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Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes

Hi All

I'm unsure if anyone is following this thread but I've done another cycle of aggressively losing weight with diet. I lost 6lbs over a space of 7 days and then came off the diet. Out of the 6 days when I was testing for FBGs I had 4 days with un-diabetic numbers sub 100mg/dl and 2 days over. I am quite healthy in terms of exercise. I've logged nearly 5,000 miles of cycling since February of this year and probably more like 7000 miles of cycling since September of of 2016.

I woke today with a high number that seems somewhat un-explanible, I'm going to migrate back to having a few extra days of fasting mimicking again. I'm getting tired of high glucose numbers..

My diet whilst I was doing it was mainly thin packet onion soups with fresh green (spring) onions + fresh sliced mushrooms. My BMI is in the 24's currently and I've lost 5 BMI units of measure since diagnosis. I have no remission so far. Other than the T2DM I'm feeling quite good..
 
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For those interested in Dr Valter Longo's work on fasting, here are a couple of recent Youtube interviews re his new book, The Longevity Diet:


 

I would also recommend checking antibody levels. I worry that antibody levels might have gone up instead of down! I did FMD about ten times last year and my c-peptide levels dropped by 50%.

I have a few ideas why this may have happened:

1) I lost my insurance for GLP-1, which is a known beta cell regen agent, and glucagon suppressor.
2) Too aggressively re-feeding and leaving ketosis. I think it's better to stay in ketosis, fasting or not, and just vary the overall daily calories and protein levels to go into protection / trigger regeneration ready state, then activate IGF-1 with protein and only moderate carb increase. Avoid carb binging! Very, very bad.
3) Low carb tolerance and lowered insulin sensitivity, meant I had higher sugars when not fasting. It was a nightmare, really uncomfortable. This is why I stopped.
4) You must exercise aggressively to maintain decent insulin sensitivity. I did not do this, as I was busy with life and work and had lost tons of weight too.

So FMD is counterproductive for type 1s, or could work in the right conditions, but you still need to avoid carbs even during the first feast, and you certainly shouldn't stop taking GLP-1 which is a wonder drug. I'm back on it now, if my next c-peptide is higher I know 100% it's because of that and that alone. My sugars are great again now on Ozempic (1/week GLP1), and insulin TDD is much lower than last year.

I'm trying to find out if the keto variant of FMD is suitable for those of us who don't want so many carbs, even when we are starving. The best way to avoid stressing beta cells too much is to not give them too much work at a time. So re-feeding is potentially what killed off a lot of my beta cells last year, or maybe my immune system was actually invigorated which increased my antibodies (don't think this, but it's a possibility), or maybe just having hyperglycemia due to low insulin sensitivity is what happens any time you leave ketosis anyway so this isn't news. Maybe I should ask the keto subforum about that point. It just seems weird that I'd need more insulin rather than less, each time I re-fed myself. Extremely frustrating experience, but maybe a learning opportunity. I forwarded all my notes and observations on the matter to Dr Longo's team, to see if there's some rationale to this lowered insulin sensitivity issue or if this is a discovery. Even negative discoveries can help illuminate the right way forward.
 
Well I remember binging on carbs the very first meal since I was absolutely starving by the end (I usually didn't eat anything at all the last 24 hours to really drive the regeneration signals home). That was a big mistake. I'm talking indian curry with naan bread galore, or even pizza. Ouch, my toes hurt even thinking about it. Super elevated sugars for many hours after eating, no matter how much insulin I took.

I'll share the team's responses when I get some. I don't know if what they'll say will be 100% restricted to type 1s, probably not.

But I would say, yes, when re-feeding just increase overall calories back to normal slowly, over 2 days minimum (4 would be better), and mix in cardio exercise to maintain sensitivity, but keep carbs relatively low all the time and definitely don't binge, no matter the temptation of a treat waiting for you on the finish line. Even a low-carb diet places more demand on type 1's beta cells than we can manage without external insulin, so don't stress them too hard. IGF-1 should rise in response to higher % of protein after the fasting is over, even if you don't spike carbs. I think protein doesn't need to be too much lower than fat either, according to the videos on the subject about the conditions when protein gets converted into sugar. It happens much less when the body is in a catabolic state so being low carb is enough to keep elevated protein levels from spiking your blood sugar and insulin requirements. You do need some sugar for IGF-1 levels to rise for regeneration, and for rebuilding itself, in addition to protein going much higher, but I wouldn't worry about it too much. The important thing is managing insulin insensitivity which is the worst thing about FMD, at least for me.
 
