This study is a bit of a mess because there are no control groups. People either got the safflower intervention or the conjugated linoleic acid intervention, then they were crossed over:
Comparison of dietary conjugated linoleic acid with safflower oil on body composition in obese postmenopausal women with type 2 diabetes mellitus
I'm going to ignore all of the CLA/post CLA data and look at the subjects who got just safflower oil, a total of eight capsules per day, two with each meal plus two at bedtime, eight grams a day of the oil for the first 16 weeks of the study. The safflower oil was 78% linoleic acid, regularly checked by gas chromatography.
Looking at Table 3 there was no change in total fat mass (and subjects didn't gain any weight on the scales) by DEXA scan while there was a loss of 1.2kg of "truncal" adipose tissue. With a PUFA supplement. It appears that DEXA scanning cannot differentiate between visceral and subcutaneous fat in the trunk area. The authors can't quite claim that there was selective loss of visceral fat but I think it is very likely that this did happen.
Throw in a fall in fasting glucose and a downward trend in fasting insulin levels coupled with a rise in adiponectin, some muscle gain and well, that's pretty impressive. You can, absolutely, see why people might have the idea that PUFA could be very positive for metabolic health.
How might one view this from a Protons perspective, other than reaching for a bottle of safflower oil?
I think the first thing to consider is the (probable) loss of visceral fat. Visceral fat, in my opinion, is utterly harmless. It contains the most insulin sensitive adipocytes in the body. If you are chronically hyperinsulinaemic, especially overnight, your insulin may never drop low enough to release any significant lipid from your visceral fat. So visceral fat is a surrogate for nocturnal hyperinsulinaemia, which is what is actually bad for you.
We have values for 10h fasting insulin; at enrolment it was 19.9microU/ml and this dropped to 18.2microU/ml over the first 16 weeks of the study. I would not expect 19.9microU/ml to maintain visceral fat and 18.2microU/ml to melt it away. I think it is much more likely that the gross hyperinsulinaemia induced by the sort of evening meal recommended by the ADA for diabetic people might well have resolved faster with safflower oil supplementation than it did without safflower oil, ie the duration of the period of gross hyperinsulinaemia through the night was reduced. Fasting levels were unchanged but the time spent above this ought to have been reduced.
We just have to revisit the Spanish study to see why:
This graph is over eight hours, 10 hours would be similar. These are healthy volunteers, the hyperinsulinaemia would be worse in DMT2 patients eating a high carbohydrate meal. Black squares are butter, white triangles are a high PUFA seed oil. The higher the PUFA content of the meal, the faster insulin level drops. Adding PUFA a mixed meal should allow insulin to drop faster and sooner than saturated fats. This happens because PUFA fail to generate the ROS needed to maintain the physiological insulin resistance which ought to occur post prandially to limit calorie ingress in to cells, adipocytes included. This leaves glucose and fatty acids available to signal satiety to the brain. Also noted in the Spanish study was that PUFA induced more rapid clearance of chylomicrons and more rapid drop in FFAs compared to saturated fats. As I wondered at the time, where do the FFAs and chylomicrons go to?
They go in to adipocytes, because the adipocytes cannot say "no" if PUFA generate too little ROS.
So this drug (safflower oil) allows increased insulin sensitivity (reminiscent of the "glitazones") or, rather, it fails to generate the ROS needed to limit the over expansion of adipocytes, which shows as increased insulin sensitivity during peak insulin exposure. This increased insulin sensitivity puts calories in to adipocytes rapidly so reduces the need for sustained hyperinsulinaemia. All adipocytes gain fat, but the faster fall in insulin allows an increase in the time window where visceral fat can actually release at least some FFAs to the systemic circulation via the portal vein and liver. Visceral fat shrinks, non-visceral fat expands.
