Physiological Insulin Resistance

I’ve been meaning to do a deep dive into physiological insulin resistance for quite a while now, but the universe keeps conspiring to take my time.  Because I haven’t had time to read, learn more and write about it, I thought I’d share the links I have accumulated thus far. Mostly because I’ve now been asked a variant of the following multiple times, or have seen the following posted on various forums for discussing nutrition, health, and low carbohydrate diets:

“Why has my blood glucose gone up on a low carb diet?”

Typically this is accompanied by a good deal of anxiety and fretting over glucometers.

I should know, I watched my blood glucose increase by a few points as I’ve sustained my low carb diet. My understanding is that this is a known adaptation completely unrelated to the insulin resistance concomitant with diabetes.

While I’m not the person you should ask about anything health related, I’ve wanted an answer to this question myself. The explanation I’ve read is that after going low carb, your muscle tissue becomes insulin resistant in order to preserve serum glucose availability for the brain. If your muscle tissue did not do this, reduced availability of glucose in the serum could (theoretically) put you in dire straights if your brain can’t meet minimal demand for glucose. (Mind you, even on a zero carb diet you can meet all your glucose requirements via gluconeogenesis. The point is, your body needs a way to tell your muscle mass to stop taking all the glucose it makes. This is that way.)

Because of this physiological insulin resistance (which I should mention is a benign state that is not making your diabetic insulin resistance worse) you wouldn’t want to take an oral glucose tolerance test while you are low carbing.

If you took a glucose tolerance test while on a low carb or ketogenic diet, you would fail. If you need to take such a test (and you want it to be accurate), increase your carbohydrate intake to ~150g for a few days and then take the oral glucose tolerance test.  The few days of increased carbohydrate intake will apparently let your body adapt to increased carbohydrate availability and your physiological insulin resistance will go away.

At any rate, that’s my extremely flawed, 2 minute brain dump on it based on a very limited bit of reading on the subject. For the record, I discussed my increased blood sugar with my doctor. I asked him if the explanation I gave above is the reason, and he indicated it was…but we didn’t spend a lot of time on this point.

If you are interested, here are some links that I started collecting on the subject of physiological insulin resistance. Not all are good sources, some are likely blind alleys, but they were part of my research notes, so I’ll share them in the Resources section below in the hopes that they will be of use to someone.


21 Responses to “Physiological Insulin Resistance”

  1. Hi Michael,

    I haven’t gone through all your links at this time, lack of time. I find the explanations for PIR strange and have a question that may straighten out this at least for me.

    First I think that eating 150 g carbs per day for a few days would clearly “restart a dormant carb/insulin cycle”, and does not need to have anything with insulin resistance to do. Insulin resistance cannot be reveresed in a few days what I know.

    The other thing is that from what I have read it appears that blood sugar goes way over 5.5 as weight loss stalls, a high blood sugar which would be a reason to worry. But the explanation “preserve blood sugar” seems then totally flawed to as I work very well with at BS 80 (or below 4). Why should the set point suddenly shift up when BS 4 was sufficient for muscles and other only glucose dependent tissues before?

    If it is like that I would buy it, but only if it happens to (young) people that have never been insulin resistant ! Not owerweight, fasting insulin at 3-5 and good fasting blood sugar taking up a low carb diet with the PIR developing. Are there any such examples ?

    What I mean is that for older people with some overweight – those ones who go on a low carb diet for good reasons – the chain of events is different:

    First there is insulin resistance present, as it is hard to gain unwanted weight without it.

    Subsequent weight loss through LCHF reduces this somewhat and during the same time the low blood sugars starts up glucogenesis, something that have been dormant often for decades while feeding on the SAD. I call this period the “honey moon period” when it comes to weight loss and blood sugar. It may take 6 months on a low carb diet before the liver has adapted to produce the glucose not coming from the food any more, seemingly starting tp make ketones much sooner as we know.

    Nut once the honey moon is over, weight loss ceases and morning sugar starts increasing. This is what some calls PIR, which I am not quite sure it is. Only reason I can see that sugar (again!) starts to be regulated over 5.5 is that the pancreas glucagon production was out of wack before the low carb diet and is then STILL(!) out of tune. The very reason we became fat in the first place. One answer may be to get the pancreas MRI-scanned to measure the fat inside it and around it. Visceral fat (VF).

    Or just start an intermittent fasting period to get that last (skinny fat) visceral fat to go away. If people that are truly skinny can have such bad fat it does not seem strange that it is the last to remain also for people that were fat before. If it fails get the MRI scan and find out !

    The crucial fact is that a UK (Newcastle) doctor succeeded to restore normal pancreas insulin and glucagon regulation permanently for (new?) diabetics and measured the VF around the pancreas before and after. It showed a 25% reduction; indicating for me where the problem may be.


    • Hi Sten!

      Thanks for your comment! There’s a lot there, and I think my time is as pressed as yours is at the moment.

      Sitll, I’m fascinated by your explanation… and the reference to the Newscastle Dr. Do you have any links where we can read more on this?