Some of us have been discussing carbs during refeeding. Should we allow our blood sugars to be high? How much insulin?

Since I'm a newbie, I won't post a link, but point you to a recent article entitled
Cells that change jobs to fight diabetes


"Researchers at the University of Geneva (UNIGE) have succeeded in showing how part of the pancreatic α and δ cells, which usually produce other hormones, can take over from the damaged β cells by starting to produce insulin.
...
First hypothesis: hyperglycaemia. In transplanted but non-diabetic mice, whose β cells remain perfectly functional and do not have hyperglycaemia, some α cells of the graft began to produce insulin when the β cells died in the transplanted islets. Consequently, hyperglycaemia does not cause α cell reallocation. The cellular pancreatic environment surrounding the islets is not involved either
.....
the researchers blocked, in non-diabetic mice, the receptors located on α cells surface to detect the presence of insulin. Some of these α cells then began to produce insulin, indicating that insulin itself would act as a brake, preventing the reprogramming of α cells.
​
Could similar mechanism be taking place during refeeding in FMD? To me, the lessons of this are: take your minimal insulin during refeeding, allowing higher than usual glycemia at least some of the time.
 
millenium said:
What is a proper feed meal like? Low carb, high fat, high protein?
Click to expand...
I have been doing monthly FMD since August, 2017, starting with 3 days, then 4, and now 5 days for the last three months.

This month, for the first time since I started the FMD, I feel I have improved blood sugar control. I have cut my Lantus from 6 to 3 (while keeping FBG around 84mg/dL), and decreased the frequency of my small boluses (1-2 units humalog as needed). I can only hope this is for real.

I don't think I was refeeding properly until this month's FMD. Before, I would use extra insulin to keep my sugars as controlled as possible and I would limit my carbs more than usual since the IR seemed higher; my diet would be high in fat.

After reading the information on refeeding in this forum and in Longo's book, I decided on higher carbs and a little less blood sugar control for this refeeding. For the 3 refeeding days, I went from HCLF to LCHF while ramping up my calories toward my usual 3200 (BMI 22, active lifestyle). I purposely allowed sugars in the 150mg/dL range for periods of hours, while keeping overnight sugars well-controlled. I exercised much more than usual to control my sugars without using as much insulin and to promote IGF-1. Before my morning injections, I also took 20min sauna-like showers to get my BPM to 130 in order to increase IGF-1.

Here is the profile of my refeeding days:

  • day 1: 2072kcal; P/C/F: 120g/190/64, or 23%/49%/28% of calories
  • day 2: 2447kcal; P/C/F: 148g/156/116, or 25%/34%/42%
  • day 3: 3243kcal; P/C/F: 132g/142/221, or 16%/24%/60%
After refeeding I returned to my usual LCHF diet, with around 65g carb per day.
 
That's interesting. But I think you still need to simply look at c-peptide levels before and after. I've checked mine again and again and my highest level was 0.51 in 2015 (on all kinds of drugs like GLP-1 and so on) and now it's 0.044. It's possible I didn't test scientifically enough using the same sugar challenge, or maybe my beta cells are just wiped. My anti-GAD is in the normal range for non-diabetics but I have no values for any other antibodies so I can't be sure what's killing off my beta cells now. I managed to boost them pretty high in 2015, close to half of what a normal person has (or even someone like Dan Darkes, who is probably still far from full up in terms of beta cell count, but past the finish line so he can manage without insulin shots given his regime). I eat pretty low carb and have an A1C of 6.1, which could be better but I don't have a CGM, any GLP-1 script, or a pump, so I'm doing OK I think all considering. I still want to try metformin and maybe will do another fasting cycle next spring, after I get fit from running. I had a foot ulcer which is healed now, thankfully. My buddy died and I coped by overeating for a couple days, that was enough to cause an ulcer in my big toe. Scary stuff but I'm back to being very rigorous. Sorry for the rambling post. I was so hopeful for FMD before but I don't think it will regenerate beta cells in type 1s, at least not fast enough to prevent them from being destroyed. Hyperglycemia is necessary to bring new beta cells to maturity aka fully functional to both detect blood sugar then release insulin in response, but if they're too stressed from constant hypers then that's bad too. I am 99% sure that my overconsumption of carbs during refeeding last year after my dozen or so FMD cycles (up to weekly, 4 days FMD 3 days feeding at one point), actually hurt my health more than helped it. I believe you need to simply boost protein and mild calorie uptake when refeeding to not over-do it. Anyway, that's my theory. I overdid it thinking that it would be really good to have high contrast between low-IGF-1 periods and high IGF-1 periods, but I think you can do that just fine with re-adding animal protein to your diet during refeeding and not blast your pancreas with sugar it can't handle. Trust me, if your sugars are above normal, even a little bit, whatever beta cells you have are already at their limit, pushing them further will only result in their demise. It's like pushing more on the gas when you have a near-empty tank and no coolant in the radiator. Take it easy and you'll go farther, I think.
 