The "benefit" of reducing visceral fat in this way during fasting is paid for by increasing the non-visceral fat depots in the immediate post prandial period. The extra fat in non-visceral adipose tissue will come primarily from the diet and the lost fat from visceral adipocytes will be used to provide fasting calories. In this particular study, the amount gained by non-visceral adipocytes was roughly equal to that lost by visceral adipocytes, it's probably random chance that the numbers balanced. And DEXA seems a pretty crude technology to use to work in small numbers of grams of adipose tissue, just looking at the non-balancing cited changes in fat and lean tissue mass in the results.
These processes can continue until non-visceral fat mass eventually become high enough that the loss of FFAs due to adipocyte distension over rides the insulin sensitising effect of the safflower oil. At this point overall insulin exposure will increase and visceral fat will return, on top of a higher mass of non-visceral adipose tissue. It will take longer than 16 weeks.
If you are an obese diabetic taking part in a study like this you should see a prompt but transient improvement in insulin sensitivity. This enhanced sensitivity should allow more non-visceral fat gain until you convert to being a somewhat more obese diabetic. It nicely illustrates that extra PUFA convert you from being established "obese" to being "pre-more-obese". Time is all that is needed to convert you from being "pre-more-obese" to simply"more-obese".
But your lab numbers will improve transiently in the first part of the intervention.
Peter
Looking at the possibly transient improvement in various markers just reminds me that this whole field will continue to wallow around with opposing hypotheses until someone can figure out both:
ReplyDelete(a) a mechanistic model for the cause of insulin resistance
(b) a way to test it against competing models.
I've seen various contradictory claims for insulin resistance causes, and I have generally stuck to the low carb low seed oil low sugar paradigm, ever since Taubes in 2008. But uncertainty persists. You run a narrative that fits all the available data into your model, opponents do the same with theirs.
What research do you think really hammers home the LCHF hypothesis?
What research could be done to remove reasonable doubt?
What could falsify your position?
Maybe these are not fair questions but I would love to know your thoughts, and those of anyone else who contributes in these comment sections.
Books have been written to answer this. Do you expect a comprehensive answer in a comment? :)
ReplyDeleteWe can argue whether keto or low carb (with some unrefined carbs, like legumes) may be better for insulin sensitive people. We can discuss whether we should eat some lectins, occasionally, or avoid them as much as possible. I won't go there. These are tough questions.
But if you ask if high carb and high seed oil is objectively bad: Studies may be manipulated, but paleopathological studies (watch Mike Eades talks on this) and epidemological data of whole populations can't (at least not easily). We know what they ate, we know which diseases they had.
Every time I drop something it falls to the floor. So I do not question the theory of gravity.
Every time a healthy population is introduced to refined carbs, they develop civilization diseases, quickly. (Even the Kitavans. Even if we are talking whole grain, no sugar - check the ancient egyptians.) Conclusion?
Richard, I think a few snippets which have tricked down to me over the years are in the blog. Hard to be more specific than that really. As Frunobulax says, there are some things which are self evident...
ReplyDeletePeter
This comment has been removed by the author.
ReplyDeleteFrunobulax, I have to agree that the shift to refined carbs, sugars, and seed oils by traditional populations provide strong evidence for the dangers of these foods. We don't get the slam dunk though, because like all epidemiological studies, these are loaded with confounding factors.
ReplyDeleteMy questions were more specific. There is still no established cause of insulin resistance.
Look at the following:
"Insulin resistance is usually triggered by a combination of factors linked to weight, age, genetics, being sedentary and smoking."
https://www.endocrineweb.com/conditions/type-2-diabetes/insulin-resistance-causes-symptoms
https://www.webmd.com/diabetes/insulin-resistance-syndrome
...does a little better adding
"Diet high in carbohydrates" as one item in a list of 12. Progress - that was not there a decade ago.
https://www.healthline.com/nutrition/insulin-and-insulin-resistance#insulin-resistance
...skirts the issue by pointing out that -
"Numerous studies show that high amounts of free fatty acids in your blood cause cells to stop responding properly to insulin" but "The main cause of elevated free fatty acids is eating too many calories and carrying excess body fat". No mention that excess carbs will raise triglycerides and plasma saturated fat levels more that a saturated fat low carb diet will.
