Natural History Phase 2 – T2D 33

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Type 2 diabetes actually happens in two phases. The first phase, which lasts approximately 10-15 years shows a slow increase in insulin resistance. However, the body compensates by increasing insulin levels. This keeps blood glucose relatively normal.

But something suddenly changes after approximately a decade of rising insulin resistance. Hyperinsulinemia can no longer keep up with the pace of insulin resistance. Pancreatic beta cells, responsible for insulin production are unable to keep up. As this compensatory mechanism fails, the blood glucose rises quickly. It takes only two years or so before full-blown type 2 diabetes is diagnosed.

Beta cell production peaks and eventually starts to fall. The progressive decline in insulin production is often called beta cell dysfunction or sometimes pancreatic burnout. But what caused this burnout?

One thought is that hyperglycemia destroys the beta cells. But there’s an obvious problem. During the development of type 2 diabetes, blood glucose stays relatively controlled. Not until after beta cell dysfunction develops does the glucose go way up. The beta cell dysfunction caused the high blood sugars, not the other way around. This crucial point is often forgotten or ignored – especially by academic physicians and people focused on type 1 diabetes such as Dr. Bernstein.

Others have suggested inflammation or free radicals as the mechanism. However, none of these theories can explain how type 2 diabetes is so readily reversible with dietary changes. The use of anti-inflammatory or anti-oxidant medications is useless in the treatment of type 2 diabetes. That is, if free radicals caused the T2D, why does dietary change reverse it where anti-oxidants are completely useless?

The prevailing concept is the pancreatic beta cells are simply worn out from massively overproducing insulin for so long. Like a decrepit engine that has been revved too many times, irreversible damage is done over many years by the excessive workload. Certainly some evidence exists to support this concept, but only in the very end stages of type 2 diabetes. Autopsy studies occasionally show scarred and fibrotic beta cells in the pancreas of long standing diabetics.

However, three main problems exist with this paradigm. First, the suggestion that beta cells are irreversibly damaged and function is permanently lost is clearly false in the vast majority of cases. Studies of bariatric surgery and weight loss have conclusively shown that type 2 diabetes is reversible and therefore the beta function can be recovered even in massively obese patients with decades of disease. Further, Dr. Roy Taylor, of the Newcastle University in the UK specifically demonstrated pancreatic function recovering with an ultra-low calorie diet. There is no permanent burnout in most cases.

Secondly, beta cell burn out implies that damage occurs only due to long standing excessive use. With type 2 diabetes now being diagnosed in children as young as three years old, it is inconceivable that any part of their body has already burned out. Disease reversal with dietary intervention in that case emphasizes that type 2 diabetes is not an irreversible process.

Finally, with excessive use, the body generally responds with increased, not decreased function. If you exercise a muscle it gets stronger, it doesn’t burn out. With overactive secretion, glands generally get larger, not smaller. If you think too much, you get smarter. Your brain doesn’t burn out. It takes decades of over-activity to produce scarring and fibrosis.

The same holds true for the insulin producing cells. They should grow larger (hypertrophy) and not smaller (atrophy). The rising epidemic of type 2 diabetes in children and adolescents clearly proves this concept false.

So, here’s the million-dollar question. What causes the beta cell dysfunction in the first place? Recent research has identified the likely culprit. Fatty liver and fatty muscles produced the increased insulin resistance. Fatty pancreas creates the beta cell dysfunction. The pancreas is clogged with fat.

2017-10-12T21:38:00+00:00 50 Comments

About the Author:

Dr. Fung is a Toronto based kidney specialist, having graduated from the University of Toronto and finishing his medical specialty at the University of California, Los Angeles in 2001. He is the author of the bestsellers ‘The Obesity Code’ and ‘The Complete Guide to Fasting’. He has pioneered the use of therapeutic fasting for weight loss and type 2 diabetes reversal in his IDM clinic.

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Kok-Hong Wong
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The recent central injection of FGF1 protein induced substained remission in rodents/mice study by Dr Michael Scharwz group suggest an additional pathway…
http://www.nature.com/nm/journal/v22/n7/abs/nm.4101.html

Brain control of glucose homeostasis and the future of diabetes treatment
https://www.youtube.com/watch?v=qSE-H3mTNKM

Elena
Guest

FGF1 is increased by fasting and high fat diet…….

