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%.

Peter

123 comments:

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.

Thanks

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.

Thanks

Peter

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....

Peter

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

Peter

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...

Peter,
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.
Thaaaaaaaaaaaaaaaaaaanls!!!

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.

Ta,

Peter

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...

Thanks

Peter

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...

P

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...

Peter

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,
Zach

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...

Peter,
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....

Peter

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....

Peter

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

Peter

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?

~Tracy

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

Peter

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!

Peter

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...

Peter

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...

Peter

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).

Thanks!

Deb

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?

Thanks,
Deb

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...

Peter

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.
Sten

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.

Peter

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…

Peter

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...

http://www.ncbi.nlm.nih.gov/pubmed/24348462

Peter

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

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.

Peter

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.

Peter

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?

Thanks,
Friday

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.

Peter

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.

Vivica Menegaz said...

Peter,
I am curious about the role of cortisol in the FBG levels.
Do you think that individual cortisol levels affect htis reading (depending on adrenal health) the same way they affect the reading after intense exercise?
I have not seen you in all the answers ever address the issue of how other hormones (other than insulin) will influence general BG readings...
That said I have been on a keto diet for a year now, starting out as a pre-diabetic. I brought my FBG values form 120s to about 80s for about a year but recently I am seeing them go back to the 100s. Looks like a poster case of the Physyiological insulin resistance, no?
I was thinking adrenal fatigue but I am now supporting the adrenals for a while so it should have resolved itself.
Would love feedback!!
Thank you
Vivica

Starchild said...

Very useful, one of a kind post. Thanks for sharing your thoughts & the references.

My FBG numbers spiked up above 100 after a year of low carbing (with last ~6 months on strict nutritional ketosis). I have the belief that low ketone levels may be responsible for the elevated FBG. Why? Because my high FBG tended to be coincident with 0.4-0.5 mmol/dl blood ketone readings. When ketones are low, brain naturally needs more glucose.

What the solution? Perhaps less frequent meals or less protein? Or, somehow boost up your ketone levels? I tried switching to eating 1/day at noon. My FBG normalized to a level below 90, and morning ketone readings jumped to 1-2.5 => Fasting well controls FBG. IF may do the same. Even Alternate Day Fasting may work similarly.

I, for one, am worried about highish FBG. Cancer cells love glucose, the less glucose available in your blood, the better? (Not that I have cancer, but speaking out of caution).

Maybe we should try to control our FBG by binging on carbs occasionally, and fasting on keto otherwise? That, to me, seems a little more natural/paleo than pure keto. What do you think?

Thanks in advance for your answer.

Sarah Reck said...

If the brain needs energy and it has little ketones, then it will get glucose somehow. So isn't it better that the brain gets the energy and so we have transient high glucose as a result?

George Henderson said...

Here's the paper on "benevolent diabetes" in CRON and rapamycin-treated mice. The appendix in interesting. This seems relevant to ketogenic diet which should also lower insulin and induce physiological IR by inhibiting mTOR.
http://www.impactaging.com/papers/v4/n5/full/100461.html

The model of TOR-driven hyper-functional aging almost automatically solves paradoxes of aging, including the insulin paradox (see paradox 7 and figure 4 in "Paradoxes of aging" [58]). From the TOR perspective, insulin resistance is beneficial or harmful when it is associated with ether low or high TOR activity, respectively (Appendix, Fig. 1 and 3). And this should not be surprising. Consider insulin resistance as a symptom. The assessment of symptoms depends on the underlying cause. For example, weight loss due to calorie restriction is good, whereas weight loss in terminal cancer is bad. Positive Tuberculosis Skin (PPD) Test due to vaccination indicates protection from tuberculosis, whereas positive test due to tuberculosis is a symptom of tuberculosis. Similarly, hyperlipidemia in obesity is bad, whereas hyperlipidemia due to rapamycin-induced lipolysis is good (see figure 2 in reference [53]). The list of examples is endless. Similarly, insulin resistance, associated with TOR overactivation, is bad (Fig. 1 B-C). But either insulin sensitivity (Fig. 2) or insulin resistance (Fig. 3), associated with inactive TOR, is good.
Type zero or benevolent diabetes

