Good to read!
Sorry about the continued delay in posting this. I have spent about 3 hours at work today trying to finish this off and I still have a little way to go. Itās probably going to be Monday. I will try to upload the report as a Word file - itās way too long to post direct.
Joel
Here is my review of Cheng et al 2017, Fast-Mimicking Diet Promotes Ngn3-driven Ī²-Cell Regeneration to Reverse Diabetes. Cell 168:775-788. I have tried to include a running commentary in red which is a more personal take on the paper, what I think its strengths and weakness are and how it might shed light on potential treatments or even cures for T1 and T2D.
review of Cheng et al 2017.docx (94.6 KB)
Well, this is the brilliant assessment for which weād hoped! Thank you, Joel.
Obviously so far Iāve only read your red but will reread several times with your other notes.
Thank you so much!!!
I go back to my previous noteā¦in the olden days they fasted patients because they had no insulin to give them, feeding them every 2 -3 daysā¦they had early death and loss of limb and other complications. WE HAVE INSULIN NOWā¦it has been shown and proven to rest the pancreas and enable the regeneration of cellsā¦Any Diabetic presenting with numbers >250 should be considered needing temporary if not permanent insulin therapyā¦
And a great many people would agree. Without getting into a debate about which number is the right number, itās worth noting that Joslin often puts newly diagnosed T2s on insulin right away, even if just temporarily.
I think you may be misinterpreting the comments here and the research talked about. No one is suggesting that insulin is no longer needed, or that we return to the horrible days of the āDiabetes Dietā / Starvation Diet for Type 1 diabetics. This is preliminary research showing that limited fasting for periods during the day may help beta cells to regenerate. There are also fasting-simulating diets that have some promise of promoting beta cell regeneration without forgoing nutrition.
We arenāt going to lose insulin because of this research, and you are absolutely right that anyone with high BG should have insulin as a first-line option. But this kind of basic research (which isnāt about solutions or treatments, itās about understanding the processes of the body that might lead to treatments in the future) is really important if we ever want to experience better treatments than we have now.
Will this particular research lead to the next big breakthrough? I have no idea, and it is unlikely (as the vast majority of basic research doesnāt lead directly to major breakthroughs). But itās really important to support all research into diabetes (and everything else, for that matter). Basic research is what leads to the understanding that eventually leads to major breakthroughs. The important point about this research is to not be hysterical about it: this isnāt a cure for diabetes; itās also not a sign that weāre returning to the dark days of Starvation Diets.
Hear, hear
Thank you @jjm335 for this review. What frustrates me is that it has been shown in the past that the pancreas can regenerate beta cells. I believe Dr. Denise Faustman demonstrated this almost 10 years ago with the backing a Lee Iaccocca.
What I donāt understand is why is there almost no talk/research on the Auto-Immune response? Restoring beta cells is pointless b/c they will be killed off again and again. Where is this research??
I am so frustrated.
There is an enormous amount of research into autoimmune causes of Type 1 and into how to moderate or stop the process. It is, by far, the largest area of research on Type 1 diabetes (because of exactly what you suggest: beta cell regeneration is important, but autoimmune destruction is more important). The problem is that the autoimmune research doesnāt lend itself to easy headlines and summaries like āfasting promotes beta cell regeneration in diabetics.ā Most autoimmune research is about gene expression and/or complex biochemical responses. Most people are not equipped to understand or even find such research. I can help with the latter (since Iām a research scientist by trade):
- type āscholar.google.comā into your internet browser address bar
- type āautoimmune response in type 1 diabetesā into the search bar
- click āsince 2013ā on left hand side, unselect āinclude citationsā and āinclude patents,ā and sort by date
If you do those things, you get this page, showing thousands of peer-reviewed research articles on how autoimmune response mediates type 1 diabetes, as well as research into how to stop or moderate the process.
Just an anecdote but I was able to temporarily stave off going on insulin with extensive diet restrictions and regularly fasting (e.g. eating window between 12pm and 6pm). But eventually my pancreas pooped out regardless.
So Iām curious too if there would have been a way to make it work, like maybe fasting is just one component, and the other would be halting/reducing whatever is damaging the pancreas?
Thank you @david49. I know this research exists. I think what I meant to say is, āWhen will we get a cure from all of the Auto-Immune researchā.
Thanks.
I have to say, I donāt think weāll ever have a cure for Type 1 diabetes, or Type 2 diabetes. Now, Iām a researcher, although not a human medical researcher, so take my āI donāt thinkā with a pile of salt. But, hereās my reasoning:
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We really donāt understand autoimmune responses very well, and not just when it comes to T1 DM. What we do know is that the immune system is insanely complex, involving not only gene expression and biochemistry but also the extended microbiome.
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Complex systems are nearly impossible to āinterveneā in without producing unpredictable and often undesirable effects. An example of this is the current treatment for extreme autoimmune disorders: suppression of the immune system, which often results in terrible issues.
