It’s the Insulin, Stupid

Is too much insulin the cause of common obesity? Yes, most likely.

Here’s another embarrassing high-profile study for all insulin deniers out there: Rats genetically modified to secrete less insulin from their pancreas stay slim even on a diet that makes other rats fat. Apart from the pancreatic insulin there was no difference between the slim (low insulin) and the fat (high insulin) rats.

The researchers, publishing the study in the high-impact journal Cell Metabolism, conclude that too much fat-storing insulin is a necessary cause of common diet-induced obesity (press release).

In humans the main cause of elevated insulin is eating too much junk carbohydrates. So it’s no coincidence that low carb diets consistently outperform other diets for weight loss.

It’s the insulin, stupid.

Earlier: The #1 Cause of Obesity: Insulin

More about the free updates that people get.

More

left
Guyenet, Taubes and why low carb works 78
Before and After a Year with LCHF 25
“Even If the Scale Isn’t Changing, the Body Is” 67
Can You Prevent Childhood Obesity with a Lot of Carbohydrates? 17
Discovering Airline Diabetic Meal 109
Yet Another Example of the “Dangers” of an LCHF Diet 33
Low-Carb High-Fat Changed My Life! 34
Career Officer Challenges Doctors and Dietitians 5
Small Steps or Radical Changes? 27
Fruit is candy 154
Even Tour de France Cyclists Avoid Carbs to Stay Lean 111
All Diets are Equally Good … Or Are They? 70
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154 Comments

  1. +1
  2. Peggy Holloway
    Personally being living proof of this metabolic truth, I applaud the researchers' conclusions. I challenge anyone to live in my body for a day and continue to deny the role of insulin and insulin resistance in blood sugar and weight management disorders.
  3. Beefeater
    I have a friend who has been depended from insulin since highschool. She didn't eat healthy. Many sweets, lots of bread with merenda, pies... She used two shots of insulin a day. It was impossible for her to get fat. But since she put a small machine on her body that enables her to have insulin all day long, she has paid the price of her bad diet and has become fat.
  4. p01
    Reducing insulin levels Simply Works™. Intense anaerobic exercise and pure paleo even with starches included (after (if) regaining insulin sensitivity) puts the cherry on the cake. Everything else is just noise.
  5. Peggy Holloway
    I wish there were a way for me to regain insulin sensitivity, but I believe that my genetics made me insulin resistant by birth and I've gradually gotten more, not less, insulin-resistant despite 14 years of low-carbohydrate living. I suspect the same is true for all of my family members.
  6. Daniel FE.
    dietitian and doctors at my hospital keep insisting its "excess calories" i have spoken to them about how i think insulin makes a better case rather then just having more caloric intake, and they refuse, but i mean REFUSE to even consider this point.

    they agree that insulin helps store fat, but how they cant even consider that its insulin and not all excess calories that make you gain weight

  7. Oly
    If the "more-insulin-the-better" camp is so certain it's a magic thinning hormone, then they should start wearing insulin pumps. Shouldn't take long to answer their own questions.
  8. It is my layman opinion that "insulin resistance" should be move under "bad food, too much food" and split into three, Liver, muscle, and fat cell insulin resistance. Liver insulin resistance occurs frequently as the glycogen stores become full (after a too large meal), as does muscle insulin resistance (muscle storage full). Both liver and muscle insulin resistance must occur before obesity. Insulin resistance is what the body uses to partition where energy is stored. When fat cell insulin resistance occurs, we have a problem, diabetes. It is the inability to get glucose out of the blood that causes insulin concentration to rise, aka hyperinsulinemia. But what do I know.
  9. tess
    Peggy, maternal nutrition can also make a baby start life with poor carbohydrate tolerance! there are ways to improve insulin sensitivity, even if it can't be "fixed". :-)

    Doc, THANKS for this article!!! the more individuals in your profession who "get it" the more hope i have for the future!

  10. The original chart had "high fat diet" in place of "bad food."

    http://www.cell.com/cell-metabolism/retrieve/pii/S1550413112004536

  11. Demosthenes
    Why do we need a weak mild diabetic rat study, when the exact same phenomenon can be easily observed on type 1 diabetes patients that don't get enough insulin?
  12. Marg
    @ Drew

    I wonder who changed the words? Inaccurate reporting is something scientists/researchers are often accused of doing. It just shows that we should not always take what we read at face value.

