6 ms·

Insulin Resistance is the start of (all?) metabolic disease. So easy to resolve using fasting, intermittent fasting, keto, carnivore etc diets. Unfortuneately

by 49para 6y ago

Insulin Resistance is the start of (all?) metabolic disease. So easy to resolve using fasting, intermittent fasting, keto, carnivore etc diets. Unfortuneately it slowly builds up over decades and only once disease has progressed do Drs move on to treat the resultant disease (and mainly with cholesterol lowering drugs). Instead of measuring fasting glucose levels (which indicate diabetes), insulin levels should be measured as they are the leading indicator.

Trasmatta 6y ago
> Insulin Resistance is the start of (all?) metabolic disease. So easy to resolve using fasting, intermittent fasting, keto, carnivore etc diets. Definitely not all. Not the least of which is Type 1 Diabetes, which is marked by the inability to produce insulin, not insulin resistance. And it's currently impossible to resolve, all Type 1 Diabetics have to be on insulin therapy to survive.
- ashtonkem 6y ago
  Is Type 1 diabetes considered a metabolic disease? I've only heard of "metabolic disease" in reference to "metabolic syndrome", the precursor to Type 2 diabetes and heart disease.
  - asplake 6y ago
    There are many metabolic disorders - some due to specific genetic issues, and some severely life-limiting (eg children unlikely to reach adulthood). And as per the Wikipedia page for metabolic disorders, not to be confused with Metabolic syndrome or Diabetes.
  - Trasmatta 6y ago
    It's a metabolic disorder. I guess I don't really know the difference between metabolic disease / metabolic syndrome / metabolic disorder. All problems of the metabolism, but I'm sure there's some medical distinction between them.
- dreamcompiler 6y ago
  > And it's currently impossible to resolve, all Type 1 Diabetics have to be on insulin therapy to survive. Not quite impossible but granted, islet cell transplants are still experimental. https://en.m.wikipedia.org/wiki/Islet_cell_transplantation https://en.m.wikipedia.org/wiki/Islet_cell_transplantation
  - Trasmatta 6y ago
    True, technically it's also possible to get a pancreas transplant. But in both islet cell and pancreas transplantation, the risk of rejection and the burden of immunosuppressive regimens are high enough that they are rarely ever recommended for T1 diabetics. From my understanding, it's usually only recommended for a diabetic requiring some other transplant at the same time (since they'll have to be on immunosuppressive drugs anyway).
- bad_user 6y ago
  T2D also leads to impaired insulin action, when the beta cell function of the pancreas is impaired. Sometimes impaired insulin action comes before insulin resistance and it is still T2D. The difference is that T1D is an auto-immune disease, wereas T2D is caused by energy poisoning.
conistonwater 6y ago
> So easy to resolve using fasting, intermittent fasting, keto, carnivore etc diets. Or, you know, you could resolve it by eating a balanced diet too.
- arcticbull 6y ago
  There's a solid argument to be made that when you eat, and how often you eat, is more important than what you eat. Specifically, the thesis is that if you eat constantly, you constantly have a high level of insulin, which your body becomes used to, and then has to produce more to actively control your blood sugar. Insulin resistance is a runaway positive feedback process. Insulin is particularly challenging because it actively causes sugar from your blood to be converted to fats and stored in your adipose tissue -- and blocks the release of fats from your adipose tissue. Eating frequently actively inhibits your ability to lose weight. By creating long gaps between meals, your body re-establishes what baseline level of insulin should be. Studies are starting to bear this out, more are needed. I can dig up some more papers if you like, but this is a good place to start [1]. [1] https://www.sciencedirect.com/science/article/pii/S1550413118302535 https://www.sciencedirect.com/science/article/pii/S155041311...
  - conistonwater 6y ago
    I got into it when I read https://www.nature.com/articles/nrn.2017.156 https://www.nature.com/articles/nrn.2017.156. The thing is that a lot of nutrition research is rather low-quality compared to the rest of science (low n in studies, small effect sizes, low study power, high chance of finding false positives, etc.), and it gets even worse once you start reading sports science papers especially nutrition for sports performance. The best conclusion I found was that a lot of these things like intermittent fasting have small but noticeable effects, meaning that if you can follow IF easily then you may as well do it (like Pascal's wager!), but there is no solid evidence that you actually should do it because the effects are uncertain and small. One pitfall of a lot of these discussions is that people point to papers that show "an effect exists", but forget to ask "how big is the effect?". I was okay with IF for uncertain small positive brain effects, because my brain is important to me, and it's kind of free, so IF will do. But I think people overstate the effects a bit compared with what's actually known by science. Take the study you linked to, for instance. I can quite believe that IF would increase insulin resistance based on what I've read, and it's cool that they found lower blood pressure and higher insulin resistance in pre-diabetic men. But the study has 12 people (mid-50's pre-diabetic overweight men) in it, and I don't really know what to make of that? Is this type of study particularly expensive to conduct? Should I find it convincing because I already agree with the result? My gut reaction to the study is even simpler (not scientific, just personal): Why on Earth would anybody eat dessert for breakfast (Honey Nut Cheerios, waffles with maple syrup, etc, in Figure 1)? If you're already overweight and pre-diabetic, why is the control diet making you eat that? But they get a boiled egg, I'm guessing one?, to, you know, control cholesterol levels or something, two eggs would be crazy. They were probably trying to separate the effect of IF from the effect of eating a normal diet, as compared to the standard American diet, so didn't include a normal diet at all.
dcolkitt 6y ago
