9 ms·

Associations of body mass index, fasting insulin and inflammation with mortality

Afton 4y ago
I can't read the study directly (and it's not my field, which makes reading it directly challenging), but this is the abstract conclusion: ` Higher fasting insulin and higher c-reactive protein confound the association between BMI and the risk of all-cause mortality. The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity.`
- oaktrout 4y ago
  Excess fat -> insulin resistance -> higher fasting insulin.
  - danwills 4y ago
    This is mentioned in the article, I must admit I previously thought it was as you say, but: "available evidence in humans suggests that hyperinsulinemia precedes weight gain (rather than the other way around)"
vorpalhex 4y ago
This isn't surprising. BMI increases bring reduced insulation sensitivity, which in turn is what causes the issues. The fix is to diet and exercise. At the end of the day we don't care about BMI, we care about insulin sensitivity - but it is easier to measure BMI than blood insulin. BMI isn't a perfect indicator but it's a pretty good one.
- 0xB31B1B 4y ago
  "The fix is diet and exercise" is not correct at all. There is no evidence on population level data or studies that diet and exercise produce durable BMI loss on a population level. From a "calories in calories out" perspective it is naively true, but in practice it doesn't work at all. The issue is that when people have BMI>30, their bodies endocrine system gets pretty messed up and their bodies will basically request 3500 calories per day. There have been a number of breakthrough medicines in the past few years that disrupt this cycle and reliably produce weight loss on a population level through hormonal changes that reduce appetite and delay gastric emptying. Some examples of these drugs are Tirzepatide and Semaglutide.
  - aaaaaaaaaaab 4y ago
    >their bodies endocrine system gets pretty messed up and their bodies will basically request 3500 calories per day And what if they don't eat that much? They die or what?
  - ralusek 4y ago
    A caloric deficit will produce weight loss. If you're arguing that this isn't sustainable due to the amount of calories being "requested" by people's subjective desires and experiences, that's a completely different (and also incorrect) argument.
    - 0xB31B1B 4y ago
      There are many double blind studies on this. On a 2+ year time horizon, the huge majority of obese people who follow a "eat less exercise more" regime lose weight and then gain it back. This happens because the people never stop being hungry due to the disruption that obesity puts on their endocrine system. There are a number of medicines (saxenda, liraglutide, ozempic, mounjaro, wegovy) that produce reliable robust weight loss on a 2+ year time horizon. These medicines work best with a change in diet and exercise habits, but reliable weight loss on a population wide scale is not something you treat with "diet and exercise" advice.
      - vorpalhex 4y ago
        Not really? Yes a lot of crash diets fail, for obvious reasons, but once a diet has stabilized the cravings will go away. It does for many people mean they will need to cut out or dramatically cut down the eating out, drinking and instant meals. Most people don't want to do that.
        0xB31B1B 4y ago
        Substantial weight loss is possible across a range of treatment modalities, but long-term sustenance of lost weight is much more challenging, and weight regain is typical1–3. In a meta-analysis of 29 long-term weight loss studies, more than half of the lost weight was regained within two years, and by five years more than 80% of lost weight was regained (Figure 1)4. Indeed, previous failed attempts at achieving durable weight loss may have contributed to the recent decrease in the percentage of people with obesity who are trying to lose weight5 and many now believe that weight loss is a futile endeavor6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/
- henryfjordan 4y ago
  You risk alienating people by focussing on BMI though. Weight has been moralized in the US (being fat is seen as a moral failing). People do not easily accept advice that is given through a moral lens. The data shows that there is a better measure than BMI which doesn't carry all the stigma, so why not use that one?
  - ble 4y ago
    > why not use that one? Taking any of the more accurate measurements of body composition requires effort, unlike BMI. It's easy and lazy and not yet acknowledged as an ineffective practice so doctors do it. It's also not always wrong, just because BMI and obesity do correlate.
    - PuppyTailWags 4y ago
      My understanding is the argument is not whether to use someone's fatness as a measure of health if there's a much better, specific metric besides being fat (ie. resting insulin levels) to prescribe exercise and diet over. I don't think it'll reduce stigma or whatever of fat people, but I do agree that if someone is fat but their insulin is normal maybe a doctor can pay attention to something else like if they came in for an allergy test or something they may not need the diet/exercise spiel. Similarly if someone's thin but their insulin is crazy its time to talk diet/exercise.
