Association of insulin resistance marker with severity and mortality of Covid-19
cardiab.biomedcentral.com
cardiab.biomedcentral.com
The calculation of TyG is ln (fasting blood sugar) x triglycerides/2). Many studies make the error of calculating it as (ln (FBS x TG))/2. The only online calculator I've found, I think, falls into the latter category, or has worse errors - I didn't go through it too rigorously, but I put in values beyond what human life can sustain and didn't get close to the cut-off for this paper's bottom risk tier.
If you look at studies/calculator using the latter calculation, it looks like this study looks at really, really severe diabetics.
If you compare with the appropriate calculation, though, they're looking at more run-of-the-mill "not optimally treated and obese" diabetics.
Hosseini 2017 did a paper analyzing a number of other TyG papers and calculating results under both calculation methodologies, for context.
Please also note that this paper does not state when the results were collected. Insulin resistance/hyperglycemia is a symptom of sepsis - if these labs were drawn on already-severe patients, it would be entirely unclear whether they reflect a cause or an effect (or, as is almost certainly the case, both!).
You have a extra right parenthesis, which makes it ambiguous. Do you mean
ln (FBS) x triglycerides/2
Or
ln (FBS x triglycerides/2)
?
The word you are looking for is associative.
ln x
ln(x)
ln (x)ln(5 * 10 / 2) ~= 3.219
So it does matter.
* Cut our glucose number in two
* multiple their result by 2
Assuming you’re saying they are incorrectly dividing the ln by two, when they should be dividing blood sugar by 2.
So we need to manually adjust the blood sugar, and multiply their final result by two to adjust for their ln.
What’s an optimal result? Using the method above I got 7.5
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586318/
Some influenza strains hit young, healthy patients harder than the elderly by triggering a cytokine storm. This was particularly bad in the 1918 H1N1 pandemic.
For that matter DM2 is an area of quite active research (and, like diagnosis, has been quite active for decades) as the financial payoff for any success is enormous.
The only downside for transdermal diagnosis is the lack of consumables, which makes it a tough market to enter and to be funded for. That is an area that's good for Apple as they are already selling the platform, so this would be a feature that would add to sales. And one I'd use.
You’d be surprised how many med products are designed specifically to require consumables.
* (funny analogy to use in a med context)
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.
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.
Not quite impossible but granted, islet cell transplants are still experimental.
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.
Or, you know, you could resolve it by eating a balanced diet too.
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/S155041311...
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.
Yes, there is good research suggesting that fasting can offset many (most?) of the ill effects of eating poorly.
> By creating long gaps between meals, your body re-establishes what baseline level of insulin should be.
One of the nice things about Keto is that you can get many (if not most) of the benefits of fasting without needing to fast. Some research suggests that some of the benefits of fasting likely come from being in ketosis during the fast.
It's starting to look like ketones do more than deliver fat to your cells. They are also treated sort of like a hormone, which has other beneficial effects on your health.
Probably the worst advice ever.
Ironically, margarine was arguably worse for your health than butter because it contained transfats (a side effect of the hydrogenation process on oil) which are now known to definitely cause heart disease[2]. In fact the link is so clear that a 2006 review flatly stated that "on a per-calorie basis, trans fats appear to increase the risk of [coronary heart disease] more than any other micronutrient"[3].
[1]: https://www.npr.org/sections/thetwo-way/2016/09/13/493739074... [2]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955571/ [3]: https://www.nejm.org/doi/full/10.1056/NEJMra054035
The Western diet is highly unbalanced in favor of carbohydrates and sugar because these are easy to farm, store, transport, and sell. The food pyramid we all know and love is a product of over two centuries of industrial agriculture.
Note that hunter-gatherer human societies didn't just eat meat, they almost certainly ate berries and fruits (both of which contain sugars and are thus excluded from Keto diets -- though to be fair, modern fruits are quite different to their ancient counterparts). And early human societies definitely consumed grains.
