[HN Gopher] Associations of body mass index, fasting insulin and...
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Associations of body mass index, fasting insulin and inflammation
with mortality
Author : elefantastisch
Score : 40 points
Date : 2022-08-29 20:51 UTC (2 hours ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| alfor wrote:
| And... one big factor in inflammation is our modern lack of sun
| exposure (infrared).
|
| 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 wrote:
| 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.
| hprotagonist wrote:
| _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.
| PragmaticPulp wrote:
| 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 wrote:
| > 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
|
| 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).
| josephcsible wrote:
| This seems like a textbook example of the model 11 "bad control"
| from <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 wrote:
| 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 wrote:
| 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 wrote:
| > 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.
| evol262 wrote:
| > Then my father is irrelevant, being diagnosed with
| prediabetes at 6', 165lb.
|
| BMI is a population-level metric, and population-level
| analyses of health risks, from an epidemiological
| perspective to inform healthcare providers and public
| health officials of risks, frankly, don't care about your
| father.
|
| Yes, it's irrelevant numerically, and it's irrelevant
| numerically because there's little evidence that any
| significant portion of the population (much less millions
| of people) falls into this category, whereas we are one
| of the fattest countries on Earth, which has absolutely
| no need to minimize or downplay the health effects of
| that.
| Cenk wrote:
| PDF here: https://www.nature.com/articles/s41366-022-01211-2.pdf
| kaesar14 wrote:
| Is this more or less saying there's no definitive link between
| obesity and mortality risk?
| Etheryte wrote:
| Not really, their conclusion is simply worded in a highly
| misleading way. They say the increase in mortality is due to
| hyperinsulinemia and inflammation, however both of those are
| caused at least in part by obesity.
| swatcoder wrote:
| > both of those are caused at least in part by obesity
|
| You're letting the word "are" carry a lot of weight where
| "often" or "can be" might be more accurate.
|
| They're correlated with obesity, which means that they're
| _more likely_ to be present in obese patients. But they exist
| independent of it: not being present for _all_ obese patients
| and sometimes being present for non-obese patients. And since
| they 're measurable on their own, it's kind of a big deal to
| draw them out as obesity-associated factors more closely
| correlated with all-cause mortality than obesity as a whole.
| Etheryte wrote:
| Of course you can have inflammation without being obese, no
| one here is arguing for that. The point is it's very rare
| to find someone who is obese without inflammation. In other
| words, A implies B does not mean B implies A.
| swatcoder wrote:
| > very rare
|
| Can you more specifically characterize what you mean by
| that and what your references are?
|
| Because you're taking a statistical correlation and a
| hypothesized mechanism and turning it into logical
| entailment. It's hard to believe that even a extremely
| high correlation is anywhere near 100% but I would love
| to see real data saying otherwise.
| Etheryte wrote:
| For whatever reason you seem to be building a lot of
| strawmen here. No one prior to you was talking about
| 100%. Similarly for shifting the onus, you can pick up
| most any study on obesity and inflammation. Not liking
| medical facts does not make them go away.
| pessimizer wrote:
| This is not the way to react when asked for evidence of
| your claim. Instead of talking about 100%, subtract "very
| rare" from 100%, and supply evidence for that. It's
| difficult not to like "medical facts" when none have been
| offered.
| swatcoder wrote:
| Sorry. Maybe I lost sight of the context of your original
| reply.
|
| I think I took it to mean you saying the study hadn't
| meaningfully narrowed down mortality risk to less noisy
| factors than obesity, when I see now that you may have
| just been helping the prior commenter see that obesity
| itself is still correlated with mortality _through_
| these. Probably because I can 't even grok how they got
| to that idea. :)
| slymon99 wrote:
| Not really - it's just saying that the definitive link is
| almost entirely caused by hyperinsulinemia and inflammation,
| and if you control for them, there's no other causality.
| Hyperinsulinemia and inflammation are _massive_ metabolic
| problems, controlling for them is effectively like controlling
| for lung cancer in a study of smoker. Like, sure, people aren
| 't choking to death on cigarettes.
|
| This is still a useful study though! It's useful to know that
| the cause is almost entirely through those factors. Though this
| is also an epidemiological study with no randomization and some
| of the hazard ratios are not particularly high.
| rileymat2 wrote:
| 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.
| stingraycharles wrote:
| 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 wrote:
| It means that you aren't insulin resistant and it actually
| does its job.
| mbesto wrote:
| 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)?
| PuppyTailWags wrote:
| Since obesity is often caused by a poor diet/lack of
| exercise maybe that causes obesity and also causes
| insulin resistance, not that poor diet/lack of exercise
| causes obesity causes insulin resistance. So you can be
| fat off salad and be ok and also be thin off canned chili
| and not ok.
| evol262 wrote:
| There aren't people who are fat from salads, except for
| the loosest definition of the word.
|
| Weight gain is caused by an overconsumption of calories,
| barring a narrow range of medication side effects.
|
| Insulin tells your body to uptake glucose into cellular
| bodies. If glycogen stores aren't depleted (in the liver
| from normal/basal metabolism, in muscular tissue from
| activity) and there's nowhere for it to go, it's
| converted via de novo lipogenesis and stored in adipose
| tissue. If there's no free room, new fat cells are
| created. Lipogenesis and the creation of new adipose
| tissue are not instantaneous processes.
|
| Insulin resistance is because your body has continued to
| see that blood glucose is high because it cannot be taken
| up quickly enough, so it sends out more insulin. As high
| circulating levels become more normal, the alpha channel
| on the insulin receptor requires more insulin to activate
| a signal transduction pathway to open the GLUT4
| transporter for glucose.
|
| Very strictly, excess blood glucose causes insulin
| resistance. That excess blood glucose is caused by
| caloric overconsumption, which causes obesity. It is not
| the inverse.
