#140

[@shelchicago8997]

Am I the only one who’s listened to this interview 5 times and still got new info from it?

[@Jonathanmissinglink]

It's interesting, I'm a type 2, 22+ years diagnosis, and about 2 years ago started getting serious about my blood sugar management. In two years, I've come off three of my medications (glimiperide, Januvia and lastly Metformin). In the weeks I've been off Metformin, my blood sugars have remained consistent. I was 288 lbs, and am now 198, walk 5-8 miles per day (some jogging in that) and resistance train 3x per week. I should have listened to this podcast sooner.

[@lornarutter9179]

Congrats for your success.

[@CatChiou]

Well done! That's big accomplishment.

[@NonExistChannel]

Congrats! Did you make changes to your diet (e.g. more fat / less carbs / different kinds of carbs)?

[@dant.6364]

heroic

[@pcfreakx]

Thanks so much to Peter and Gerald for this. I had NAFLD at 35 and was pre-diabetic at 40. After years of keto dieting there's no longer any trace of either. But I'm still on Metformin because I believe it has long term benefits. Even my pharmacist has no clue how Metformin works but luckily my doc says she will keep me on it as long as I wish. I struggle with Metformin because some like David Sinclair now seem to think it should not be used by healthier indiividuals. I look forward to future content focusing on Metformin and life extension, insulin resistance. Again, thanks to Peter and Gerald. There's lots of us nerds who love the deep dive but would never have access to your deep brains otherwise.

[@Greg_Chock]

If you exercise regularly I would consider easing off the metformin as it has been shown to decrease muscle gain. Metformin seems to have less of a benefit for active individuals.

[@erastvandoren]

Switch to very low fat diet, and you will be cured. Preferably plant-based.

[@jellybeanvinkler4878]

David Sinclair still takes metformin, last I heard, but not on days that he works out.

[@dant.6364]

no @@erastvandoren

[@cantflipforship]

How do you find a doctor like that 😂 my doc had my fasting glucose in the pre diabetes range and never told me anything. Then wen I bring up wanting to test my Apob he says no

[@Philusteen]

I'm no doctor, but this is the first podcast that prompted me to go out and buy a year's membership. And yeah - the podcast notes are flat-out awesome. Nice work, all of you (as a copywriter I'm looking at all you layout, back-office and support folks. Dr. Attia.....yeah, you can stay too. 😆 )

[@HybridDrJ]

What an amazing deep dive into the physiology of diabetes and insulin resistance. As a health sciences professor I really appreciate the fine detail. Thanks Peter and Gerald!

[@dineshverma9097]

Absolutely fantastic and mind blowing. I have listened to many talks on insulin resistance and it is the first time I have understood it well and how it translates into clinical practice. I will pass the information to all my patients. Thanks you Peter and Gerald. You both are awesome. Gratitude.

[@Artzimer1958]

This podcast shed a light on my condition with hyperlipidemia, insulin resistant, and now finally Reynolds disease. I do have Reynolds but my endocrinologist or neurologist couldn’t figure out why in the past year or so I have developed numbness in my hands my toes especially when I get cold. I tried calling Dr. showman‘s office but unfortunately they told me that he doesn’t see new patients. I begged her to make an exception and have Dr. Shulman see me or talk to me but they didn’t. I feel so helpless I have been dealing with these issues for the past three years but I’m sure I was a diabetic and I had insulin resistance way before my diabetes was diagnosed. When Dr. Attia mentioned renal disease I couldn’t believe how my doctors have been so wrong about first my diabetes and now the complications from diabetes. By the way I am not overweight I am only 5‘1“ tall and I weigh only 105 pounds. I don’t have fatty liver but I don’t know how to fix my Neuropathy in my feed on my hands. I have tried many times to contact Dr. Attia but I’ve never been able to talk to him. Now I know you have to take control over your health I wish I had all of this knowledge 10 years ago this wouldn’t have happened to me. Take care of yourselves.

[@gtm5650]

Vitamin B1 Benfotiamin could help with nerve damage especially for diabetics. It's a fat soluble B vitamin unlike B complex vitamins which are water soluble. Good luck 😃

[@Artzimer1958]

@@gtm5650 I have been taking that on and off for the past year or so. Thank you so much

[@LTPottenger]

Fasting, low intensity exercise, low carb diet, no vegetable oils, eat more eggs for the choline. Also red light therapy for your neuropathy and general health.

[@TheShumoby]

@@Artzimer1958 Do your own research. There's a bunch of research and practicing physicians that help their insulin resistance patients with Keto diet, like Dr. Fung, Dr. Berry, and Dr Berg. Dr Berg has a recent video on the best diet for peripheral neuropathy : kzbin.info/www/bejne/lWmQlp97rJynkK8

[@dana102083]

Remember your nerves need proper nutrition so removal or grains and refined/processed goods of ALL kinds is key. Is it Reynauds Syndrome? Do your hands turn purple/blue etc? I second following dr fung and also dr sarah hallberg and dr Westman. I recommend a video by dr sten eckberg called "the mathematics of weight loss". It spells out the basics as a good review. 🙏 you got this!!