Don't get me wrong, feel free to have whatever diet you prefer. But Keto is by design not an example of a balanced diet, nor is it accurate to make an appeal to nature when discussing it.
> The Western diet is highly unbalanced in favor of carbohydrates and sugar
I don't disagree with the sentiment that modern western diets are on the whole incredibly unhealthy (though large quantities of unhealthy fats are hardly blameless). But carbohydrate consumption is not limited to the Western world, nor is it a new phenomenon.
Rice has been a food staple in Asia for an incredibly long time (having been domesticated in the Neolithic Period). And bread has existed in the Middle East and Europe for even longer.
One can safely eat berries and fruits on Keto, just not too much of them. It's entirely possible that those hunter-gatherers were in ketosis even if they sometimes at berries and possibly other fruit. Not to mention fruit wouldn't have been available all year, which means they were likely in ketosis for most of the year.
> by definition the goal is to place your body into ketosis
You say that like ketosis is somehow a strange state for your body to be in. But given that fat is a more efficient fuel source for your cells, it seems that ketosis might be the normal state for your body to be in, and running on carbs the uncommon state.
> but I wouldn't call removing an entire class of macronutrients "balanced".
You're not necessarily removing it, you're reducing it so that it's no longer your primary fuel source. It's also the only macronutrient humans can survive without consuming. Gluconeogenesis provides enough glucose for the parts of your body that require it, and everything else runs on fat, which is more efficient than using sugar.
> Rice has been a food staple in Asia for the vast majority of human history (having been domesticated in at least the Neolithic Period). And bread has existed in the Middle East and Europe for even longer.
Human evolution is much much longer than human history, which is just a blip in comparison.
And fittingly, was provided to us by the Department of Agriculture, not the Department of Health as one might expect.
This was during the 1940s. There were nine children and the parents on a farm in a small rural area. So no extravagant purchases no pop, candy, etc. My mom told me one Christmas her present was an apple and she was excited! The apple came from the tree out back.
Sounds good? But all the women (grandmother and aunts) in the family developed diabetes, one male (uncle) too.
Type 2 diabetes isn't always due to a poor diet.
I'm not sure all the causes of Type 2 diabetes but I would wager that the current epidemic of Type 2 Diabetes is caused by too much sugar.
But my understanding is that some carbohydrates get turned into sugar more slowly, and this "flattens the curve" of blood sugar relative to consuming sugar.
That's not a balanced diet.
1. it doesn't matter what you eat, what matters are the calories; you could eat whole plants all day, but add a lot of added fat to your meals (e.g. French fries) or sugar, and there's plenty of potential for caloric excess, even from salads. And I don't know about your family, but my family living in the country side drank a lot of alcohol.
2. People have a "personal fat threshold", when that threshold is reached there's nowhere for the excess to go and people develop diabetes; this is why some people develop diabetes sooner than others. So yes, it is possible even for skinny people to get diabetes and genetics definitely play a role.
I find it baffling that even on this site people don't understand the value of anecdotal evidence (near zero), or that evidence has to come from a clinical setting with a control group and that epidemiological data must "disprove the null hypothesis".
Before trusting your own anecdotes, are you sure you isolated the variables? Have you watched them day in, day out? You know, it's a curious thing but overweight people in public don't eat much, overeating happens in private.
You should read the evidence for "energy poisoning" and then take a more critical look at your family.
Further, diet is one of many factors. Those factors are: multiple (possibly unknown) genes, environment, gut microbiome, weight, and yes, diet. Here is a nice diagram that illustrates how many genes touch this thing: https://i.imgur.com/STg7X74.png -- these are the most common 5-10% of markers!
I know we're talking about type 2 here, but it's actually a bit insulting to declare "energy poisoning" and that they're piggish in private. It's what my 10 year old classmates told me when I was diagnosed t1d.
What I said is that overweight people tend to overeat in private, not in public. This is a fact.
