapid release of dead insulin-autoreactive T cells supports the hypothesis, first demonstrated in the NOD-mouse model of autoimmune diabetes, that BCG ameliorates the advanced autoimmune process underlying type 1 diabetes by stimulating TNF, which selectively kills only disease-causing cells and, further, permits pancreas regeneration”. In addition, the authors wrote, “The transient increases in C-peptide, found after both an acute EBV infection and with BCG vaccinated subjects, suggests a positive impact of these immune perturbations on beta cell function”.
This study is quite remarkable and shows that a transient suppression of autoimmunity in type 1 diabetes can be achieved and restoration of insulin secretion by beta islet cells accomplished. This study is still preliminary and needs to be reproduced on a larger scale. Several scientists in the field have expressed doubt concerning the validity of the results. If the study findings are confirmed, this should pave the way for future research into a possible cure for type 1 diabetes. Additional research is needed to determine if a more permanent suppression of disease causing autoimmune T cells can be obtained.
The authors concluded, “Our findings provide proof-of-principle evidence that insulin-autoreactive T cells can be specifically targeted and eliminated, albeit briefly, in vivo, even in long-standing disease with a transient restoration of C-peptide. This paves the way for either higher doses or more frequent BCG administered in future trials for patients with advanced disease to maintain or restore C-peptide levels”.
Reference:
Denise L. Faustman et al. “Proof-of-Concept, Randomized, Controlled Clinical Trial of Bacillus-Calmette-Guerin for Treatment of Long-Term Type 1 Diabetes” PLoS ONE 7(8): e41756. doi:10.1371/journal.pone.0041756
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