Michele W
Guest

A disproportionately large proportion of cancer cases among people I know has been and continues to be pancreatic cancer. As I understand it, the incidence rate and death rate are still on the rise. I’m sorry to say that I haven’t researched this yet, but it does seem like a high carbohydrate/high sugar diet on the way towards type 2 diabetes would be a continuous double whammy for the whole pancreas, including the beta cells. Creating a super-metabolic cancer. Any thoughts?

Ken Stephens
Guest
This blog post surprises me, coming from someone who understands the role of hyperinsulinemia in type 2 diabetes. High blood sugar cannot be caused by lack of insulin when there is not a lack of insulin but an excess of insulin. Insulin function does get downregulated as T2 progresses but this is actually a protective mechanism. The idea that we do not secrete enough insulin because our blood sugar is high is a very dangerous one and is what fundamentally drives the mismanagement of our disease. It is completely foolish to look at beta cell capacity and then say well… Read more »
Walt
Guest
Ken, if you haven’t already, please view the below referenced talk given by Dr Roy Taylor (Reversing the Irreversible), the Dr/Professor credited with discovering T2D was reversible. At about the 26 min mark he displays 4 graphs, the first is the control group showing a normal insulin secretion rate over time. The second is the diabetic insulin secretion rate should an almost non-existent phase 1 rate and pathetic phase 2. Then he shows his study group at 1 week on a 700kcal diet, then after 4 and 8 weeks. The 8 week graph is pretty much identical, arguably better, than… Read more »
monica
Guest

Hi Ken,
You are absolutely in agreement with Dr. Fung as far as insulin is concerned, but today you seem to think that he states that type 2s have too little insulin. I don’t feel this to be true at all, he says too little insulin to overcome the resistance, not lower than normal levels. And, eventually, very late during the disease, there might be too little insulin. I like your blog by the way.

Dr Peter Haynes
Guest

For goodness sake Ken, you have completely misread this blog and your comment leads me to believe that you have not read any previous blogs from this site. Jason has written nothing that contradicts you. He refers to a ‘relative insulin deficiency’ not an absolute one.

Please re-read the article.

Carlos
Guest
I know the answer on this one, had the same discussion a couple of weeks ago somewhere else: As usual, it’s a matter of semantics. What do we mean by too much/too little insulin? too much/too little for WHAT? It’s like this: T2D is related to IR, and the pancreas will overcompensate by secreting more insulin. So too much insulin. Yet, since this will make IR raise and raise, the pancreas is actually not able to secrete enough insulin to stabilize BG. So too little insulin. Woot?? Yes, it can be both too much and too little: too much compared… Read more »
Dr Shivanand Nelogal
Guest

Carlos,
I completely agree with you.

Gloria
Guest
Thank you Dr. Fung for this article/this blog and your book on fasting. Last year, I experienced a burn out state in my health, specifically my digestive function and nutritional balance. After enduring and managing chronic diarrhea for several weeks (which I sort of managed with chicken broth and very mild foods), I sought the professional advice of a new doctor, who upon test results, concluded I was possibly on the early stages of T2D, as in the way you characterize in this article. I had not advanced to full blown T2D, but my test results indicated concerning levels of… Read more »
Diane T
Guest

How does one avoid a fatty pancreas? My diet is low-carb and higher healthy fat. I do intermittent fasting. I am borderline pre-diabetic. Last A1c was 5.7 Don’t know what else to do to come down to a healthier number. I also have higher fasting glucose in the morning (sometimes upper 90’s and even upwards of 108). Dawn effect? High cortisol?

Walt
Guest

5.7 is not bad Diane. Upper 90’s is still normal range. It’s hard to characterize cortisol as, to do so, would mean quantifying your stress level. Do you feel anxious about anything, social life, finances, work life, security? If you suspect undue stress, try meditation, massage, thoughtfulness (I think that’s what the new thing is called). Dr Fung, to my recollection, says dawn phenom is a 4am thing prior to and in preparation of, you waking up.

Stephen T
Guest

I wouldn’t worry, Diane, you’re clearly on the right path.

I’ve never had any tests, but lost weight easily, felt much better physically and mentally and don’t feel hungry. I don’t need tests to tell me I’ve done the right thing.