[@Reewnat]

Great information. Has Dr. Attia ever done a comparison of all of the guests who have talked about metabolic disorder, hyperinsulinimia, type II diabetes, NAFL to explain where is harmony and disagreement? That would be very helpful.

[@erastvandoren]

Well, Peter often had charlatans on.

[@dmackle3849]

@@erastvandoren *[citation required]

[@Eldooodarino]

@@erastvandoren who? I know he interviewed Jason Fung who’s a quack IMHO but most of them are pretty good

[@allanchino35]

@@Eldooodarinowhy is Fung a quack?

[@dant.6364]

still waiting for that citation a year later 🤣@@erastvandoren

[@jnjf3]

Loved this! It would be sooo nice if this podcast was available in video too. Just a suggestion.

[@DessicatedCadaver]

The best and most interesting episode in a long time and for a long time after. More such science filled and educational episodes, please! I learned more from this about insulin resistance than any other video or podcast. This is the gold standard.

[@Rene-uz3eb]

46:35 he says if there is too much fatty acid coming in vs what mitochondria can handle, you get diacylglycerol accumulation, which then signal insulin resistance in the muscle cells. I guess the body indirectly is throttling the supply of energy that way: while the IR only affects reduced uptake of glucose, the same insulin now can attach to more fat cells triggering fat storage. So at the end of the day, we have too much energy being sent to the mitochondria induces insulin resistance, which gives feedback via insulin resistance to reduce that incoming flow, whether it was in the form of too much fatty acids or glucose. That points to the inability of the mitochondria to process enough substrate to be at the core of insulin resistance, with signs such as mitochondrial decoupling etc. Too much ROS generation during ATP production must be the reason for mitochondrial throttling.

[@Rene-uz3eb]

10s summary: Insulin resistance can be caused immediately from stuffing cells with lipids.

[@dmackle3849]

And lipids can be caused by stuffing faces with calories. Problem solved in under 20s.

[@evec2022]

tl;dw

[@jaym9846]

Is the flow of fat from plasma into muscle cells controlled in some way similar to glucose?

[@Rene-uz3eb]

Good question. It doesn't look like that's understood yet. But a super interesting paper ties insulin resistance due to a high fat diet to a lack of omega 3 acids. So a high fat keto diet with 10% of the fats being omega 3 would be sufficient to prevent causing insulin resistance (if a lot of the fat is polyunsaturated, then fish oil long chain omega 3 is needed, otherwise plant omega 3 ALA is sufficient. I don't trust fish omegas not to be rancid so best to me seems saturated fat heavy + plant omega 3) Influence of Dietary Fat Composition on Development of Insulin Resistance in Rats, 1991 (Edit: the paper points out that you don't want to dilute the ALA with linoleic acid because they are used competitively, so Flax seed oil would be a much better option than hemp oil)

[@edwardlopez3618]

Really hope this evolves into a JRE style podcast with cameras. Might be strange but I find myself able to easier sit and understand the content of a podcast if I can watch it aswell.

[@WideAwakeHuman]

Same here... I just try to listen to these while I'm running or driving so it doesn't bother me as much that there's no video. I'll watch ones with video if I'm just sitting down to watch and have time to just chill

[@davidblackwell1753]

kzbin.info/www/bejne/o6PTgpiIjpydjrc here is the 2018 Banting lecture by Schulman showing an earlier version of the slides.

[@WideAwakeHuman]

@@davidblackwell1753 awesome thanks

[@alexanderohanlon8825]

Same

[@donnaschnare7029]

Wonderful as always and will definitely be listening with my notebook again 😉 thank you

[@danielevans5864]

Don't rigorously exercise everyday. Take metformin in the evenings of off days. No metformin on workout days. This is how I take it and I get no inflammation or soreness in muscle groups I may have gone over a week without working out.

[@bellelacroix5938]

Learned a lot. Thank you. We got to get this under control.

[@VishalPendharkar]

Can't see the screen shared by Gerald

[@howuuu]

Excellent video..peters language and thinking super sharp and to the point..thank you!!

[@johnhugo9761]

Love to see this new means of learning! Carry on!

[@bennguyen1313]

Regarding Dr. Shulman's point that the first type of cell to become insulin resistant is muscle.. which he found by using Heparin (which activates lipoprotein lipase (LPL)) to breakdown Trigs and cause infusion of fatty-acids into muscle cell... Any thoughts on Ben Bikman suggestion that muscle cells that take up fat to make Trigs, are inert and don't contribute to insulin resistance. Instead, excess consumption of linoleic acid causes *FAT* cells to have hypertrophic growth (as opposed to hyperplastic growth), and this causes them to be the first domino of cells that become insulin resistance. In addition, like cholesterol, fat in the blood does not primarily come from diet, but rather from the endogenous saturated fat produced by the liver (palmitate), which when combined with amino acids in response to stress*/inflammation/hyperinsulinemia**.. create FAT cells (ceramide ) that can disrupt a cell's normal insulin function (inhibition of protein/glucose breakdown, stimulation of glucose uptake). BTW, which is the preferred clinical definition of T2D... the HbA1C >= 6.5% OR the OGTT (30-120min later blood sugar >= 200 mg/dl, insulin is 70)? *Stress/Sleep-Deprivation : cortisol + catecholamine and their analogs are insulin antagonist **Muscle insulin resistance->Peripheral Hyperinsulinemia IR + Portal Vein Hyperinsulinemia .. fatty liver to liver IR -> muscle IR. The spectrum from hyperinsulinemia -> impaired glucose disposal ->, mafld/nafld/nash , and finally to type 2 diabetes (hyperglycemia), is what determines the severity of other diseases: atherosclerosis (hyperlipidemia) , inflammation, high uric acid / High Cholesterol-Trig (TRIGS should normally be < 100), cancer/PCOS, dementia

