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The only misleading word here is "new."

Edit: Thanks admins for fixing.

I haven't heard of ChREBP before. Is it something that has been well known in the research community for awhile? Has there been consensus as to its role in the disease pathway, or is it recent?

(I took two semesters of immunology in my biochem undergrad--courses that I would have expected to cover this. I was never exposed to literature or material on this protein. I also haven't heard of it in the primary literature I do occasionally still read.)

The most major finding, which appears to be this:

> The study found that fructose initiates a process that causes the liver to keep making glucose and raising blood glucose levels, even as insulin tries to keep glucose production in check.

Is not ground-breaking. It's how the liver metabolizes fructose. The liver can't respond to insulin because it needs to metabolize the fructose.

I don't think that's fair. This is just a press publication; we'd need the actual paper to see what its specific claims are. Besides, very little in science is "ground-breaking" at first. Scientific progress happens most often through an accumulation of evidence over time.
tl; dr: A mouse study (corroborated by in vitro experiments with human liver tissue) found that a liver signaling protein, ChREBP, is activated by fructose consumption and causes the liver to produce glucose in a way that isn't shut down by high insulin levels. IMO this is not so much a "new theory" as an insight into the behavior of a particular pathway that would be part of a theory.
My retired, at the time, 71 year old doctor was thrown out of a medical conference. (Don't know if he was literally thrown out, but that's what he told me. Maybe for dramatic effect?

Why? He stood up, and said there's no such thing as Metabolic disease. He said they(my patients) are just inactive, and out of shape, and eat the wrong foods.

He told me this at point in my life when I was drinking to excess, and not exercising. (I was drinking because I had a anxiety disorder that didn't respond to anything other than alcohol. It came on in graduate school. It came on after a series of bad anxiety attacks. The anxiety was unrelenting.)

My point is when I cut back on my alcohol intake, lost a few pounds, and got back to exercising; I didn't have Metabolic syndrome anymore.

(I haven't followed metabolic disease. There might be something to it than being out of shape, and drinking/eating too much? I don't know. I just know Dr. Shepard was the last good doctor I had. Last doctor who actually listened to my heart murmur. The last Doctor who palpated patients for obvious tumors. The last Doctor who appeared to care. A Doctor of a different generation?)

The connection to the consumption of animal products to diabetes is rarely the focus but we know there is a big connection. Consider Kempner's Rice Diet which used sugar to successfully treat diabetes! So I doubt sugar is a sufficient condition. This is politics not science.
I've never heard of a connection between consuming animal products and diabetes. Perhaps you can expand on this.
I recognize the text pattern from before. Pretty sure I've dealt with this user before, on articles about Diabetes.

In the end, it's a whole lot of breathlessness about veganism will "fix diabetes". Of course, no citations, or cited articles that are completely 180deg out of phase.

I know what worked for me, was a form of Atkins diet (extremely low carbohydrate diet) backed up with my glucometer. I plot trends of foods, and how they respond to me. My limit is 140mG/dL, where we know neurons in agar petri dish die.

Yes, my diet consists of a lot more meats, veggies, cheese, some nuts, some 'dryer' fruits. But no bread, rice, sugar, or things that cause my body to rise.

How many carbs a day do you stick to?
Total carbs, I'm not entirely sure. My body reacts to Net Carbs, which is (Total - Fiber). As for net carbs, I eat anywhere from 5-15g

Some diabetics cannot subtract fiber, because they respond to the whole load via their glucometer. Fortunately, I'm not one of them.

Ah, you're pretty strictly keto then. I try to follow keto and have had good success with it, but after a month of strict 20 grams of carbs or less, I've relaxed it a bit and I often creep up to 30 or 40 net grams of carbs a day.

Still feeling great and losing weight, although perhaps I'd lose a bit faster if I remained stricter about it. I'm also not diabetic, although my A1C numbers were getting close to prediabetes levels before I started the diet. I expect that to drop the next time I get my blood checked, though.

I'm 6'5", at time of type 2 diagnosis, I was 320 lbs, 44" waistline, a1c=7.1, fasting glucose=161 mG/dL . That was last December. They caught it in time before I really had many symptoms, although I was starting to get erectile dysfunction (one of the first things to cause problems, BTW).