Hoping4Cure, as always, thank you for your informative, kind and thoughtful posts.

You may well be right out the moderate glucose challenge, but we just don't know what the best level of blood sugars is during the re-feeding. From what I understand, there is significant variability in c-peptide, due both to variability in the overnight fasting measurements and variability due to food intake. So I don't know how much faith to put in the c-peptide number. As I have said, last month's fast was the first one that gave me good results, with lower Lantus needed through the past month. But of course there are always confounding factors that make a definite assessment all but impossible.

I will be trying the Prolon for the first time during my fast starting next Friday. I bought three months' worth to save some money, and I hope to post a review after the first one.

I will keep trying and failing until it gets better.
 
MikeFailBetter said:
So I don't know how much faith to put in the c-peptide number.
Click to expand...
I found this interesting recent study by Wentworth, et. al. "Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables " (search for full-text pdf link at immunetolerance.org). They calculate their estimate of true beta cell function from fasting c-peptide, HA1c, fasting blood glucose, weight, height, and number of daily units of insulin (presumably long-acting, but I'm unsure). The pdf contains a link to a spreadsheet calculation.

This could be a worthwhile way to track any progress in beta cell regeneration. What do you think?
 
MikeFailBetter said:
I will be trying the Prolon for the first time during my fast starting next Friday. I bought three months' worth to save some money, and I hope to post a review after the first one.
Click to expand...

I look forward to hearing your review. I'm a bit low on funds otherwise I'd try prolon too.

But whatever you do, get a baseline c-peptide reading before doing it. Whenever you wake up (fasting since supper the night before), before getting your blood drawn, just eat a pastry or something, and wait 90 minutes before the blood draw.

90 minutes post-challenge is guaranteed to max out your c-peptides, trust me. They've studied this.

It's every bit as good as an OGTT.

Google my curetype1 blog, there is a lot of c-peptide testing discussions there, as well as results. The forum is kind of dead lately, but there are an amazing amount of useful and insightful links to studies and discussions about them, including FMD.
 

Apparently there's also a way to measure beta cell function using a simple urine test and the ratio of two non-c-peptide numbers, which are apparently easier to measure. I can't remember it off hand. Got it stored on my blog somewhere. But I couldn't find a supplier for it. If I could test my c-peptides cheaply (at home), that would be a game-changer for DIY type 1 reversal.
 
My FMD in November, which was the first time I had used Prolon, was terrible for its high blood sugars. I felt compelled to stop after 3 days because of the persistent highs, which I had not experienced with my previous DYI FMDs. I am guessing the problem stems from the sugary granola bars and refined rice flour soups, despite the low calories. The company was very nice about refunding my two unopened boxes for future FMDs; I had purchased them as a 3-pack to get a lower price.

Obviously, it would be great if they made a T1D FMD, but their current product might not work for us. I can't say they didn't warn us, given Longo's statements and the advisories on the packages.
 
Hopin': I see a reference to c-peptide measurement without a serum test: "Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study" (high correlation 0.69, but not very exact), and of course this uses a urine c-peptide, and you said non-cpep.
 
I wonder if the "mimicking" part makes FMD really better (about β cell regeneration and whatever can help people with T1/T2 diabetes), that is, it makes sure FMD "triggers" something real fasting won't, or it's there only for better compliance.

I couldn't find anywhere that doing real fasting instead of FMD (same cycles, same number of days) would bring worse or better results than FMD. Is there any info about that?

Thanks
 

I can't think of any mechanism that is promoted by fasting that would be made "better" by buying Prof Longo's FMD mix.
Also of course no profits from simply not eating so...
 
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