I could go on, but my point is that answers are vague, and many still point to saturated fat:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587882/
The paper argues that insulin resistance begins with increased inflammation of the hypothalamus: "Excess nutrient intake (especially saturated fat) can also indirectly cause inflammation in the hypothalamus by activation of the TLR-4 receptors in the microglia...etc etc"
Peter has a long history here of eviscerating many similar papers by pointing to errors in method and conclusions drawn from the data. I've enjoyed every minute of it. But saturated fat is still widely demonised even after meta-analysis of the literature by the Cochrane Collaboration and others show no evidence of a link.
So...to my point, which I should re-frame. There are competing, and surely testable, hypotheses about the causes of insulin resistance. I suppose it frustrates me that in this field we have nothing but a heterogeneous stack of research from which partial conclusions are possible, which seldom control for one variable alone, and which still provide fuel for the arguments from all corners. What we seem to lack is solid evidence in the form of
(a) hypothesis as to cause based on a mechanistic explanation of pathological insulin resistance. (Something Peter has offered)
(b) controlled tests of the hypothesis, contrasting with alternative hypotheses (differing predictions).
How do we convincingly and compellingly test our way out of this mess? What would you do if someone provided a hundred million dollars to run a research program on the subject?
Peter - what is self evident, evidently varies hugely from person to person. To you, to me, to Frunobulax, perhaps, but not to the army of people still demonising saturated fat, the latest assault coming from the growing vegan community (which I expect ultimately to be self limiting through human-damaging failure).
Richard: last not least butter and dairy shaming in the name of climate protection. I nearly blew my top when saw an ad by one of our largest semi-public health insurers to avoid butter to save the planet. I clicked and saw that they had hired a full time PR specialist who is running a blog from their homepage in which she also promotes veganism. Talk about mandatory health tax Euros misspent.
ReplyDeleteCouples of questions I had when reading your new article, Peter:
ReplyDelete- Were the capsules on top of whatever the folks were eating or instead of? Does safflower oil just not generate ROS or would it suppress the generation of ROS if butter was eaten together with the capsules?
- If you consider visceral fat as harmless, why is most of the establishment condemning it?* You give a hint that it is a surrogate for nocturnal hyperinsuinaemia which might explain that the establishment is confuding the messenger with the culprit, but who is the culprit then? Is subcuteanous fat not harmless, then?
- Your description of fat moving from the abdomen to other areas reminds me of shiny happy Americans. Seriously, there are a lot of beefy people around there who are heavy but don’t have much of a protruding belly.
- I have been meaning to ask this ever since reading about the croissant diet: it it a good idea to eat carbs and sat fat together? After all, it will result in elevated blood sugar (glycation!) and elevated insulin (cancer?). I would assume eating the same or preferably a smaller amount of carbs without fat makes more sense because they get absorbed before they and the insulion excretion they cause can do any damage. It’s just that bread or potatoes taste so much better with butter…
• https://www.webmd.com/diet/what-is-visceral-fat#1
Dangers of Visceral Fat
Too much of any body fat is bad for your health. But compared to the fat that lies just underneath your skin (subcutaneous fat), the visceral kind is more likely to raise your risk for serious medical issues. Heart disease, Alzheimer’s, type 2 diabetes, stroke, and high cholesterol are some of the conditions that are strongly linked to too much fat in your trunk.
Researchers suspect that visceral fat makes more of certain proteins that inflame your body’s tissues and organs and narrow your blood vessels. That can make your blood pressure go up and cause other problems.
@Richard
ReplyDeleteOK, let's get distracted for a moment :) Insulin resistance.
There is even discussion on whether it's insulin resistance at all. Jason Fung argues that it's more complicated than that. https://www.youtube.com/watch?v=eUiSCEBGxXk
Personally, I have a different conjecture: The first step towards diabetes is impairment of glycogenesis (and omega-6 fatty acids could play a role). The glucose doesn't go into the muscles because muscles store glucose as glycogen. Then we see rising insulin levels (the liver is slow to convert glucose to trigs), and after a few years we do get systemic insulin resistance, liver can't convert glucose, fat cells will store less triglycerides, blood glucose and triglycerides explode.