  13. CU
    If this model is correct why do concentration camp survivors are never fat, always skinny, yet were fed a high carbohydrate diet in prison?
  14. Ondrej
    No it's calories. I know fat low carbers and skinny chocolate addicts. Calories count. Even some major proponents of LCHF aren't that fit. Did you notice? Yeah, the truth is boring and one sometimes really needs to made the full circle through all that crap back to "calories". Good luck to you all.
  15. NM
    Cu: they weren't fed a high-ANYTHING diet. They were starved of every macro and micro nutritional requirement. Even bearing in mind the minuscule amount of starch that was the basis of their meagre rations, they were all on a low carb, almost-nonexistent-protein, no-fat "diet" that couldn't sustain even their plummeting basal metabolic requirements.
  16. Zepp
    I didnt know that concentration camp prisoners have hyperinsulinemia.. could you revel some more about geting hyperinsulinemia by being a prisoner?

    Its about a medical condition, that is hyperinsulinemi!

    And its about that this condition is the cause to obesety!

    Its not about what causing hyperinsulinemia.. but it revels that obesety comes after hyperinsulinemia!

    And if those guys is right then we need to know what causing the medical condition in the first place!

    Is there somebody that have whole acces to the report, I can only read the abstract.

  17. Zepp
    If one want to speak about human metabolism.. one cant explain anything with calories.. becuse there is not a singel calorie receptor in our whole body.. one must talk about the different macro and micro nutrients.. its the only way to explain anything about metabolism.
  18. Hemming
    When I read "Johnson concluded that extra insulin produced in the normal mice by the high-fat diet caused their obesity" I'm thinking that contradicts the LCHF theory, except for if there is some caveat to the actual diet. Can anyone tell what exactly these mice were eating? I know Andreas has changed "high-fat diet" to "bad food" so at least he should be able to share it.

    I'm still a little confused if this study supports the LCHF diet as it both talks about insulin resistance and hyperinsulinemia and which way the causality goes. Can anyone (who have read the study) give and explanation to this?

  19. Zepp
    Another scientist how refers to this study.. mayby he have whole acces?

    "Type 2 diabetes is characterized by insulin resistance, and the hyperinsulinemia commonly observed in patients is thought to be a compensatory response. Yet it has been difficult to disentangle cause and effect. Mehran et al. (2012) provide genetic evidence that a reduction of insulin secretion prevents high-fat feeding-induced obesity."

    http://www.sciencedirect.com/science/article/pii/S1550413112004627

  20. CU
    This insulin, sugar, carb, fat, protein theories appear on the surface to be very plausible.

    However, I'm not aware of any clinical evidence that supports the notion that a person can't lose weight eating less total calories of whatever.

  21. Zepp
    Im am not aware of any clinical paper that says that peopel is verry happy to going hungry all the time.

    You know humans have a regulation of energy inatke that is manifested by the mecanism of apetite?

    Our apetite react on diferent conditions and can be manipulated altso.. try to eat butter on a spoon, you cant eat that much befor the aversion system react and make you want to puke.

    Ad some sugar and some flavor, for exampel choklade flavor. then you can eat a lot more.. probably more then whats healty for you?

    There are a lot of studies about energy restriction, but one need to stay on the diet to keep the weight away.. and ther is the problem!

    Peopel often come to be depressed from energy restriction a long time, and those how persist seems to develop Chronic Dieters Syndrome!

    They become lasy bums with low resting energy expenditure and gain weight and less muscles in the end.

  22. CU
    Mr. Zepp, no matter how you want to dress the monkey it's still a monkey.

    At the end of the day people loss weight because they ate less calories than they burned.

    Macronutrients are not the key. Calories are.

    There is no way in the universe that anybody can lose weight without creating a calorie deficit.

    And once you reach target weight, you have to eat the same way that got you there calorie wise.

    People re-gain weight because they return to their eating habits. They eat more calories than they burn. Doesn't this sound familiar? Eat more than you burn = gain weight and eat less than you burn = lose weight.

    It doesn't matter what you eat; eat less than what you burn = lose weight.

    Reply: #23
  23. Hemming
    I'm not sure Zepp disagrees with you. But I think his take is more that "all calories doesn't affect the body in the same way".