The cause of overeating can be debated of course. Eating is a primary instinct, we are not very rational when it comes to our primary drives and on the market there are certainly foods engineered to be overeaten. However it is undeniable that T2D happens because people eat too much. And before 1950, people did not get T2D so often because a majority of the population suffered from hunger and malnutrition.
Humanity has never dealt with an abundance of food, especially an abundance of food high in calories. It's also not wrong to say that binging happens most often in private. Even if the reasons for why that happens are debatable.
---
> "The evidence from clinicians and people who study this is pretty clear: genetics is a massive factor. There are monogenic forms: if you have the gene, you will get diabetes, often in your 20s or 30s, and there is nothing you can do about it."
We agree that genetics play a big factor.
However we disagree on the inevitability — the super low, almost inexistant rates of T2D in the 19th century disagree with you and evolution doesn't happen this fast, it takes thousands, tens of thousands of years for a gene to spread throughout the population and this assuming that it confers a massive survival or reproductive advantage to influence selection (e.g. ability of adults to tolerate lactose in Europe), otherwise it can take hundreds of thousands of years.
Our genes did not change and we did not suffer from T2D before the 20th century, the far simpler explanation is that our environment changed, our genes cannot cope with it and the totality of evidence we have points to "energy poisoning", aka people eat too many calories.
I do think there are, again, many other confounding factors. Environment and diabetes are closely linked. Incidence of Type 1 Diabetes, for example, has increased five-fold in the past 50 years or so. As well as many other weird epigenetic diseases that seem to be linked to genes + our modern world somehow.
Off the top of my head, the super low rates of pre-modernity T2D could also be linked to:
- no antibiotics, which destroy huge swathes of gut bacteria
- very different, less sanitized environment
- far more time outdoors, sunlight, dirt, etc.
- fewer strong chemical soaps, antiseptics, etc.
- different diet, fewer processed foods
- different gut flora due to all of the above
- different physical lifestyle, more movement, etc.
- diagnosis criteria
Yes, being fat is a big problem for many reasons, but it is quite far from the only problem, and may even not be the causal problem. Just closely linked to some of the above. Sorry for being rash, I get testy when people hint at the diabetic = fat equivalence, for obvious reasons.
>People have a "personal fat threshold", when that threshold is reached there's nowhere for the excess to go
Ok with you so far
>and people develop diabetes
Then this leap. How does the fat having nowhere to go lead to diabetes? What's the middle step?
Skinny people can't have a calorie surplus or they would gain weight no?
Some people can store very little or no subcutaneous fat at all, all of the accumulated fat is stored as visceral fat (around their organs), which is limited, so they look skinny on the outside, fit even, but suffer from T2D nonetheless.
Here are some references:
https://portlandpress.com/clinsci/article/128/7/405/71158/No...
https://diabetes.diabetesjournals.org/content/63/12/4369
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774584/
Basically insulin resistance, high blood glucose and the ensuing loss of beta cell function in the pancreas happen as a result of adipocytes starting to reject excess energy, which then remains in the bloodstream and is being pissed away. Insulin resistance in many circles is understood as the cause of T2D, however insulin resistance is actually a defensive mechanism, in response to energy poisoning.
https://www.pnas.org/content/106/42/17787
And the source of that excess doesn't matter, all macro nutrients can cause insulin resistance, even if via different pathways:
https://pubmed.ncbi.nlm.nih.gov/3421919/
https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2362....
What they're referring to is visceral fat (around their organs), so in their experience treating thousands of patients, that's their primary advice.
Something to think about.
This comment contains no actionable information. What is a balanced diet? Follow the food pyramid? That clearly isn't working.
Keto appears to be a balanced diet, i.e. it has the right balance of macronutrients for the human body to run well. Likely it's not the whole story, since there's still a lot we don't understand, but it certainly seems to be on the right path when compared to a standard western diet.
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-...
Because, like most things, genetics and environmental factors do play a part, even if it's a small part.
There was an article recently on the front page of a founder of an AI company finding out that he has cancer throughout his body and a massive blood clot next to his heart.