|
| Carbohydrates have poor satiety, so when the stomach is
| empty (fats and proteins have a longer processing time in
| the stomach), ghrelin is released, which stimulates
| hunger, and the person eats again. Probably more simple
| carbohydrates, possibly before the previous ones have
| been taken up by cells.
|
| Caloric overconsumption -> obesity
|
| Insulin resistance is a side effect here, one which is
| seen because simple carbohydrate consumption is part and
| parcel of obesity in the western world. It's very hard to
| become clinically obese without cheap sugar. The same
| mechanisms (overconsumption of calories) cause obesity
| and insulin resistance, so they're two sides of the same
| coin.
| mrandish wrote:
| Well said. I was _almost_ T2D then lost >100 pounds with
| strict keto going from terrible BMI to ideal and my N=1
| experience fully supports your explanation.
| PuppyTailWags wrote:
| 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 wrote:
| 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.
| [deleted]
| [deleted]
| emeraldd wrote:
| That's what the conclusions appear to be saying:
|
| > 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.
| bilsbie wrote:
| But isn't the obesity causing the higher fasting insulin?
|
| Isn't high BMI interchangeable with obesity in most studies?
| mgarfias wrote:
| What does this mean for us T2D types that need the insulin? Are
| we just fucked?
| woleium wrote:
| 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 wrote:
| > 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).
| pmdulaney wrote:
| 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 wrote:
| 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 wrote:
| 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.
| pessimizer wrote:
| > 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.
| ajross wrote:
| That's a very unfair strawman.
|
| The linked article is about an epidemiological measurement
| often used to flag health risks. And it's pointing out that
| the real causality is likely due to other factors. I'm
| pointing out that those other factors are hopelessly
| conflated with the first anyway, so we might as well keep
| measuring BMI and treating it as a risk factor.
|
| Are there other things we should measure? Of course there
| are. Propose a test and let's look at the tradeoffs. I'm
| just saying let's not stop treating BMI as informative,
| because it still is.
| tomjakubowski wrote:
| 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.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]
| codefreeordie wrote:
| I mentioned this in the other thread, but the really
| interesting part to me is "When fasting insulin and the natural
| logarithm of c-reactive protein were included in the model, an
| inverse association between BMI and mortality was present"
| which says that, if the study's findings are correct, that
| hyperinsulinemia and inflammation are the _only_ material
| contributors to obesity-linked mortality.
|
| It's not surprising to find these causes are significant
| factors in obesity-linked mortality, but it is moderately
| surprising, at least to me, to find that they're the _only
| significant_ ones.
| bilsbie wrote:
| I'm not getting it? Can you dumb it down?
| pmdulaney wrote:
| First off, I'm no doctor or even close.
|
| In recent years there has been a back-and-forth discussion
| about whether being overweight is bad for your health.
| Intuitively one might think that being overweight is bad. But
| in 2015, for example, there was this article, which reflected
| a story making the rounds at the time:
|
| https://qz.com/550527/obesity-paradox-scientists-now-
| think-t...
|
| What I take this study to be saying is that obesity in itself
| is not really the problem, but it is (presumably) highly
| correlated with high A1C measurements and inflammation, which
| do indicate a poor state of the endocrine system (i.e., Type
| 2 diabetes), which can in turn lead to heart disease and
| stroke if not treated.
|
| I'm hoping that someone who knows more than I do will poke
| some holes in what I have just written so as to give you a
| better answer.
| msrenee wrote:
| >It's true that these groups are slightly more likely to
| suffer from heart disease and some other life-threatening
| conditions in the first place. But many factors influence
| the likelihood of a person getting heart disease. And a
| strong link between weight and disease only emerges among
| people with severe obesity.
|
| That seems like a place where the article should maybe have
| a citation or two.
| DoreenMichele wrote:
| One possible explanation is that obese people lack adequate
| muscle mass. The lack of muscle -- protein -- is associated
| with insulin resistance and it may be lack of muscle rather
| than additional fat per se that is one of the actual root
| causes of health issues _associated with_ obesity and
| routinely attributed to fat per se.
|
| https://news.ycombinator.com/item?id=14667430
| evol262 wrote:
| Key takeaway: higher fasting insulin and higher fasting blood
| sugar are both signs of being prediabetic or having type 2
| diabetes, which is correlated with obesity.
|
| This takeaway is basically "the increase in mortality that has
| been attributed to fluid in the lungs is likely due to a lack
| of blood oxygenation rather than being submerged underwater".
| swatcoder wrote:
| The correlate of my correlate is not... me. Or something like
| that.
|
| There exist obese individuals that are not positive for those
| markers, and there exist non-obese individuals that are.
|
| In a clinic, that might look like more proactively monitoring
| an obese patient for these indicators but not focusing _as
| much_ on their obesity if those are doing well. Likewise, it
| might look like adding these tests to a 5 year physical (or
| whatever) for non-obese patients, since they appear to be
| especially suggestive of concern.
| evol262 wrote:
| No, really. Insulin resistance and elevated fasted blood
| are clinical markers of diabetes and prediabetes. There is
| no arguing this.
|
| Yes, non-obese individuals with type 2 diabetes exist,
| though they are rare. Obese individuals who are not
| prediabetic or already have pathological type 2 diabetes
| are unicorns.
|
| Patients are already having their blood sugar monitored in
| a clinical setting, especially diabetic ones or ones likely
| to be prediabetic. And those patients are... obese.
|
| There is no getting around his fact.
|
| Non-obese patients also have this checked regularly.
| Clinicians _frequently_ ask for fasting the night
| beforehand to check blood values. They are checking for
| this. Nothing here is new, even remotely.
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