Tuesday, October 23, 2007

Physiological insulin resistance

Back in mid summer 2007 there was this thread on the Bernstein forum. Mark, posting as iwilsmar, asked about his gradual yet progressively rising fasting blood glucose (FBG) level over a 10 year period of paleolithic LC eating. Always eating less than 30g carbohydrate per day. Initially on LC his blood glucose was 83mg/dl but it has crept up, year by year, until now his FBG is up to 115mg/dl. Post prandial values are normal.

He wanted to know if he was developing diabetes.

I've been thinking about this for some time as my own FBG is usually five point something mmol/l whole blood. Converting my whole blood values to Mark's USA plasma values, this works out at about 100-120mg/dl. Normal to prediabetic in modern parlance. However my HbA1c is only 4.4%, well toward the lower end of normality and healthy. That's always assuming that I don't have some horrible problem resulting in very rapid red blood cell turnover. I don't think so...

I spend rather a lot of my life in mild ketosis, despite the 50g of carbs I eat per day. So I can run a moderate ketonuric urine sample with a random post-chocolate blood glucose value of 6.5mmol/l.

What is happening? Well, the first thing is that LC eating rapidly induces insulin resistance. This is a completely and utterly normal physiological response to carbohydrate restriction. Carbohydrate restriction drops insulin levels. Low insulin levels activate hormone sensitive lipase. Fatty tissue breaks down and releases non esterified fatty acids. These are mostly taken up by muscle cells as fuel and automatically induce insulin resistance in those muscles. There are a couple of nice summaries by Brand Miller (from back in the days when she used her brain for thinking) here and here and Wolever has some grasp of the problem too.

This is patently logical as muscle runs well on lipids and so glucose can be left for tissues such as brain, which really need it. Neuronal tissue varies in its use of insulin to uptake glucose but doesn't accumulate lipid in the way muscle does, so physiological insulin resistance is not an issue for brain cells.

However, while muscles are in "refusal mode" for glucose the least input, from food or gluconeogenesis, will rapidly spike blood glucose out of all proportion. This is fine if you stick to LC in your eating. It also means that if you take an oral glucose tolerance test you will fail and be labelled diabetic. In fact, even a single high fat meal can do this, extending insulin resistance in to the next day. Here's a reference for this.

The general opinion in LC circles is that you need 150g of carbohydrate per day for three days before an oral glucose tolerance test.

I did this carb loading thing, then performed my own OGTT. It came out very normal except for mild reactive hypoglycaemia.

So, I often walk around with a fasting blood glucose of 5.9mmol/l and in mild ketosis, yet have normal pancreatic and muscle function, provided I carb load before the test. BTW my FBG dropped to 4.3mmol/l after three days of carb loading.

That then raises the question as to whether Mark "iwilsmar" and myself are typical of LC eating people, or an oddity or two.

This brought to mind the self selected macronutrient study performed on mice by Ortman, Prinzler and Klause. They allowed mice to select their own diet and, lo and behold, the mice chose (by calories, not weight!) 82% fat and 5.6% carbohydrate. Sensible mice.

NB These German mice should each be given Professorships of Nutrition at medical schools in the most obese nations of the world. Quite what we should do with the current professors I'm not sure, but I bet the mice could think of something.

Anyway, these mice are cool. The only thing that bugged me when I first read the paper was that they had a higher fasting blood glucose than those poor mice fed the normal junk which passes for laboratory mouse "chow".

This now fits in to an overall pattern. Elevated non esterified fatty acids induce physiological insulin resistance and a higher than expected FBG level. A simple switch to higher carbohydrate eating (in myself) allows the normal underlying pancreatic and muscle function to show. It also fits in with the FBG of 3.5mmol/l found in the carbohydrate fuelled natives in the Kitava studies.

So do I worry about a FBG of over 5.5mmol/l?

Not while my HbA1c is 4.4%.



leahys said...

this is a brilliant analysis. I have not seen this discussed anywhere before but it makes lots of sense and explains why I feel more sensitive to carbs now than ever before.

I have not seen any other comments on your blog. I hope you have lots. I really enjoy your comments and your take on the often covoluted reasoning (?) of researchers.


Peter said...

Hi leahys,

I put the blog up to help me keep my ideas/refs together in neat groups. My hard drive is chaotic. I wasn't really expecting comments on the blog but the few that are posted let me know that other people do see the world in a similar way to me, which is nice.



JohnN said...

