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

BarbaraG said:

I am, however, planning a fast of up to 6 days in the summer, when my husband is away and can't object. It remains to be seen whether I've got the determination to do it, though.

Click to expand...

FMD is much safer than water fasting, and compliance is much easier too, since one can remain productive and still feel full due to eating a fatty meal and going deep(er) into ketosis, which is just more of the same for you since you're already on that path (the right path for both types of diabetics, IMO).

So not much "determination" is needed to my mind. I've found it really easy, even as a type 1. If you're not on insulin injections then you probably wouldn't even need to worry about my main suggestion which is just to cut insulin shots down during fasting. That is the main risk here, insulin OD and catatonia. If you do take insulin, then definitely do NOT water fast for six days all alone. None of us wants to hear about someone dying due to this. It will just add a stigma to self-empowerment through returning to the feeding schedule of our forebears. (sporadic and intermittent).

I'm not on insulin - metformin only, so no hypo risk.

On a 6-day fast I would definitely use bone broth, or some other source of electrolytes. Possibly some cream in coffee. And considering a small amount of food, e.g. half an avocado and a few strips of bacon.

What's the macro prescription for the FMD?

Hoping4Cure said:

Being a type 2, does your alpha-beta cell signalling work? In other words, do you get hypos? Ever? I would totally do water fasting if I wasn't so afraid of sudden death. My partner is well-versed in how to operate my glucagon pen and what to do if I can't be awoken (call 911 then test my blood and administer the shot depending. if it's super high obviously you want to give insulin instead of glucagon and vice versa).

But my suggestion to you is...if you're already capable of water fasting nearly two days, eating the 1-2 avocados / per day plus some vitamins is going to be way easier, and if type 1s can do it, then surely a type 2 can do it too. (and pseudo-fast for longer). I find avocados delicious and filling, definitely one of nature's superfoods.

Click to expand...

According to my Freestyle Libre, I do occasionally go mildly hypo (3.x), usually overnight. However, it doesn't last long, my BG bounces up by as much as a point. Dangerous hypos are not going to happen. I've been eating keto for 8 months now, and there's evidence thathat keto-adapted people can cope with lower BG levels than sugar burners without ill effects.

I do love avocados.... either with bacon, or cream cheese. Would either of those be acceptable on the FMD protocol?

Hoping4Cure said:

FMD is much safer than water fasting, and compliance is much easier too

Click to expand...

Really? I find it harder to eat very little than to eat nothing at all that's why I consume all my calories on a "fasting day" in liquid form I find once I start to eat I have huge problems with stopping. I guess that's my old food addiction coming out to show it's not completely under control.
Also why do you think water fasting isn't safe?

For type 1s it is life-threatening, but if I weren't diabetic or type 2, and water fasting for days while driving and going to work? Yeah, that I think is still risky. Even non-diabetic, non-hypoglycemic people can feint for various reasons including low blood sugar. But I'm not an expert on that. I just know what works for me, and what I've learned from these papers + vids. Type 1s have died while fasting, even under clinical supervision (although according to Dr Longo, it can be reduced to human error, i.e. insulin OD).

Water fasting is pretty extreme I think, both physically and psychologically. My own experience. I do like it for my last day of FMD though, prior to re-feeding That was fun last week.

Hoping4Cure said:

For type 1s it is life-threatening, but if I weren't diabetic or type 2, and water fasting for days while driving and going to work? Yeah, that I think is still risky. Even non-diabetic, non-hypoglyucemic people can feint for various reasons. But I'm not an expert on that. I just know what works for me, and what I've learned from these papers + vids. Type 1s have died while fasting, even under clinical supervision (although according to Dr Longo, it can be reduced to human error, i.e. insulin OD).

Water fasting is pretty extreme I think, both physically and psychologically. My own experience. I do like it for my last day of FMD though, prior to re-feeding That was fun last week.

Click to expand...

