Response to JDRF Public Statement Of BCG Human Trial

I find it interesting the JDRF & ADA felt compelled to issue a joint statement against Faustman’s research. Admittedly, I rarely pay attention to the JDRF. Do they make a habit of issuing statements like this?

An HbA1c of 6.5 is considered the threshold of diabetes diagnosis. In the supplemental data of this study, the BCG group started with an average HbA1c of 7.36 and decreased to an average of 6.38 over the years 5-8 followed. In contrast, the control’s group average HbA1c remained relatively the same and even slightly increased from the initial 7.08-7.10 range over the same time period. The data is highly statistically significant (p<0.0002). Semi-annual surveys confirmed the BCG group reported no significant hypoglycemia episodes within the years 5-8 followed. The placebo group continued to show hypoglycemia events during the same time periods of monitoring. Dr Faustman investigated why these significant changes occurred in the BCG treated group when they discovered it was not due to regeneration of islets (based on C-peptide levels). Through extensive research, they found that the blood sugar control was attributed to a shift in the body’s ability to metabolize glucose from “oxidative phosphorylation” to “aerobic glycolysis” (a state of high glucose utilization) on a tightly regulated cellular level throughout the body. In other words, blood glucose uptake and regulation of this uptake by the cells appears to prevent hypoglycemia since the cells stop transporting glucose when the blood sugar is in the normal range.
Dr. Faustman has been corroborating her research with other scientists around the globe who are all part of a BCG coalition meeting annually. These scientists have been studying the history of BCG (it’s been around for 100 years) and its effects on the immune system, other autoimmune diseases and allergies. The strain of BCG and the # of doses one receives is very important on how it effects the immune system. Dr. Faustman and a group of scientists in Italy who are using the same strain and dosing for human trials in MS patients are sharing very similar results. In fact, they are the ones who told her that the changes that they started to see in MS patients did not come out until 2-3 years after dosing and they followed them for 5 years out. This is why Dr. Faustman applied for FDA approval to extend her phase I trial and continued analyzing and monitoring subjects from the 3 year - 8 year time frame.

With JDRF and Faustman, the oddly worded public official communications goes back at least 14 years:

JDRF’s internal “mission creep struggles” aka “insider baseball” occasionally surface in terms of odd public official communications but are actually quite common in terms of internal communications between HQ and chapters and members. I think what we are seeing here, is Suelr joining tudiabetes to promote her viewpoint in this internal-to-JDRF discussion/disagreement. I think JDRF has done a great job re-orienting itself to a world where kids with T1 grow up to live a good chunk of a century as adults with T1, to include treatment and long lives as well as cure-cure-cure, but it wasn’t easy or automatic for the factions inside JDRF to make this change.

I’m not interested in second guessing any member’s motive for joining/posting. I’m aware of past history between JDRF & Faustman. The fact remains that JDRF has issued a public statement disputing (attacking) Faustman’s research. I can’t recall that happening any time over the past several years, & I can’t help but wonder why.

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At same time, you should recognize that Suelr joined tudiabetes only to post this internal-to-JDRF disagreement. She posted that the same day she joined tudiabetes so it’s not like she’s part of the community here.

I’m fine with folks inside JDRF refining their mission, and I think they’ve done a good job at it recent years. But I don’t see how them taking their disagreements to tudiabetes helps anyone.

On Faustman - it’s interesting stuff but many odd disconnects and I see why some in the establishment are suspicious. I’m more willing to believe that a couple folks in the study markedly improved their bg control through hard work. The 4 year delay after BCG dose before claimed A1C improvement is really odd and makes me doubt cause and effect. The Faustman proposed effect, an entirely new non-insulin-moderated process for glucose metabolism, certainly wasn’t in any of my 40-year old textbooks so makes me scratch my head. Like Seydlitz wrote earlier, we see our bg’s change all the time anyway not only for good reason but also for no reason!

Also, it is important to keep in mind that the human immune system is a vastly complex, finely-tuned instrument, and tinkering it in any way, as BCG does here, is always dangerous. For example, the immunosuppression required for organ transplants causes, as a side-effect, a 30% chance of cancer after a decade.

BCG has an impeccable 100 year safety record and has been administered to millions. It is not in the same category as an immune suppressant.