He was super fit and had a very low resting BP, and no previous signs of any of this. Complete surprise to him.
However, this is not the norm, and neither is otherwise healthy people suddenly waking up to find they have T2D. There is conclusive evidence that key factors (like weight gain, visceral fat etc) play in severely increasing the risk of T2D.
I understand and I'm opposed to things like fat shaming, especially in light of people actually having hormonal issues that they struggle to control. It makes no sense to point out these people as problem actors because they didn't bring it upon themselves.
But I know for a fact, witnessing myself how people gorge on junk food and massively sugary starbucks drinks around me, that no, a good portion of those fat people have no hormonal problems - they're fat because of terrible lifestyle choices, and put themselves at risk not just of T2D, but of every other problem from head to toe.
Half the country doesn't get declared "obese" because of some mysterious disease that is genetically passed on from their parents or grandparents. They get declared obese because mega corps en large advertise and sell them shit to eat from a very young age, and parents find it hard to eat healthy themselves.
and then we jump right into it
> witnessing myself how people gorge on junk food and massively sugary starbucks drinks around me, that no, a good portion of those fat people have no hormonal problems
Interesting you brought up genetics earlier in your comment but then ignored it when discussing the "lifestyle choices" of fat people.
It is now established that genetic variations can be responsible for a 1.67 fold higher rate of obesity [1] Just having the wrong genes means more of the calories you consume end up as stored fat, with a subsequent reduction in mitochondrial thermogenesis by a factor of 5 in those cells.
Lets stop blaming "lifestyle choices" and fat people's lack of willpower for this public health crisis and find ways to control it through meaningful interventions that address the real issues underlying the phenomenon.
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.
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/No...
https://diabetes.diabetesjournals.org/content/63/12/4369
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/
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....
https://pubmed.ncbi.nlm.nih.gov/11872656/
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.
On the topic of refined sugar my understanding was that because it is processed by the body more quickly it spikes blood sugar levels short and sharp rather than more spread out in the case of protein and fat which take longer to digest. Because of the limited rate of creating adipocytes this means that the same concentration of blood sugar delivered over a shorter time period would stimulate insulin resistance where if it were delivered over a longer period of time blood sugar levels would not cross that threshold. I'm sure that if you eat a caloric surplus that you will trip the threshold but could it not also be tripped by eating lots of high sugar foods to the same amount of calories of fat and protein which would not cross the threshold?
1. https://obesitymedicine.org/obesity-and-insulin-resistance/
1. https://www.medrxiv.org/content/10.1101/2020.04.08.20058578v... 2. https://pubmed.ncbi.nlm.nih.gov/26375925/
So perhaps part of the reason why COVID-19 morbidity is lower in Japan/Korea/Taiwan compared to the U.S. is due to lower prevalence of metabolic syndrome. I wonder if that's also true for Europe.
No, if it can be taken at face value, it suggests a protective effect of a healthy lifestyle.
Neither of you are particularly wrong necessarily, but a third option is that someone could be sedentary and eating carbs every day and have low TyG. It's common to state that "activity XYZ will provide action-at-a-distance medical benefit ABC" because stating accurately what's going on takes more words that sound less certain:
"Paleo and keto diets may weaken Covid-19 by lowering insulin resistance"
"A healthy lifestyle may weaken Covid-19 by lowering insulin resistance"
But it's really worth saying it like this, even though few do. (And yes, these aren't 'maybe' enough, but they're an improvement.)
You're seeing a distinction between these two words that I apparently do not, since I take them both to indicate "this is a possibility, though not the only one, and a far from proven certainty."
I would add that, even there, my statement was predicated on making an inference about dietary habits - something I cast doubt on with the opening, "if taken at face value." Something I further opined on in my other post, where I pointed out that the paper may be reversing causality.
I feel like you're criticizing a strong inference having been made, that I think pretty clearly wasn't.
(Nothing against a keto/paleo diet, just it's not really necessary.)