      - vorpalhex 4y ago
        There is a rare, rare, rare chance you can some weird diseases that mess up insulin sensitivity, so you can be skinny and have issues. Those are rare and not solved by diet and exercise. Otherwise if your insulin is high, you need to diet and exercise. Measuring blood insulin is a lab procedure - you go to a collection lab, you get jabbed, they mail it for testing. Measuring BMI requires stepping on a scale and knowing how tall you are.
        PuppyTailWags 4y ago
0xB31B1B 4y ago
This is interesting in a "of course" kind of way. If you look at a bunch of variables, including BMI, and then you remove the impact of well known negative health impacts of obesity (prediabetes/T2D), then you see that high BMI doesn't not correlate well with mortality. IMO, what this indicates to me is that (1) BMI is not a good indicator of obesity in this study. There are many healthy people with low body fat and high BMI, I am one of them. All you need to do is be tall and lift weights occasionally. If you remove the obesity related negative health signals, you also remove obesity(2) Being fat in and of itself is not the issue, the issue is prediabetes/T2D which is extremely reliably caused by obesity, and the treatment for prediabetes/T2D is weight loss.
- Kerrick 4y ago
  If you do a study of the mortality rates of driving cars and control for crashes, it’s probably near zero.
  - athenot 4y ago
    This may have been meant in a tongue-and-cheek way but assuming that were true it would still be useful information: signifying that crash-prevention is where the focus should be. (Leaving out the discussion: effects to environment, sedentary lifestyle, etc)
- codefreeordie 4y ago
  What is interesting here is their finding that the two specific known major causes of obesity-linked mortality that they considered (c-reactive protein and high resting insulin -- effectively "obesity-linked diabetes") explained slightly more than all of the increased mortality associated with obesity. That suggests that there is no other material contributor to mortality from obesity[1], which is a somewhat unexpected result. -- [1] it is possible that there are negative contributions to mortality associated with obesity which could potentially "hide" other positive contributors
- PuppyTailWags 4y ago
  I think I'm a little confused by your definition of obesity. As far as I know, obesity is defined by BMI measure which is defined by a specific ratio of weight and height, so I don't understand how being tall would affect your being obese or not. [Unless you're saying the measurement doesn't work for tall people?]
WaitWaitWha 4y ago
As a side note, BMI is a terrible measure of obesity for outliers. I have several first hand experiences where the BMI indicates obese or even morbidly obese, while the DEXA scan would show fat in single digits.
- ok_dad 4y ago
  Yea, ask many athletes at the US military academies about this. All of the football players basically had to have a waiver for BMI for the military standards or had to get taped (body dimensions measured) to do a more-complex calculation to determine a more accurate fat content. They also had to make standards in off-season, so the big linemen were constantly eating before the season to put on weight, then working hard at the end of the season to lose it.
- spywaregorilla 4y ago
  BMI is a terrible measure in general, not just for outliers. It doesn't normalize well to fairly obvious factors. You could arguably get a better reading just by looking at someone and visually estimating how fat they are. Waist measurement is a stronger measure but still flawed.
- xboxnolifes 4y ago
  > BMI is a terrible measure of obesity for outliers That's basically tautological. Outliers are outliers because they don't fit the model.
Cenk 4y ago
PDF here: https://www.nature.com/articles/s41366-022-01211-2.pdf https://www.nature.com/articles/s41366-022-01211-2.pdf
kaesar14 4y ago
Is this more or less saying there's no definitive link between obesity and mortality risk?
- rileymat2 4y ago
  If I am reading it correctly, if you can maintain good fasting blood sugar - yes. However, that is a big “if”, because those are related.
  - PuppyTailWags 4y ago
    I'd be curious for a follow up study to measure if thin people with high fasting blood sugar can be predicted to have the same mortality as fat people. The confirmation of skinnyfat, basically.
    - pessimizer 4y ago
      Is there any evidence that "skinnyfat" people have high fasting insulin levels? The OP actually says that BMI is negatively correlated with mortality if you control for insulin levels, so that would mean that thin people with high fasting blood sugar would have more mortality than fat people in the same situation.
  - stingraycharles 4y ago
    I’m not very well versed in this terminology, what does a “good fasting blood sugar” mean? Does that mean that generally speaking, your blood sugar remains relatively stable / low? Eg a person eating mostly meat and no sugar?
    - evol262 4y ago
      It means that you aren't insulin resistant and it actually does its job.
    - mbesto 4y ago