Hello Peter,
A very nice post.
The term "insulin resistance" is curious in the absence or very low level of insulin but I know what you mean. Shouldn't we say: without insulin, muscle cells withdraw the glucose transporters and resort to burning fat instead?
Until brain activities kick in or short bursts of high intensity physical activities are required(either of which would generate a demand for glucose) one could expect a slow drift of BG up to a level high enough where other control mechanisms are activated or until the next meal.
Can it drift high enough to cause long-term problem, I wonder.
I suspect in the distance past when game was scarce other carb sources (fruits, tubers, roots and leaves) acted to induce some production of insulin to encourage glucose uptake.

Peter said...

Hi Johnn, I'd certainly agree, insulin resistance is probably not the correct term, but you would still be labelled diabetic if you took an OGTT in this state. It seems that this may be where the idea that fat causes insulin resistance comes from. Your comment about people eating whatever carbs they could get, I suspect even when hunting was OK, may have something to do with the drive to not get too far in to this state. After all, humans do seem to like carbs, even if it means burying crab apples in the ground over winter to get rid of the tannins, or soaking ground acorns in a stream for a week with the same objective. I can't believe we are driven to do these things in the absence of starvation if there isn't some advantage beyond weight gain....


PS From a few other places on the net it seems the rising FBG may be generic to very LC eating.

Sasquatch said...

I've noticed that since I've reduced my carb intake, eating a high-carb meal kicks my butt. I feel like... my blood glucose is through the roof and all my proteins are being glycated!! Seriously, I feel warm all over and tired as if I were having a systemic inflammatory response. Although it may just be my overactive imagination.

I eat a meal like this once a week or twice a month, when I'm invited out for example. Do you think I could be doing worse than if I were eating a regular "balanced" diet all the time? I guess the HbA1c might be the place to look huh?

Peter said...

I know exactly what you mean. I was thinking in terms of serotonin spikes. But yes HbA1c is undoubtedly the place to look. Oddly enough I never really noticed this effect during the three days carb loading before OGTT


PS We just had a high carb (sugar!) weekend with a guest who did the desert cooking. My wife got really really sleepy post pudding and crashed for the afternoon. She had three isolated ectopic heart beats within a 10 min period today. I'd really have expected that in the immediate post sugar binge period but no, 24 h later is what shelled out! Generally the occasional "bad day" I accept and get on with normal eating afterwards. We're lucky it's probably less frequent for us than once a month.

Misty said...

I just read this post of yours...and explains a lot of what has been happening to me.
An regarding my HbA1C still being high I will retest it in December and check it out...but regarding my BG levels your post explains it all.
I will stick to JK/Peter version of LC/high fat and in December will report results.

Walter said...

Robb Wolf had a post on this you might find interesting:

Gestational Diabetes

Posted on June 25, 2008

Peter said...

Hi Walter,

Robb Wolf clearly knows what he's talking about.



LPrice said...

BioEssays 29:811-818, 2007

Several protective cellular mechanisms protect against the accumulation of reactive oxygen species (ROS) and the concomitant oxidative stress. Therefore, any reduction in glucose or fatty acid flux into cells leading to a decrease in the production of reducing equivalents would also lead to a decreased ROS production and protect cells against oxidative stress. In the presence of insulin, FOXO proteins are localized from the nucleus to the cytoplasm and degraded.

An increase in cellular glucose uptake will lead to increased production of ROS. This in turn activates the stress-responsive Jun-N-terminal kinase (JNK), which promotes nuclear translocation of FOXO proteins, upregulating some important target genes including stress resistance.

Consequently, insulin resistance should result in decreased cellular ROS production. For this reason, insulin resistance could be a physiological mechanism activated at the cellular level in response to conditions stimulating ROS production and leading to the prevention of oxidative stress, and extension of life. Concerning the whole organism, however, IR is a maladaptive process in the long term causing a diabetic state.

Peter said...

Hi L Price,

If I follow the jist of this it's looking at insulin resistance as a physiologically protective mechanism. This seems very probable and it's our modern lifestyle which makes it maladaptive. Comparable the the CV response to blood loss being maladaptive in heart failure...



westie said...

About physiological insulin resistance:

When going low carb, butyric acid inhibits excess lipolysis but as You see in a case of diabetes insulin is also needed to prevent ketoacidosis.

What do You think about an idea that high blood sugar with low carb is also physiological and it's ment to give a minor rise for insulin concentration to cool things down and let all things go smoothly?

auridicyl said...

You mention your fasting blood glucose, post-prandial blood glucose and hba1c numbers, but you do not mention whether or not you regularly (or ever) had your serum insulin levels checked. I am curious if you do, and if so, whether or not they have fluctuated over this time period. I ask because I recently had a ridiculously high blood insulin level reading (which I was told indicates hyperinsulinemia, a precursor to diabetes), and have started on a low-carb diet in the hopes of staving off full-blown diabetes. I will ask to have my insulin levels tested again this week, though I've only been low carbing for a short while. I'm hoping that I will see a difference, but in case I don't, I'd love to have your feedback (if you've had your insulin measured) as someone who has been doing this for a long time. Might help me get over a "disappointment hump" if my readings don't come back lower just yet. :)

Peter said...