    Mr. Zepp, no matter how you want to dress the monkey it's still a monkey.At the end of the day people loss weight because they ate less calories than they burned.Macronutrients are not the key. Calories are.There is no way in the universe that anybody can lose weight without creating a calorie deficit.And once you reach target weight, you have to eat the same way that got you there calorie wise.People re-gain weight because they return to their eating habits. They eat more calories than they burn. Doesn't this sound familiar? Eat more than you burn = gain weight and eat less than you burn = lose weight.It doesn't matter what you eat; eat less than what you burn = lose weight.

  24. mezzo
    I wish people would stop using concentration camp survivors and their "diets" as examples. Nobody denies that fasting for a long time will make you lose weight and eventually kill you - as it did many inmates of concentration camps. They were given so little that it wouldn't have mattered if those few calories came from carbs, protein or fat.
  25. Maki
    In some other study they had called hi fat rat diet, a diet that was 40% fat, and that had plenty of fructose syrup, abstract are useless, people mean to many different things using the same wording.

    "At the end of the day people loss weight because they ate less calories than they burned.

    Macronutrients are not the key. Calories are."

    You are forgetting to give prove that macro nutrients don't influence how much somebody burns or where the calories will be stored. Human body isn't a closet system, and we are even talking about fat tissue specifically, body builders know from quite some time that ketogenic diet makes them loose fat while loosing the least amount of muscle mass.

    In the weight of the nation documentary they had shown weight watchers that walk every day, and eat ~1400kcal/day to not get fat, with exercise they should be able to eat over 2000kcal, why dietitians who were making this show didn't announce that they had disproved 2nd law of thermodynamics?

    "People re-gain weight because they return to their eating habits. They eat more calories than they burn. Doesn't this sound familiar? Eat more than you burn = gain weight and eat less than you burn = lose weight."

    When people start to eat like they were eating then they diet has the same effect of insulin as it had, so that doesn't go against any hypothesis.

  26. CU
    Mr. Hemming, there are numerous (at least 30 that I know of) metabolic ward studies where no significant weight loss difference was found among subjects that were fed high/low carb/prot/fat diets.

    But assuming that "all calories doesn't affect the body in the same way," you still need to create a calorie deficit to lose weight.

    Mr. Mezzo, the concentration camp example is not to suggest people eat a concentration camp diet. It is to prove that you'll lose weight if calories are low enough so that you create a calorie deficit, regardless of macronutrient composition.

    Mr. Mako, please show me clinical evidence showing that you cannot lose weight with high insulin even though you have a calorie deficit (you burn more calories that you consume).

    If you like the LCHF diet and it works for you, congratulations. If that's the only diet that WORKS FOR YOU, fine. But many other people have lost weight with other diets as long as they had a calorie deficit.

    Reply: #30
  27. Zepp
    CU.. nobody says that one dont need to achive a energy defiency to lose weight!

    Its only that talking about calories dont help a lot!

    Its to say that to go to the North pole one have to go to the north!

    Its trutht but no help to anybody, how they should eat to came to that energy defiency!

    Its just another platitude.. merely coming from an atitude that obes person is lasy bums that eating to much!

    There is a lot of medical conditions that make peopel geting obese, some medicines to, and a lot of heredity for insulin resistance, hypoglycemia and diabetes.

    This study only revel a singel component of the complex metabolism, and it have to be repeted to make any firm conclusions of there findings!

    And to say that macro and micro nutrient dont have any implications on our healt is to deny all knowledge about human nutrishion.. and to say that we dont need any dieticans att all?

    Becuse what they tell us about essentiall nutrient is bullshit.. the only things that counts is calories, how wee dont have any receptors at all for?

    The lesson from concetration camp diet is.. that if one dont get essential nutrients and enough of energy.. one lose weihgt and in the end one dies.. as simple as that!?

    So to say that only calories do counts.. its to saying that it is the concentatrion camp diet that works to lose weight.. and yes its works.. but you dies in the end!

    Its a full success story.. it worked, but the patient died!

  28. CU
    Mr. Zepp, you said and I respond:

    “CU.. nobody says that one dont need to achive a energy defiency to lose weight!”

    I’m glad we have a common agreement.

    “Its only that talking about calories dont help a lot!”

    I agree, You have to eat less than you burn to lose weight.

    “Its to say that to go to the North pole one have to go to the north!”

    Evidently, my friend. If your girlfriend looks like a used catcher mitt, no matter how much make up you put on her, she’ll still look like an old catcher’s mitt.

    “Its trutht but no help to anybody, how they should eat to came to that energy defiency!”