      Ya, I'd like to understand this too. How do you manage this? And do obese people generally have this problem (hence the correlation, but not causation)?
pmdulaney 4y ago
Key takeaway: "Higher fasting insulin and higher c-reactive protein confound the association between BMI and the risk of all-cause mortality. The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity."
- ajross 4y ago
  I don't know that that's very informative, clinically. How many obesity cases are there that don't have one of those two issues in some co-causal way? Likewise how do you treat these people to reduce their insulin swings in such a way that they... would fail to lose weight? It seems almost like a joke, but "hyperinsulinemia and inflammation" seems more or less identical with "chronic overeating", right?
  - andrewmutz 4y ago
    I am not a nutrition expert but I believe inflammation can be a problem without high BMI. For example, eating lots of highly processed foods but staying within your calorie limit, would have this outcome.
  - tomjakubowski 4y ago
    You're missing the other direction: those people who have insulin resistance and inflammation and aren't clinically obese. https://www.ahajournals.org/doi/10.1161/circ.128.suppl_22.A11251 https://www.ahajournals.org/doi/10.1161/circ.128.suppl_22.A1... [Metabolic syndrome] doubles the risk of all vascular complications in patients often erroneously considered at lower CVD risk because of their normal BMI.
    - deleted 4y ago
      [deleted]
  - pessimizer 4y ago
    > How many obesity cases are there that don't have one of those two issues in some co-causal way? You can't imagine there are a few million people like that out of the billions in the world, and that we might want to give effective medical care to those people also? > Likewise how do you treat these people to reduce their insulin swings in such a way that they... would fail to lose weight? Is this an actual question asking about the state of the research, or do you think that it's unimaginable that science could ever be able to directly manipulate people's insulin levels? I get the impression from most of the top level comments on this thread that some people would be upset if fat people's mortality could be reduced or normalized without weight loss. Like there's an urge to see fat people punished rather than happy and healthy.
PragmaticPulp 4y ago
The researchers tried to subtract out the mortality risk of elevated C-reactive protein (aka CRP, inflammation market) and higher fasting insulin. However, both elevated CRP and higher fasting insulin are correlated with obesity, so controlling for these variables seems misleading.
- t_mann 4y ago
  > However, both elevated CRP and higher fasting insulin are correlated with obesity, so controlling for these variables seems misleading. Well: https://en.wikipedia.org/wiki/Multicollinearity https://en.wikipedia.org/wiki/Multicollinearity Summary: highly correlated variables don't fundamentally mess up the inference (coefficient estimates are still unbiased), the estimation becomes numerically unstable, however, and individual coefficients might be messed up because of that. This is reflected in the standard errors, so you're more likely to miss effects (type II error).
hirundo 4y ago
"The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity." That's encouraging because I've been able to fix the hyperinsulinemia and inflammation, but not all of the excess BMI. Maybe fit & fat aren't mutually exclusive.
alfor 4y ago
And... one big factor in inflammation is our modern lack of sun exposure (infrared). https://www.youtube.com/watch?v=wadKIiGsDTw https://www.youtube.com/watch?v=wadKIiGsDTw Taking someone sick with high inflammation and putting them in a hospital bed is terrible for their recovery.
- joe-collins 4y ago
  If someone is in sufficiently acute danger that a hospital bed is under discussion, I suspect that the manner of lighting and any putative benefits thereof is a relatively small concern.
  - alfor 4y ago
    Look at the research. Inflammation is naturally removed from mitochondria with the use of naturally occuring infrared light. (I know it sound far fetched and hippie) We have created an environment devoid of it and we reap the consequences: increase amount of chronic autoimmune diseases and many other things. Personally I had to deal with eczema every winter that I got rid of with a simple infrared heater. A friend of mine was dying of IBS in the hospital, he say f*ck it if I am going to die it will be under the sun. He checkout of hospital (Canada), went to mexico and healed himself while ditching the medication.
mgarfias 4y ago
What does this mean for us T2D types that need the insulin? Are we just fucked?
- woleium 4y ago
  it's saying that high BMI as a cause of premature death is likely just a proxy for high fasting insulin and inflammation and is not _by itself_ life shortening. for folks like yourself with T2D, noting changes. Keep on keeping on (i.e. follow current medical advice)
  - evol262 4y ago