Fast forward to now. 260 lbs, waver between 36" and 38" waistline, and feel better than I have in decades.

My only problem is my stomach is a perfect sensor for "Hidden Carbs". I'll get wonderful things like stomach pains and bad indigestion over things like flour in gravies or sauces, or hidden corn starch, or sugar sprayed on salads.

Now, Metformin. I have a prescription for it. I don't need to take it, UNLESS I'm eating somewhere I cannot control my carb load, let alone know what my carb load is. Holidays are notorious about this, as are buffets and similar places. My solution is, I take metformin before I go to sleep the day before, through the whole day of, and 1 pill the morning after. It effectively is a form of a PID control loop for glucose.... which is what I need.

What fruits do you allow yourself to eat? I've cut out fruits entirely and miss them greatly.
My experience is, I can still have: blueberries, raspberries, blackberries, strawberries (well, some), a little bit of apple (we're talking about splitting a tart apple half with wife), and some grapes.

It's not 100% true, but the more tart, the better in terms of sugars. More fiber also helps slow down absorption... But 10g fructose = 10g fructose, no matter what else you put with it.

EDIT: I figured these out the hard way. Go get a cheap glucometer. ReliOn brand is good at Wal-Mart. $25 meter, 9$/50 strips. And eat foods you like. Test before you eat, and 1/2 hour increments afterwards for 2 hours. Wash-rinse-repeat :) Make your own decisions based on your own health data.

You are here often saying this and downvoting people who don't agree with you. Please comment on this:

The Cause of Insulin Resistance What’s gumming up the door locks on our muscle cells, preventing insulin from letting glucose in?

It’s fat. Intramyocellular lipids, or the fat inside our muscle cells.

Fat in the bloodstream can build up inside the muscle cell and create toxic fatty breakdown products and free radicals that can block the insulin signaling process. When that happens, no matter how much insulin we have in our blood, it won’t be able to open the glucose gates. That causes blood sugar levels to build up in the blood.

Source: The article linked in my previous comment. Yes there are sources cited.

@ mchmch (dead response)

> The Cause of Insulin Resistance What’s gumming up the door locks on our muscle cells, preventing insulin from letting glucose in? It’s fat. Intramyocellular lipids, or the fat inside our muscle cells.

Yeah. There's something going on with fat. Majorly. I agree with that. And also, whatever it was that was making me crave carbohydrates also made me gain weight like crazy. And you know, when I went on a carb-free (<15g net carb) diet, my weight at the fastest was dropping by .54 lb/day . Yes. A day.

I've also seen research, and talked with researchers who've also discovered that losing as little as 1g of fat on the pancreas can alleviate all symptoms of T2 diabetes. The problem, is there's no known way to target inter-organ fat.

> Fat in the bloodstream can build up inside the muscle cell and create toxic fatty breakdown products and free radicals that can block the insulin signaling process. When that happens, no matter how much insulin we have in our blood, it won’t be able to open the glucose gates. That causes blood sugar levels to build up in the blood.

Then why does doing a low/no carb diet cause us T2 diabetics along with prediabetics to lose weight on a massive scale? It seems to me that there's something wrong with the metabolics/genetics that do something funky to carbohydrates. Something like

Carbohydrates -> sugar -> fat -> stored

And it seems to short circuit what should normally just work.

Source: The article linked in my previous comment. Yes there are sources cited.

I also have been on keto for past 1.5 years. For last 6 months I have been measuring ketone and glucose levels with blood meter every evening (whenever possible). I have a journal of my diet, exercise and other health-related activities.

Still have to analyse/normalize my data, didn't find time yet to build tools for it. Here is just a quick graph where I dumped the numbers into a google spreadsheet:

https://dl.dropboxusercontent.com/u/559047/keto-readings-01....

High glucose implies lower ketones in my case (the correlation is pretty obvious from the plot above). My explanation is that when I get higher glucose in blood, my pancreas increases insulin level and that in turn not only drives glucose down, but also ketones (somehow).

I could be considered a healthy, relative active individual 37yrs, 182cm, 78kg, ~15% BF.