[@Copperline828]

Insulin gets the cells to take in the glucose for either energy usage or energy storage. If a person is overfed they will add to their energy storage (Fat). What I'm having a hard time understanding is when insulin resistance is finally developed, and the cells are not allowing glucose to enter within, therefore not adding to the storage, how does a person gain weight? Is the liver taking in the glucose and turning it into fat and then distributing it throughout the body? Or does the predicament cause even more over eating due to cell starvation and eventually with enough insulin the cells respond and now you end up with more energy then needed and therefore additional fat added to the body? Any thoughts?

[@stoopz3634]

​@@Copperline828 Insulin is the hormone that makes you gain weight. All you have to do to make a patient gain weight is prescribe them insulin. (Look up diabetic lipohypertrophy for an an example). When people are insulin resistant the body makes more insulin than normal because Glucose levels are high and Not Going Down. The brain signals the pancreas to release increased concentrations of insulin (to control sugars preventing hyperglycemia) making it more likely that insulin binds to its receptors allowing glucose clearance. An oversimplified explanation of what Dr. Shulman is saying is that insulin resistance begins with a transport problem of glucose from your bloodstream into glycogen stored by the liver and cells (like skeletal muscle). When people are very very late stage such as with DKA you get the opposite - the pancreas has shut down insulin production (think of it like long term work related stress). Glucose has nowhere to go and quickly shoots up. With those patients - glucose cannot enter the cells at all, the cells starve, you get rapid unexplained weight LOSS leading up to emergency ketone production (alternative fuel). The excess glucose in this emergency causes the three polys because glucose is way overconcentrated: Uria to extrete hyperconcentrated glucose, phagia because your cells are literally starving, dypsia to replace water you're losing.

[@Ceciliaseg64]

Seems the problem here is that this scient only adheres to the current accepted lifestyle and not looking outside the box. He needs to check on what causes these fats(mostly linoleic) to disrupt themetabolism in the mitochondria. Perhaps they are actually not meant to be consume at the levels we are currently doing due to our fear of animal fats.

[@erastvandoren]

Bikman is an idiot, forget Bikman.

[@anujam2951]

It would be interesting to know what role Vit D has to play here. I heard in your other talk that animals eat fruits before hibernating to build fat. It seems to me they eat fruits whenever they get them. It may be that vit D levels going down plays a role here and it's not just about sugar.

[@jaym9846]

You may be correct. We likely wouldn't have wanted to get fat in the summer.

[@ericwarmath1091]

Dr Barrie Tan has some interesting work in vitamin E tocotrienols on Nafld. Wonder if they play a role in this discussion on fat at cellular level.

[@jeffrey4577]

Vit d is valuable fat soluble vitamins. Along with low carb diet E helped me reverse my mafld.

[@martinirving3824]

I'm listening to the discussion around 1;57;00 about maintaining weight loss. I hear smart people, trained doctors, many I could name, talk again and again about how you just need weight loss to turn things around. Shulman, like many others, expresses frustration that people lose weight initially then slowly regain it. The assumption (which may or may not be true) is the patient is just going back to bad habits and regular diet.... What about the idea that the body has adapted to the new protocol that worked initially but is now less effective as time goes by? Isn't this an indication that the protocol isn't actually working, at least not in the long term? I would argue the best protocol is some sort of intermittent fasting regimen, whether it be 16;8 to 20;4, Mosely protocol - 5:2, or alternate day. The body works better (more efficiently) with intermittent deficits, not steady-state "balance" that that may be optimal for a top-down engineered machine.. I think the medical establishment and the fitness industry really needs to appreciate this. The calorie model is just not adequate for a biological machine such as a human.

[@Greg_Chock]

Shulman might be frustrated but Peter is a promoter of time-restricted diets and has had Jason Fung among others on his podcast.

[@richardzhang8312]

Shulman never said that you cannot do that; everyone has their own bias, and what works for you might not work for other people.

[@veraarena1583]

Excellent explanation of insulin resistance and its serious chronic health consequences! Congratulations to Dr. Attia ( great questions) and Dr. G. Shulman ( I’ll follow him now). Thank you!!

[@erastvandoren]

However, Attia still fails to make the transition to the diet.