Need a little time on this one. Insulin drops fast though, 1-2 weeks and it will be well on the way...


Peter said...

Hi Auridicyl,

I've only measured my insulin once, that was fasting and about 4 years in to LC, high saturated fat and high cholesterol eating. It was 2.5microIU/ml which I think is about 15.0 pmol/l. It's quite low.

From the studies I've seen it's simple to reduce fasting insulin from 10 microIU/ml to 5microIU/ml in 6 weeks. I'd expect the higher you start the faster the levels will fall. Relatively few studies give you the insulin levels (it's not the easiest or cheapest thing to measure) and you have to trawl some uninspiring papers to get numbers.

But two weeks should show you if you are on the correct track. There is no other approach I'm aware of that is half as effective as LC eating...


Zachary said...

I met Dr. Bernstein in person. What an absolute hero. Peter, I've been going through your archives over the last couple of weeks and discovering really great posts and comment exchanges from over the last few years. Hope this comment finds you doing well.
Best Regards,

Zachary said...

"There are a couple of nice summaries by Brand Miller (from back in the days when she used her brain for thinking)"

I assume this comment is also related to when she used her brain for thinking when she wasn't getting paid in government grants to not use her brain for thinking....

Zachary said...

"There are a couple of nice summaries by Brand Miller (from back in the days when she used her brain for thinking)"

I assume this comment is also related to when she used her brain for thinking when she wasn't getting paid in government grants to not use her brain for thinking....

Zachary said...

Sorry for the troika rapid post fest, but as I read through the comments and after pondering it hit me that Auridicyl is correct. Wouldn't in the physiological insulin resistance scenario you describe the main indicator regarding the difference between a Lowcarber and a developing diabetic (aside from the HbA1c reading!) be fasted insulin level?

Seems to me that a fasting insulin level would be so much more informative than a fasted blood glucose level? Not sure whether this is an appropriate question, but if given a choice which measurement between fasted insulin or fasted blood glucose levels do you think is more informative?

And with that, I'm off to spike my insulin levels with a bottle of red. Cheers.

Peter said...

Hi Zachary,

Glad you're enjoying the blog.

In many ways a post prandial measurement is more interesting, for both measures. A newly diagnosed type 2 diabetic always has neuropathy as they have been diabetic for many years if you look for post prandial hyperglycaemia/insulinaemia. If people fasted all the time then fasting would tell us useful things about their physiology. The OGTT plus pre and 1h insulin is a reductionist equivalent of response to a meal, it's useful but needs thought to interpret.

The other problem with insulin on an individual basis is I'm not sure what the lab accuracies are, ie how repeatable a measurement is, and even if it is accurate some people seem to show classical metabolic syndrome problems such as hypertrigyceridaemia on relatively low insulin levels.

But ultimately yes, a fasting insulin is useful but probably not in isolation or as a sole parameter....


Tessan said...

Hi Peter! I träd somwhere (Taubes?) that insulin is very volatile. Is it sö in the boet as well? If so, does that have any bearing on this physical insulin resistance ting? Can insulin circulate Long after it has been called upon? If so, hos does that effect us? I also fall race down into the carb pit every other week, and since I Care abort what elevated insulin does to Me more than blood glucose, that might be a good motivator. My glucose is omkull mildly effected by half an Italian pizza these days.

Peter said...

Insulin vs hyperglycaemia as drivers of illness is a complex problem, I'll get to it one day...

Dr. Will Mitchell said...

How is it possible to have an A1c of 4.4 and a fasting glucose over 100? How does that glucose in the blood not cause glycation and show up on the A1c?

Peter said...

Hi Dr Will,

It's my morning value at peak GH induced lipolysis. Other times it's in the low 70s/80s.

I have no suspicion that I have pathological RBC loss but my intake of PUFA has been quite low for years and glycation seems to mark RBCs for destruction. Hard to glycate palmitic acid....


Gman said...

Hey Guys!... Found this article today cause I was kinda worried about my glucose levels... they where arround 105 - 110... but I am in a low carb diet and surprisingly my HbA1c is only 4.3%... Really Nice article and now... I am soooo not worried... jejeje.

wayne said...

thanks man, I was starting to worry about my FBG readings. I've been lo carb (hi fat) for almost a year.

atkins addict said...