Agree completely that it is much harder psychologically.. I will admit I only lasted until 6 pm today and had to have a coffee with cream... the black stuff just doesn't cut it for me.. I guess that insulin management when fasting for a Type 1 needs careful monitoring but would you need any insulin if water only fasting? I must admit I have no idea?

Yes, you need some insulin (via shots or natural) to live, every day, otherwise DKA + death occur within 3 days, guaranteed.

The question is, how much insulin? When you burn fat the metabolic pathway is different, but I think regardless of your diet, even if you're just burning fat from your own gut, your body is also synthesizing sugar and protein continuously which can get broken down into sugar so I believe exogenous insulin is necessary all the time.

Back on my other blog, we've talked about this many times, like, if you become super skinny, eat very very low carb, and low overall calories per day too, then even having a small-ish amount of c-peptides might allow me to get by without much, perhaps no, external insulin.

Exogenous insulin shots also suppress internal insulin production from what I've read (this makes sense, right? If you have an external reason why your sugars are lowering, then the body will naturally produce less because it just doesn't need to. Of course this assumes perfect control, which is impossible, even with a pump). Then the question is, is the super-tight control offered by a closed-loop, dual hormone pump system, actually ideal or detrimental towards beta cell regen? We don't know this yet. What we do know is that pump users don't spontaneously heal, despite having better overall control than non-pump users. So perhaps FMD is what's missing.

However, for beta cell maturation to occur (which is when the fun starts), they need to be challenged by glucose: this is known from the research on babies weaning (eating solid foods with more carbs and less fat content than their mothers' milk) and the hyperglycemia-induced beta cell replication study (shared on my blog). Elevated sugars stimulate beta cell maturation, replication. This is known.

There are lots of variables at play. Which takes me back to my question about how many carbs should be eaten in the re-feeding phase. It's likely a balancing act, I think.

More carbs/sugar => more IGF-1 => more regeneration post-FMD seems to be the flow.

But glucotoxicity due to hyperglycemia also stresses / damages / kills beta cells, so too many carbs is bad for beta cell survival. I'm still taking verapamil for that. But on its own, verapamil doesn't seem to be a cure, it (likely) helps boost c-peptides by a bit, but then other processes reduce this over time (auto-immunity kicking back into overdrive?).

Hoping4Cure said:

I lost 8 pounds (stone? to you Brits) .

Click to expand...

14lbs = 1 stone.

Dave.

bulkbiker said:

Sorry to butt in on a Type 1 themed thread but I think us fasters need to stick together !

Click to expand...

No problem - I'm with you on that.

Many years ago I was discussing type 1 & 2 with my consultant who said - "Eventually most Type 1's turn into Type 2's and most Type 2's turn into Type 1's"

Dave.

Hoping4Cure said:

However, for beta cell maturation to occur (which is when the fun starts), they need to be challenged by glucose: this is known from the research on babies weaning (eating solid foods with more carbs and less fat content than their mothers' milk) and the hyperglycemia-induced beta cell replication study (shared on my blog). Elevated sugars stimulate beta cell maturation, replication. This is known.

Click to expand...

I wasn't aware of that - Interesting indeed. You have obviously done more digging than I have.

And it might explain something .
After my first FMD session, I saw improvements coming in between the 3rd and 8th day after resuming normal eating. Then it levelled off. However about 2 1/2 weeks in there was another drop in BG's which I wasn't expecting. However now you have mentioned it - on the 18th March I was on a "Lad's day out" in which was consumed several pints of fine ale and large helpings of Chinese buffet food of the type not normally recommended by diabetes specialists. Ahem..... Cough ....

BG's on my Libre were high for several hours including overnight and peaked at 26 mmo/L (Though the Libre does tend to read on the high side, it would probably have been around 20 on my meter I guess)

A day or two later I had to re-tweak my basal rates down slightly. Coincidence ? Perhaps ?

----------------------------------------------

It does seem fairly obvious when you think about it that mother nature isn't going to equip you with the ability to make large quantities of insulin by default if your body does not require it, It's probably analogous to muscle, if you exercise it then you build it up.