There are two types of diabetes, which at advanced stages may become similar. Insulin resistance may develop in type I diabetes (due to high glucose), whereas insulin insufficiency in type II diabetes (due to loss of beta-cells). Both types of diabetes lead to complications. In comparison, starvation diabetes [28] is only superficially resembles either type of diabetes. Also, diabetes-like symptoms may occur in rapamycin-treated mice and animals with genetically inhibited insulin/IGFI signaling (Fig. 3). To encompass all these cases, I suggest the term type 0 (zero) or benevolent diabetes. It is possible that some patients with diabetes have inactivating mutations in the insulin/IGFI pathway and thus "suffer" from benevolent diabetes. Furthermore, the condition can be imitated by chronic administration of rapamycin at least in some strains of mice. Both calorie restriction and rapamycin extend life span in mice. Rapamycin prevents retinopathy and nephropathy. Also CR prevents type II diabetes and other diseases [59, 60-62]. One can suggest that type 0 diabetes should prevent type 2 diabetes. Should type 0 diabetes be treated? Perhaps CR-associated type 0 diabetes should not. What about rapamycin-associated diabetes? Definitely, it should not be treated with insulin. It was discussed that in theory the most rational combinations with rapamycin are mild calorie and fat restriction, physical exercise and metformin [52]. Metformin may in theory counteract rapamycin-induced gluconeogenesis in the liver. And this rational drug combination may be also considered as treatment of type 0 diabetes.

Peter said...

George, nice find. My only complaint is that I have ref 52 through my wife's Athens account and NOWHERE does it suggest fat restriction. Caloric restriction is the phrase, used repeatedly. Nothing about fat restriction. Never mind Lost in Translation. Lost in Citation would make an epic film. Or Made in Citation perhaps. Though no one would notice 'cept a few nerds...

Peter

Marcin Chyczy said...

Hello Peter, great post and comments - very informative!

I have a slightly different problem/question - I've been in ketosis for around 6 months (trying to stick to 50g of carbs daily limit), I had good weight loss and my fasting glucose levels are normal (80-100 mg/dl), my HDL shot up to almost a 100 while triglycerides dropped to 50 (I'm also relatively thin and muscular, exercise/weight lift regularly). Everything would be peachy except for two issues:
- my fasting insulin level stubbornly stays at the 7.5-8 µIU/ml which concerns me as I think it should be below 5 (I've never tested for this before going LCHF so no idea where I was before but I'm not your regular diabetic material)
- i often feel slightly nauseous through the day - not sure what's the reason for that but I suspect it's either too much or too little carbs on a given day

Can you please comment on the above? Should I be doing more carbs than 50g/day?

Victor said...

I have this PIR probably. Starting in the morning my BG is in the range 95-105,
however after first meal around 1 pm it drops sometimes to low 80s and stays low.
It started to happen after 3 months om my LC diet.
My ketones behave opposite. They start at 0.5-0.7 in the morning and grow thru the day
to reach 1.5-2.5 at 11pm.
Do we need to do anything about that BG higher level? and what can be done? Someone suggested wine and no protein the evening. Peter, what is your opinion now on those morning BG numbers and all this situation? Also, what is your opinion/experience on Berberine supplementation?
Thanks,
Victor

Peter said...

Hi Marcin and Victor (with apologies to Marci for the marked delay in getting round to answering),

I really don’t have data on this but I am unaware of any suggestion of glycaemia-related damage with a BG of 105mg/dl. I don’t see how this is comparable with 140mg/dl which appears to be where the problems kick in. I’m aware of one person where the fasting glucose was 8mmol/l, i.e. over 140mg/dl which might be an issue but again, you have to ask if 8mmol/l with glycolysis shut down is quite the same as 8mmol/l on a high carb diabetic diet. An interesting area to think about but not one I’ve looked at. Ditto insulin for Marcin.

Marcin, I’d think about fish oil/fish consumption, if you are indulging. Omega 3 fatty acids are well known to cause insulin resistance. This usually shows as mildly elevated glucose. But, given a decent pancreas, high insulin and normal glucose might be the result. As would the use of MCTs which, if you take enough, will raise insulin and drop glucose, albeit in the first few hours post ingestion…

As for whether carb variation might influence the number, your glucometer will say better than I might guess.

Peter

Unknown said...