I'm curious as to what you are getting for postprandial readings 45 min or even 2 hrs after a meal? Thanks!

Emily said...

Thank you for this article! Really helped. Not worried about a FBG of 100 when A1C is 4.9%.

maria said...

How much protein do you eat? Amino acids have a glycemic index and according to some great people like Nora Gedgaudas and Ron Rosedale we only need about 50-70g a day.

Peter said...

Oddly enough 50-70g/d, via Kwasnieski. My main dietary indiscretion is the occasional protein overdose, probably not a great idea but...

Oh, Atkins Addict: I did some recently, mostly 5 point some thing. Just occasionally crack 6mmol/l


alan said...

not sure if you will get this comment so long after you posted, but i just found it and was thankful.

quick question, what is the effect of a high carb meal (say pizza and beer) on the body if you are in a ketogenic, insulin resistant state due to a high fat/low carb diet from a health stand point? i can manage weight gain, but am i risking serious heath complications from the periodic mocha, pizza or beer?

perhaps A1C test would be best indicator? are there other tests that i might look into?

Heather Lea said...

Thanks for this! I have been extremely concerned about my fasting blood sugar for that last few years which can be 105-140, Depending what I eat the day before. I am gluten free and carb low for the last 12 years. I find that if I eat more carbs than normal on a given day my fasting blood sugar is higher the next day. My A1C is around 4.7.

My mother is diabetic and just lost the tips of a couple toes, so I am hypervigilant about my blood sugar.

For example, I can wake up and my FBS is 107, I then exercise intensely for an hour and my FBS will go up to 118! My BS only drops after I eat and will go to 89 or lower at 1 to 2 hours after I eat.

My arm chair analysis has been that my liver is dumping glycogen into my system to maintain enough glucose for my brain and will release more glycogen into my system as I exercise to compensate for the exertion. But, my pancreas will only put out insulin when I eat food, not in response to the glycogen from my liver. So my blood sugar only drops after the consumption of food.

It has been very confusing to me, to have my FBS go up more and more with less and less carbs. Thanks for your analysis.

Bumbling Our Way To Sustainable Living said...

Hi Peter,

I know this post is old, but I have some questions.

I am currently 35 weeks pregnant and I was diagnosed with gestational diabetes at 28 weeks. I'm 39, no history of diabetes in my family, single fetus and pre-pregnancy weight was 115 lbs (5'4").

About 4 years ago, I tried a low carb diet... not for weight, just trying to be healthier. I actually put on weight from the diet so I went back to eating whatever I wanted with carbs and sugar and lost what I had gained (if it ain't broke, don't fix it!). I suppose that a low carb diet was not for me.

With this GD diagnosis, the first 50g glucose test had me at (American value) 160 the first hour. I had to go back and take the OGTT (100g of glucose I think?). Fasting (11 hours) was: 88, 1st hour: 206, 2nd hour: 189, 3rd hour: 164.

Now I'm on a low carb diet. My post prandial numbers are good, but my fasting numbers are slowly increasing (around 102 currently). The GD nurse is telling me it's because the placenta is growing and outputting more hormones and will continue to do so until birth. I can't help wonder if the low carb diet is, at the very least, contributing to the rising FBG? AND I'm somehow still consistently putting on weight beyond baby growth. Go figure.

What's going on?


Peter said...

Hi Tracy,

It doesn't really matter. What injures your baby is hyperglycaemia. I don't know exactly where this kicks in but 140mg/dl is a reasonable guess. So skipping anything containing 100g of glucose on an empty stomach is a good idea!

The cells in your baby don't care about a FBG, just peak levels and LC is the only way to avoid having this spike. There is no choice, exogenous insulin excepted.

Weight gain on LC is quite possible and weight gain in pregnancy on LC is equally possible. Progesterone acts much like cortisol to induce some degree of insulin resistance and very strict LC might be needed to stop this. Putting up with it is the easiest answer. You can ketogenically diet once lactation is up and running. It ups the fat content of your milk quite nicely.

Ultimately all that matters is peak glycaemia. This matters quite a lot. Relaxing LC will usually drop your FBG post partum at the cost, usually, of elevated post prandial BG levels. With a healthy baby you can make this choice later...

Sorry for the delay


TL said...