[@allanchino35]

I still have some questions about what was said if anyone would be nice enough to answer. ​So they said that sucrose and fructose predispose the liver to nafld but it’s the insulin resistance in the muscle cells that leads to insulin resistance in the liver and fatty liver. Where do sucrose and fructose play a role if fat in the cells is that cause of insulin resistance? I don’t think Shulman ever clarified where the diaglyceride in the muscle cells is coming from - is it from dietary fat or denovo lipogenesis from eating carbs? Also, why does fat accumulate in the muscle cells before it does in the liver? I’m still very lost on how the overall pathway of muscle fat, muscle IR, liver fat, liver IR works and how this eventually leads to fatty pancreas and beta cell dysfunction. In the diabetic where all of this is happening, the liver isn’t making glycogen or fat from glucose and is making glucose from acetylcoa produced from lipolysis, so shouldn’t they be losing weight? Thanks

[@atanaslambrev8424]

Great podcast. But I have some questions. The DAG's are building up close to the membrane and block some of the glut 4 transporters and they can't fuse with the membrane. So far so good. But what is the reason for accumulation of the DAG's. Is it impaired fat oxidation or is higher saturation of lipids in the blood. Or maybe both?

[@LTPottenger]

The cause of the cell being fat is that you are constantly bombarding it with insulin and not exercising or fasting enough to reverse it.

[@atanaslambrev8424]

Yeah, that's obvious! But I was asking about the mechanism of DAG's accumulation. It will be good to know why.

[@metabolicentanglement6303]

What I see here is a pattern. When you have higher saturation of glucose and lipids in the blood at the same time, then the problems starting to appear.

[@erastvandoren]

DAGs block IRS-1, which is the first step in the insulin signaling. GLUT-4 translocation is farther downstream. "But what is the reason for accumulation of the DAG's" 1. High-fat diet -> High level of fatty acids in the blood -> Too much of fatty acids in cells. 2. High fat diet -> Insulin too low -> muscle LPL too high -> too much TGs are unloaded in muscles 3. Hardly any exercise -> overfed cells -> too much fat in cells

[@Agerhell]

@@erastvandoren A lot of people are saying that a diet rich in carbohydrates, especially in a form that quickly raises blood sugar nad fructose tend to eventually lead to diabetes. You are basically saying the opposite?

[@Xavaje]

Stan Efferdin sent me this link. What an awesome guy. 👊🏾💪🏾

[@dylantracy7784]

That’s what I’m talking about. Funky intros and masterclass sessions!

[@vulvoxify]

He made a nanoparticle formulation of dintrophenol that homes in on the pancreas and leaves the rest of the body undosed. DNP was a diet drug in the 20s and 30s. It worked and people lost weight like crazy but it caused a lot of heart attacks. The new drug bypasses the heart so it should be safe. He claimed that it cured diabetes in rats

[@nathanredmon96]

I thought I heard mention of the visual diagrams being on the KZbin version of the podcast but I’m not seeing anything here.

[@ironkitt]

1:20:18 if body has tones of fat tissue from which it can craft glucose if needed, why would it shut the glucose gates to muscle cells and liver causing lipid spill into cells and insuline resistance? In that case fasting (not starving) on keto or 24h interim fasting would trigger insuline resistance spiral that would get worse everyday, no? anybody can explain this?

[@edwigcarol4888]

Extremely interesting as long as the biochemical pathways and regulations are treated. As soon as it comes to reversing IR, Diabetes amd Fatty liver disease I will quitt this interview and switch to Jason Fung, Dr Bikmann, Dr Robert Lustig.. Jason Fung: "Fasting is profoundly different from starving". My experience: fasting can be pleasant stimulating and you know you will eat up to satiety! (No carb).. Of course: low carb, real food, time restricting eating, circadian rhythms. Cortisol ? Sleep? Breathing? Movement? I will simply tell friends: the body is made of switches. On fed state. Off fasted state. On sympathic mode, off parasympathic mode. There is no such thing like half a state.. and everything is hormonal.

[@erastvandoren]

Just forget Fung, Bikmann, Lustig. They are either morons, or not honest, and I don't know which is worse.

[@kulata]

@@erastvandoren Dude you don't match up to any of them, so calm down

[@davidleu7506]

Thank you for a wonderful master class content! just a question in relation to DAG, is DAG increase due to dietary trigleride ? if so under what circumstances( eg. in presence/absence of carb intake) ? I thought that insulin inhibits the action of LPL or is this inhibition conditional and location specific?

[@erastvandoren]

Basically what you want is low fatty acid level in the blood. For that, you need a low fat diet and not being overweight.

[@alexanderohanlon8825]

Is there no video to this?

[@MrKarolWlodarczyk]

Half way through. Did I completely misunderstand it (probably), or is he saying that fasting will promote insulin resistance?

[@patriciahoke4722]

@Mr, yes, he's saying it evolved as a survival mechanism in the face of starvation.

[@kgempel]

I feel like the gastric bypass patients are usually on a liquid diet for at least a week or so and general diet before longer. Maybe that is why you don't get the expected liver results?

[@helloman5576]

What diet does he recommend?

[@Greg_Chock]

Shulman? He said essentially whatever works - he is diet agnostic. Peter Attia would recommend time-restricted or keto if you can adapt your lifestyle to long-term adherence.

[@stoopz3634]

Intermittent fasting and exercise.

[@erastvandoren]

Obviously, his work shows that fats are toxic. Do low-fat plant-base.