Walt
Guest

Congrats on finally mentioning the pioneering work of Dr Taylor

https://campus.recap.ncl.ac.uk/Panopto/Pages/Embed.aspx?id=c3bef819-e5f4-4a55-876f-0a23436988ed

This video is a must view!

Diabetologia. 2011 Oct; 54(10): 2506–2514.
Published online 2011 Jun 9. doi: 10.1007/s00125-011-2204-7
PMCID: PMC3168743
Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol
E. L. Lim,1 K. G. Hollingsworth,1 B. S. Aribisala,1 M. J. Chen,1 J. C. Mathers,2 and R.

Paragraphs 1 and 2 should reference the pioneering work of Dr Joseph Kraft on categorizing the 5 distinct patterns gleaned from over 14,300 glucose tolerance tests over 20 years from Euinsulin to diabetes-in-situ and finally, type 1 diabetes.

Walt
Guest

Diabetes Epidemic & You by Dr Joseph R Kraft is copyrighted 2008 and available in the usual places (Amazon) and likely many others.

The X axis on the first graph above is time and the original of that reflected weeks 0-8 weeks in Dr Taylor’s 8 week trial(s). It reflects the recovery of insulin secretion from baseline to end of study. Dr Taylor has done many iterations of this study to add questions to be answered such as recovery against duration of t2d diagnosis and replicating the results in a non-hospitalized (primary care) environment.

Max Salogni
Guest
Interesting doc, as always. I just tweeted back one question, perhaps Twitter not the right place for that. Sorry if not adeguate. Anyway, I read your book on “The Obesity code” many times (I think more than 4 !) to grasp all possible details and info. I have no medical education at all but I feel as being extremely curious and willing to learn more especially about healthy food. My son (now 14 yo) has developed T1DB when he was 3 yo. For the first 8 years we have been following carefully all the instructions received from the hospital’s dieticians,… Read more »
Walt
Guest
Max, I am going to answer you, at least in part, as I am pretty sure Dr Fung will not. He doesn’t seem to. I suspect the principal reason is there is a fine line between stating general stmts and giving medical advise. There is an ad on these blog entries for Dr Doctor. On there are often Q&As with Dr Fung. You did say you cut out bread, yet you have pizza regularly. Pizza dough is bread, by any other name. Pills do not solve the problem, they mask it. The problem occurs long before the addition of pills… Read more »
Walt
Guest

sorry, I meant Diet Doctor

Max Salogni
Guest
Thanks Walt, I agree with yoy even though I wasn’t actually asking for medical advise. Pizza is only once per month (one pizza is divided in 4 portions and each of us has a slice), not even regularly. I’ve been checking GI after pizza and see very high values even after 3-4 hours ! However, I’m not sure if all these thin people eating high sugary producs are “well equipped” and able to handle that by nature. I think perhaps 2-3% could do but the others perhaps haven’t started yet to have problems, so they cannot recognize their bad eating… Read more »
Walt
Guest

All of the above, plus age. People’s metabolism change with age. I’ve been on here over a year now and ppl ask Dr Fung questions all the time, I’ve not seen hide nor hair of him on here in about that same length of time. But, try Diet Dr link and/or fasttalk w/Jimmy Moore.

Val
Guest
Questo sarebbe interessante per Lei, Max. Il libro da Dr Valter Longo. Non e ancora disponibile in Ingelese. Si chiama “La dieta della longevita. Dalla scienzato che ha rivoluzionato la ricerca su staminali e invecchiamento, la dieta mima-digiuno per vivere sano fino a 110 anni” . He devised the fasting mimicking diet for therapeutic purposes after he had difficulty finding enough cancer patients willing to do extended water fasts. He has published over 400 peer reviewed scientific articles and there are many interviews with him, and lectures by him on YouTube. His primary interest is not diabetes, but his work… Read more »
Stephen T
Guest

Max, you’re not solving any problems with drugs as an alternative to dietary changes. That’s just hiding the problem until it’s done so much damage that it can’t remain hidden any longer. If you really like pitza, have it occasionally, within a usually low carb framework and with some fasting. Dietary changes for most people, don’t have to result in the perfect diet, but I prefer to avoid sugar and wheat whenever I can.