I too might have thought any relation BCG and T1 diabetes might be related through the immune system.

Faustman, at least in the 2018 paper, is not hypothesizing that BCG is changing the immune system.

Faustman in the 2018 paper proposes (invents?) a novel previously unknown channel for glucose metabolism that doesn’t require insulin, they call aerobic glycolysis, that results in lowered bg’s.

I wholeheartedly support Dr. Faustman’s BCG research and am hoping to get into her next trial. I have read all of her papers on BCG and although so far it doesn’t seem to be a cure it would certainly improve my quality of life. BCG is less dangerous than a modern flu shot IMO (you couldn’t pay me to get one of those).

I stick to a strict protocol of low carb, CGM, exercise, and umpteem other things to try and control my diabetes but I often fall short of my goals and the lowest I’ve ever got my A1C is 6.7. I am usually very skeptical of studies that claim they can cure diabetes and while that is Dr. Faustmans goal she has clearly stated that that hasn’t been achieved yet, but that is why they are doing more trials to see if they can increase the effectiveness of the BCG vaccine. Even if they never figure out how to cure diabetes with the BCG vaccine I still want to get it and will enjoy the possible benefits in approximately 3 years.

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Dr. Faustman published in 2017 the effects of BCG found on the immune system based on this phase I human trial. She presented this research at the 2017 ADA conference.

In the past decade, interest in the century-old tuberculosis vaccine, bacillus Calmette-Guerin (BCG), has been revived for potential new therapeutic uses in type 1 diabetes and other forms of autoimmunity. Diverse clinical trials are now proving the value of BCG in prevention and treatment of type 1 diabetes, in the treatment of new onset multiple sclerosis and other immune conditions. BCG contains the avirulent tuberculosis strain Mycobacterium bovis, a vaccine originally developed for tuberculosis prevention. BCG induces a host response that is driven in part by tumour necrosis factor (TNF). Induction of TNF through BCG vaccination or through selective agonism of TNF receptor 2 (TNFR2) has 2 desired cellular immune effects: (1) selective death of autoreactive T cells and (2) expansion of beneficial regulatory T cells (Tregs). In human clinical trials in both type 1 diabetes and multiple sclerosis, administration of the BCG vaccine to diseased adults has shown great promise. In a Phase I trial in advanced type 1 diabetes (mean duration of diabetes 15 years), 2 BCG vaccinations spaced 4 weeks apart selectively eliminated autoreactive T cells, induced beneficial Tregs, and allowed for a transient and small restoration of insulin production. The advancing global clinical trials using BCG combined with mechanistic data on BCGs induction of Tregs suggest value in this generic agent and possible immune reversal of the type 1 diabetic autoimmune process.

_TNF, TNF inducers, and TNFR2 agonists: A new path to type 1 diabetes treatment - PubMed

In this 2018 publication of the long term results of the phase I BCG trial, it does explain the surprise finding of 2 doses of BCG increasing the beneficial T regulatory (Tregs) cells of the immune system to almost normal limits.

I guess I’ll weigh in from two perspectives: I am a university-based scientific researcher (although I do not do clinical studies in humans); and I am a diabetic, diagnosed a couple of years ago.

As a scientist, the BCG human trials are in the very early stages, and the trials have been conducted in only a very small cohort. The results from Faustman’s lab are very interesting from a scientific standpoint, but seem to be incredibly preliminary in order to be producing the amount of hype that is surrounding this discussion. I hope that this line of research is continued, but I’d caution people to not get too excited about research that is in the early stages (no matter that these experiments have been taking place over many years now). There is a lot of work to be done before these trails can be shown to have clinical relevance for a significant portion of Type 1 diabetics.

An experiment that has statistically significant results is not the same thing as a set of trials that has clinically significant results. These trials need to be repeated at much larger scales, in different laboratories, by different scientists, and those results must be justified with a clear explanation of an underlying mechanism.

So, as a scientist, I genuinely get annoyed by people letting the word “cure” creep into the discussion of these results. For any number of reasons, talking about a “cure” is incredibly premature in this case. One of the biggest reasons, as others (notably Seydlitz) above have pointed out, is that the Type 1s who showed improvement were still using insulin to treat their diabetes. Using the language from the study, a “transient and small restoration of insulin production” is not a cure. The BCG vaccine might very well be an effective therapeutic agent, or it is possible that it could be shown down the road to be a cure, in part or whole. But the evidence so far doesn’t show that.