But back to your main question. Don't get lost in studies. A LOT of studies do no plausibility check, they find something but don't give a f whether that's consistent with real-life observations.
If you browse the internet for insulin resistance, 90% of the sources are obvious bs. Most list "genetics" as primary factor. Now, we had a factor 10 increase in diabetes over the last ~60 years. Are the diabetics more active in bed while the non-diabetics look for different, um, recreational activities? :) Please...
The only way to keep your sanity is to accept that there are a lot of counterintuitive results that are completely consistent with good science.
ReplyDeleteLet's take one example. We know that high carb, high fat is worse than high carb, low fat. (Salad and whole grain bread beats the chocolate bar diet.) Take people following a chocolate bar diet (i.e. the majority of our western population), reduce fat, and they will become healthier. The headline would be "more carbs, less fat = healthy". Of course this is completely wrong: If you do the same with people on a low carb diet, they will get sicker.
Sometimes the effect is a matter of time. I mean, take weight: If you're overweight, fasting for a week makes you healthier. Try this for 2 years, well, not so much.
Now, I firmly believe that too much omega-6 is poisonous. (Even n-6 has a u-shaped curve, but most of us are way down the "too high" leg.) And yet, there will be studies that show better health with omega-6. The real fun starts when we try to analyze _why_. (Which Peter did in this blog post.) That's when we start to make progress.
Hello Peter and Everyone!
ReplyDeleteWould like to pick your brains on a couple of issues.
After eating a fat meal, where does the fat predominantly get stored first? That is, if visceral fat is the most insulin sensitive, as opposed to subq fat, would it not make sense that the incoming fat gets stored as visceral fat first?
Also, this is vanity related, but have you any suggestions regarding losing subq fat, especially the stubborn fat areas? I have been re-reading your previous articles re alcohol and fructose causes the subq adipocytes to release their contents!!!
Cheers
OK, I'm almost following along. The safflower oil is easily pushed into the fat cells because of the high Omega 6. So that allows it to go in faster and thus clear the blood faster. This clearance allows the insulin to work quicker / better. The insulin then lowers a bit quicker because of all this.
ReplyDeleteThe lower insulin then allows the non-visceral fat to release more FFA's than before.
But, why doesn't the lower insulin also allow the visceral fat to do the same?
What's different between non-visceral and visceral fat in this context?
Steven, fire in the bottles offers an interesting answer to your question.
ReplyDeletehttps://fireinabottle.net/fat-from-the-previous-meal-sets-the-metabolic-table/
Lifo principle and small fat storage at inside of the intestine does the trick. Provided that the fat stored is saturated.
At first meal, at "swallowing" the small storage is mobile and does the visceral transiently insulin resistant, before the fast absorbed glucose comes knocking. A'la Peter's ROS explanation.
JR
Based on my tests of a high saturated fat diet as per Fire in a Bottle, I think this has to be modified:
ReplyDelete"Let's take one example. We know that high carb, high fat is worse than high carb, low fat. (Salad and whole grain bread beats the chocolate bar diet.)"
I don't think the first statement is true (it depends on the fats) and a chocolate bar diet would be better than salad. In other words, if you're eating high carb and high PUFA, that is different than eating high carb and high saturated fat.
What we need are some well controlled studies of:
- Doughnuts fried in soybean oil (or choose another high PUFA oil) versus the same doughnuts fried in beef tallow (very low PUFA, higher saturated fat)
- Potatoes (aka french fries in the US) fried similarly
I have been low carb/keto since 1/1/14. I've gone from high fat, Jimmy Moore type keto, to low fat, Ted Naiman type keto, to now carnivore-ish, meaning I eat some veggies sometimes. When I started, I did not know anything about PUFAs, so I'm sure I ate too many.
