Insulin resistance is a spectrum

The history of low fat diets is riddled with crappy low fat food-like products.

Food quality matters.

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Take a group of obese people and assess insulin sensitivity however you like: some researchers demand nothing less than a hyperinsulinemic-euglycemic clamp (Gold Standard), others are OK with insulin levels during an oral glucose tolerance test.

Next, divide the people up based on this — there are a few ways you can do it.  You can: take the top half vs. the bottom half (a method which includes everyone); take the top third vs. bottom third (excluding the middle third); take the top quarter vs. bottom quarter (excluding the middle 50%), etc.

THIS MATTERS because in referencing this topic, many people claim most obese are insulin resistant.  They may be more insulin resistant than lean people, but even within obese people, there’s a spectrum, and the spectrum matters in this #context.



In Gardner’s recent study, he chose the first path, ie, included all patients, and divided them in half based on insulin levels during an OGTT.



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  • Very nice 😀 I like how these “insulin sensitive” populations would probably be considered “insulin resistant” by lean-person standards, and yet the functional difference in diet macronutrients was so significant.

    The low carb diets used are also definitely not ketogenic, which likely takes any of the effects of ketone production out of the picture. ie: this is quite a fair comparison of fatty acid metabolism vs carb metabolism in the face of higher level insulin mechanics.

    Peter @ Hyperlipid is spot on with the mechanics, like how predominantly fatty acid metabolism would lower delta psi at the mitochondrial level and reduce the action of insulin on a cell. But this doesn’t account for higher level feedback mechanisms that govern everything from how much insulin is secretion, to how much of an effect an amount of insulin has on a cell.

    Yes, in a particular cell, lower delta psi means lower insulin action, but how do we know that an absolute measure of delta psi confers the same physiological effects on different people? Low level mechanics are good for discussing direction and likely effects of a change, but those signals still needs to be interpreted by many higher-level components (mtDNA, nuclear DNA, cell membrane, groups of cells, entire organs, entire systems of organs, hormones, etc ….)

    Incidentally, those low level mechanics would probably explain the added insulin resistance experience by the “insulin sensitive” groups on higher fat diets. It’s almost like these people “require less insulin to drive metabolism” and “easily short-circuit themselves” when physiologic insulin resistance is forced through a higher fat diet.

    Anyway, I like this 😀 I good showing for how high and low level mechanics interact in the context of a real diet.

  • Gearoidmuar

    Good stuff Bill. I’d read this stuff before but you summarised it well. My own experience was losing 20lb just not eating sweet things and eating starch fruit etc. After 18m I’d regained 7lb and I was always a bit hungry. Went lchf. Lost 26 lb or so from that starting point and have kept it off two and a half years. I’m deffo in top half. Real food really works but refined carbs should go for all and high load carbs for IR. People should not fear natural fats. Seed oils are devils’ juice.

    • “Real food really works but refined carbs should go for all…”


  • rs711

    Corniet et al.: randomized for 16 weeks to either a
    – Standard control diet (55% CHO, 30% fat, and 15% protein) for 3 days
    – Hypocaloric diet (400 kcal deficit/d) comprised of either
    – 60% CHO, 20% fat, and 20% protein (HC/LF)
    – 40% CHO, 40% fat, and 20% protein (LC/HF) for the following 16 weeks

    Pittas et al.: randomized for 24 weeks to either a
    – high–glycemic load diet (60% carbohydrate, 20% protein, 20% fat, 15g fiber/1,00kcal) mean estimated daily glycemic index of 82 & glycemic load of 116g /1,000kcal
    – low-glycemic load diet (40% carbohydrate, 30% protein, 30% fat, 15g fiber/1,00kcal) mean estimated daily glycemic index of 53 & glycemic load of 45g /1,000kcal
    – at 30% calorie restriction compared with baseline individual energy needs

    Ebbling et al.: randomized for 6 months to either a
    – Low–Glycemic Load Diet […] target macronutrient composition was 40% of energy from carbohydrate, emphasizing low-glycemic index sources, 35% from fat, and 25% from protein
    – Low-Fat Diet […] target macronutrient composition was 55% of energy from carbohydrate, 20% from fat, and 25% from protein

    Amongst the 3 studies the LowEST-carb diet contains 40% carbohydrate. Who here thinks this is actually low-carb? For a humming bird it’s super low-carb…

    In evolutionary terms, 40% carbohydrate is on the high-carb end of modern-hunter gatherers (see Ströhle & Hahn 2011).
    In modern terms, 40% carbohydrate is your average ‘moderate-to-high-carb’ diet.

    In neither case is it a low-carb diet – not by any reasonable definition.