[@chrisconklin2981]

Thank you for this presentation, as I have just watched the mentioned video. Dr. Lustic among many others advocate the carbohydrate insulin model. For instance I have studied Dr. Bikman and describe insulin resistance but he really does not describe the underlying process. Peter Attia's KZbin: "#140 - Gerald Shulman, MD, PhD: Insulin resistance..." or page 100 of his book give a good presentation. Bottom line is the tremendous amount of misinformation that the likes of Lustic and Bikman give is worrisome.

[@DeniseCummins]

I find it interesting that the majority of the podcast devoted to metabolism consists of very complex biochemistry. But when it comes to treatment, the discussion devolves to simple "calories in vs calories burned", or "carb restriction." These are not answers to a very complex metabolic problem. Sure, if you restrict calories or carbs, the patient will lose weight. But that is not sustainable, and it isn't because the patient "goes back to eating wrong." The problem is that the metabolic problem wasn't really fixed. For example, the patient may be told that they have to restrict calories to 800-1,000 daily and/or carbs to 20 grams daily, but that isn't sustainable in the long run. If the patient then increases caloric/carb intake to a reasonable level (that is, a level that is typical for those who don't have metabolic syndrome), they will put on massive amounts of fat. The body rebounds with a vengeance. (We saw that with the Biggest Loser study.) To solve this problem, medical researchers need to think outside of the simplistic "energy input vs energy expenditure" trope and ask the question, "Why do some individuals become obese even when they eat what is considered a reasonable diet?" Telling patients to somehow find a diet that works for them constitutes handing the problem back to them. Maybe, just maybe, the problem isn't diet at all.

[@LTPottenger]

It doesn't work like that at all. Insulin resistance isn't obesity and you can be very fat without being insulin resistant and losing weight won't necessarily help at all. Reducing the CARBS does not need to reduce calories and the point is not to lose weight. These people are insulin resistant in the first place largely due to eating way too much carbohydrate especially simple carbs. Simple carbs are not good for you and should not be eaten in the very large amounts. If you ate 300 grams of carbs eating beans you would probably not have too much problem but if you eat the RDA of 300 grams of carbs with bread, soda and the other garbage most people do then you can be almost 100% sure you are overeating carbs unless you are extremely active. Insulin resistance is mostly caused by the liver becoming overstuffed and then fatty. If your liver is not fatty you don't have insulin resistance, if you do you are on the fast track to t2 diabetes. Fructose and alcohol are very very hard on the liver and can only be processed in the liver. If your liver glycogen is full then there is nowhere else for the fructose and alcohol to go but turn into fat. The more fat you have in your liver the more sugar your liver shoots out and the smaller the glycogen store becomes because it is damage. So to lose insulin resistance forget about weight loss, it doesn't matter how much your weight is only your liver fat. To fix this reduce carbs FOREVER to much more reasonable levels or even down to zero for a while and NO SIMPLE CARBS AT ALL. Exercise as well as this will get rid of the excess sugar and liver fat. Do some fasting as ALL the weight you lose in this manner will come from your liver fat directly. DO NOT do a low calories diet for long periods, though you can do it for short periods of a week or less at a time without reducing the metabolism too much. High insulin reduces your metabolism as well so if you can reduce carbs then fat will naturally tend to come off anyway so if you are too fat this should help in that regard as well. When you fast it actually raises your metabolism for the first three days so if you want to get rid of t2 diabetes and insulin resistance then doing a schedule of fasting like eating every other day is the fastest way. Eating foods like egg with choline also reduces liver fat. Vegetable oils also cause insulin resistance and are one of the big problems with processed foods. So if you avoid these bad foods and eat some of the better ones like egg and do occasional fasting then you can eliminate this problem basically right away. If your actual pancreas is ruined it is much harder to recover but if it's still OK then t2 diabetes can be eliminated basically overnight if you change your behavior to stop eating modern garbage food.

[@dana102083]

Agree with Pottinger's Human. Completely. An addition, humans were meant to have subcutaneous fats, not visceral. Humans were meant to eat when it was available and fatten up, and then use fats for ketones efficiently to support our very large brain size and our reproductive capabilities. The whole point is that we evolved tapping into both amd we need to emulate our ancestors. Agriculture is relatively new and metabolically healthy people are hard to come by. Top 4 changes are 1) eliminate refined sugars 2) eliminate refined grain, especially wheat 3) eliminate processed factory fats 4) eliminate transfats. High fructose foods should only be consumed if having intensity exercise and in small amounts..and best in some ancestral form, like honey.

[@DeniseCummins]

@@LTPottenger no one said all obese people are insulin resistance, nor that insulin resistance always leads to obesity (e.g., “skinny fat”). But insulin resistance can indeed lead to obesity. To deny that is to deny facts. Fasting can help reverse the condition, but it must be done carefully. Simply putting people on unsustainably low calorie diets and then blaming them when the “edit” fails may make thin people feel smugly superior, but it doesn’t solve the problem.

[@DeniseCummins]

@@dana102083 well, you can continue to insist that the only reason people get fat is because they eat too much and exercise too little, or you can actually update your prejudices to bring them more in line with facts.