    Au contraire. It will always help if you eat less than you burn.

    “Its just another platitude.. merely coming from an atitude that obes person is lasy bums that eating to much!”

    I’ve never seen anyone become obese because he eats very little whether or not he is a lazy bum. Some of my obese friends tell me they eat like a bird, certainly like an aepyornis, the extinct 400 kg. bird.

    “There is a lot of medical conditions that make peopel geting obese, some medicines to, and a lot of heredity for insulin resistance, hypoglycemia and diabetes.”

    None as effective as eating too much.

    “This study only revel a singel component of the complex metabolism, and it have to be repeted to make any firm conclusions of there findings!”

    Metabolic ward studies clearly show no advantage for low/high carb, fat, or protein diets

    “And to say that macro and micro nutrient dont have any implications on our healt is to deny all knowledge about human nutrishion.. and to say that we dont need any dieticans att all?”

    I’m not denying. Metabolic wars studies speak for themselves. Besides, if dieticians are so good, why do we have an obesity epidemy?

    “Becuse what they tell us about essentiall nutrient is bullshit.. the only things that counts is calories, how wee dont have any receptors at all for?”

    I agree what they tell us is bullshit, but I never heard about receptors in that context. Are you talking about any of various specific protein molecules in surface membranes of cells and organelles to which complementary molecules, as hormones, neurotransmitters, antigens, or antibodies, may become bound? What does this have to do with weight loss? Please explain.

    “The lesson from concetration camp diet is.. that if one dont get essential nutrients and enough of energy.. one lose weihgt and in the end one dies.. as simple as that!?”

    Wrong! The lesson is that you lose weight regardless of diet composition if calories are less than you burn. Not every concentration camp inmate died. Many survived, all skinnier.

    “So to say that only calories do counts.. its to saying that it is the concentatrion camp diet that works to lose weight.. and yes its works.. but you dies in the end!”

    You are missing the point. I’m not promoting a concentration camp diet. No need to go that low to lose fat and reach a healthy weight.

    “Its a full success story.. it worked, but the patient died!’

    In a way, you are right. When you are dead, you lose weight. And if you cut your arm, you lose weight. So what’s your point? Are you saying we need to die to lose weight?

  29. Janknitz
    Did you see Guyenet's take on the Cell Metabolism study? He discounts the authors' conclusion because it conflicts with other studies. Maybe why it conflicts is a point of exploration, rather than to simply discount this study.

    Meanwhile, he states that "Roughly 20% of obese humans are insulin sensitive and have normal circulating insulin levels", therefore concluding that insulin resistance cannot be a factor because this small percentage is not insulin resistant.

    Perhaps there are multiple causes of obesity. Just because a mere 20% are not insulin resistant does not mean that insulin resistance can't play a role in the remaining 80%--How can one possibly ignore that number???

    Oh, wait, I remember someone else who tried to ignore a large majority population very recently. Someone who will never be called "Mr. President".

    Reply: #36
  30. Hemming
    CU - I'm not necessarily disagreeing with you. I'm just trying to explain what Zepp is thinking. Personally I do think that calories matter but also that they affect the body differently. I also think that a LCHF diet often leads you to consume fewer calories overall, which would then lead to a weight loss.
    I'm just trying to say that I don't we disagree as much, it's more about how we present our "theories".
  31. FrankG
    Focusing on calories is a simplistic approach for the simple-minded. It doesn't help... it would be like my saying "I can save on my car fuel bills by using less gasoline" -- well duh!

    Let's stop spouting platitudes and focus on the "how". How do I burn less gasoline while still getting to my workplace everyday? How do I sustainably eat to feel satisfied and stop when I have had enough to fill my body's nutritional requirements? How do I optimise the partitioning of what I eat to meet my nutritional needs -- needs which are far more than just for energy (AKA calories).

    Oh and CICO, or ELMM, or however you want to dress it up this week, is also a great tool for those judgemental folks who like to feel morally superior to the rest of us. Look around you and see for yourself just how well this fabulous piece of advice is working out. Thanks for nothing... See You!

  32. FrankG
    To expand on the car analogy:

    I could try multiple approaches to improve the overall efficiency...