    > it's saying that high BMI as a cause of premature death is likely just a proxy for high fasting insulin and inflammation and is not _by itself_ life shortening. No, it is not. We should be very clear that high BMI is, in fact, life shortening. High BMI is, in fact, strongly correlated with atherosclerosis. It is, in fact, strongly correlated with decreased lung volume and risk pulmonary edema. It is correlated with clot formation and stroke. It is correlated with fatty liver disease. It is correlated with decreased bone density, which leads to a heightened risk of throwing embolism-causing clots if a fall leads to a break. It is correlated with a variety of cardiac events, mostly around hardening valves and fat buildup in cardiac tissue causing lessened output while there is more circulating blood volume. It is correlated with difficulties administering anesthesia or intubating patients in case of emergency. It is correlated with... Being obese is still horrifyingly unhealthy even if high fasting glucose is just a proxy for some of those factors (which it is not, as this study is terrible).
    - mgarfias 4y ago
      Well shit, my BMI is 35. And I've got a pair of stents in my ticker. OTOH I'm doing crossfit 3x/week. And can dead lift over 300# so I feel like I'm getting better. ALso, I'm built like a fireplug, so probably not fat as just big. BMI is a shitty measure.
      - 4y ago
hprotagonist 4y ago
Using the primary cohort, time to mortality was regressed on all three exposures of interest: BMI, fasting insulin, and CRP. A number of parametrizations of these three exposures were explored. The models with the best fit used linear and quadratic terms for BMI, a linear term for fasting insulin, and the natural logarithm of CRP. and we chose not to justify or explain those parameterizations in any way, because what we probably actually did was diddle SAS until the model did what it was supposed to. yawn.
- dang 4y ago
  "Please don't post shallow dismissals, especially of other people's work. A good critical comment teaches us something." "Don't be snarky." https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
josephcsible 4y ago
This seems like a textbook example of the model 11 "bad control" from <http://causality.cs.ucla.edu/blog/index.php/category/back-door-criterion/ http://causality.cs.ucla.edu/blog/index.php/category/back-do...>. X is BMI, Y is mortality, and Z is fasting insulin and blood sugar. Basically, if X causes Z and Z causes Y, then controlling for Z hides the relationship between X and Y.
- pessimizer 4y ago
  Does it hide, or does it actually clarify the relationship if after you do that BMI is negatively correlated to mortality at the same fasting insulin and level of c-reactive protein? It also means that if we can control people's reactions to sugar, their weight becomes irrelevant (or possibly even protective.) Losing weight is usually the way to fix your sugar, but plenty of people who aren't fat have sugar problems, and sugar problems might not be reversed by weight loss in a particular individual.
  - evol262 4y ago
    The percentage of people with normal BMIs and type 2 diabetes or prediabetes is so small that is irrelevant from a mass health perspective. There are a plethora of studies correlating a change in diet with improved blood markers for fasting blood glucose and insulin response. Sugar "problems" are resolved by diet, and resolving diet goes along with reversing weight loss. It cannot be any other way. There is no evidence that obese BMIs are negatively correlated to mortality, only the opposite. Obese BMIs still come with increased arterial plaque, complications in anesthesia and surgical healing for medical interventions, fatty liver disease, ocular pressure, lung function, cardiovascular health, and so on. Obesity is up with smoking as a cause of preventable death. Let's not try to put a pretty face on it. A spade is a spade. Insulin resistance/high fasting glucose and obesity are inseparable peas in a pod.
    - pessimizer 4y ago
      > The percentage of people with normal BMIs and type 2 diabetes or prediabetes is so small that is irrelevant from a mass health perspective. Then my father is irrelevant, being diagnosed with prediabetes at 6', 165lb. So is it really irrelevant numerically, or is that hyperbole? Does your irrelevance include millions of people? ----- edit: > There is no evidence that obese BMIs are negatively correlated to mortality, only the opposite. TFA mentions that it is negatively correlated when you control for two things that are positively correlated with BMI. So, while the study doesn't say that high BMI reduces mortality (it in fact observes the opposite), nobody claimed it did. But in finding the negative BMI correlation when controlled for insulin, it does make a very good case that > Obese BMIs still come with increased arterial plaque, complications in anesthesia and surgical healing for medical interventions, fatty liver disease, ocular pressure, lung function, cardiovascular health, and so on. are largely irrelevant to the mortality of the obese relative to the thin, and inflammation and insulin resistance are decisive.
Markoff 4y ago
TLDR this is only about obese people, don't bother reading if you have healthy BMI, heck median BMI of participants was 27, way beyond healthy since overweight starts at 25 and I would say even that is very generous ~20.3 here