> fasting, intermittent fasting, keto, carnivore etc diets. To preface, I'm a long-time intermittent fasting, and tend to eat fairly carnivorous (though supplement with a lot of vegetables and legumes). But none of what you've listed is a silver bullet. The research is pretty conclusive that the proximate cause of all metabolic disease is caloric intoxication.[1] Regardless of the timing and consumption of calories, if a person continuously has an excess energy balance they're at risk of metabolic disease. In particular, the more dogmatic proponents of keto are refuted by the fact that some hunter-gatherers, like the Hazda, consume up to 50% of their calories from simple sugars. And like all hunter-gathers, they have virtually zero incidence of metabolic diseases. That isn't to say that diet isn't important. Excess calories are the proximate cause, but the type of food being consumed ultimately influences satiety and therefore overall consumption. In particular, the highly processed, hyper-palatable, easily digestible, highly convenient, hyper-varied, calorically dense food found in the industrialized West makes it extremely easy to overeat. In some sense, we're literally getting fatter because our food is becoming more delicious. Quoting the famous Matt Crowley tweet: "We take it for granted today, but a single Dorito has more extreme nacho flavor than a peasant in the 1400s would get in his whole lifetime." Low-carb, low-fat, intermittent fasting, six small meals a day, no eating after 6, cleanse detox, vegetarian, carnivore, keto, high-fiber, high-protein, gluten-free, etc. They all seem to work to a certain extent, even when they directly contradict one another. And that's largely because any arbitrary restriction on food consumption decreases variety (fewer options), reduces convenience (arbitrary rules makes it harder to eat take out), and lowers palatability (many recipes require substitutions or removals that ruin the taste). The upshot is that the older and more popular a fad diet becomes the less effective it will be. When enough of the market's on a diet the food industry will figure out how to make hyper-palatable that still conform to the rules. [1] https://www.stephanguyenet.com/why-the-carbohydrate-insulin-model-of-obesity-is-probably-wrong-a-supplementary-reply-to-ebbeling-and-ludwigs-jama-article/ https://www.stephanguyenet.com/why-the-carbohydrate-insulin-...
- Der_Einzige 6y ago
  Bingo! This post is what I wish every person was taught about health. It always goes back to calories in/calories out...
- 6y ago
bad_user 6y ago
The cause of insulin resistance is energy poisoning (i.e. people eating too much). The only cure for insulin resistance is weight loss. That's it. There's no study, not one, showing reversal of IR with keto/fasting independent of weight loss. Macros are absolutely irrelevant for either weight gain or weight loss in controlled studies. Only protein seems to have an effect on satiety, but the effect is not very significant in the context of whole foods. Even more serious is that drops in HbA1C, a surrogate marker for blood glucose, cannot be shown to drop independent of weight loss. Ketoers might avoid sugar spikes after meals better, they might get off some meds sooner, but this is only disease management and for the HbA1C, which represents a 3 months average, it doesn't seem to matter. The whole notion that insulin resistance is cause by sugar or carbohydrates, or that the cure is cutting carbs, is bullshit similar with anti-vaxxing and homeopathy. Not evidence based.
- partyboat1586 6y ago
  How do you explain skinny people getting type 2 diabetes? They can't be in caloric surplus or they would be gaining weight.
  - bad_user 6y ago
    Skinny people getting T2D have a less flexible adipocytes tissue (aka fat tissue). They cannot store excess energy as subcutaneous fat, because they don't have a subcutaneous fat layer that can store that energy. But once you look at their organs, they are covered in visceral fat. Adipocytes, the fat cells, have a limited capacity and new adipocytes can be created, but only in certain conditions and slowly. This isn't an infinite supply and genetics play a role. In other words people have a "personal fat threshold": https://portlandpress.com/clinsci/article/128/7/405/71158/Normal-weight-individuals-who-develop-Type-2 https://portlandpress.com/clinsci/article/128/7/405/71158/No... https://diabetes.diabetesjournals.org/content/63/12/4369 https://diabetes.diabetesjournals.org/content/63/12/4369 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774584/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774584/ Once the adipocytes start rejecting the energy excess, with that energy excess building up in the bloodstream as glucose and triglycerides, being then pissed away, this is effectively insulin resistance, which is actually a defensive reaction to "energy poisoning": https://pubmed.ncbi.nlm.nih.gov/11872656/ https://pubmed.ncbi.nlm.nih.gov/11872656/ However it's important to understand that this energy poisoning can happen as a result of overeating fat or protein as well, even if the pathways are different from that of glucose: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2362.32.s3.3.x https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2362.... https://pubmed.ncbi.nlm.nih.gov/11872656/ https://pubmed.ncbi.nlm.nih.gov/11872656/ https://pubmed.ncbi.nlm.nih.gov/3421919/ https://pubmed.ncbi.nlm.nih.gov/3421919/ More importantly is that "weight loss" is the only measure shown in tests on humans to revert insulin resistance significantly. Another factor would be exercise, which was shown to work independently of weight loss, but the effect wasn't significant AFAIK. Everything else is confounded by weight loss. And this goes in the other direction — most (not all) risk factors for the diseases associated with the metabolic syndrome, including high blood pressure and heart disease, are confounded by weight gain. There are independent risk factors of course, like smoking or a high LDL, which most often has genetic causes, but most negative effects of foods you've heard about are in the context of a caloric surplus. This includes fat driving cholesterol and triglycerides up. Including sugar causing fatty liver. Sugar (fructose) was never shown to cause fatty liver unless it's in the context of a caloric surplus, sugar was never shown to cause T2D unless it's in the context of a caloric surplus, but that didn't stop some people writing books claiming otherwise.