I am having the exact same experience as Heather Lea. I've been following it for a while and while I go to bed at 90ish, my blood glucose starts to climb around 2am, peaks between 5-7am (between 100 - 130) and if I don't eat then it goes back down so that it appears 'normal' around 10am. Eating breakfast almost immediately brings it down and it stays in a good range (70 - 110) all day...until it repeats again in the morning. I have been racking my brain to understand if this is a problem, if its something I should present to my doctor, if its been happening my entire life, if its dawn phenomenon or if its due to my low carb eating. I have never taken an official (doctor's office) blood test before 10am and so the doctor's office has no idea. My A1C is low but I've just discovered that I have strangely shaped red blood cells (elliptocytosis) which makes A1C results inaccurate. I would never have discovered that this was going on without taking the initiative and getting a meter on my own. Would love some further explanation on the subject.
Thanks Peter! BTW, my insulin level was 5 in the last test.

Peter said...

Hi TL, you can get marks out of 10 for your glycaemia using fructosamine. This "views" the last two weeks rather than the last 3-6m but doesn't care about your RBC type... Very rapid albumin turn over would mess it up but you would normally know you have a medical problem to be doing this!


freakingout said...

I don't know whether this post is still active. I was doing ultra low carb for 5 months (30 grams or less a day). During that time I had a FBG of 96 on a random test which gave me concern, as I'm usually in the low 80s. I quit doing ultra low carb over 3 months ago, and my fasting blood glucose is now 100-118. Post-prandial has gone as high as 162. So have I permanently made myself diabetic by this low carb diet? I would think that 3 months after going back to a more balanced diet, my glucose levels would have recovered.

freakingout said...

I was on an ultra low carb (ULC) diet for 5 months. A random blood test showed fasting blood glucose (FBG) at 96, which concerned me, as I'm usually in the low '80s. Since then, I have quit the ULC diet. I've been eating moderate carbs for 3 months now. Yet my FBG is now 100-120 and post-prandial can get as high as 162. Have I given myself diabetes from this ULC diet? It seems it is not reversing itself once I stopped ULC. I'm very worried that I've impaired my ability to eat carbs permanently.

Peter said...

Hi freakingout,

I think it is quite clear that there is zero evidence base for your having given yourself diabetes by carbohydrate restriction. The physiology is quite straight forwards, I see no reason why it should happen.

There are a stack of unknowns about your circumstances. I would be very concerned about a BG over 160mg/dl post prandially and would do whatever was needed to stop it going there. You have only two tools, LC and drugs. You need to know if you need drugs. You do need LC, on the most simplistic of generic observations...


randian said...

I know this is an old post, but I wasn't sure where else to ask this question.

If low or zero carb causes insulin resistance, why do type 2 diabetics become less insulin resistant on VLC/ZC diets?

Peter said...

Hi radian,

LC exposes the body to chronic normpglycaemia, There is minimal activation of the polyol pathway, reduced free radical production and minimal stimulation of the intracellular antioxidant systems. With reduced background antioxidants the H2O2 spike needed for insulin to act is much less damped, insulin works. That's the Protons explanation.

In more superficial terms you down regulate glycolysis and up regulate ox phos, ie you start using your mitochondria. Lots of mitochondria mean lots of insulin sensitivity. You still need some carb loading pre test or to be running at minimally ketogenic carb levels before you test with an OGTT or the physiological resistance effect predominates. Healthy folks can get by on 24h of 100g cabs to flick the switch. Traditionally 150g for 3 days.

You must be careful with the physiological effects vs the pathological effects...


Deb (Smoothie Girl Eats Too) said...

HI Peter,

Re. Sasquach's comment way up there, it reminds me of John Keifer's Carb Nite program, where you eat <30g carb for 10 days, then eat lots of carbs from ~4pm til 10pm or thereabouts. I haven't delved into it, but something about the insulin spike makes for fierce fat burning after the fact. Then you go back on VLC for a week and continue like that for a finite period of time. Do you have any thoughts as to why this might work and if you feel that it would work (Keifer has tons of testimonials that say it reduces fat, even while building muscle).



Deb (Smoothie Girl Eats Too) said...

Hi Peter,

I believe I just submitted my question to you and if so, please delete this one.

It was in regards to Sasquach's comment about a big carb meal. Are you familiar with John Keifer's Carb Nite? He has many testimonials and claims a huge amount of success with people shedding fat while gaining muscle. The basic premise is 10 days VLC (<30g) then a 'carb nite' with a specified eating window. Followed by another 6 days of VLC, then another carb nite. Etc. It's meant to be used as a weight loss tool and has to do with spiking insulin on the carb night. Do you feel that this makes sense from your perspective? Or is it just the result of a reduced calorie diet, or eating VLC MOST of the time?


Peter said...

Hi Deb,

The answer seems quite complex re the benefits vs risks of fat/carb cycling and I'm a bit stuck on to other lines of thought to pay it too much attention. You can't avoid the possibility that a glucose spike may do just the correct amount of damage to trigger some repair, ie more mitochondria. But I would expect any useful information about the biochemistry to be pretty thin on the ground...