    * Ensure the tyres/tires are correctly inflated and of an appropriate tread & rubber compound
    * Ensure the tires are balanced and the wheels are aligned correctly
    * Consider using a smaller tire, and/or lighter wheels, to lower the rolling resistance
    * Remove any extraneous items from the outside of the car; such as roof-racks and load-carriers than add to the weight and wind-drag
    * Remove any extra weight from inside the car; like that tool box in the trunk/boot
    * Ensure the engine is optimally tuned: use a clean high efficiency air filter, clean and gapped spark-plugs, fresh oil and filter, good quality spark leads that maintain the correct electrical resistance, clean fuel injectors, correct coolant thermostat pressure temperature and coolant level etc...

    and of course, look to your driving style -- smooth and controlled, looking well down the road ahead...

    NONE of these things directly address fuel (calories) but taken together they represent an efficiently working car with YES the net result being fuel savings BUT constantly restating "I must use less gasoline" like a stuck-record, did not get me there!

    After decades of struggling with excess fat mass and many associated health issues -- all the while buying into the moralistic advice of know-it-alls like this person who calls themselves CU -- I have now become a lean, mean, fat-burning machine... I have list significant excess fat and maintained that balance over several years now, all without starving myself.

    Reply: #35
  33. FrankG
    Metabolic Ward studies prove nothing that we don't already know: that over time (not just from one meal to the next) my nutritional intake (again NOT just energy) will exactly balance what my body uses in one way or another... and that includes FAR more variables than how many calories I burn on a treadmill*. This is a fact of nature and is as true of my own body today, as it was when I was morbidly obese -- just as it is true for every other living thing.

    The fact that these studies revealed no magical "metabolic advantage" inherent in any of the three macronutrients should be no surprise, as that would violate our known physical laws. Again, the simplistic approach of constantly restating the bleedin' obvious DOES NOT HELP us get to the "why" and "how" of the matter.

    As I recall there was a recently published study that showed those on an LCHF-type diet did in fact burn up to 300 more calories per day while at rest, than the other groups in the study BUT I have no doubt that their overall "energy balance" if measured in a metabolic ward, would still have come out "balanced".. so what does that tell us?

    * http://junkfoodscience.blogspot.ca/2008/10/first-law-of-thermodynamic...

  34. FrankG
    Those who religiously focus on metabolic ward studies seem to ignore the basic fact that energy storage and release are an integral part of our overall energy balance... a part of our homeostasis.

    In other words: a person who is gaining, or losing excess fat mass (or lean mass), is STILL in energy balance.

  35. Hemming
    After decades of struggling with excess fat mass and many associated health issues -- all the while buying into the moralistic advice of know-it-alls like this person who calls themselves CU -- I have now become a lean, mean, fat-burning machine... I have list significant excess fat and maintained that balance over several years now, all without starving myself.

    So what exactly did YOU do to lose the fat?

  36. murray
    Janknitz, regarding Guyenet's take, this study places high insulin as the cause of the obesity and insulin resistance as coming after obesity. The fact 20% of obese people are not insulin resistant does not refute the paper, which does not claim insulin resistance is the cause of obesity. Guyenet's take appears to assume insulin resistance is the only cause of high insulin levels, or perhaps he was making another point.

    Regarding "calorie is a calorie", I recall a study in which obese mice were made to starve without losing weight. Admittedly, this is a caloric balancing act. You need enough carbs throughout the day to have high enough insulin to block utilization of stored fat, but low enough calories to starve.

    Personally, I have noticed a big difference in macronutrient effect. To test a hypothesis, for 3 weeks I ate over 5000 calories per day of fat on very low carb. The result was zero weight gain. I expect the reason is that the excess fat is not absorbed through the gut. I had read a study showing cells low in energy signal to the liver to increase enzymes to absorb fat. That seemed a lot of trouble to evolve, unless fat would otherwise pass through unabsorbed. Thus my experiment. I expect one can tell whether fat is passing through by whether the feces floats or not. This is consistent with what I observe regarding times I am eating more fat.

    There are other interesting quirks I have noticed since I started measuring blood sugar and ketones every morning. I find when I restrict carbs, keep protein modest and eat fat (mostly butter) ad lib, my blood sugar drops and ketones go up and I can see my abdominal muscles more clearly the next morning. this is so reliable that I have quit using a scale and instead just use a mirror.