[@LTPottenger]

@@DeniseCummins You are wrong, not much else to say. If the 'calories in calories out" nonsense worked no one would be obese in the first place, it is just a slogan made up by a coca cola thinktank to make stupid people think it's ok to eat sugar but it's not, it's very unhealthy. When people eat low carb or fast they don't flame out and rebound, they break their dependence. If you are insulin resistant it is the only way to get over it with a reasonable success rate. When you get a t2 diabetes diagnosis the average life expectancy is ten years, that is all you will get out of the CICO mantra. Do the same thing you get the same result, what a shock. Expecting otherwise is the definition of insanity.

[@jaym9846]

In a healthy person, what controls the entry of fats from blood stream into muscles? Lipoprotein Lipase? Where does LPL come from and what causes it to be released?

[@jamesgordon8867]

Inflammation response to photobiomodulation?

[@usama1532]

Essentially, seems as if intracellular DAG in the myocyte is the root cause of insulin resistance. And there seems to be a reason evolutionarily for increased DAG in the myocyte. But if this was preserved from fruit flies to humans, it seems as if every human in the world should be primed for insulin resistance as a protective means during starvation. Why is that we see some people are innately insulin sensitive, even some that are overweight? As a contrasting example, the sickle cell gene variant occurs in certain humans as an evolutionary protection against malaria, but this gene sequence has only diverged amongst humans (I'm assuming, don't know if other species have sickle cell or can get malaria). Why are only certain humans disproportionately affected by insulin resistance in the muscle? Also during the podcast, Dr. Attia mentioned that they know where the increased DAG is coming from but I'm confused because they alluded that increased DAG in the muscle cell is due to fatty acid flux dynamics, which seems to be genetically determined? Can you help please clarify this??? Thanks. - Dr. Usama Siddique MD

[@martinirving3824]

"Glucose disposal." Interesting terminology. Makes it seem like it's garbage, waste, or litter. Maybe it is. But it is a useable fuel that needs to be reallocated from the blood stream to storage relatively efficiently. The main problem is people are overfed and overfat. The body becomes focused on burning glucose - glucose-centric metabolism. The solution? Eat less glucose-generating foods and eat less frequently - two meals or even one meal per day.

[@stoopz3634]

I think you have it backwards - its not because they're 'overfed and overfat'. Diabetes is a hormone problem. These people who are insulin resistant overeat because they are starving on a cellular level. Hormones such as leptin (known to increase insulin sensativity) don't act the same way in resistant people. Dr. Shulman and his wife Dr. Petersen have published countless papers on issues such as this. Tldr: You don't get fat because you eat to much. You eat too much because you're fat (or insulin resistant). Also, uncontrolled/elevated blood glucose IS clinically shown to be a major health detriment - its horrible for your arteries and veins. Poor blood supply to the eyes: retinopathy. Poor supply to the feet - infection, gangrene, necrosis, amputations. Effect on the heart: Cardiac diseases explode.

[@martinirving3824]

@@stoopz3634 , Yep, this is also what Gary Taubes and David Ludwig have been saying for years. No one listens. This is because the solution to controlling hunger is eating less carbohydrates, particularly refined ones. Why, then, are we talking about "glucose disposal" from the blood stream rather than not eating glucose producing foods in the first place?

[@stoopz3634]

@@martinirving3824 I'd agree restricting carbs helps some people or consuming alot more fiber. There are also populations that do quite ok on high carb diets like the Japanese. Their culture is different and consume a lot less sucrose.

[@jellybeanvinkler4878]

@Erast Van Doren no need for derogatory name calling. 😞

[@parrisgjerde9212]

Does adopting a plant based diet, no nuts or oils, help with type-2 diabetes?

[@markt9075]

What amazes me is that this gentleman has spent his entire career elucidating the mechanisms by which carbohydrates induce insulin resistance and type 2 diabetes, but apparently (1:45:00) it has never occurred to him to solve these problems by restricting carbohydrate intake. It is the government-recommended low-fat diets that have been an abysmal failure; low-carb diets are sustainable in the long-term due to the satiating effects of their protein and fat content.

[@jaym9846]

I think he said fat-derived DAGs in muscle cells cause them to resist glucose. Some can reverse diabetes on a potato-only diet.

[@SteveHazel]

can we please please see the cartoons for free? so where are the DAGs that stop glucose transport coming from? diet? or is it generated by fat cells when they're over-insulin-sensitivized by omega6s as Peter of hyper lipid blog points out? Where do these DAGs originate?

[@liutasx]

DAG are synthesized then body is in calorie excess. Over 90% fats in DAG's comes from fatty acids, also body can synthesizes from carbohydrates if body have calorie excess. One fatty acid molecule in DAG's is saturated fatty acid another unsaturated. Peter hypothesis is incorrect, not going deep peroxide generated in mitochondria from electron transfer chain complex 3, can only reach cytoplasm and regulate insulin sensitivity. Not from complexes 1 or 2 about which Peter talks. So it's irrelevant how that fatty acids are metabolized, because complex don't discriminate between NADH or FADH2, because it receive electrons from ubiquinol (kzbin.info/www/bejne/bpXSn2OImLadgq8 ). All boil down to energy balance.

[@SteveHazel]

@@liutasx weird :) consistently one fatty acid of the 2 is unsaturated? i'd guess monounsat then? i thought the body generally preferred making triglycerides out of sat fat. are there any other conditions than just calorie excess where DAGs might be made? Very interesting. I'm just a computer programmer, but this biochem stuff is so interesting.