by 49para 6y ago

Trasmatta 6y ago

> Insulin Resistance is the start of (all?) metabolic disease. So easy to resolve using fasting, intermittent fasting, keto, carnivore etc diets. Definitely not all. Not the least of which is Type 1 Diabetes, which is marked by the inability to produce insulin, not insulin resistance. And it's currently impossible to resolve, all Type 1 Diabetics have to be on insulin therapy to survive.

ashtonkem 6y ago
Is Type 1 diabetes considered a metabolic disease? I've only heard of "metabolic disease" in reference to "metabolic syndrome", the precursor to Type 2 diabetes and heart disease.
- asplake 6y ago
  There are many metabolic disorders - some due to specific genetic issues, and some severely life-limiting (eg children unlikely to reach adulthood). And as per the Wikipedia page for metabolic disorders, not to be confused with Metabolic syndrome or Diabetes.
- Trasmatta 6y ago
  It's a metabolic disorder. I guess I don't really know the difference between metabolic disease / metabolic syndrome / metabolic disorder. All problems of the metabolism, but I'm sure there's some medical distinction between them.
dreamcompiler 6y ago
> And it's currently impossible to resolve, all Type 1 Diabetics have to be on insulin therapy to survive. Not quite impossible but granted, islet cell transplants are still experimental. https://en.m.wikipedia.org/wiki/Islet_cell_transplantation https://en.m.wikipedia.org/wiki/Islet_cell_transplantation
- Trasmatta 6y ago
  True, technically it's also possible to get a pancreas transplant. But in both islet cell and pancreas transplantation, the risk of rejection and the burden of immunosuppressive regimens are high enough that they are rarely ever recommended for T1 diabetics. From my understanding, it's usually only recommended for a diabetic requiring some other transplant at the same time (since they'll have to be on immunosuppressive drugs anyway).
bad_user 6y ago
T2D also leads to impaired insulin action, when the beta cell function of the pancreas is impaired. Sometimes impaired insulin action comes before insulin resistance and it is still T2D. The difference is that T1D is an auto-immune disease, wereas T2D is caused by energy poisoning.