After seeing The Croissant Diet, I've been testing high saturated fat with both carbs at times (targeted ketogenic diet, TKD, so carbs after working out and periodically when not working out) and keto. My experiments have shown that regardless of how I do it, if I get enough saturated fat in me, I experience dramatically reduced hunger. I think the carbs fit in here, mainly because they really suck up the fat and provide a concentrated source of saturated fat. If you try to get the same amount of fat without carbs/starch, you really have to gobble down fat.
I do not know the effect of high carb + high sat fat on my blood sugar. I wore a CGM (Free Style Libre) for over a year and can confidently say that no amount of protein on a keto diet causes any blood sugar rise whatsoever. I've eaten 160+ grams of protein in single meals, zero blood sugar rise. Meanwhile, rice (sushi), potatoes, wheat, etc., all cause my blood sugar to explode.
That was before I started the TKD, but the Free Style Libre prices have skyrocketed and went from about $60/month when I first got them (from Sweden) to $150/month. I can't pay that much just to test a theory, especially with covid-19 shutting everything down.
So, I think high PUFA intake is bad. I'm still not convinced that high carb in any form (even without high PUFA) is "good". I'd need more time with a CGM for this. I do think there is a possibility that high carb + high sat fat could be "good", especially if it means we eat less. I'd like to see more well controlled studies on this (even using myself, if I can afford it in the future), though.
Anyway, when I see the formula "high carb + high fat = bad", I think we might need to revise this.
Hi Unknown,
ReplyDeleteLets say all adipocytes accept fat from chylomicrons post prandially. Because insulin is at high peak physiological (guesstimate 150pmol/l), all adipocytes accept fat. Does that answer your query Stephen? The idea fructose and alcohol might help suborn fat is interesting but I’ve never chased it.
Overnight insulin should fall. Let’s say below 30pmol/l (for illustration, not in reality) subcutaneous adipocytes release FFAs. Visceral fat is so insulin sensitive that this 30pmol/l still keeps fat in the visceral adipocytes but not the sc adipocytes. Visceral fat is preserved. If insulin drops below (let’s say for argument) 20pmol/l then visceral fat can join in and release FFAs. If you keep insulin high all the time and it never drops below those 20pmol/l then visceral fat will just get bigger and bigger because it is never exposed to a low enough insulin level to release FFAs. Think diabetics on basal insulin with rather distended abdomens.
Eric, yes they were but there was no rigid enforcement of controlled calorie intake. Insulin signalling is the culprit, not even insulin per se. These people are obese DMT2 patients. By definition they are not eating butter and are on as little fat as practical, what they do eat is probably PUFA rich. However the 8gm per day did alter the linoleic acid level measured on blood sample, upwards by about 10%. The veg*ns do quite well at lowering insulin if they can keep fat absolutely basal, ditto the potato diet. Personally I eat the butter and avoid the potato, but then I’m not trying to change either my weight, body comp or visceral fat depot size…
Richard, you should explore the idea that insulin causes insulin resistance by facilitation caloric ingress until cells feel the need to resist it. ROS signal this. It is the persistence of insulin resistance beyond the acute post prandial period that needs thinking about. A bit like if you mainline heroin you will develop acute opioid induced opioid resistance, which may save your life. This too is ROS induced. But some degree of reduced sensitivity to heroin persists well past the acute high and subsequent doses need to be increased to get the same relief from pain that you got from the first hit… I think insulin will be the same.
Peter
Peter, OK, I think I'm really close now : )
ReplyDeleteSo why is visceral fat's insulin sensitivity different from non-visceral fat?
Or another way, Isn't fat just fat, it's just that some is with the organs and some under the skin.
Eric: "I have been meaning to ask this ever since reading about the croissant diet: it it a good idea to eat carbs and sat fat together? After all, it will result in elevated blood sugar (glycation!) and elevated insulin (cancer?)."
ReplyDeleteI just want to point out that Brad says he included carbs in the croissant diet *experiment* for two reasons: to prove that ketosis was not causing his weight loss, and to make it easier to eat a lot of fat. A lot of people overlook this detail. It's perfectly OK to leave out the carbs.