    If the “LC=>IR LF=IS” distribution is true, as you argue Bill (it could very well be), I don’t see how it’s supported by these 3 particular studies (or Gardner’s for that matter).

    • there is some evidence that suggests lowER carb may not have produced greater benefits (in either population?)

      • rs711

        yeah very possible, if not likely Bill.

        But those 3 studies are useless in helping us answer that question :/

  • Wab Mester

    “people spontaneously eat less and lose weight (for whatever reason)”

    I want to know that reason. Seems kind of key. What aspect of processing transforms “healthy whole foods” to evil obesogenic foods?

    A low-carb diet tends to be a whole-food diet. And it tends to be low glycemic. And it tends to be ketogenic. So why wouldn’t it tend to be the best diet for all, even those with above-average insulin sensitivity?

    IOW, by what mechanism would a low-fat diet lead to more weight loss than an isocaloiric low-carb diet?

    • “IOW, by what mechanism would a low-fat diet lead to more weight loss than an isocaloric low-carb diet?”

      if truly isocaloric, then increased energy expenditure could account for the difference

      also, wrt “ketogenic,” check out this post:

      • Wab Mester

        B-OHB was .2 vs .33 mmol/L on low vs lower. Both below what keto-fans would call “keto.” Would love to see a bigger difference. I’m not convinced there’d be a big impact on short-term weight loss, but maybe appetite.

        In any case, I’d love to see the debate shift to long-term sustainability. If IS vs IR helps people find their groove, that’s a Good Thing.

        • imo, ketones don’t need to be elevated in this #context, see:

          as to “long-term sustainability,” the studies will never be “long enough” for many people’s satisfaction, but Gardner’s follow-up is 1 year which is pretty long! (as far as diet studies are concerned)

          • rs711

            wrt weight loss, ketones are sometimes a useful surrogate marker for where one wants/needs to be, but certainly not a weight loss marker in & of themselves.

            Some people have a ‘normal’ appetite & just pile on the flab. Some people have a voracious appetite & can’t on body fat if their life depended on it.
            Clearly, this tells us that keto’s appetite suppression is will be more or less helpful for fat people depending on the nature of their appetite.

          • Wab Mester

            So a theory emerges: two classes of fat people with broken appestats. One (IR) can be fixed with low-carb. The other (IS) can be fixed with low-fat.

            Or somehow both are fixed by “whole food” and IR subset reaps additional benefits from low-carb.

            I lean towards the latter. Still would love to know mechanisms of appestat dis- and re-regulation. Also would like to see clear separation of health benefits of weight loss vs carb restriction (also perhaps vs simply not being in a state of chronic excess consumption).

          • rs711

            “2 classes of fat people with broken appestats” ==> Not necessarily.

            Skinny fat people can have poor body composition (high %body-fat & low non-fat mass%), which by definition means inappropriate accumulation of adiposity & possibly its distribution (think lipodystrophy for an example of the latter).

            However, a dysregulated appestat is often a major cause of overeating (duh, sort of a truism) & unfortunately tends to synergize with the divergence of calories for storage in adipose tissue rather than being burned off as heat, NEAT or being heard as the “i’m full, stop feeding me!” signal.

          • Wab Mester

            Yet another spectrum: efficiency of fat storage. Probably a factor in the health effects of overconsumption. Those who can’t grow new adipocytes fast enough suffer additional damage from ectopic fat.

            That could be the difference between IR and IS.

    • David Birsen

      “people spontaneously eat less and lose weight (for whatever reason).” This phenomenon doesn’t seem so mysterious to me.

      Most processed, low-fat foods (think pretzels, chex-mix, etc.) contain additive seasonings/flavoring that would never be present in the whole-food form.

      These additives create temporary psychological addictions of some form, leading to excess consumption. This is similar to the “potato chip is just a vessel for delivering salt” idea.

      The food industry is pretty good at optimizing consumption, taking the “bet you can’t eat just one” approach.

      • Wab Mester

        Right. Hyperpalatability. It explains some binge behavior, but what about satiety and longer-term appetite control? That seems to be the domain of leptin and other factors.

        Binge/snack on almonds, for example, and they say you’ll eat less for dinner.

        • David Birsen

          I would hypothesize it explains “a lot” of binge behavior, which may or may not be a major factor in excess consumption.

          I agree the mechanism of satiety/longer-term control remains unanswered. We know that keto dieters may experience suppressed appetite (reduced carb craving makes sense).

          Regardless, whole foods seem to result in people eating less. In the pursuit of designing an ideal personalized diet, regardless of the individual, I think whole foods is key.

          • “We know that keto dieters may experience suppressed appetite (reduced carb craving makes sense).”