[@liutasx]

@@SteveHazel en.wikipedia.org/wiki/Diglyceride#Metabolism : Since diacylglycerol is synthesized via phosphatidic acid, it will usually contain a saturated fatty acid at the C-1 position on the glycerol moiety and an unsaturated fatty acid at the C-2 position. It's not clear cut. DAG is energy source in muscle. Athletes have higher content of DAG, but have normal insulin resistance. www.ncbi.nlm.nih.gov/pmc/articles/PMC3178290/ : Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. In one context DAGs are energy source in another they block insulin signaling. I think that insulin sensitivity depends on energy status of cell. I don't know how much you have understood from Peter from, but I recommend to read this article, I hope will understand something :DDD (www.ncbi.nlm.nih.gov/pmc/articles/PMC3313496/ ). I'm opposite, I was biochemist, but now have transitioned to programming :D

[@SteveHazel]

@@liutasx i won't be transitioning to biochemist :) but it sure is interesting - thank you so much for the links and info - i'll be studyin' up :)

[@LTPottenger]

Saturated fat is nothing to do with anything in fact it is the safest energy form you can eat. There is no reason to care about DAGs or even triglycerides from the layman's standpoint. If your insulin is very low and triglycerides very high for example, you could be fooled to think you are storing a lot of fat which is what makes triglycerides bad, but in a low insulin state you are not. So it is basically useless info to try and optimize just like most blood tests are. When you eat excessive carbs especially simple carbs, you get insulin resistance. Same with vegetable oils. Basically your liver eventually gets fatty from eating these and then it shoots out lots of sugar into your system and the rest of your body simply cannot soak it all up and you get insulin reistance. Once this happens to the extent your liver is damaged and you cannot store glycogen in the liver then you immediately get t2 diabetes, like flipping a switch. You are just constantly shooting out sugar. To solve this exercise at moderate to low intensity or with HIIT training, eat lower carb and eliminate simple carbs especially fructose, remove vegetable oil from the diet, do some intermittent fasting, avoid alcohol. Do all this and you can very quickly reverse the issue but if you just try and do what the typical doctor says or to "lose weight" you will eventually wind up on insulin if you already have a problem.

[@kulata]

This guy's version of insulin resistance is different from what I've heard. Interesting though

[@erastvandoren]

It's not a version, it's the truth. The scientific consensus. Fats are bad. kzbin.info/www/bejne/m5-sp5l5bp1oi5o

[@patriciahoke4722]

go away@@erastvandoren

[@jamesgordon8867]

What about fat with protein?

[@adomasjasiukenas1425]

Wow, this is so super different from Roy Taylors work. Strange. :) I think you are going too deep into the waters where there is nothing to look for, but you sound smart, that is great. Would be interesting to know what do you think about R. Taylor and his work in this area and his proposed mechanism of diabetes, which I believe, is more convincing.

[@vin6455]

Trying to sell more for pharma.... Try something practical...intermittent fasting

[@jaym9846]

People want to enjoy Micky D's without Metabolic Mayhem.

[@TinselDoll]

The fact that Shulman failed to discuss time restricted eating and focused on pharmacologic interventions is all you need to know about him. This episode was my first listen (as a podcast, not here) and I immediately unsubscribed from Attia's podcast. The fact that he did not bring it up this time, is also all you need to know. Shulman needs to protect his little niche? At some point all I heard is "caloric restriction", blah, blah, blah, "pharmacologic" treatments, blah, blah, blah. All the cell science presented here does not make up for the clear abdication of duty by both.

[@AI-vs7sm]

I don't get it! At about 40 minutes he starts touching on the Randle Cycle, and eventually mentions Randle, but he is putting the opposite spin on every explanation that I have seen. As I understand it, ( I'm not medically trained, unless three years of you tube counts?), but, what I understand is that basically if glucose is being burned for fuel, then chemistry of the cell blocks out fat burning process, and vice versa, fat blocks glucose from being burned! So, what he is imply ing is that all the extra lipids induced in study CAUSED the problem! But, if you didn't double up the fat content, then the problem isn't magnified. Or, and please stop me if you have heard this before somewhere, IF YOU DIDNT INTRODUCE EXCESS GLUCOSE in the first place, then, YOU WOULDNT HAVE THE PROBLEM AT ALL! Being in main stream medical, it apparently hasn't occurred to you that carbs are adding excess glucose to the bodies baseline glucose and starts the cascade! How obvious does it have to be before you guys look up over the edge of your cubicle and see the rest of the picture?

[@AI-vs7sm]

Also, when he talks about being able to find IR four hours after introducing fatty acids, he is referring to glucose being used up by four hours, and NOW glucose is gone, fat is now being burned and is BLOCKING the burning of glucose, AKA, looks like IR, the glucose cannot be cleared because fat is burning. That is not insulin resistance, that is the Randle Cycle!!!

[@markran7253]

No mention of sugar consumption...hmmmm

[@bellelacroix5938]

Yes they did.

[@danieldosen5260]

This podcast could use a ELI5...