  37. FrankG
    @Hemming - "So what exactly did YOU do to lose the fat?"

    I started an LCHF diet (simply means "what I eat") that I see no reason not to continue for the rest of my life :-)

    Above I posed the question about what we could learn from the study showing an extra 300 calories per day at rest for the LCHF group as compared to the control groups... to me it follows on from the car analogy above: the focus was NOT simply "energy balance" (CICO, ELMM, blah blah...) but rather the focus was on making the car as efficient as possible, with fuel savings being a natural consequence of that.. among other beneficial consequences; such as a smoother and quieter ride, for example.

    In the same way my focus is no longer about continually (for the rest of my life) starving myself to lose "weight" -- as it was so succinctly put above, if all I wanted to do was to "lose weight" I could have just cut off my leg! Instead my focus has been on working WITH my body instead of struggling against it, to make it work efficiently and healthily. With one major consequence of that being that it no longer needed to hold on to excess fat mass

    AND the lesson from the "LCHF 300 extra calories study" is that to make THAT happen, macro-nutrients DO count. Why flog myself at the gym to burn 300 calories (all the while working up an appetite) when WHAT I eat can improve the at rest efficiency of my metabolism? :-)

    Reply: #39
  38. FrankG
    Just to add that I realise there are some who find it useful to keep track of calories and/or macronutrient ratios. I don't.. much like murray mentioned, I don't even use a weighing scale any more.. my clothes tell me everything I need to know.

    But for those who do like to count: I'd simply extend the car analogy to state that at times I might carefully track each fill-up and the mileage, so that I could accurately determine the fuel efficiency. These are just numbers though, they do nothing in and of themselves, and they certainly do not change my focus from the "why" and "how" of it.

  39. Hemming
    @Hemming - "So what exactly did YOU do to lose the fat?"

    I started an LCHF diet (simply means "what I eat") that I see no reason not to continue for the rest of my life
    Above I posed the question about what we could learn from the study showing an extra 300 calories per day at rest for the LCHF group as compared to the control groups... to me it follows on from the car analogy above: the focus was NOT simply "energy balance" (CICO, ELMM, blah blah...) but rather the focus was on making the car as efficient as possible, with fuel savings being a natural consequence of that.. among other beneficial consequences; such as a smoother and quieter ride, for example.
    In the same way my focus is no longer about continually (for the rest of my life) starving myself to lose "weight" -- as it was so succinctly put above, if all I wanted to do was to "lose weight" I could have just cut off my leg! Instead my focus has been on working WITH my body instead of struggling against it, to make it work efficiently and healthily. With one major consequence of that being that it no longer needed to hold on to excess fat mass
    AND the lesson from the "LCHF 300 extra calories study" is that to make THAT happen, macro-nutrients DO count. Why flog myself at the gym to burn 300 calories (all the while working up an appetite) when WHAT I eat can improve the at rest efficiency of my metabolism?

    I was just curious if you actually meant LCHF.

    Besides that, I can only say that I've experienced exactly the same as you. Except that I went from very lean to extremely lean (I have the problem of gaining weight now) by cutting exercise and eating LCHF.

  40. Ben Kennedy
    "Insulin denier"? There are many basic observations that confound the theory that insulin is the proximate cause of obsesity. For example, genetically engineered LIRKO mice have 10x the circulating insulin of normal mice, yet don't get fat. Also, in people, high circulating insulin can be correlated to higher resting energy expenditure. Obsese people release *more* fat from fat cells after eating - and so on. Guyenet covers a lot of this at:

    http://wholehealthsource.blogspot.com/2011/08/carbohydrate-hypothesis...

    Reply: #44
  41. FrankG
    So are you volunteering to have ALL the insulin Receptors Knocked Out from your Liver so we can do a human trial of your "confounding observation"?

    Read on...
    http://high-fat-nutrition.blogspot.ca/2011/05/lirko-mice-1.html

    And I've long since given up reading Guyenet's blog... he is doing a grand job of saying all the right things to keep those research grants a-comin' -- he'll go far no doubt!

  42. Ben Kennedy
    Why do you discount one mouse KO study but trumpet another? Are you volunteering to get your pancreatic beta-cells knocked out for a human trial?

    CarbSane takes on hyperlipid's analysis on LIRKO:

    http://carbsanity.blogspot.com/2011/11/bloggo-science-lirko-wars-edit...

    I've never seen Guyenet call anyone stupid either - when confronting different points of view, he offers evidence and citations - not insults

  43. FrankG
    I don't see where I "trumpet" another mouse KO study? Do you seriously accept genetically altered rodent trials over an increasingly large body of human evidence?