If, a decade from now, we are talking about a 20% reduction in A1c in studies of 1,000+ Type 1 diabetics, then we’ll have evidence of a new therapeutic tool. If, a decade or more from now, some of those 1,000 people have been cured of Type 1 (as in, they no longer need exogenous insulin to achieve normal range blood sugars throughout an extended period of time), then we’ll really have something to talk about. And I’m sure all of us will rush to be vaccinated according to the new miracle protocol. Until that time, talking about a “cure” is irresponsible and misleading.

Now, as a diabetic and Tudiabetes member. I find it disconcerting that a new forum member with a financial investment in the therapy being discussed is promoting the therapy on these forums. I’m not saying it isn’t right, or is against the rules. I honestly don’t know whether it is or is not against the rules.

I spend enough of my time being marketed to, billed, and seen as a freaking cash cow by the medical, pharmaceutical, and insurance industries to be well and truly sick of it. I don’t know why the JDRF is at odds with Faustman and her work, but I don’t like this forum being used to push research that is financially motivated.

If one of the scientists from Faustaman’s lab wants to talk about the trials here, I’d very much welcome that. But if @DrBB is right that the OP is a private investor in the research, I feel that this is not an appropriate forum.

edit: IT appears OP does not have a financial stake in this research. For future cases like this, it would be very helpful if posts were exceedingly clear about their relationship to the lab or research. We’ve been burned here in the past, and it makes me (and some others, I suspect), a bit jumpy…

David49, I agree with almost all of what you said regarding these BCG human trials being in the very early stages and a lot more research/trials etc must be done before finding out if BCG will even have clinical relevance for a significant portion of TIDs. (I thought that was clearly stated in my original post). However, I don’t think anyone on this forum used the word “cure” when discussing Dr. Faustman’s phase I results.
I posted my original letter not to only this forum but to every TID website/forum/blog that I could find in addition to sending the letter to the CEO of JDRF and every one of the 83 JDRF Chapters across the country. The content of that JDRF/ADA public statement is nothing but misleading and inaccurate when it comes to informing the TID community. They have done nothing but try to squash this research like a big foot squashes a little ant. I believe that people can make their own minds up with the correct facts.
Last thing, I take great offense in your comments about calling me a “financial investor” and insinuating that my posting of Dr. Faustman’s research is for financial gain. That could not be further from the truth. My daughter was diagnosed with TID the week of her 3rd birthday and she will be 25 years old this year. My financial investment included, for the most part, annual fundraising bike rides that helped raise the initial $11 million with the Iacocca Foundation to get this research to human trials. There is no financial gain what so ever from this research because BCG is a very CHEAP substance (maybe $9/vial). That was one reason why I was so attracted to this research because if it ends up being a treatment for the TID community, it would be readily available and affordable for everyone. My only gain would be having a treatment or maybe even a cure to better my daughter’s life.


Elevating a patient’s tumor necrosis factor long term is not a safe thing to do, especially in a patient whose immune system has already been shown to be abnormal, such as is the case with type 1 diabetics who, by definition, already have developed one autoimmune condition. So, since BCG elevates TNR, we shouldn’t regard it as a safe drug. It’s generally benign profile comes from short-term use for tuberculosis and bladder cancer, which is not the way it is used in this diabetes treatment.

To be clear, what the link I provided says is that the OP is a philanthropic benefactor of the research, not an investor.

In the interest of transparency on our part: we flagged the post originally in order to determine whether there was any pecuniary or other interest behind it (also see my reply to the OP). A little googling indicated that there was not, and it was also implicitly apparent (even before she said so) that her stake in this was personal–a child with T1–not financial. Since it seemed a sincere and detailed response on the JDRF statement, akin to what many members have posted on similar topics (the ADA affordability statement for example), we let it stand. As things have developed she has remained engaged, so it is clear that this wasn’t a case of post-and-disappear. Hope that clarifies any question about the administrative logic here.


Dear @Suelr,

I have nothing against you personally. I’m sorry to hear your daughter has the same disease most of us here do, and I hope that her health is excellent. I won’t apologize for stating that (in my opinion) those with financial motives shouldn’t be posting opinions worded as scientific fact in this forum.