In which case I might do my best to keep decent BG's for the next week (till my 8 days post diet #2 are up) then run my BG's high for a few hours overnight (Large curry & naan should do it) to see if that helps. If not, then at least I've enjoyed the curry !

Dave.

I've definitely had a couple of hyper episodes, and not always on purpose. Time to cut off the "refeeding" I think. We just don't know what a good level of hyperglycemia is the ideal compromise between maximizing pressure for regeneration / maturation to occur, and avoiding overly stressing new or prior beta cells with extra workload and the harmful effects of glucotoxicity on top of that. There's also the new data posted here on d co uk about signalling being broken in beta cells which are capable of producing insulin but not of detecting elevated glucose levels to know when to activate themselves. This is what's meant by the "maturing step", and it seems less than optimal to build insulin production aspect prior to glucose detection aspect, since glucose detection in beta cells, when low, signals to alpha cells to start producing glucagon which will raise your blood sugars and avoid hypos. So if you see reduction in hypos there's a distinct chance that it's from more beta cells reaching the mature state, although alternate hypotheses such as less IR, like you said type 1s having type 2 symptoms and vice versa. These two diseases are both related to gut dysbios in some way, that's also known. And that means they both likely have a diet-driven component, if not necesserily for the initial cause of the disease but for its progression. I believe it's a feedback loop, some types of germs in the gut feed more on simple sugars and others more on fibers and complex nutrients, which in turn makes the IR and/or auto-immunity worse. This overlap is why, in retrospect, it doesn't seem odd at all that metformin and incretin mimetics work in both diseases. Apparently metformin doesn't even reduce IR, at least not directly, it helps by suppressing glucose production in the liver while simultaneously increasing healthy gut microbes in the lower gut, amongst other things! (like anti-aging).

I think it's becoming obvious that there's still a lot we don't know yet and the pieces of the puzzle are coming in every day. It's very exciting but also frustrating. I am so sick of this disease, enough already!

Mr Whippy said:

It does seem fairly obvious when you think about it that mother nature isn't going to equip you with the ability to make large quantities of insulin by default if your body does not require it, It's probably analogous to muscle, if you exercise it then you build it up.

Click to expand...

Spot on.

"Recent studies revealed a surprising regenerative capacity of insulin-producing β cells in mice, suggesting that regenerative therapy for human diabetes could in principle be achieved. Physiologic β cell regeneration under stressed conditions relies on accelerated proliferation of surviving β cells, but the factors that trigger and control this response remain unclear. Using islet transplantation experiments, we show that β cell mass is controlled systemically rather than by local factors such as tissue damage. Chronic changes in β cell glucose metabolism, rather than blood glucose levels per se, are the main positive regulator of basal and compensatory β cell proliferation in vivo.

Intracellularly, genetic and pharmacologic manipulations reveal that glucose induces β cell replication via metabolism by glucokinase, the first step of glycolysis, followed by closure of KATP channels and membrane depolarization. Our data provide a molecular mechanism for homeostatic control of β cell mass by metabolic demand."

http://www.sciencedirect.com/science/article/pii/S1550413111000854

Mr Whippy said:

No problem - I'm with you on that.

Many years ago I was discussing type 1 & 2 with my consultant who said - "Eventually most Type 1's turn into Type 2's and most Type 2's turn into Type 1's"

Dave.

Click to expand...

I wonder if he ment SOME type1s become insulin resistant and SOME type2s wear out their pancreas beta cells?

My thoughts on this are - If cells are to proliferate, then they must exist in the first place, so making the assumption that Valter Longo is correct and that I have regenerated some β cells by FMD then it seems to me a good plan would be to let those cells settle in for a while and then "flex" them with short periods of high glucose, by under-bolusing for food, then correcting back to normal levels after 4 - 5 hours. Running constant high BG's without respite for the cells I don't think is a good idea.

Worth a bash I think....