I can't read the study directly (and it's not my field, which makes reading it directly challenging), but this is the abstract conclusion: ` Higher fasting insulin and higher c-reactive protein confound the association between BMI and the risk of all-cause mortality. The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity.`

oaktrout 4y ago
Excess fat -> insulin resistance -> higher fasting insulin.
- danwills 4y ago
  This is mentioned in the article, I must admit I previously thought it was as you say, but: "available evidence in humans suggests that hyperinsulinemia precedes weight gain (rather than the other way around)"

vorpalhex 4y ago

This isn't surprising. BMI increases bring reduced insulation sensitivity, which in turn is what causes the issues. The fix is to diet and exercise. At the end of the day we don't care about BMI, we care about insulin sensitivity - but it is easier to measure BMI than blood insulin. BMI isn't a perfect indicator but it's a pretty good one.

0xB31B1B 4y ago
"The fix is diet and exercise" is not correct at all. There is no evidence on population level data or studies that diet and exercise produce durable BMI loss on a population level. From a "calories in calories out" perspective it is naively true, but in practice it doesn't work at all. The issue is that when people have BMI>30, their bodies endocrine system gets pretty messed up and their bodies will basically request 3500 calories per day. There have been a number of breakthrough medicines in the past few years that disrupt this cycle and reliably produce weight loss on a population level through hormonal changes that reduce appetite and delay gastric emptying. Some examples of these drugs are Tirzepatide and Semaglutide.
- aaaaaaaaaaab 4y ago
  >their bodies endocrine system gets pretty messed up and their bodies will basically request 3500 calories per day And what if they don't eat that much? They die or what?
- ralusek 4y ago
  A caloric deficit will produce weight loss. If you're arguing that this isn't sustainable due to the amount of calories being "requested" by people's subjective desires and experiences, that's a completely different (and also incorrect) argument.
  - 0xB31B1B 4y ago
    There are many double blind studies on this. On a 2+ year time horizon, the huge majority of obese people who follow a "eat less exercise more" regime lose weight and then gain it back. This happens because the people never stop being hungry due to the disruption that obesity puts on their endocrine system. There are a number of medicines (saxenda, liraglutide, ozempic, mounjaro, wegovy) that produce reliable robust weight loss on a 2+ year time horizon. These medicines work best with a change in diet and exercise habits, but reliable weight loss on a population wide scale is not something you treat with "diet and exercise" advice.
    - vorpalhex 4y ago
      Not really? Yes a lot of crash diets fail, for obvious reasons, but once a diet has stabilized the cravings will go away. It does for many people mean they will need to cut out or dramatically cut down the eating out, drinking and instant meals. Most people don't want to do that.
      - 0xB31B1B 4y ago
        Substantial weight loss is possible across a range of treatment modalities, but long-term sustenance of lost weight is much more challenging, and weight regain is typical1–3. In a meta-analysis of 29 long-term weight loss studies, more than half of the lost weight was regained within two years, and by five years more than 80% of lost weight was regained (Figure 1)4. Indeed, previous failed attempts at achieving durable weight loss may have contributed to the recent decrease in the percentage of people with obesity who are trying to lose weight5 and many now believe that weight loss is a futile endeavor6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/
henryfjordan 4y ago
You risk alienating people by focussing on BMI though. Weight has been moralized in the US (being fat is seen as a moral failing). People do not easily accept advice that is given through a moral lens. The data shows that there is a better measure than BMI which doesn't carry all the stigma, so why not use that one?
- ble 4y ago
  > why not use that one? Taking any of the more accurate measurements of body composition requires effort, unlike BMI. It's easy and lazy and not yet acknowledged as an ineffective practice so doctors do it. It's also not always wrong, just because BMI and obesity do correlate.
  - PuppyTailWags 4y ago
    My understanding is the argument is not whether to use someone's fatness as a measure of health if there's a much better, specific metric besides being fat (ie. resting insulin levels) to prescribe exercise and diet over. I don't think it'll reduce stigma or whatever of fat people, but I do agree that if someone is fat but their insulin is normal maybe a doctor can pay attention to something else like if they came in for an allergy test or something they may not need the diet/exercise spiel. Similarly if someone's thin but their insulin is crazy its time to talk diet/exercise.
    - vorpalhex 4y ago
      There is a rare, rare, rare chance you can some weird diseases that mess up insulin sensitivity, so you can be skinny and have issues. Those are rare and not solved by diet and exercise. Otherwise if your insulin is high, you need to diet and exercise. Measuring blood insulin is a lab procedure - you go to a collection lab, you get jabbed, they mail it for testing. Measuring BMI requires stepping on a scale and knowing how tall you are.
      - PuppyTailWags 4y ago