Why I'm posting this here? Eventually I would like to build a tool with a protocol to follow for people who want to follow similar diet and compare their results. I believe this crowd-sourced data could potentially be also an interesting data-set for researchers.

Any hackers interested in building something similar?

Given the GP's user name, I suspect that not many share a love for ingesting that kind of "animal product".
What!?

Do you have a background in biochemistry, medicinal chemistry, or a related field, or perhaps some evidence to back this up? Forgive my skepticism, but this is so far off topic and, frankly, sounds like a homeopathy / "conspiracy theory" subject.

Diabetes is a complex disease, but I don't think you underplay the preponderance of evidence implicating the role of sugar. (It is, after all, one of the principle elements of the insulin pathway.)

Easy to test. Get 80% of your calories from fructose syrup. The rest from plant food. Feel free to report in a year.
> Get 80% of your calories from fructose syrup.

Pretty sure you would die in less than 38 hours.

You won't. But you may as well wish to ...
I think this is the most interesting point:

>The new findings suggest fatty liver disease may be a red herring, Herman said. The likely cause of insulin resistance may not be the buildup of fat in the liver, as commonly believed, but rather the processes activated by ChREBP, which may then contribute to the development of both fatty liver and increased glucose production.

My capstone project was actually about how sugar affects metabolism. There is a lot of interesting research and unexpected interactions in this area.

One of the things that is most interesting is that they have found the same proteins that form our taste buds in the walls of our small intestine. It appears that the gut "tastes" food and "tells" the body what kind of food is coming and how to prepare for it. One of these pathways ends up producing insulin.

The interesting thing when it comes to sugar is that sweetness is not directly correlated with caloric content (or glycemic index, which is the measure of the sugar insulin actually works on). An obvious example are artificial sugars, which taste incredibly sweet and have zero calories. Natural sugars vary in sweetness as well though - using sucrose/table sugar as a baseline, fructose is 1.73 times sweeter for its caloric content. Furthermore, fructose a glycemic index of 19, compared to 55 for table sugar.

This is really interesting because body regulates hormone levels with feedback loops. So, if the taste buds in your gut taste sweetness and initially trigger a release of insulin that would be appropriate for table sugar, you could have 5 times more insulin floating around in your blood stream than your body was expecting. This might trigger some of these sugar taste buds to stop sending the signal to release insulin when they taste sweetness.

Worst case scenario is when someone drinks a diet pop on an empty stomach. All of the sudden there is the HUGE burst of sweetness, with no sugar in the bloodstream for the insulin to bind to.

This might seem very speculative, but there is some physical evidence that the body actually behaves this way. When a gastric bypass is preformed, a length of the small intestine closest to the stomach is removed. This section would have the most deactivated "taste buds", since it would be receiving the full load of unabsorbed sugars from the stomach. "Taste buds" further down the small intestine would not be deactivated because they haven't been triggering falsely.

Indeed, after the surgery, people appear to lose weight much faster than expected based on their previous metabolic rate, and their diabetic symptoms decrease far more than expected as well.

The question I get asked the most after talking about this is whether it's better to drink diet pop or normal pop. Unfortunately, it appears the best thing to do is to not drink pop at all. Limiting your sugar intake is a good idea for a lot of reasons, and soda is just far too sweet and/or too sugary to be healthy as a regular part of your diet.

Can you actually measure an insulin spike for a fasting person that eats or drinks some artificial sweeteners?
That's actually a really interesting suggesting for further study. It's probably possible. I don't know if the research has been done though. The discovery of the "taste bud" proteins in the gut was a fairly new when I did my project 5 years ago. I don't have journal access so keeping up to date is fairly difficult.

Side note, I made a video for it as part of my senior capstone. I often think about making an updated version. For one thing, I'm not sure if everything in it is correct. On top of that, I was incredibly tired, because the only time I could reserve the space I needed was after midnight. I also flubbed a few lines and lost all my b-roll, so editing was a nightmare. In any case, here's the video I did:

https://www.youtube.com/watch?v=8ZGSBi0OFwM

There are so many things I'd like to change about that video.

My graduating class was the first one at my college that was required to perform a senior capstone to graduate, so everything was done by the seat of my pants. I learned later that the Biology department actually used my project as the example for what they wanted all projects to be like. It's far from perfect, but my goal was to take what I had learned and share the information in a way the general public could understand.