Sten Björsell said...

Hi Peter,
I wish to stick my neck out and ask if "physiolgical insulin resistance" really explains the dawn phenomen.
Q1: Why is BS 6 required (for you) when we operate fine on BS 4.5 and hypoglycemia is defined below 3.9 and added ketones provide reserves for "glucose only" systems. And individually higher and lower BS?

Q2: After more than a year with LCHF and weight loss stagnation ( after 10 kg drop need to drop 8 more), my morning blood sugar could now be as bad as yours....And it was not high during first 6 months! Could the morning high BS be due to something else, alone or in combination with so called "physiolgical insulin resistance"?

I suffered from persistent heart disease (angina) for 7 years that cleared up 100% in the first few months of very strict LCHF. I suspect that I still have some visceral fat around - and inside - both liver and pancreas and that my pancreas set point could be wrong, evolved to some average I had when I smoked and fed myself twice a day with large high carb meals over some 40 years.
Before my average BS may well have been 6.5, derived from 2-3 large postprandial peaks and normal fasting BS, of course
rising to that slowly over the years.

My take is this: During the first (6-9) LCHF-months my glucogenesis was going slow because the liver was gradually getting its act together considering largely unused glucogenesis up to then. As a result I then enjoyed low blood sugar,low insulin and good weight loss! When the liver later got adept on glucogenesis, it resulted in rising morning sugars, morning insulin and the observed weight loss stagnation.
I have during this time noted 3 ways to keep morning blood sugar down:
1/ Exercise the day before (empty gycogen stores to be filled again by glucogenesis first (?) ,
2/ Drink a glass of wine the day before and liver capacity is tied up getting rid of resulting aldehydes.
3/ Reduce protein intake leaving "less easy rawmaterial" available to make blood sugar from.
With none of above I have read morning sugar up to and over 6.5!

Pancreas key:
According to a Newcastle team (Dr. Taylor), BS regulation was restored to normal in DB2's with 8 week calorie severely restricted diet aimed to force visceral fat reduction.
See: http://www.ncbi.nlm.nih.gov/pubmed/18726585?ordinalpos=183&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

After normal blood sugar regulation was restored in the Newcastle trials, visceral fat around pancreas had reduced from 8% to 6% ( a 25% drop). (typical or average).
A DB2- friend experienced identical problems that I described, but his morning sugar could shoot up well over 7 if he didn't exercise, had wine or reduced proteins the day before, just as for me.
In your own case current values look better, but I guess you too did not take up low carb high fat eating without having good reasons?

Finally looking at assumed metabolic healthy children on LCHF, and far from diabtes 2, could provide the explanation:
From Carrie Loughran. a keto dietitian, childrens target values:
Glucose 3.0- 4.2mmol/L AM/PM
• Ketones > 3.0mmol/L – “high”
Consequently I believe the "dawn syndrome" is an unresolved metabolic syndrome and have started out on IF to see how it goes.

Peter said...

Hi Sten,

That's a lot of questions.

Q1 really relates to why FFAs are released at dawn (GH surge) and which FFAs are released, in terms of their ability to trigger insulin resistance. There is also the issue of down regulation of glucokinase in LC eating which I would expect to worsen the dawn phenomenon. Out of interest, what is your HbA1c?

Q2. A blood sugar of 6mmol/l is doing no harm to anything, so I'm not sure "bad" is quite the term. Recall that 3 days of carbs >150g/d gives me a FBG of 4.3mmol. What else may be going on is a wide open question.

I don't see visceral fat as an issue if you LC. It specifically targets the liver and induces hepatic insulin resistance. If you LC you do not need hepatic extraction of insulin or glucose to control metabolism perfectly well. It's why LC is essential to control diabetes, peripheral (injected) insulin works as well as portal vein (secreted) insulin, if there is no gradient across the liver.

Bernstein, the most conventional LC diabetologist, limits protein to 60g/d, uses exercise seriously and adds drugs as needed.

Taylor reduced carbs to about 60g/d with crashing reductions in everything else until his patients were food fixated and ravenous. The results would be catastrophic by Bernstein standards. By week 12 "HbA1c was unchanged (6.0±0.2 vs 6.2±0.1% [42±2 vs 44±1 mmol/mol]; p=0.10) and fasting plasma glucose increased modestly (5.7±0.5 vs 6.1± 0.2 mmol/l; p<0.01), with a 2 h OGTT plasma glucose of 10.3±1.0 mmol/l. Three participants had recurrence of diabetes as judged by a 2 h post-load plasma glucose >11.1 mmol/l".