0xB31B1B 4y ago

This is interesting in a "of course" kind of way. If you look at a bunch of variables, including BMI, and then you remove the impact of well known negative health impacts of obesity (prediabetes/T2D), then you see that high BMI doesn't not correlate well with mortality. IMO, what this indicates to me is that (1) BMI is not a good indicator of obesity in this study. There are many healthy people with low body fat and high BMI, I am one of them. All you need to do is be tall and lift weights occasionally. If you remove the obesity related negative health signals, you also remove obesity(2) Being fat in and of itself is not the issue, the issue is prediabetes/T2D which is extremely reliably caused by obesity, and the treatment for prediabetes/T2D is weight loss.

Kerrick 4y ago
If you do a study of the mortality rates of driving cars and control for crashes, it’s probably near zero.
- athenot 4y ago
  This may have been meant in a tongue-and-cheek way but assuming that were true it would still be useful information: signifying that crash-prevention is where the focus should be. (Leaving out the discussion: effects to environment, sedentary lifestyle, etc)
codefreeordie 4y ago
What is interesting here is their finding that the two specific known major causes of obesity-linked mortality that they considered (c-reactive protein and high resting insulin -- effectively "obesity-linked diabetes") explained slightly more than all of the increased mortality associated with obesity. That suggests that there is no other material contributor to mortality from obesity[1], which is a somewhat unexpected result. -- [1] it is possible that there are negative contributions to mortality associated with obesity which could potentially "hide" other positive contributors
PuppyTailWags 4y ago
I think I'm a little confused by your definition of obesity. As far as I know, obesity is defined by BMI measure which is defined by a specific ratio of weight and height, so I don't understand how being tall would affect your being obese or not. [Unless you're saying the measurement doesn't work for tall people?]

WaitWaitWha 4y ago

As a side note, BMI is a terrible measure of obesity for outliers. I have several first hand experiences where the BMI indicates obese or even morbidly obese, while the DEXA scan would show fat in single digits.

ok_dad 4y ago
Yea, ask many athletes at the US military academies about this. All of the football players basically had to have a waiver for BMI for the military standards or had to get taped (body dimensions measured) to do a more-complex calculation to determine a more accurate fat content. They also had to make standards in off-season, so the big linemen were constantly eating before the season to put on weight, then working hard at the end of the season to lose it.
spywaregorilla 4y ago
BMI is a terrible measure in general, not just for outliers. It doesn't normalize well to fairly obvious factors. You could arguably get a better reading just by looking at someone and visually estimating how fat they are. Waist measurement is a stronger measure but still flawed.
xboxnolifes 4y ago
> BMI is a terrible measure of obesity for outliers That's basically tautological. Outliers are outliers because they don't fit the model.

Cenk 4y ago

PDF here: https://www.nature.com/articles/s41366-022-01211-2.pdf https://www.nature.com/articles/s41366-022-01211-2.pdf

kaesar14 4y ago

Is this more or less saying there's no definitive link between obesity and mortality risk?

rileymat2 4y ago
If I am reading it correctly, if you can maintain good fasting blood sugar - yes. However, that is a big “if”, because those are related.
- PuppyTailWags 4y ago
  I'd be curious for a follow up study to measure if thin people with high fasting blood sugar can be predicted to have the same mortality as fat people. The confirmation of skinnyfat, basically.
  - pessimizer 4y ago
    Is there any evidence that "skinnyfat" people have high fasting insulin levels? The OP actually says that BMI is negatively correlated with mortality if you control for insulin levels, so that would mean that thin people with high fasting blood sugar would have more mortality than fat people in the same situation.
- stingraycharles 4y ago
  I’m not very well versed in this terminology, what does a “good fasting blood sugar” mean? Does that mean that generally speaking, your blood sugar remains relatively stable / low? Eg a person eating mostly meat and no sugar?
  - evol262 4y ago
    It means that you aren't insulin resistant and it actually does its job.
  - mbesto 4y ago
    Ya, I'd like to understand this too. How do you manage this? And do obese people generally have this problem (hence the correlation, but not causation)?