    As for knocking out beta cells... have you ever heard of Type 1 Diabetes? But then of course Guyenet discounts Diabetics as "outliers".

    And trust me.. you don't even want to get me started on Evil-lyn.. read these people at your peril Ben... but keep reading other views as well and please don't let them tell you what to think.. don't rely on others to interpret the studies for you.

  44. Also, in people, high circulating insulin can be correlated to higher resting energy expenditure. Obsese people release *more* fat from fat cells after eating - and so on. Guyenet covers a lot of this

    What's rarely mentioned by insulin deniers is that high circulating insulin is even more strongly correlated to... being fat.

    Of course bigger people have higher energy expenditure. It simply takes more energy to sustain a big body.

  45. Ben Kennedy
    Ok, perhaps not you trumpeting, but certainly that is the focus of the original post.

    But really, where is the human evidence of the carbohydrate-insulin theory of obesity? Directly infusing non-diabetic animals with insulin does not induce weight gain. Yes, mice aren't people, but we can still learn a lot from animal models. Here is that mouse study:

    http://www.sciencedirect.com/science/article/pii/0361923080902233

    I am genuinely interested in any study that can conclusively link insulin to weight gain in a non-diabetic scenario

    Reply: #47
  46. FrankG
    Ben - Doctor Andreas will probably bear me out on this but included in the very first advice given to Type 2 Diabetics if and when they start injecting insulin is that this will likely cause weight gain.

    Back in the days of the movie A Beautiful Mind when psychiatric (but not Diabetic) patient were given large doses of insulin to put them into comas, they all rapidly gained weight.

    Insulin is an anabolic hormone.. look it up. Look up the actions of insulin in any physiology textbook.

    Type 1 Diabetics have little or no naturally secreted insulin, so back in the day the were limited to a couple of injections a day and to play safe, rather than risk low blood glucose, they would err on the side of too little insulin.. as a result they were invariably skinny. Nowadays there are game-changing devices known as insulin pumps which continuously infuse insulin throughout the day... a much closer approximation to "normal". This technology also allows Type 1 Diabetics to eat more like "normal" people and guess what... many more of them are gaining excess fat mass along with other symptoms of Type 2 Diabetes.. double-Diabetes!

    I have given you Diabetic examples because A) I see this as perfect examples in humans of what happens with too little or too much insulin and B) the rate of both types of Diabetes is increasing at an alarming rate, along with many other metabolic issues such as obesity, hypertension, Alzheimers etc... ALL of which have been associated with high levels of insulin!

    Guyenet and Evil-lyn may like to post links to studies but I wonder how many folks critically read those studies, to see if they hold up under scrutiny. That is why I gave up reading both of them... I don't trust their word any more. That and Evil-lyn is just plain vicious and nasty.

    Then there is the whole "But I'm a *real* obesity researcher.. I have a PhD!" -- in my experience, when someone has something worthwhile to say they don't have to back it up with credentials, or other appeals to authority... their words stand on their own two feet.

  47. Zepp
    Ben.. high insulin levels that reach your brain tells it that you just have eating!

    Its the same effect after a high carb meal.. your apetite system goes to aversion of eating more!

    But its a stupid laboration.. it dont reflect an normal reaction from a meal!

    And its still not insulin thats the problem.. the problem is Hyperinsulinemia, caused by heredity, medical conditions, medecine biefects, and junkfood!

    This study only shows that hyperinsulinemia comes before obesety!

    You know insulin is an important hormone, without it you should die.

    The problem with hyperinsulinemia is that insulin is the major regulator of esterification and reesterification of triglycerides, it inhibits fatoxidation, and it promotes LPL to store more fat.

    Its the major regulator of net fat storage!

  48. Ben Kennedy
    The problem with these studies is that with non-diabetic humans, insulin sensitivity and circulating insulin rise in parallel. When you decouple the sensitivity from circulation you can certainly change fat mass - but that is not the common case in obesity

    If insulin by itself increases fat mass, then it must either stimulate food intake, or decrease energy expenditure. It doesn't do either of those things. The following study shows that when calories are held constant, it really doesn't matter what the macronutrient ratio is with respect to energy expenditure:

    http://ajcn.nutrition.org/content/54/1/10.long

    So how does chronically high insulin causes people who are not overconsuming calories to gain fat mass?