conistonwater 6y ago

> So easy to resolve using fasting, intermittent fasting, keto, carnivore etc diets. Or, you know, you could resolve it by eating a balanced diet too.

arcticbull 6y ago
There's a solid argument to be made that when you eat, and how often you eat, is more important than what you eat. Specifically, the thesis is that if you eat constantly, you constantly have a high level of insulin, which your body becomes used to, and then has to produce more to actively control your blood sugar. Insulin resistance is a runaway positive feedback process. Insulin is particularly challenging because it actively causes sugar from your blood to be converted to fats and stored in your adipose tissue -- and blocks the release of fats from your adipose tissue. Eating frequently actively inhibits your ability to lose weight. By creating long gaps between meals, your body re-establishes what baseline level of insulin should be. Studies are starting to bear this out, more are needed. I can dig up some more papers if you like, but this is a good place to start [1]. [1] https://www.sciencedirect.com/science/article/pii/S1550413118302535 https://www.sciencedirect.com/science/article/pii/S155041311...
- conistonwater 6y ago
  I got into it when I read https://www.nature.com/articles/nrn.2017.156 https://www.nature.com/articles/nrn.2017.156. The thing is that a lot of nutrition research is rather low-quality compared to the rest of science (low n in studies, small effect sizes, low study power, high chance of finding false positives, etc.), and it gets even worse once you start reading sports science papers especially nutrition for sports performance. The best conclusion I found was that a lot of these things like intermittent fasting have small but noticeable effects, meaning that if you can follow IF easily then you may as well do it (like Pascal's wager!), but there is no solid evidence that you actually should do it because the effects are uncertain and small. One pitfall of a lot of these discussions is that people point to papers that show "an effect exists", but forget to ask "how big is the effect?". I was okay with IF for uncertain small positive brain effects, because my brain is important to me, and it's kind of free, so IF will do. But I think people overstate the effects a bit compared with what's actually known by science. Take the study you linked to, for instance. I can quite believe that IF would increase insulin resistance based on what I've read, and it's cool that they found lower blood pressure and higher insulin resistance in pre-diabetic men. But the study has 12 people (mid-50's pre-diabetic overweight men) in it, and I don't really know what to make of that? Is this type of study particularly expensive to conduct? Should I find it convincing because I already agree with the result? My gut reaction to the study is even simpler (not scientific, just personal): Why on Earth would anybody eat dessert for breakfast (Honey Nut Cheerios, waffles with maple syrup, etc, in Figure 1)? If you're already overweight and pre-diabetic, why is the control diet making you eat that? But they get a boiled egg, I'm guessing one?, to, you know, control cholesterol levels or something, two eggs would be crazy. They were probably trying to separate the effect of IF from the effect of eating a normal diet, as compared to the standard American diet, so didn't include a normal diet at all.

dcolkitt 6y ago

> fasting, intermittent fasting, keto, carnivore etc diets. To preface, I'm a long-time intermittent fasting, and tend to eat fairly carnivorous (though supplement with a lot of vegetables and legumes). But none of what you've listed is a silver bullet. The research is pretty conclusive that the proximate cause of all metabolic disease is caloric intoxication.[1] Regardless of the timing and consumption of calories, if a person continuously has an excess energy balance they're at risk of metabolic disease. In particular, the more dogmatic proponents of keto are refuted by the fact that some hunter-gatherers, like the Hazda, consume up to 50% of their calories from simple sugars. And like all hunter-gathers, they have virtually zero incidence of metabolic diseases. That isn't to say that diet isn't important. Excess calories are the proximate cause, but the type of food being consumed ultimately influences satiety and therefore overall consumption. In particular, the highly processed, hyper-palatable, easily digestible, highly convenient, hyper-varied, calorically dense food found in the industrialized West makes it extremely easy to overeat. In some sense, we're literally getting fatter because our food is becoming more delicious. Quoting the famous Matt Crowley tweet: "We take it for granted today, but a single Dorito has more extreme nacho flavor than a peasant in the 1400s would get in his whole lifetime." Low-carb, low-fat, intermittent fasting, six small meals a day, no eating after 6, cleanse detox, vegetarian, carnivore, keto, high-fiber, high-protein, gluten-free, etc. They all seem to work to a certain extent, even when they directly contradict one another. And that's largely because any arbitrary restriction on food consumption decreases variety (fewer options), reduces convenience (arbitrary rules makes it harder to eat take out), and lowers palatability (many recipes require substitutions or removals that ruin the taste). The upshot is that the older and more popular a fad diet becomes the less effective it will be. When enough of the market's on a diet the food industry will figure out how to make hyper-palatable that still conform to the rules. [1] https://www.stephanguyenet.com/why-the-carbohydrate-insulin-model-of-obesity-is-probably-wrong-a-supplementary-reply-to-ebbeling-and-ludwigs-jama-article/ https://www.stephanguyenet.com/why-the-carbohydrate-insulin-...