pmdulaney 4y ago

Key takeaway: "Higher fasting insulin and higher c-reactive protein confound the association between BMI and the risk of all-cause mortality. The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity."

ajross 4y ago
I don't know that that's very informative, clinically. How many obesity cases are there that don't have one of those two issues in some co-causal way? Likewise how do you treat these people to reduce their insulin swings in such a way that they... would fail to lose weight? It seems almost like a joke, but "hyperinsulinemia and inflammation" seems more or less identical with "chronic overeating", right?
- andrewmutz 4y ago
  I am not a nutrition expert but I believe inflammation can be a problem without high BMI. For example, eating lots of highly processed foods but staying within your calorie limit, would have this outcome.
- tomjakubowski 4y ago
  You're missing the other direction: those people who have insulin resistance and inflammation and aren't clinically obese. https://www.ahajournals.org/doi/10.1161/circ.128.suppl_22.A11251 https://www.ahajournals.org/doi/10.1161/circ.128.suppl_22.A1... [Metabolic syndrome] doubles the risk of all vascular complications in patients often erroneously considered at lower CVD risk because of their normal BMI.
  - deleted 4y ago
    [deleted]
- pessimizer 4y ago
  > How many obesity cases are there that don't have one of those two issues in some co-causal way? You can't imagine there are a few million people like that out of the billions in the world, and that we might want to give effective medical care to those people also? > Likewise how do you treat these people to reduce their insulin swings in such a way that they... would fail to lose weight? Is this an actual question asking about the state of the research, or do you think that it's unimaginable that science could ever be able to directly manipulate people's insulin levels? I get the impression from most of the top level comments on this thread that some people would be upset if fat people's mortality could be reduced or normalized without weight loss. Like there's an urge to see fat people punished rather than happy and healthy.

PragmaticPulp 4y ago

The researchers tried to subtract out the mortality risk of elevated C-reactive protein (aka CRP, inflammation market) and higher fasting insulin. However, both elevated CRP and higher fasting insulin are correlated with obesity, so controlling for these variables seems misleading.

t_mann 4y ago
> However, both elevated CRP and higher fasting insulin are correlated with obesity, so controlling for these variables seems misleading. Well: https://en.wikipedia.org/wiki/Multicollinearity https://en.wikipedia.org/wiki/Multicollinearity Summary: highly correlated variables don't fundamentally mess up the inference (coefficient estimates are still unbiased), the estimation becomes numerically unstable, however, and individual coefficients might be messed up because of that. This is reflected in the standard errors, so you're more likely to miss effects (type II error).

hirundo 4y ago

"The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity." That's encouraging because I've been able to fix the hyperinsulinemia and inflammation, but not all of the excess BMI. Maybe fit & fat aren't mutually exclusive.

alfor 4y ago

And... one big factor in inflammation is our modern lack of sun exposure (infrared). https://www.youtube.com/watch?v=wadKIiGsDTw https://www.youtube.com/watch?v=wadKIiGsDTw Taking someone sick with high inflammation and putting them in a hospital bed is terrible for their recovery.

joe-collins 4y ago
If someone is in sufficiently acute danger that a hospital bed is under discussion, I suspect that the manner of lighting and any putative benefits thereof is a relatively small concern.
- alfor 4y ago
  Look at the research. Inflammation is naturally removed from mitochondria with the use of naturally occuring infrared light. (I know it sound far fetched and hippie) We have created an environment devoid of it and we reap the consequences: increase amount of chronic autoimmune diseases and many other things. Personally I had to deal with eczema every winter that I got rid of with a simple infrared heater. A friend of mine was dying of IBS in the hospital, he say f*ck it if I am going to die it will be under the sun. He checkout of hospital (Canada), went to mexico and healed himself while ditching the medication.

mgarfias 4y ago

What does this mean for us T2D types that need the insulin? Are we just fucked?