I was a little overambitious. I learned later that several professors thought I wasn't going to graduate. (I wish I had known that at the time, I would have been doubly motivated.) I'm pretty jealous of the younger students, they turned an old building in to a film studio for producing videos like this. My rig was a bunch of halogen work lights and the best camera I could afford at the time (read: really terrible).

The capstone project is why I'm 100% in favor of requiring open journal access. With journal access, anyone can contribute to the scientific community (and society as a whole). I made a video, but people can come up with their own questions and try to answer them, such as the question you asked. Watching the projects other people are doing on YouTube, I'm 100% convinced that open journal access would lead to a scientific revolution.

From your description of the issue , it seems that DouxMatok's sweeter sugar technology[1] could solve this dillema - by giving the tongue the same sense of sweetness , but in the gut, where sugar dissolves, only 1/2 of the sugar enters.

[1]By coating inert mineral particles that have no caloric value with sugar molecules, DouxMatok developed a sugar substitute that (allegedly) tastes just like pure sugar.

The sugar-dusted particles have the same amount of sweet surface area as a full sugar particle. Because this is the only part of the particle that touches your tongue, the DouxMatok substitute triggers the same perception of sweetness as real sugar when it hits your sweet taste receptors.

http://www.popularmechanics.com/science/health/a18737/sugar-...

The actual problem is that less sugar enters the blood stream than is tasted. The real solutions are really unexciting, like eating fewer sweetened foods, and eating foods sweetened with natural sugar.

Honestly, my biggest take away from the research is that there is no substitute for eating healthy. For instance, vitamin supplements don't appear to convey the same health benefits as consuming the vitamins in foods in which they naturally occur. There are a lot of reasons for this, but what my take away was that it is easier to eat a balanced diet, than it is to eat a poor diet and then fix it through science. Same goes for health in general really -- it's better to take steps to stay healthy, than it is to lose your health and try to get it back.

> The real solutions are really unexciting, like eating fewer sweetened foods, and eating foods sweetened with natural sugar.

It would be easy to test that real solution by comparing diets from a place where they don't eat as much sugar.

Well, we know that high-sugar diets are highly correlated with diabetes. The biochemistry is the interesting part.

That being said, there is a lot of easy research that never happens. There are a lot of reasons. Funding is difficult to get, and it's hard to get funding to research things that are "obvious". Furthermore, there are a limited number of scientists -- they have to choose what they are going to research.

>> The actual problem is that less sugar enters the blood stream than is tasted.

But tasted where ? do we have any knowledge what happens when the tongue measures one level of sweetness and the gut another ?

And don't the case of the gastric bypass implies that if the gut senses less sugar(either because of less sensors, or because of less sugar) , we get positive results ?

>> no substitute for eating healthy.. than fix through science.

Currently that's good health advice, i agree.

The taste buds in your gut are on the same side of the gut as the food. So your gut can taste sugars that pass through you without being absorbed.

Given that fact, we can speculate that sweet things that aren't absorbed might be more harmful than ones that are absorbed, as they have a chance to activate taste buds all the way through the gut as they go past, rather than just the earlier ones.

True, there might be such mechanisms.

Hopefully the guys at DouxMatok are think about this and optimizing their sweetener to quickly dissolve in the gut.

And sure, this definetly needs full animal testing before claiming things about it.

Interesting. Any ideas on how the bacterial flora interacts with the sensing small intestines? Would they react as well when the sensation of sweetness goes over them?
I don't know a lot about the flora of the gut, especially the flora in the small intestine. There is a lot of really interesting research going on in that area though. I'm really interested in the relationship between diet and the flora in the gut myself.
Interesting. What do you think about sugarless gum? I chew it because it helps with my acid reflux. I'm wondering if it might cause a spike in insulin, like diet soda would.

I guess one good thing is I usually chew it after a meal, but I do occasionally chew on an empty stomach if I'm having trouble burping.