Val
Guest

It appears fasting is the most helpful thing we can do for ourselves if we have T2.

http://www.cell.com/cell/pdf/S0092-8674%2817%2930130-7.pdf

If Longo’s Fasting Mimicking Diet has the ability to regenerate beta cells, would water fasting get better/quicker results?

Walt
Guest
They don’t actually regenerate, they were clogged with fat. Regeneration implies they were dead or non-existent. Dr Taylor disproved that notion. I would disagree actually in that the singular best thing you can do is cut out simple carbs, sugars, refined flour, any flour, starches, anything that grows underground. T2D comes about by high and persistent insulin levels. Nothing triggers insulin levels as much as simple carbs. Cutting out mid meal snacks, like breakfast – snack – lunch – snack – dinner – snack is imperative as well as that becomes the persistent in the persistent and high. An exaggeration… Read more »
Val
Guest

You obviously didn’t read the article I posted. Dr Longo et al did find that cells regenerated. Indeed, that’s in the title of the article.

Walt
Guest

right, I have no clue what cell.com is. I do know what National Institute of Health is. I do know that the work of Dr Taylor has been replicated and peer reviewed. For all I know Dr Longo is a chiropractor or PhD in mechanical engineering. See the difference?

Stephen T
Guest

Walt, Dr Valter Longo is a widely respected professor in California who studies fasting in connection with health. Someone as interested in the subject as you would almost certainly find his work to be valuable and high quality.

https://www.youtube.com/watch?v=d6PyyatqJSE&t=1459s

Charles
Guest
Walt http://gero.usc.edu/faculty/longo/ Valter Longo, Ph.D. Edna M. Jones Professor of Gerontology Professor of Biological Sciences Overview Dr. Longo is the Edna Jones Professor in Gerontology and Professor in Biological Science. He is also the Director of the USC Longevity Institute. He is interested in understanding the fundamental mechanisms of aging in yeast, mice and humans by using genetics and biochemistry techniques. He is also interested in identifying the molecular pathways conserved from simple organisms to humans that can be modulated to protect against multiple stresses and treat or prevent cancer , Alzheimer’s Disease and other diseases of aging. The focus… Read more »
Walt
Guest

Guys, as mentioned earlier, I tend to limit my sourcing to that vetted by NIH. Too many internet drs and non-peer reviewed ‘data’.

Brigitte
Guest

Walt, sometimes it is advisable to keep one’s mouth shut. Or at least admit that one does not know what others are talking about. Makes you look less like a prick.

https://news.usc.edu/28753/Valter-Longo-Receives-11-5-Million-NIH-Award/

Charles
Guest

Walt

Are you familiar with studies showing reversal of T2D within 21 days on a high carb low fat macrobiotic diet?

http://sci-hub.bz/10.1002/dmrr.2519
Ma-Pi 2 macrobiotic diet and type 2 diabetes mellitus: pooled analysis of short-term intervention studies

http://www.hoajonline.com/internalmedicine/2052-6954/2/3
Ma-Pi 2 macrobiotic diet intervention during 21 days in adults with type 2 diabetes mellitus, Ghana 2011

http://www.medicc.org/mediccreview/articles/mr_119.pdf
Ma-Pi 2 Macrobiotic Diet Intervention in Adults with Type 2 Diabetes Mellitus

https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-11-39
The effect of the macrobiotic Ma-Pi 2 diet vs. the recommended diet in the management of type 2 diabetes: the randomized controlled MADIAB trial

Your thoughts

Kok-Hong Wong
Guest

I would certainly think so. Wasn’t Dr Valter Longo trying to micmick the effects of multi days extended water fast? 😀

Val
Guest

Indeed 🙂

Roger Bird
Guest

My million dollar questions is, What constitutes an “ultra-low calorie diet”?

I am currently doing about 200 to 250 calories per day, which is roughly a 92% reduction in calories. It is very high fiber and ketogenic. Is that fasting? Is that ultra-low calorie? My metabolism has not tanked, and I can easily tell because I am too wired to get all of the sleep that I would like, and my hands are warm, although my feet are a little cool.

What say you, one and all?

BobM
Guest

High fiber? Why? I find fiber=bad. (Add to fiber, resistant starch=bad.)