  2. is it normal for my blood glucose to rise to 150 after a meal only of protein, fat and veggies? I’m not eating VLC, but I use coconut oil. I eat veggies, one/two servings of fruit and one sweet potato. Should I be concerned? Why does this happen? I though this “physiological insulin resistance” only happened to those who do VLC and have high fasting blood sugar. My fasting blood sugar is always 70.

    • I think what you get is perfectly normal and has nothing at all to do with PIR.
      The the food you listed contains a sweet potato and 1 or 2 fruits, suspected culprits. Suggest you leave out all of that for ONE meal and measure BS one hour after and compare with as now.
      Guess you will then be much closer to 100, implicating those carbs.
      Then add back one apple and see if you can tolerate it, and so on.
      Add salad and other greens, but skip store bought salad dressing and/or sauces in bottles as they are often packed with sugar! Real olive oil and vinegar instead.
      And if you don’t feel full add some (molten) butter on the protein which also enhances taste. Same for molten cheese….
      Good Luck!
      Google postprandial blood sugar track your plaque to see how the method above is used by a cardiologist to actually reduce arterial plaque!

  3. As far as I can tell, this notion of a low-carb diet inducing insulin resistance in peripheral tissues is an internet myth that is propagating across keto-websites. The list of references you provide mostly contains blogs, and 2 of the scientific papers (Borkman et al. and Bisschop et al.) both reported no change in peripheral insulin resistance (however, Bisschop et al. reported an increased hepatic insulin resistance). Read the papers and not the echo-chamber blogs.

  4. Hi Michael, I just wanted to say that after losing 6kg in 8 weeks by following my own low carb or virtually no carb diet, I was delighted I had also brought my cholesterol reading down from 6.4 to 5.2. I was however shocked and upset that my blood sugar had risen from 5.3 to 6.4. I was dumbfounded because I have never been healthier, and even my running time has lessened. I started reading about ketosis and low carb of which I knew nothing about, but now believe my high sugar reading must be due to my diet. It has frightened me enough though to start eating carbs again because I can’t figure out if it is ok to be in a constant state of ketosis or if I will do damage in the long run. I do feel cheated though that I finally found a diet that worked for me, but might also be bad for me. Thankyou for your article which I found very interesting.

  5. You need to cut down your evening proteins to achive better morning blood sugar. I am 68 years old and had same experience as you: after about 6 months weight stalls and morning blood sugar way too high.
    I believe it is the fat around my organs that is still left. By cutting protein -replace with fat – the system can be restored I think, but not 100% sure. Jimmy Moore did it at least, but combined with hard work outs.

  6. Duke R

    I am type 2 diabetic and I eat VLC (20-30 per day), since March I have had higher fasting (105-118) and post meal tests (5-10 carbs at most, yet a glucose rise of 50 points or better) and it has in turn caused my a1c to rise an entire point to 6.2.

    How do I break this cycle?
    While numbers like this are “fine” for norms and ADA followers, I can’t stand, emotionally, being beyond 100, yet since March I have had only three fasting tests below 100.

    My typical diet is 75-80 percent fat, 15-20 percent protein and 5-10 percent carbs.
    I am not showing ketones on the urine strip, and cannot afford a blood monitor.

    Any ideas would be truly appreciated.

    • Hi Duke,

      I really think this is something you need to discuss with your physician. They are the ones in the best position to understand your unique medical history, current context, and how this all relates to your current blood glucose levels.

      With that said, I’d like to applaud you for your diligence. Keeping carbs low is critical for Type 2’s. Please don’t read too much into the urine strips not showing elevated levels of ketones… Check out this post on ketostix for more information on that.

      And lastly, sometimes we need to separate the emotional response from what the numbers are indicating. You may be disheartened to see them over 100, but how does this compare to before you were restricting carbohydrates? Is it part of a general trend of improvement? Again, discuss this with your doctor, and check back in with what you learn. Your experience can help others…

    • Google Jason Fung as he has written a lot about this and insulin resistance. Your doctor will say that you are just fine, until the FBG is over 120, when he adds metformin, or he may suggest that already. 2 days water fast per week (2-5) for 6 months would reduce waist and thereby the underlying insulin resistance that definitely is behind. You can ask to test fasting insulin and try to get it down from maybe even over 7 now. Add vitamin C – 1gram just before every meal -. This cleaning agent (antioxidant) will then enter cells with other nutrients including glucose when insulin feed them after each meal. Do NOT eat any proteins like cheese after evening meals. Proteins raise blood sugar just over 50% of what carbohydrates do.
      Insulin resistance means that a normal healthy level of insulin is not enough to feed cells, instead blood sugar rises. I guess when morning produced blood glucose is vitalizing cells every morning instead of building up in the blood stream, insulin works well for us. I am almost sure it is the insulin!