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Current immune suppression techniques are really only used when illnesses would otherwise be immediately and unavoidably fatal (certain kinds of cancers, organ transplants including islet cells, and in the case of autoimmune attacks on the heart and lung tissues).
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There are likely other issues going on with T1 we donāt fully get. We know that there is a genetic component (without which you canāt get T1). We know there are ātriggers,ā likely including both certain viruses and intense periods of stress. We know that the autoimmune responses are multifaceted and different in different people (which is why we take a battery of tests, rather than a single antibody test). This means there are multiple pathways for the body to attack islet cells.
So, I just donāt see a ācureā coming, especially not in our lifetimes. I certainly hope it does, but it seems to me that the only actual hope would be direct manipulation of the genetic code in infants, which wouldnāt help those who already have the disorder (at least not in the way we currently understand gene therapies). Even implantation of insulin-producing prostheses isnāt a cure, but rather a different form of insulin production (which may be fantastic, by the way).
I guess, as a scientist, that Iām not that sure that science has all the answers. I believe we are quite limited in what we can understand and achieve, at least in realistic timescales. Altering immune responses to cure diabetes seems to me to be on the same order of difficulty as traveling faster than the speed of light. Itās appealing, itās something we can kind of wrap our heads around, and itās something many of us desperately want. But physics is against us.
Hope that isnāt too depressing. What I firmly believe weāll have in the next five years is better insulins, and I think on the 10 year scope weāll have artificial multi-hormone pancreases (that can produce insulin and glucagon on demand), and maybe on the 20 year scope having T1 diabetes will be seen as little more than a medical inconvenience. But I donāt see a cure coming. Then again, Iām no human doctor, so my opinion likely doesnāt count for much
I whole-heatedly agree with you, @David49. Mentally, I placed too much weight on this FMD research and am left disappointed. Iām a Type1 of several decades, so I should know better. Itās actually better mentally, to think a cure is not coming.
But I do agree that technology will solve this for the most part. It just seems like itās just so close and within our reach (e.g. hybrid closed loops systems, faster insulins). They seem like they are just around the corner and I cannot wait any longer mentally.
@jjm335, Iāve enjoyed reading your review very much. Thank you for taking the time to prepare the review in a form understandable by non-specialists. The results with STZ mice (T1D model) look pretty amazing. As youāve pointed out, the model does not include the assault on beta cells by the immune system. Nevertheless, significant beta-cell regeneration in the model, as well as improved understanding of the regeneration mechanisms could turn out to be important. Itās way too early to speculate how any of this could translate to any treatments, but it does not hurt to speculate a bit. If we could find a way to stimulate beta-cell regeneration in T1D humans, this should result in some increase in endogenous insulin production even in the presence of the ongoing assault by the immune system. No cure, but any endogenous insulin production, however small, could make bg control easier (still using external insulin of course), and with better results. In any case, I think itās worth keeping an eye on next steps by this research group. Thanks again for contributing your time and expertise.
I agree with Leela. The child was not treated for his diabetes. His parents chose not to treat him and he died as a result. He was 15 years old and weighed 37 lbs.
Hi there, I logged in just to respond to this. Yes, Iāve tried FMD for my type 1, three times now. Since two years ago when the first news reports about mice regen appeared. Iāve also spoken to Dr Longo a few times and he told me in no uncertain terms to not try the original water fasting diet which can be deadly for type 1s even WITH medical supervision, for obvious reasons. So obviously heās honed the diet to be safer for type 1s by only needing to cut to 1/3rd your normal adult calories per day, which is relatively safe and to my experience, easy to do for 4-5 days out of the month.
I co-run this site for āenthusiastsā who are self-experimenters:
https://groups.google.com/forum/?utm_medium=email&utm_source=footer#!forum/curetype1
Over the years Iāve tried many drugs and diets to cure myself and have had some temporary success in boosting my c-peptides only to have them reduce again over time. I believe even if you can boost your beta cells back they will die off again and your auto-immunity will āwake upā and go on the offensive, but FMD feels great to me. And I LOVE eating carbs afterwards as a reward. I normally eat paleo / low-carb around 1200-1400 calories max per day so cutting to 1/3rd of that is dangerous (especially for work), but the important thing is to keep checking your sugars, cut your lantus in half, and cut your short-acting too. Basically, if you avoid insulin OD and lower your exogenous insulin levels then fasting is not super dangerous. I love low-carb dieting and eat veggies and meats and stuff normally, so to FMD I basically just cut out most protein too and red wine during fasting weeks and that makes me lose ten pounds each time. Then I gain it back. I plan on doing this over and over and refining the diet as I get better at it. I think protein + fat + simple carbs are basically all anti-āstarvationā signals and simple carbs are poison to diabetics anyway so losing the protein on top of my paleo diet is not too hard. I also cut out dairy and drink tea and cut out red wine during FMD weeks (resveratrol FTW).