Cure is not a word I like. HbA1c of 6.0% under starvation is not a cure in any serious sense.

I took up LCHF eating because I read the literature and realised that any other approach is rubbish, and nothing has convinced me otherwise since. I admit it's only been 10 years so far. I was a 68kg athlete at the time I went LC.

I would expect dawn phenomenon to worsen with IF... Eades noticed this in a significant number of his patients and went off the idea.


Sten Björsell said...

Hi Peter, many thanks for your reply.
I will try to rephrase some without reply. Or condensate the key qustion about what the dawn phenomen is:
Why did I not have high morning BS (dawn phenomen) when I had good weight loss first 9 months of my LCHF ,and why did the dawn phenomen occur after this "honey moon" ?
I take it that it is a hard question that takes time to answer but there is no rush.
Q2: Do epileptic children on LCHF exhibit dawn syndrome?

granny miller said...

Thank you so much for this!
I've been LC for a little over a month and have been confused and worried watching my FBS numbers rise.
You have reassured me that my diet is not harming me and I'm not becoming diabetic.

mk07 said...
This comment has been removed by the author.
Peter said...

Hi mk07,

Elevated BG under deep fasting/ketosis varies from person to person and from time period to time period. It’s hard to tease out what makes the difference but my wife can, in deep ketosis, work long hours with a BG which is through the floor. I can’t remember whether it was 1.9mmol/l or 2.9mmol/l at the end of a 12 hours shift when she was an intern. Despite the low FBG she would almost certainly have failed an OGTT without the obligatory 3 days carb load…


Bob Smith said...

I assume you have low FBG because you have adequate beta cell capacity. In people lacking the genetic defects that cause Type 2 diabetes, beta cell volume increases in response to load. It doesn't matter that you have high insulin resistance, your body adapts to it.

mk07 said...
This comment has been removed by the author.
Peter said...

I eat most of my carbs with my evening meal, not really planned, that's just how life pans out. This guy (who is wrong about stacks of things) has an interesting observation on fasting hyperglycaemia. Personally, I'm a carnivore...



Wilson said...

Hi Peter, you say the poor performance on OGTT taken by low carbers - called the Randle effect - normalises after 3-4 days of ‘normal’ carb eating. I have been curious about this. I am naturally active and thin but a year ago thought I’d give low carbing a go for general health and to lower a slightly high (5.5) fbg. I now notice that I have become extremely carb intolerant and despite introducing more in the way of rice, fruit, yogurt in an attempt to eliminate the Randle effect I remain more carb intolerant than I was before going low carb. My food choices are more restricted now – has my body ‘forgotten’ how to deal with carbs altogether and how much harm are the high blood sugars seen after say having plain yogurt and fruit doing? (9.8) my fbg is now around 4.9 but HbA1C 5.3%


Wilson said...

Hi Peter, the poor performance on OGTT taken by low carbers - the Randle effect - normalises after 3-4 days of ‘normal’ carb eating. I have been curious about this. I am naturally active and thin woman but a year ago thought I’d give low carbing a go for general health and to lower a slightly high (5.5) fbg. I now notice that I have become extremely carb intolerant and despite introducing more in the way of rice, fruit, yogurt to eliminate the Randle effect I remain more carb intolerant than I was before going low carb. My food choices are more restricted now – has my body ‘forgotten’ how to deal with carbs altogether and how much harm are the high blood sugars (9.8) seen after say having occasional carby snack like plain yogurt and fruit doing? Could it me that in my case (and studies only seem to focus on a certain physiology) a high carb diet has done me no favours at all? HbA1C was 5.3%

Peter said...

Hi Wilson,

Try 150g of carbs per day (I used yams, sweet potatoes and bananas) for 3 days then take a 75g OGTT. The ultimate LC diet is the water fast. Water fasting will make some people frankly diabetic until they are glycogen replete. If this was permanent damage it would suggest that going without food for a week under conditions of poor food availability would have humans dropping in to type 2 diabetes. While frank starvation may be a gift of agriculture (high population, crop failure), groups of hunter gatherers routinely had episodes of short term starvation. That's certainly true in the accounts of living with the Inuit from Stefansson.


Wilson said...

Thanks Peter - 150g for 3 days then 75g of glucose is quite an assault for someone of 48kg! Surely glucose spikes of any description - be it from frank diabetes or physiological insulin resistance - take the same toll on the body? Hunter gatherers must have experienced the same extreme glucose spikes on the few occasions they came across and gorged on fruit, honey or tubers so you'd think we'd have developed the ability to up regulate the necessary enzymes rather more quickly than 3 days.