For a couple of reasons I have embraced stearic acid, and have been shunning PUFAs for several years now. So, inspired by Brad's croissant *experiment*, now I cook mostly with butter and cocoa butter. It's easy to eat only one meal a day. And I do not mind eating what is essentially sautéed meat in a soupy base of melted butter and cocoa butter (use a spoon). Or sometimes leave the fat in the pan and use it to sauté some brussels sprouts or broccoli with a splash of lemon juice.
Thanks for your reply, Peter.
ReplyDeleteIf for example, one eats 10g of sat fat, does most of that fat get stored equally in both subq and visceral fat almost simultanaeously? And if one eats 100g of butter, then it is assumed, once again, both subq and visceral fat would accept that too. The difference there would be the time it would take for all the NEFA to be absorbed.
Unknown:
ReplyDelete"So why is visceral fat's insulin sensitivity different from non-visceral fat?". Now you're asking. It is simply measurably so as in https://www.ncbi.nlm.nih.gov/pubmed/16567516. There is a thread about it somewhere on t' blog. I think it is used to minimise hunger to allow us to wake up able to hunt before having breakfast. FFAs to the liver suppress hunger as in https://www.ncbi.nlm.nih.gov/pubmed/16890966. I feel it gets saved for the time furthest from our last meal.
Steven, as far as I know no-one has done that study. There may also differences in the level of insulin at which insulin-induced insulin resistance kicks in. Lots of work to be done.
Peter
Peter wrote: "Richard, you should explore the idea that insulin causes insulin resistance by facilitation caloric ingress until cells feel the need to resist it. ROS signal this. It is the persistence of insulin resistance beyond the acute post prandial period that needs thinking about."
ReplyDeleteThanks Peter, yes I get your position.
What I am asking for is a test of this hypothesis, something that can make predictions that distinguish it from all the other hypotheses out there. See below, and Frunobalax has made yet another hypothesis as to root causes. Early on your blog clarified to me the distinction between physiological (temporary, essential) insulin resistance and pathological insulin resistance, the kind that results in metabolic syndrome.
This is to me the gargantuan question of medicine today - given so much pathology is linked to metabolic syndrome. So how do we pin it down, what experiments do we need, to really nail the cause(s). Honestly, I am hoping for something we can put out there solving the question once and for all.
Solid evidence in the form of
(a) hypothesis as to cause based on a mechanistic explanation of pathological insulin resistance. (Something you have offered)
(b) controlled tests of the hypothesis, contrasting with alternative hypotheses (differing predictions).
What would you do if someone provided a hundred million dollars to run a research program on the subject? Sorry to repeat myself but its a straightforward question even if the answer is likely to be convoluted.
Frunobulax : "The first step towards diabetes is impairment of glycogenesis (and omega-6 fatty acids could play a role). The glucose doesn't go into the muscles because muscles store glucose as glycogen. Then we see rising insulin levels (the liver is slow to convert glucose to trigs), and after a few years we do get systemic insulin resistance...etc"
Yet another insulin resistance hypothesis. What testable predictions does it make to distinguish it from other hypotheses about insulin resistance?
-------------------------------
Lets make this fun. Forget all the ethics and limitations. How would you, given cart blanche, establish the primacy of one metabolic syndrome hypothesis over all others???? (I am an evil scientist with unlimited funds, and I WILL make your research dreams come true!)
Richard,
ReplyDeletethat is not how science works :)
You make a hypothesis, and you test it.
By testing you may prove it wrong,
but you can never prove a hypothesis right.
Cheers,
LeenaS
LeenaS is absolutely right!
ReplyDelete@Richard: I'm only making a minor tweak to the carbohydrate insulin model. "Resistance" is a term for something we observe but can't explain. There are no little green men in the cells, pushing the glucose out. No, it can be one of these: (a) the cells are full, or (b) glucose transport is impaired.