I am sorry that I mistook you, based on information in this thread, as having a financial stake in the concern, and I’m glad that’s been clarified by @DrBB. A little transparency in the original post might have helped with that. We’ve had those with actual financial stakes in treatments bombard this board with all kinds of pseudoscience (and even some legitimate science) in the past, and it pains me as both a scientist and a diabetic to see it.

I’m also glad we agree that more trials are needed, that there is no indication of whether this intervention will benefit many or most diabetics, and that research into all possible interventions should be funded and continue.

I was merely interpreting the information I was reading (above) in this thread. I was unclear about what your relationship was to Faustman’s lab or this research, and there has been a lot of chatter about “cures” here in the last month or so. If you read the other threads on the vaccine-related research findings, you’ll find that both media articles and topics/comments here on tudiabetes have liberally used the word “cure” in relation to these results.

I maintain a stance that is quite simple: until we have a therapeutic intervention that enables a diagnosed Type 1 diabetic to cease using exogenous insulin and maintain normal blood sugars (which are closer to 4.8% A1c than 6.5%, by the way) on a “normal” diet, it is premature (and irresponsible) to talk about a cure.

Thank you for the clarification, @DrBB, and I hope I haven’t caused any undue agitation for other readers!


Thanks @David49. I’ve emended the text of my link from “financial supporters” to the less ambiguous “benefactors.”


Incidentally, I was a little curious about this one as well… I have to admit my somewhat cynical mind was bending towards an Epipen 2.0 kind of situation, but I’m glad to hear that your involvement is closer to “angel investment” than for-profit.

Thank you for the work you do, and please note that I’ve amended my original comment to reflect this clarification.

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While I believe that the publication of the Kühtreiber paper which is causing all of the hype is very interesting and certainly worthy of further investigation, I see T1D primarly as an auto-immune disorder and the first step towards treatment is going to be restoring immune tolerance. To that end I am much more interested in any results which look to that result instead of an A1C measurement, which to my knowledge have not been published. I would love to get clarification from someone in the know but it appears to be that BCG was simply a convenient/inexpensive/safe vector to produce TNF. Really any TNFR2 antagonist would do and this leaves the door open for more traditional pharma development, but BCG is the one with the least amount of regulatory obstacle.

I certainly want to believe that pancreatic recovery would happen naturally should the autoimmune issue be resolved, I have not found any (non-case study) evidence of this, although I would love any references if someone knows of any. It’s my guess that any “cure” is going to involve two phases, the first being the correction of the immune system and then the second being beta cell recovery. Personally I am quite optimistic about the Faustman lab’s line of research as a possible new therapeutic pathway which may mitigate the first. Although I obviously was not in the room when such decisions were made, I am not sure looking at blood glucose is such a good idea as the primary measure for these studies instead of an immunological metric. As always I would love feedback for clarification about this decision.

Since BCG has such a great safety record there is a logic to be had of “why not try” which is very compelling I would be surprised if this research moved away from BCG should the phase II trial yield convincing results.

People are not lizards, and if you cut off a human arm it does not grow back as a chameleon’s tail would. The same applies to any aspect of the human body which has been seriously injured. For examples, damaged kidneys and eyes tend to grow worse on their own rather than repair themselves spontaneously, or even reman stable. Becoming blind in one eye in and of itself can increase the chances of the other eye going blind. While it is normal for a patient’s gum tissue to become hypertrophied in response to immunosuppressive drugs, this overgrowth does not occur if the patient’s gums are already badly receded prior to the initiation of immunosuppression. It is consistent with these observed patterns that pancreatic beta cells will not spontaneously revive to a clinically significant degree after the autoimmune attack on them is stopped; Dr. Faustman herself has spent years looking for the additional something which will stimulate regrowth after the attack on the beta cells ceases, including spleen cells and the INGAP polypeptide.

And while BCG is not especially dangerous if used only short-term, as in the examples we already have of its use in tuberculosis and bladder cancer, no one wants its concomitant effects on the immune system long-term. The human immune system is a highly complex system which produces countless interactions for every small adjustment made to it, and many of these cannot be anticipated. So fooling around with tumor necrosis factor levels over the long term in diabetes therapy, especially since you’re doing it with a group predisposed to the development of autoimmune disease, is risky.