Maybe this paleo thing is more suited to beefy blokes than skinny women! After all women naturally needed carb induced fat to remain fertile. I wonder if low carb is right for me - if my glucose metabolism corrects itself I will be eating far more in way of unrefined carbs. Here goes with the OGTT!

Peter said...

You have to consume enough carbs to switch hepatic metabolism from fat to glucose, deplete the lipid stores in LC hepatocytes and also up regulate glucokinase in your pancreas. There is a need for the liver to be able to respond adequately to insulin and the pancreas to secrete it. Evolution appears to have “decided” that transient hyperglycaemia is a reasonable cost for allowing the pancreas to stop wasting ATP on glucokinase production. And a few other adaptations.

Under LCHF you should have large numbers of mitochondria using the products of beta oxidation, each cycle generates one acetyl CoA, one NADH and one FADH2. The FADH2 bypasses the krebs cycle so this is only turning to use the acetyl-CoA/NADH component. The ETC is running at low voltage, low electron through-put and mitochondria are present in large numbers. Once the carb loading kicks in you should be more insulin sensitive than before LC because the whole drive of running on beta oxidation is to generate more mitochondria. Once you convert to glucose they should all come on line at peak performance…

Let’s see.


Friday Dragnet said...

Hi Peter,

Great blog post. Does this apply when a patient has a had a history of traumatic brain injury? I'm recooperating from my second traumatic brain injury, and I have noticed on days when my body syncs, that I have extremely low blood sugar when I wake up from a nap. This is usually following a the previous day of extensive walking. I eat a really alkaline diet, no processed food, and all organic whenever possible. Is there anything I can do differently or to pre-empt the low blood sugar levels when I wake up?


Peter said...

Hi Friday,

If you go to the rodent obesity literature there are a number of models based on brain injury which promote excessive insulin sensitivity. This can be achieved using a chemical injury to the glucose sensing neurons using gold thio-glucose or simple physical injury to the ventro medial hypothalamus.

The result is increased insulin sensitivity in adipocytes, increased insulin sensitivity overall, reduced blood glucose and, because the mice eat more due to increased transfer of calories to adipocytes, they get fat and subsequently become insulin resistant (from then on the phenomenon is masked by obesity induced elevated FFAa). There is a short window during rapid weight gain when the phenomenon shows and there are designs aspects to experiments which can be tweaked to stop it showing.

So a mechanism for low blood glucose due to increased insulin sensitivity does exist in the lab animal literature. I can see how exercise might make it worse, although increased muscle sensitivity to insulin would not give quite the same weight gain issues as the same phenomenon would in adipocytes.

You don’t mention whether you eat a reduced carbohydrate diet. Running metabolism on fat rather than glucose takes the whole insulin/glucose axis largely out of the equation and ketones appear to be a relatively good fuel for neurons. It may not stop the low glucose levels (there again it might), but it may render the low glucose levels less symptomatic if much of the brain’s energy s coming from ketones.

Worth thinking about.


DR. K, VMD said...

I was so glad to find this very pithy explanation of what's been going on in the complex machine called, "My Body." By the way, I'm also a veterinarian an understand all too well, "Once you have been taught to think, it's hard to stop." Anyway, been on a very low carb diet for more than a decade, feel great, only weight issue is trying to keep the pounds on. Fasting blood glucose has been persistently in the low 100's for at least three or four years, always with normal HgbA1c -until this year. Fasting sugar was 91, but A!c was elevated to 6.1 - tagging me as, "pre-diabetic." Knew this was nuts, started reading, and found physiologic insulin resistance. Dis two days of serial blood glucose checks on myself to prove this is what was going on, and I seem pretty classic - except that my spiked BG's of 130-ish after a handful of berries drop very quickly. Have read Paul Jaminet and definitely believe his theory over Rosedale's because, as a vegetarian, there's no way my problem arose from overeating protein.

So - because my A1c is now elevated, it seems clear to me that I have to make some adjustments. What do you think? Do I just add in some rice and/or potatoes (so counter-intuitive) to the diet that I've enjoyed (truly) for 13 years, or am I missing something crucial?

Thanks. I know I can't depend on the average nutritionist to answer this one.

Digby said...

This great post could use a bump up. I got here while looking for answers to both my typical higher morning fasting BG numbers, but more interestiing to me was the reason for the lower 70-85 range after a rare big carb day.

Senior Rad said...

Interesting analysis. But if ketogenic diets create high sugar serum levels. Then long term there will be cellular damage?.

George Henderson said...

Higher FPG is also seen on CRON diets and in the rapamycin model of mTOR inhibition.
These extend life in animal models.
The higher glucose is an indication of lower mTOR activity.