What I really love about this diet is how easy it is to do. I donāt get that many hypos any more due to low-carbing helping avoid insulin OD, and FMD is just another level of self-control and sugar control which has benefit me regardless.
They originally came up with fasting as a regen mechanism entirely by accident, to preserve health prior to chemo and recover faster afterward. Starving yourself helps your body purge weak / dead cells and flush them out, paving the way for new ones. Itās also the easiest diet Iāve ever tried and Iāve tried them all over the years. But probably because Iām used to paleo (well as much as cavemen used to drink wine haha).
You definitely get used to FMD. The first time was the hardest for me, itās a mind-over-matter thing. If you go into this with an āI canāt live without my beloved carbsā then this is not for you and donāt even try. If, however, you are already a low-carber who enjoys veggies and wants a chance at a non-disease-ridden-life, then by all meansā¦still donāt do it. Based on what anyone else (including me) says on the internet. Iām crazy this way, Iāll do anything (reasonable), and even some unreasonable things. Iāve tried most drugs for anti-T1DM mentioned in the news that I could get my hands on: BCG, Gleevec, Verapamil, Harmine, nasal insulin (for tolerization to the insulin molecule).
I do think that a full cure wonāt be had merely by having a āfreshā pancreas suddenly, it will come back again. But you could be in a semi-honeymoon state, wouldnāt that be something. And auto-immunity gets weaker as one gets older and the immune system naturally weakens with age, so thereās a chance that starvation might be āgood enoughā to get you there.
Donāt give up hope yāall, a cure is coming. Donāt let the cynicism get you. Some docs out there really are trying out new things in earnest and I think FMD is a winner, even if itās not a full cure I think it feels great and I plan on doing it.
PS if you do it and it kills you donāt sue me.
For the past few weeks Iāve been doing two 24 hour water fasts a week when Iām working from home and relatively sedate.
Itās the only time I can keep my blood sugars truly flat and in range, the CGM and the low glucose suspend on my pump has helped avoid any lows.
I always feel great after a brief fast. Iām convinced it helps with inflammation and gives my body and mind a rest from diabetes.
I have been doing the 5:2 diet for nearly a year, largely to try to shed some weight. The 600 calories/day on the ā2ā days is actually less than the 750 Calories that the subjects on the FMD diet in the Cheng et al paper were eating, although of course they maintained this for 5 successive days.
I have lost some weight, but I cannot honestly say that there has been any obvious regeneration of my beta cells LOL!
The 5:2 diet is not exactly the same as this, so I think itās best to replicate the actual FMD diet if you guys want results.
Reading up a bit:
https://authoritynutrition.com/the-5-2-diet-guide/
āTry to focus on nutritious, high-fiber, high-protein foods that will make you feel full without consuming too many calories.ā
No, no no. No high-protein, that does the opposite of tricking your body into thinking itās starving.
Iāve read in a few places that only after 48 hours of water fasting does this special regen mode get activated (in cancer cases), which is why the water fasting prior to chemo is often longer, like 72-96 hours. (from what I remember).
FMD is a way to extend the fasting period in a safer way for type 1 diabetics (or others) for whom water fasting four days straight is not an option. I mean, that could easily kill you, unless you are on a dual-hormone pump (glucagon to bring you back up). But it would certainly make driving your car illegal and probably wouldnāt accomplish much at the office either.
What I do normally is just cut my Lantus from 15 to 10 units per day, and my Humalog from ~45 to ~15 to match the calorie reduction from not eating much. (with barely any protein or fat, basically my normal LCHF diet minus the fat and protein from meats/fish/cheese and nuts etc).
If repeated water fasting cured type 1 diabetes then millions of muslims (and others) would have been cured already and to date not a single person has been cured, at least not verifiably so. Of course the fasting regimen for things like Ramadan is not the same as FMDās 3 week on : 1 week off (roughly) eating cycles so thatās no surprise.
Maybe that guy from the UK who is off insulin now and isnāt a faster AFAIK but a runner (unless itās a hoax or a type 2 misdiagnosis) will shed more light on this. As soon as we get confirmation on his results being real then I intend to follow his lifestyle + running regimen to a T. And still mix in this regen therapy too.
Donāt just ādo whateverā fad diet and expect FMD to work. It needs to be precisely tuned to the parameters here in the research paper. And water fasting / 5:2 doesnāt work either, thatās been around for ages and no one has been cured yet. Maybe it just takes a while, but Iād rather follow the actual research than try to shoehorn something thatās not tailored specifically for type 1 diabetics. A bigger concern for me is: since I donāt eat much carbs normally, is that actually a bad thing. There was an article on weaning in infants and how that actually triggers beta cells to mature to meet the demands of caloric increase due to non-dairy (non-fat-based) foods.
So it makes sense to me that eating carbs after starving would trigger some beta cell growth on its own, in a healthy person, but the question is: how much? too many carbs could easily kill off nascent beta cells due to glucotoxicity or cell stress.