woleium 4y ago
it's saying that high BMI as a cause of premature death is likely just a proxy for high fasting insulin and inflammation and is not _by itself_ life shortening. for folks like yourself with T2D, noting changes. Keep on keeping on (i.e. follow current medical advice)
- evol262 4y ago
  > it's saying that high BMI as a cause of premature death is likely just a proxy for high fasting insulin and inflammation and is not _by itself_ life shortening. No, it is not. We should be very clear that high BMI is, in fact, life shortening. High BMI is, in fact, strongly correlated with atherosclerosis. It is, in fact, strongly correlated with decreased lung volume and risk pulmonary edema. It is correlated with clot formation and stroke. It is correlated with fatty liver disease. It is correlated with decreased bone density, which leads to a heightened risk of throwing embolism-causing clots if a fall leads to a break. It is correlated with a variety of cardiac events, mostly around hardening valves and fat buildup in cardiac tissue causing lessened output while there is more circulating blood volume. It is correlated with difficulties administering anesthesia or intubating patients in case of emergency. It is correlated with... Being obese is still horrifyingly unhealthy even if high fasting glucose is just a proxy for some of those factors (which it is not, as this study is terrible).
  - mgarfias 4y ago
    Well shit, my BMI is 35. And I've got a pair of stents in my ticker. OTOH I'm doing crossfit 3x/week. And can dead lift over 300# so I feel like I'm getting better. ALso, I'm built like a fireplug, so probably not fat as just big. BMI is a shitty measure.
    - 4y ago

hprotagonist 4y ago

Using the primary cohort, time to mortality was regressed on all three exposures of interest: BMI, fasting insulin, and CRP. A number of parametrizations of these three exposures were explored. The models with the best fit used linear and quadratic terms for BMI, a linear term for fasting insulin, and the natural logarithm of CRP. and we chose not to justify or explain those parameterizations in any way, because what we probably actually did was diddle SAS until the model did what it was supposed to. yawn.

dang 4y ago
"Please don't post shallow dismissals, especially of other people's work. A good critical comment teaches us something." "Don't be snarky." https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html

josephcsible 4y ago

This seems like a textbook example of the model 11 "bad control" from <http://causality.cs.ucla.edu/blog/index.php/category/back-door-criterion/ http://causality.cs.ucla.edu/blog/index.php/category/back-do...>. X is BMI, Y is mortality, and Z is fasting insulin and blood sugar. Basically, if X causes Z and Z causes Y, then controlling for Z hides the relationship between X and Y.

pessimizer 4y ago
Does it hide, or does it actually clarify the relationship if after you do that BMI is negatively correlated to mortality at the same fasting insulin and level of c-reactive protein? It also means that if we can control people's reactions to sugar, their weight becomes irrelevant (or possibly even protective.) Losing weight is usually the way to fix your sugar, but plenty of people who aren't fat have sugar problems, and sugar problems might not be reversed by weight loss in a particular individual.
- evol262 4y ago
  The percentage of people with normal BMIs and type 2 diabetes or prediabetes is so small that is irrelevant from a mass health perspective. There are a plethora of studies correlating a change in diet with improved blood markers for fasting blood glucose and insulin response. Sugar "problems" are resolved by diet, and resolving diet goes along with reversing weight loss. It cannot be any other way. There is no evidence that obese BMIs are negatively correlated to mortality, only the opposite. Obese BMIs still come with increased arterial plaque, complications in anesthesia and surgical healing for medical interventions, fatty liver disease, ocular pressure, lung function, cardiovascular health, and so on. Obesity is up with smoking as a cause of preventable death. Let's not try to put a pretty face on it. A spade is a spade. Insulin resistance/high fasting glucose and obesity are inseparable peas in a pod.
  - pessimizer 4y ago
    > The percentage of people with normal BMIs and type 2 diabetes or prediabetes is so small that is irrelevant from a mass health perspective. Then my father is irrelevant, being diagnosed with prediabetes at 6', 165lb. So is it really irrelevant numerically, or is that hyperbole? Does your irrelevance include millions of people? ----- edit: > There is no evidence that obese BMIs are negatively correlated to mortality, only the opposite. TFA mentions that it is negatively correlated when you control for two things that are positively correlated with BMI. So, while the study doesn't say that high BMI reduces mortality (it in fact observes the opposite), nobody claimed it did. But in finding the negative BMI correlation when controlled for insulin, it does make a very good case that > Obese BMIs still come with increased arterial plaque, complications in anesthesia and surgical healing for medical interventions, fatty liver disease, ocular pressure, lung function, cardiovascular health, and so on. are largely irrelevant to the mortality of the obese relative to the thin, and inflammation and insulin resistance are decisive.

Markoff 4y ago

TLDR this is only about obese people, don't bother reading if you have healthy BMI, heck median BMI of participants was 27, way beyond healthy since overweight starts at 25 and I would say even that is very generous ~20.3 here