Dave.

ickihun said:

I wonder if he ment SOME type1s become insulin resistant and SOME type2s wear out their pancreas beta cells?

Click to expand...

Probably.

Some generalising going on I think, but I got his point. He was near retirement at the time, so would have had a working lifetime of dealing with diabetic patients.

Dave.

Mr Whippy said:

I wasn't aware of that - Interesting indeed. You have obviously done more digging than I have.

And it might explain something .
After my first FMD session, I saw improvements coming in between the 3rd and 8th day after resuming normal eating. Then it levelled off. However about 2 1/2 weeks in there was another drop in BG's which I wasn't expecting. However now you have mentioned it - on the 18th March I was on a "Lad's day out" in which was consumed several pints of fine ale and large helpings of Chinese buffet food of the type not normally recommended by diabetes specialists. Ahem..... Cough ....

BG's on my Libre were high for several hours including overnight and peaked at 26 mmo/L (Though the Libre does tend to read on the high side, it would probably have been around 20 on my meter I guess)

A day or two later I had to re-tweak my basal rates down slightly. Coincidence ? Perhaps ?

----------------------------------------------

Dave.

Click to expand...

Dave thats because your liver, other organs and muscles have stocked up on glucose from your excess carbs. It you dont burn it, it turns to fat!

New babies to toddlers flex their organs and muscles by using carbs for energy. New babies just lie there and wriggle, which milk can cover that. Introduction of solids provides carbs, protein and fat in solid form to develop the organs to process nutrients to the areas of the body needing it the most. Survive and immune system starts kicking in.
A kick start to life surviving independently of its mother. The body being self sufficient.

ickihun said:

Dave thats because your liver, other organs and muscles have stocked up on glucose from your excess carbs. It you dont burn it, it turns to fat!

Click to expand...

Maybe I wasn't clear -
Pre the carb indulgence day I had set my basal insulin profile, it seemed to be reasonably OK after lowering it several times between day 3 and day 8 after the FMD session 1 fast. (1 week earlier)
A day or two after the carb-fest I had to reduce my basal rates slightly once again, to avoid hypos when not eating.

Only slightly, mind, and it could well mean nothing, but it does fit with the "increased glucose drives B-cell replication" idea.

I will do a little unscientific testing of this idea in a week or two whilst monitoring things more closely.

Dave.

No

Contralto said:

Are you on CoQ10 which metformin can make deficient?

Click to expand...

@Contralto I bought an additive for yogurt or porridge etc but it didn't agree with me. Bit reluctant to try it again but I will. I'll you know how it pans out.
I'm happy with what metformin does for me. Always have. It brought my periods and fertility back, hence 2 children later.....

I re-read the original paper and it seems to me that the main reason to do only 5-day / month of FMD is for compliance, not because it's medically ideal. After thinking about it, I think it might be worth trying 2x / month. So starting monday (or tomorrow / sunday night, really), I'm going to go through this again. I enjoy the fasting actually. It simplifies life to only eat two avocados a day plus a coffee or two.

I haven't decided if I'm going to cut out GLP-1 yet, but I've already stopped verapamil, Aleve and Gaba, and re-added resveratrol instead. So now my supplements (during FMD or not) are 6x fish oil, 4x IU vitamin D, two vitamin Cs, two resveratrols, two Green+ micronutrient pills, and that's it, nothing pharmaceutical grade. So my strategy now is almost entirely based on over the counter supplements (with support from latest studies) and fasting + re-feeding. If I can get on the official FMD food program I'll switch over to that, or maybe do the prolon 1/month as directed plus one more avocado-based FMD per month.

I'm determined to see this through to the end, see how far I can take it without ending up in the hospital (or the morgue). But I think this is pretty safe stuff. I might decide to make the last 24 hours water fasting each time, to really drive home the starvation signals. Also, I'm switching from a sunday - thursday schedule to a monday - friday schedule (stopping eating normally after sunday's meal and starting again on friday PM).