Personally, I try to mix things up. I fast some longer periods, some shorter periods, and have weeks where I don’t fast (other than skipping breakfast). I find long fasting periods make me colder. The shorter ones don’t seem to have the same effect.

Roger Bird
Guest

No very satisfactory. I am asking if I am stopping autophagy and apoptosis.

Walt
Guest
There has been NIH cited research on autophagy in the brains of mice and it merely requires food, presumably caloric, reduction. What Dr Fung has said re: fasting vs water fasting is what you’re doing accomplishes the bulk of what a water only fast would do. As for fasting it is the duration between meals, is it 12 hrs, 23/24 hrs or 3 hrs. If you went from 6pm to 8am that would be 14 hrs, 6am to 12pm, 18 hrs. You want to break the persistent part of persistent and high. As for fiber, yes it is better than… Read more »
LyndaF
Guest

Roger did not specify where his fiber is coming from. There are many sources of fiber that are not wheat based (psyllium husk, chia, even many vegetables could be considered high fiber). He made no mention of wheat at all.

Walt
Guest

Yes, LyndaF, very good point. I stand corrected.

Walt
Guest
In short I think that is reasonable, if not too low cal. What you describe is my reaction too, unless I screw up and bounce myself out of ketosis. Being warm or even start sweating w/o exertion, is likely the body raising metabolism to burn excess dietary cals. When I am in ketosis at night my feet might intermittently feel cool, but never cold. Ditto with hands. What you could do is slowly start adding carbs back in to see where your personal threshold for carbs is. For instance, some could eat a huge piece of chocolate birthday cake and… Read more »
Roger Bird
Guest

Walt, I salute you for testing on yourself. I do that also. And I thank you for your suggestions.

Walt
Guest

FWIW, that NIH study I cited was the effect of autophagy on Amyloid-B (a precursor to Alzheimer Disease) in the brain. AD is also referred to as Type 3 diabetes affecting the brain. The theory is the mechanism of Amyloid destruction, therefore no plaque, is somehow short circuited due to insulin resistance in the brain, which leads to AD. But studying it in mice (easier to examine the brains of) that fasting or otherwise restricted food actually accelerates the process of autophagy in the brain, removing or impeding the build up of Amyloid-B.

Raj
Guest

True fasting (water fasting) is taking in zero calories. If you are fat adapted, you will be burning fat from day one of your fast. If you then eat pure fat during the fast, for example a spoon of coconut oil, you will temporarily stop buting body fat while you burn the dietary fat, once the dietary fat is finished you will continue burning body fat. If however, you eat some carbs during your fast, you will not only stop your fast but you will also stop fat burning as your body will now begin to burn the carbs.

Walt
Guest
That would be real purist. Looking at Fung’s fasting or even the grand-daddy Atkins that does allow or suggest a small amount of carbs, i.e. ketogenic is <20g Atkins Induction phase is < 20g. Certainly 0 is less carbs but protein and even fat will cause insulin spikes. Fung as well as other keto experts warn your body only uses one form at a time, as you said. However the brain still needs glucose for at least 30% as ketones only supply 70% of what the brain requires. Where there is individual thresholds is what level of carbs will transition… Read more »
Stephen T
Guest

Walt, won’t your body produce any carbs the brain needs through gluconeogenesis?

Walt
Guest

I believe from what Dr Fung has said the body will use fat before it uses protein. Protein is not stored so it’s used from dietary or lean muscle. But fat is favored over converting lean muscle to glucose. Species survival and evolution wise that makes sense.

Walt
Guest

correction – eating pure fat is still consuming calories, just the least prone to spiking insulin, therefor addressing the high part of persistent and high insulin resulting in IR.

Stephen T
Guest

I think it’s worth saying that fat is also the most satiating thing you can eat.

Walt
Guest

true

Roger M. Moery
Guest
Tons of respect for your work and contribution. I also have the same respect for Dr. Bernstein and his work. He has worked almost anonymously for decades and now the rest of the world is finally becoming believers. I am confused at to why you want to call him out by name. It seems to me that you somehow have an axe to grind with him. On one of your podcasts you were critical and you podcast host made a snarky comment about him. Why not give him his due and respect for what he has accomplished. Don’t see where… Read more »
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