The amount of artificial sweetener in a can of diet soda is going to weigh an order of magnitude more than your one piece of gum (which is mostly made of an undisgestible polymer anyway, with very little in the way of actual flavorings). You might as well dissolve a packet of splenda in an eye dropper and take a few drops.
I understand the GP's comment a bit differently. What matters is how much the taste buds are stimulated, not the amount of artificial sweeteners. If that is true, the sugarless chewing gum is many many times worse than the diet soda. The drink passes through your mouth in a few seconds, the gum stays in contact with your tong for half an hour (or more).
This is precisely what I'm worried about.
Ah, I see. I guess I've been unclear. The taste buds in your mouth don't cause the insulin response. There are separate taste buds embedded in the wall of your small intestine that activate the insulin response, and play a role in insulin resistance.

On a somewhat related note, my non-expert opinion is that sugarless gum is probably still better for you than gum with actual sugar in it for reasons relating to oral heath.

Thanks for the clarification. Much clearer now.
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I just replied to a comment further down the thread. The taste buds in your mouth don't play a role in insulin resistance. There are separate taste buds embedded in the wall of your gut that are responsible.

I'd still recommend chewing gum, but you'd have to weigh the evidence for yourself, cause I'm not a doctor. However I believe the oral health benefits outweigh the potential risks. Acid reflux is also correlated with a lot of really nasty health issues, like esophageal cancer and heart disease. (It's my understanding that the heart disease link may be due to the elevated calcium levels caused by consuming large quantities of antacids) If chewing gum helps control your acid reflux I'd keep chewing gum. I'm actually considering this myself now that you mention it, since I suffer from acid reflux as well.

I'm actually considering this myself now that you mention it, since I suffer from acid reflux as well.

Chewing gum greatly reduces the amount of antacids I need to consume. The other thing that really surprised me was my low-carb diet further reduced antacid use to almost zero. For a month after my low-carb diet, I didn't even think to take a single antacid.

>> If we can develop drugs to target this process, this may be a way to prevent the process early in the development of the disease

Always gotta come up with a new drug. Why not just eat a diet with no added sugar?

There's no money in eating less sugar.

These pharmaceutical companies are interested in one thing - making money, and therefore they need everyone to be a "customer" by taking one of their pills every day. This means even if there are simple (i.e. non patent-able) solutions to health problems, you won't see them pushing it - instead you'll see them ACTIVELY work to prevent it.

A good example is the recent case where these companies have spent $880 million in the last 10 years working against marijuana legalization, even though studies are showing that it can work as a good pain killer replacement for the more deadly opioids that they are eager to hand out.

See: http://bigstory.ap.org/article/4d69f4b41cbc475ca42f424524003...

While I can agree that the blame for continued marijuana criminalization falls to some extent with pharma companies, I don't think that I can 100% agree with the sugar aspect.

If pharma develops a pill for this it's because people want to eat sugar. This will be the same for pills that eliminate hangovers (should they exist), why not just quit drinking?

Simple answer is that people want to do these things, and neither should be criminalized, nor should marijuana be criminalized. Eliminating the side-effects of these products will probably be dangerous (with even more side-effects, but different ones), but I guarantee that there will still be a market for them -- especially if people can eat and drink what they want and avoid obesity, even at the cost of other aspects of their health.

I really dislike pharma for attempting to continue criminalizing things like marijuana and kratom, but to apply the same logic to a pill that keeps people from gaining weight or avoiding diabetes while eating what they want is an entirely separate issue ethically and logically.

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Does this mean insulin resistance can be partially mitigated by switching to glucose and avoiding fructose completely?
What about people who eat high fruit and blame diabetes on fat intake? Can someone elaborate? These two individuals are crushing more than 30 fruits a day with high glycemic loads

http://www.mangomannutrition.com/

http://mindfuldiabetic.com/coaching/

They are probably wrong about the fat causing problems...

That said, if they are eating raw, whole, fruits with most of their fiber intact (and from the look of their site, they are) they are reducing the glycemic index of the foods they eat.

Many processed foods are bad, not simply because they are processed, but that a massive amount of the fiber in the original food is removed. Fiber is a glycemic moderator, foods with high fibers have lower glycemic indexes. For example if you juice an orange, you've pretty much made kool-aid, it's junk food now. If you instead try to eat as many oranges in a glass of orange juice you would feel full before you finished and consumed a lower amount of calories because of that.