9 ms·

A theory on how insulin resistance, metabolic disease begin

71 points by mishkovski 10y ago

phkahler 10y ago
>> 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?
- jamroom 10y ago
  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/4d69f4b41cbc475ca42f424524003d21/drugmakers-fought-state-opioid-limits-amid-crisis http://bigstory.ap.org/article/4d69f4b41cbc475ca42f424524003...
  - moosey 10y ago
    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.
deleted 10y ago
[deleted]
debacle 10y ago
The only misleading word here is "new." Edit: Thanks admins for fixing.
- echelon 10y ago
  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.)
  - debacle 10y ago
    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.
    - echelon 10y ago
      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.
0xcde4c3db 10y ago
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.
icantdrive55 10y ago
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?)
dogdutyascetic 10y ago
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.
- oldmanjay 10y ago
  I've never heard of a connection between consuming animal products and diabetes. Perhaps you can expand on this.
  - kefka 10y ago
    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.
    - JBReefer 10y ago
      How many carbs a day do you stick to?
      - kefka 10y ago
        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.
        10y ago
mishkovski 10y ago
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.
Declanomous 10y ago
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.
- adrianN 10y ago
  Can you actually measure an insulin spike for a fasting person that eats or drinks some artificial sweeteners?
slyrus 10y ago
And here's the link to the paper itself: http://www.jci.org/articles/view/81993 http://www.jci.org/articles/view/81993
anu7df 10y ago
Does this mean insulin resistance can be partially mitigated by switching to glucose and avoiding fructose completely?
__d__ 10y ago
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://www.mangomannutrition.com/ http://mindfuldiabetic.com/coaching/ http://mindfuldiabetic.com/coaching/
- pixl97 10y ago
  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.

71 points by mishkovski 10y ago

>> 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?

jamroom 10y ago
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/4d69f4b41cbc475ca42f424524003d21/drugmakers-fought-state-opioid-limits-amid-crisis http://bigstory.ap.org/article/4d69f4b41cbc475ca42f424524003...
- moosey 10y ago
  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.

deleted 10y ago

[deleted]

debacle 10y ago

The only misleading word here is "new." Edit: Thanks admins for fixing.

echelon 10y ago
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.)
- debacle 10y ago
  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.
  - echelon 10y ago
    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.

0xcde4c3db 10y ago

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.

icantdrive55 10y ago

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?)

dogdutyascetic 10y ago

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.

oldmanjay 10y ago
I've never heard of a connection between consuming animal products and diabetes. Perhaps you can expand on this.
- kefka 10y ago
  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.
  - JBReefer 10y ago
    How many carbs a day do you stick to?
    - kefka 10y ago
      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.
      - 10y ago

mishkovski 10y ago

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.

Declanomous 10y ago

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.

adrianN 10y ago
Can you actually measure an insulin spike for a fasting person that eats or drinks some artificial sweeteners?

slyrus 10y ago

And here's the link to the paper itself: http://www.jci.org/articles/view/81993 http://www.jci.org/articles/view/81993

anu7df 10y ago

Does this mean insulin resistance can be partially mitigated by switching to glucose and avoiding fructose completely?

__d__ 10y ago

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://www.mangomannutrition.com/ http://mindfuldiabetic.com/coaching/ http://mindfuldiabetic.com/coaching/

pixl97 10y ago
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.