  7. Thanks for the article. I am type 2 diabetic and wanted to know if when you say 150gr of carbs for 3 days prior to taking the test you mean a weight of 150 grams or talk about macronutrients, because I ve been eating vlc for a while now and usually every 100 grams of let’s say pasta there is only around 70 grams of carbs, and 100 grams of pasta is A LOT of pasta (pasta is just an example, sorry english is not my first language (: )so I would need to double that amount and more for a few days.. ? It kinda worries me to be honest, but I’d be really thankfuk if you made that clear for me please because health comes first 🙂
    Thank you.

    • Hi Marta!

      The recommendation I’ve read is for 150g of carbohydrate macronutrient per day (not per meal). So if you ate a 3 meals in a day, and each included 50 grams of carbohydrate, you would meet that recommendation.

      Is that a little clearer?

  8. At last I may have the answer to the initial question, what is PIR? From the answer follows also the solution to it, if correct. “PIR” is simply a manifestation of insulin resistance of the liver: Our tissues take up glucose with elevated insulin, while our livers stop producing glucose when insulin is elevated , all relative. The insulin resistance effect on our cells is that cells become starved of glucose while the blood stream is packed with glucose. When it comes to insulin, insulin resistance means that the liver is no longer able to respond to elevated insulin and shut off/down glucose production.
    While we are awake our use of glucose is usually high which typically means stable blood sugar on low carb. During sleep however, especially during deep rest, glucose consumption is reduced and if the liver is not reacting quick enough on resulting elevated insulin, there can soon be noticable excess. But same problem will (what I know) not appear among nondiabetics that eat standard high carb food as their liver production of glucose is virtually “gone to sleep” on their high glucose diet. This very effect becomes the prime reason for the long induction phase or “honeymoon” low carbers can get initially, as it takes maybe 6 months for the liver to get glucose production up to a point where it can have this effect on morning sugar, when the liver remains insulin resistant. Without insulin resistance like for younger only overweight subjects, the problem may never arise.
    The obvious route to reduce insulin resistance is choosing less insulin elevating foods. This works because high circulating insulin increases insulin resistance while low enough circulating insulin reduces it. Proven in studies. Eating any insulin elevating food in the middle of the day and/or reduced protein intake considerably at evening meal can solve this serious dilemma for low carbers. Of course exercise and weight lifting helps too as it often direct depletes any glucose stores, as long as not replaced.
    Reduction of proteins at evening meal will work with a double whammy: Immediate shortage of raw material for gluconoegenesis during the night mean less insulin issued with normal blood glucose, and less insulin overall due to lower consumption of insulinogenic foods. To manage the evening meals with about half as much protein as before, extra virgin olive oil sprinkled generously over stake or fish helps me greatly.
    I have to get a refill for my blood glucose meter to see the progress now. After all, the simples way to measure remains the blood glucometer. I will report back!


    I’m not certain where you’re getting your info, but great topic.

    I needs to spend a while studying much more or working out more.
    Thanks for excellent info I used to be looking for this information for
    my mission.

    • Check two articles by Jason Fung
      “Can a single gram fat loss reverse DB2?” here:
      and his take on the Dawn Phenomena:
      His interpretation diverge from the idea of “physiological insulin resistance”. He means that when the liver is “full” of sugar in the morning and is given the hormonal signal to get us ready to awake, the release of glucose is higher than if the liver is less full or less fatty. See the link for details of his explanation.
      I read it some time ago and my own understanding now is that a worsening of the dawn phenomena is our western(?) habits to have main meal in the evening. We then fill up more than we consume the rest of the day meaning that the liver on average will be fuller at night than if main meal was at mid day or at breakfast!
      The old saying “Breakfast as a King, Lunch as a Lord and dinner as a pauper” could be a good pointer.

  10. I have new BG data on my PIR (I hope its just PIR and not some strange illness). As many of you, I wake up with 90-105 mg/dl FBG. When I start to move around (some stairs) etc., my BG
    drops to ~80-85 in 20-30 minutes. If i choose to do light exercise (push ups, sit ups )I can easily drop my BG to 60-70 depending on exercise intensity. All this without eating in fasted state (I do not do breakfast).
    However, if I stop be active and lay down or sit down in front of computer for ~30 minutes, my BG builds up back to 90-95. Same things later at work- after working/sitting BG aroung 90-95. Moving and walking brings it down 80-85. Getting more intensity bring it down to 65-75. Getting back to the chair for 30 min gets me back to 95. Similar picture after eating, activity bring down whole BG profile by ~10 points.
    I am in mild ketosis 0.3 mmol/l in the morning and it slowly builds up to 0.8 in the evening. My ketones do not react to these wild BG swings at all. My HbA1c is 5.1%. Fasting insulin was 4.8 last time measured (2 month ago). I lost 25 pounds in 18 months by eating 1500 Cal (20-30 grams of carbs,~80 grams of proteine). Current weight-170lb, height 174 cm. Feel good, not starving at all, sleep well. Walk 5 miles everyday, with HIIT 2 days a week.
    I am observing this pattern for 3 months now, since the moment I discovered it. It is very consistent. I wander if glycogen shortage is doing this to me, since I have a little buffer and body taps directly in to BG for its urgent needs and then slowly restores BG back?


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