[@alexanderohanlon8825]

Parents insulin resistant or diabetic = predicter of child developing later on... So is it purely a genetic factor passed down and activated no matter what? Or is it epigenetics kicking in to switch it on? Or is it a case of parents clearly have shocking lifestyle habits thus the kid learns them thus develops diabetes/IR later on? Technically I know this sounds like epigenetic but it's not it's deeper.

[@bnmsa]

Very very interesting im a type 2 diabetic with fatty liver and messed up lipids i managed to cure my fatty liver and hyperglycaemia on change of diet and some water fasting my liver is now super healthy only thing left are my increased lipids geuss I will have to change from saturated fats to more healthier fats

[@bnmsa]

Oh yh this is without any insuline metformine and statins anyone interested in how ive got rid of the fatty liver just pm me obviously im not a doctor or anything just wanna share my experiences

[@JD-rc6lq]

My takeaway is that Mr Shulman believes he has identified the cause of insulin resistance and it is....wait for it...a fat. More of the same energy balance blah blah blah. The cell has to have a trigger for knowing when to ignore insulin signalling. He likely has identified one of those triggers. But the cell must also have a mechanism for identifying when it can not take on more glucose. If he is studying healthy individuals their glucose tolerance is likely much higher than their tolerance of highly processed manufactured oils.

[@erastvandoren]

Doctors have used low-fat diet as a cure since the 1940s. Look up rice diet and Walter Kempner. Also, DAGs and blocking of insulin signaling pathways are known for a while.

[@allanchino35]

@@erastvandorenwhat are the DAGs coming from though? Dietary fat or denovo lipogenesis?

[@erastvandoren]

@@allanchino35 There is never much DNL

[@allanhatch6219]

Excellence

[@byronquinley1400]

Sooo body fat causes insulin resistance, not simply carbs, and you need to lose fat to fix it. Exercise helps. Do I have that right?

[@Dan-jo8py]

Hue & Taegtmeyer - randle cycle revisited 2009 - already made clear that fatty acid oxidation inhibits glut4....

[@ravenjason13]

Eating too much fat and being a lazy person adds up to this problem! This is what he is saying?

[@bnmsa]

Am I the only one who’s thinking do the DAG’s come from dietary fat or…does it mean we can’t eat fat?

[@t.c.s.7724]

This interview was strangely repetitive. I thought I had accidentally scrolled backwards, but no. Conversation became tiresome.

[@EmilGigov]

I am not a subscriber but I found that some of the slides/areas discussed in the podcast are referred to in this presentation kzbin.info/www/bejne/n3PKqXmbe5pmgLc

[@erastvandoren]

Good podcast. I wonder, however, does it click in the brain? It's all there-fats are toxic. How can you still advocate a high-fat diet? Do you know how diabetes can also be cured? A week on an extremely low-fat diet. Cells are delipidated, insulin resistance goes away, patient is cured. That's why a plant-based low-fat diet is optimal!

[@erastvandoren]

Seriously Peter, your guest explains all the time how fats are bad, and you ask him at the end twice if sugar restriction might be beneficial? It's an insult.

[@michaelclayton3566]

Dear

[@netto682]

👏👏👏🇧🇷👍

[@chantallipp5773]

O

[@NoKingsNoGodsOnlyMan]

Definitely not the best health content. Try Ray Peat PhD instead

[@jaleotech5918]

This is a "pay me" and I will show you the slides discussed. For $149 dollars per year you can get what you get for free from a guy like Lex Fridman.

[@jaleotech5918]

The utter amount of laziness in not producing video is incredible. But the fact that unknown defenders pop up to defend the author makes me repeat this post to light them up.

[@dana102083]

I will wait for your video with this depth and quality.. Or are you just being lazy?

[@jaleotech5918]

@@dana102083 does Peter pay his defenders? They seem to feel as if they speak and defend him. Wtf?

[@jaleotech5918]

Not producing this in video form is just plain and simple lazy. If a kid (Lex Fridman) can put out great video interviews with intellectuals that are recorded at times in hotel rooms than a grown up with many more resources can too. Lazy that's all lazy.

[@Test-eb9bj]

Hhm, as much I would like to see a video & faces I am so grateful that Peter shares all these gems for FREE with us here!

[@farshidbondar2497]

JT, It is highly disturbing that there isn't a single bit of appreciation in your post for all the immense work, effort, and time Peter Attia is putting into his interviews with world-class researchers to share their knowledge with us for free right-away.

[@sharicreamer4514]

I'm GLAD these aren't videos. I can put them on and listen while going about my day and not feel like I'm missing anything; not feel compelled to anchor myself to a screen. I think it makes them way more accessible and convenient.

[@jaleotech5918]

@@farshidbondar2497 amazing how easily people get disturbed these days. Did someone die and make you the grand Peter Attia protectorate? Peter ignore the fools and create value at the same pace as the likes of say Lex Fridman.. Stop being lazy...

[@liutasx]

There is lecture from Gerald Shulman on things they talk from 2019 (kzbin.info/www/bejne/ip_ZnniLitmikNk ). Enjoy.

[@jnjf3]

Loved this! It would be sooo nice if this podcast was available in video too. Just a suggestion.

[@MrXrisd01]

That would be an awesome Christmas gift!

[@CampCucumber]

Pre Covid they were in person

[@JasonCunliffe]

yes & With Slides as much as possible !