ReplyDeleteThere are two core observations:
(1) Many people get fat years before they have impaired glucose control. But "getting fat" stops at some point. If there is systemic insulin resistance, blood glucose control must be off. The liver would convert glucose only slowly to trigs, fat cells wouldn't store fat. But we do get fat, fast, with decent blood glucose. Something is wrong here.
(2) We observe a distinct lack of energy in prediabetics, that is not due to a hypo. They have to eat in 2-4 hour intervals to get anything done. I myself remember that I would be insufferable when I didn't have breakfast, yet my morning blood glucose was around 95 all the time (A1C was 5.7 I think). I couldn't focus, I was cranky and nauseaus until I ate.
Now, employ the engineers view. What could produce this pattern? Peters solution is that we are insulin sensitive before we become insulin resistant. But this doesn't explain observation (2). If we are not insulin resistant (we do get fat), the cells have to be full. If we lack energy just a few hours after eating, the capacity must be very low. So I thought about impaired glycogenesis, and it does explain both phenomena, conveniently. Again, this is only phase 1. Phase 2 (a few years later) is when we do get insulin resistant.
(1) happens because liver and lipid cells are still insulin sensitive. Glucose clearance is slower, therefore insulin is higher, but after a few hours all glucose was converted to fat. But only very little glucose is converted to glycogen, hence (2). The presence of high insulin prevents us from getting something out of lipid cells.
This paper https://www.ncbi.nlm.nih.gov/pubmed/18220643 assumes that impaired glycogenesis is responsible for insulin resistance. But I couldn't find an online copy, and libraries are closed now, so I have only the abstract.
So, why did we get fat starting in 1970 or so? I'm on thin ice here, but I'll speculate anyway. "We" startet do fatten up around 1970, right when vegetable oil intake would rise. Sugar OTOH has been almost constant since 1980, even though it was up in the meantime. It could be sugar, sure, but let's look at n-6 PUFAs.
ReplyDeletecAMP blocks glycogenesis. n-6 PUFAs messes with our calcium (https://www.ncbi.nlm.nih.gov/pubmed/18718873). And of course n-6 PUFAs causes oxidative stress, leading to inflammation, which we know correlates with insulin resistance. We also store a LOT of n-6 PUFAs (https://www.ncbi.nlm.nih.gov/pubmed/26567191).
There is a third observation: (3) If we switch to keto, our bloodwork will be off while we lose weight (trigs higher, HDL lower and so on). (There is no study, but this is "known" in ketogenic forums.) Why? Because we have stored linoleic acid, we're burning it when we lose weight, of course we will see some of the effects that we see if we consume n-6 LA.
It's just a hypothesis. I'll throw it out if I find something that contradicts it. But so far, research seems to line up with it.
It's possible that my theory covers only a subset of the population, I think it's Kraft IIb and/or IV (high insulin while glucose is only moderately elevated).
ReplyDeleteAgain, the CIM is not wrong. But I do think there's something extra that sends us down the path towards insulin resistance. And n-6 PUFAs/wheat are high on my list of suspects because the ancient egyptians were obese and diabetic, while having no sugar at all (watch Mike Eades, https://www.youtube.com/watch?v=VSRDfkt-wJY). And they ate mostly wheat. Maybe it's simply oxidative stress (systemic inflammation) that throws our signalling off. (Yeah, I am on thin ice here. No argument there.)
Summing it up: We start with impaired glycogenesis. Possibly due to LA consumption and sugar/fructose consumption (both cause oxidative stress), possibly due to wheat consumption (WGA is a wheat lectin that mimics insulin, and there is gluten which causes leaky gut and oxidative stress). Glucose clearance is slower but still works as the liver converts it to fat, we get fatter and fatter, insulin rises because glucose clearance is slower. Due to the higher insulin we develop insulin resistance a few years down the road. We stop getting fatter, glucose clearance is broken, blood glucose rises, we become diabetic.
"WGA is a wheat lectin that mimics insulin"
ReplyDeleteThat's an interesting rabbit hole to go down. There are dozens of papers some going back 30 years eg
https://www.sciencedirect.com/science/article/abs/pii/0003986187900865?via%3Dihub