  49. FrankG
    First off Ben you need to realise the difference between Acute and Chronic in medical terms...

    an Acute illness would be something like Influenza: that comes on quickly, goes through a fairly extreme period and then either kills the patient, or is subdued by the immune system; all in a matter of a few short days

    a Chronic disease would be something like Type 2 Diabetes: that develops slowly over many months, years, or most likely decades. Its signs and symptoms are less severe and it is less likely to kill you *quickly*... although without any remedial action you are likely to suffer a slow and painful death

    In which case, I fail to see how the 7 day study you linked sheds any light on the long-term effects of high insulin levels?

    In fact it was a similarly short rodent-study that Guyenet tried to pass off as "a model of chronically elevated insulin reminiscent of what is seen in insulin-resistant people" which was the final straw in destroying any credibility he had in my estimation.

    http://wholehealthsource.blogspot.ca/2012/01/insulin-and-obesity-anot...

    You assert that "with non-diabetic humans, insulin sensitivity and circulating insulin rise in parallel" which may be true in the short term (may be why Guyenet and others only use short term studies?) BUT in the longer term, high levels of insulin will result in the down-regulation of insulin receptors (see the LIRKO study you linked yesterday). This leads to Insulin-Resistance, where even more insulin is needed to elicit the previous response, and on in a vicious cycle of increasing insulin resistance and increasing Insulin secretion; until the beta cells become exhausted and lo you exhibit the outward signs of Type 2 Diabetes.

    This "down-regulation" is very similar to folks living alongside busy roads who (after a while) no longer notice the noise of the traffic... some even have to take white-noise generators with them in order to be able to sleep when away from home.

    You go on to say "If insulin by itself increases fat mass, then it must either stimulate food intake, or decrease energy expenditure. It doesn't do either of those things."

    Did you see my comments above regarding metabolic ward studies? The people in your study where on a fixed calorie diet for a week and yet you seem surprised that the high-carb group didn't eat more? They weren't allowed to! And Seriously? Under the scrutiny of researchers who watch your every mouthful, would YOU eat as you do naturally at home?

    No, the important point that I gleaned right from the very first paragraph of the Abstract was not that "Diet composition did not affect total daily energy expenditure..." but, read on "did affect daily nutrient oxidation by rapidly shifting substrate oxidation to more closely reflect the composition of the diet"

    Macronutrients DO COUNT! On an high-carb diet we are glucose-burners (and fat-storers) on an high-fat diet we are FAT BURNERS! and guess which hormone switches us between the two... Insulin. Gary Taubes lays this all out in Good Calories, Bad Calories and Why We Get Fat

    Finally you ask "So how does chronically high insulin causes people who are not overconsuming calories to gain fat mass?"

    Is this another loaded question like CU above: with his magical metabolic advantage which breaks the laws of physics?

    Back to my Diabetic example: or talk to *anyone* who has experienced a rapid Blood Glucose drop... ask them what was their overriding need at that time. I'll save you some time because I have been there myself... the most pressing need is for FOOD and not just any food but FAST ENERGY food. This is a primal drive (like the need to breathe if you are underwater too long) because if left unsatisfied, it could lead to coma and death.

    OK so Guyenet and his ilk like to dismiss this as acute hypoglycemia (low blood glucose) and not something that happens to the general population but consider the scenario where our diet is high in sugars and refined starches, where insulin is chronically high, where insulin-resistance is starting -- causing even higher levels of insulin but still manageable by our beta cells. We are locked by the insulin into glucose-burning and fat-storing... and increased fat mass also increases insulin-resistance AND we have a chronic gnawing hunger that never goes away despite having just eaten.

    There is no magic which makes us gain fat mass without eating more BUT insulin, mediated by our choice of diet WILL effect how what we eat is partitioned within our bodies and what is available to us to use as energy, or locked away in that fat mass. If it is locked away we NEED to eat more, or find other ways to burn less energy.

  50. Ben Kennedy
    The point of the metabolic ward studies is to demonstrate that our wonderful bodies are perfectly capable of processing different macronutrient ratios without creating energy imbalance. Given that there are population groups out there that tend to be lean and tend to eat high-carb diets, this should not be surprising at all. People can be fat burners or carb burners, and they can switch fast (under the direction of insulin).

    Nor is fat somehow "locked away" in obese people. The cells of people with insulin resistance have trouble keeping the fat inside, which is why their circulating fatty acid levels are high. The problem with obese people is that they are taking in more energy than they are burning

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