Der_Einzige 6y ago
Bingo! This post is what I wish every person was taught about health. It always goes back to calories in/calories out...
6y ago

bad_user 6y ago

The cause of insulin resistance is energy poisoning (i.e. people eating too much). The only cure for insulin resistance is weight loss. That's it. There's no study, not one, showing reversal of IR with keto/fasting independent of weight loss. Macros are absolutely irrelevant for either weight gain or weight loss in controlled studies. Only protein seems to have an effect on satiety, but the effect is not very significant in the context of whole foods. Even more serious is that drops in HbA1C, a surrogate marker for blood glucose, cannot be shown to drop independent of weight loss. Ketoers might avoid sugar spikes after meals better, they might get off some meds sooner, but this is only disease management and for the HbA1C, which represents a 3 months average, it doesn't seem to matter. The whole notion that insulin resistance is cause by sugar or carbohydrates, or that the cure is cutting carbs, is bullshit similar with anti-vaxxing and homeopathy. Not evidence based.

partyboat1586 6y ago
How do you explain skinny people getting type 2 diabetes? They can't be in caloric surplus or they would be gaining weight.
- bad_user 6y ago
  Skinny people getting T2D have a less flexible adipocytes tissue (aka fat tissue). They cannot store excess energy as subcutaneous fat, because they don't have a subcutaneous fat layer that can store that energy. But once you look at their organs, they are covered in visceral fat. Adipocytes, the fat cells, have a limited capacity and new adipocytes can be created, but only in certain conditions and slowly. This isn't an infinite supply and genetics play a role. In other words people have a "personal fat threshold": https://portlandpress.com/clinsci/article/128/7/405/71158/Normal-weight-individuals-who-develop-Type-2 https://portlandpress.com/clinsci/article/128/7/405/71158/No... https://diabetes.diabetesjournals.org/content/63/12/4369 https://diabetes.diabetesjournals.org/content/63/12/4369 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774584/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774584/ Once the adipocytes start rejecting the energy excess, with that energy excess building up in the bloodstream as glucose and triglycerides, being then pissed away, this is effectively insulin resistance, which is actually a defensive reaction to "energy poisoning": https://pubmed.ncbi.nlm.nih.gov/11872656/ https://pubmed.ncbi.nlm.nih.gov/11872656/ However it's important to understand that this energy poisoning can happen as a result of overeating fat or protein as well, even if the pathways are different from that of glucose: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2362.32.s3.3.x https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2362.... https://pubmed.ncbi.nlm.nih.gov/11872656/ https://pubmed.ncbi.nlm.nih.gov/11872656/ https://pubmed.ncbi.nlm.nih.gov/3421919/ https://pubmed.ncbi.nlm.nih.gov/3421919/ More importantly is that "weight loss" is the only measure shown in tests on humans to revert insulin resistance significantly. Another factor would be exercise, which was shown to work independently of weight loss, but the effect wasn't significant AFAIK. Everything else is confounded by weight loss. And this goes in the other direction — most (not all) risk factors for the diseases associated with the metabolic syndrome, including high blood pressure and heart disease, are confounded by weight gain. There are independent risk factors of course, like smoking or a high LDL, which most often has genetic causes, but most negative effects of foods you've heard about are in the context of a caloric surplus. This includes fat driving cholesterol and triglycerides up. Including sugar causing fatty liver. Sugar (fructose) was never shown to cause fatty liver unless it's in the context of a caloric surplus, sugar was never shown to cause T2D unless it's in the context of a caloric surplus, but that didn't stop some people writing books claiming otherwise.