            We now know this happens this happens with a whole-food based low fat diet, too! Gardner’s study showed the spontaneous reduction in appetite was roughly equal on both diets and similar in magnitude to other keto studies.

          • jasmine johend

            I’ve spent years and years looking for weight loss/appetite control/maintenance, experimented with just about everything. In the end it’s come down to the plates they sell in the pharmacy, half the plate veggies, the other half divided between whole food starchy carb and meat. I usually IF but if I wake up with hunger a bowl of steel cut oats with blueberries nuked in water will satisfy me to dinner. A fatty or protein breakfast never worked for me, it just awoke the hunger beast all day/evening. My point is if one is struggling with HFLC maybe try slowly adding more WF carbs in rather than more fat.

          • “My point is if one is struggling with HFLC maybe try slowly adding more WF carbs in rather than more fat.”

            seems pretty reasonable (with stress on the “WF” part)

          • jasmine johend

            Oats, beans, cooked/cooled potatoes – that’s about all I am prepared to add in anything else might cause a southerly spiral 🙂 but it’s a far cry from the days I avoided carrots/onions due to the starch/sugars.

          • Eve

            Suppressed or regulated? For ex., I never had the reduced appetite, but I was eating relatively nutritious foods compared to the SAD. I also wasn’t starting from an obese weight, and I made sure to supplement Mg and K.

        • ^^^ yup, nuts are “good calories”

        • I binged on almonds last night, then ate less for dinner (two eggs and a salad). Almonds have fiber!

          • fiber is probably part of it, but maybe not the whole picture…


          • Cool. Yes, this is anecdotal, but I “know” when my bowels contain fat. (Mostly, I eat < 10% fat, whole-food vegan, so I "know", trust me.) And last night, they contained fat.

          • wow, <10% fat !

          • Yeah, Dr. John McDougall and Durianrider got to me first. Lost 25 kg that way.

          • I love you Mr. Vegan. We mean you no harm. Enjoy the potatoes.

          • Joe Hufford

            You built a food locker? Awesome! I built one a few years ago to help me limit my junk food intake.. Now I find it just easier to stay away from junk food entirely. The food locker is a will power extender, or The Willy Extender as I affectionately call it. (please excuse the crudity of the construction, not my forte… but the electronics are top notch, ain’t no one pack a piece of perfboard better than me!)

          • Yep, it’s a lot easier these days with $25 touch screens. I lock up anything I’ll inhale. I don’t buy junk, but I lock up my bread. That kind of thing …

          • Mind. Blown.

          • Eve

            Raisin Bran? Don’t. Understand.

          • Incredible sale, $1.88 per box.

    • CynicalEng

      has anyone tabulated the calorie “deficit” differences in these study arms. When the “right” combination delivers a better weight loss with statistical signficance what does the energy balance look like.

  • Nutty_da_Squirrel

    “Worldwide diabetes prevalence has quadrupled since 1980″…

    Not to mention metabolic syndrome:

    Gee… I wonder why? It must be from eating too much protein and fats!

    • I think it’s the brain becoming insulin resistant – eat carbs, not full. Brain doesn’t get satiety signals.

      Brain not rewarded, people keep eating.

      Taubes/Ludwig reject the brain as being significant. They should incorporate it into their hypothesis.

  • see: the Sears study (ie, Rebuttal #2)

    people on 5% carbs lost LESS weight than those on 30% carbs

    • CynicalEng

      The Sears study is Conflict City, AZ. When the lead author is testing a diet he published using staff he employs I’ll pass on that. It was also a re-run of a previous study that trashed his diet, and magically came to the opposing conclusion.

  • David Birsen

    Totally agree that IR is a spectrum and nutritional decisions should be personalized.

    However, I think most would agree the surprise here is that the IS group performed worse on LC/HF than HC/LF. My skepticism with this finding is that the fat in the LC/HF diet was primarily based on “fattier cuts of meat.” We know that animal-based saturated fat is only one form of dietary fat.

    My point here is that we shouldn’t take the “LC/HF diet was worse for the IS group” conclusion at face value. This is an oversimplification of dietary fat.

    What if the LC/HF group had consumed zero animal-based saturated fat and instead replaced it with monounsaturated fat, plant/animal based Omega-3, and MCTs? The results for the LC/HF group may have looked drastically different. We know that different fatty acids are metabolized very differently in the body, so I think it’s irresponsible to oversimplify what a “High-fat” diet looks like.

    • “My point here is that we shouldn’t take the “LC/HF diet was worse for
      the IS group” conclusion at face value.”

      I agree! Those in the IS group lost weight on either diet, so I don’t like to think of it as “they did worse…”

      I also agree with your comments about dietary fat quality.