Hi Peter - Found my way to you just today from Dr. Peter Attia's blog. I have been following him for a couple of yrs now and just happened to read through some comments on one post and he directed to you - this post. LOVE HIM.

I can't wait to read through some of your posts. Too many to begin!! I have been LCHF for 3 months and am insulin resistant. Plan on blood testing lipids and a1c at 6 months and then 9. The only way to find out if/when I actually become INSULIN SENSITIVE again - it sounds like from this post is to do the OGTT - but do the 3 day carb load. So, should I try at 6 months or 9 or a year(for the OGTT)?

And a 2nd question is do we want to do a 3 day carb load a few times a year for any reason? Other than the OGTT test?

I have been tracking my BS and ketones 2x a day and charting them for the last 3 months. I am regularly at approx 2.0 and 4.0 ketones morning/night respectively. I have a meter to check.

My weight loss was not dramatic initially and I lost NOTHING in August but I'm truly looking at this as healing vs just wt loss - I trust it will come - slowly. But I definitely have at last 25 lbs of fat to lose.

Hey I have blah blahed - sorry.

Deep bow to you for sharing all of this great stuff!!

Sheila

Peter said...

Hi Sheila,

The question as to whether insulin resistance can be reversed is a very interesting one. Much of the pathology which follows on as a consequence of eating carbohydrate while insulin resistant can be avoided simply by avoiding the carbs. But can any of us with anything other than physiological IR get back to having a fully normal mitochondrial population? That’s a much more slippery question to answer. This takes me back to LC as a health extender vs LC as a life extender. The former outcome is undoubtedly the case. The later is much trickier to determine, even theoretically. I’m presuming you’ve read Steve Cooksey? He is an example of a perfectly controlled T2 diabetic, drug free. He is fully healthy (as far as any of us can tell), but he can’t eat pizza after years of LCHF. Something changes permanently…

I don’t see any need to carb load occasionally and weight loss certainly varies from person to person. I would always be looking for normoglycaemia as the end point of LCing. I recall from years ago a member of Dr Bernstein’s diabetes forum who was heavily in to fat acceptance (I have no issue with this) and who was somewhat embarrassed to report insidious weight loss. But she was testing, testing and testing her BG. She had a recumbent exercise bike and would exercise post prandially while watching TV, not to burn calories, but to keep her BG below 5mmol/l.

Peter

Unknown said...

Thanks for your reply Peter! Yes, it is an important question - can IR be reversed. Peter Attia states that he absolutely did - He was IR and now says he is VERY insulin sensitive.

I plan on staying on a Ketogenic diet for at least a year (3 months so far) and perhaps indefinitely. As you say, IR is managed as if it does not exist if one is LC - and that is important. But, the curious side of me wants to test then has it been reversed? And, I'm guessing this is quite individual - Peter might have done it but others cannot. Is it important to know if it has been reversed? Maybe. And, why?

I adopted a NK plan for other reasons beside addressing IR. I have been following some great work being done by Dr. Dominic D'Agostino on NK and cancer therapy - it is ground breaking truly. And as Peter says, Dominic is the "Keto King!" I NK as a possible "prevention" mechanism for cancer. Cancer cell mitochondria are not metabolically able to utilize glucose so are effectively starved w/o it. I'm sure you are up on the research on this.

Additionally, NK or LCHF variations have shown some results in treating auto immune disorders. Again, I'm guessing you are up on this area of inquiry.

I find this all fascinating and get obsessed but than think I just want to quite thinking about all of it and eat and live and enjoy my life!

Thanks again - You are the bomb! ha ha

-sheila

Victor said...

Thank you Peter, you are very important resource for us, newbies. Let me share my results and get your opinion on it.
I think I found for now a way to decrease morning BG for my PIR case. Wine, decrease
of evening protein and 2 months of IF did not help me. However, HIIT exercise (sprint8)
the day before to empty glycogen stores works! It dropped my morning BG(and all the day numbers, btw) by 10%. I have a little fear though, that body/liver will adjust again and PIR will return. Will see.
As a result of this recent changes, I got another torturing me question: I increased my total food calories (adding more fat), have the same exercise calories spent (though switched from walking to Sprint8) and yet my weight started go down again, after 3 month stall.
Where extra energy goes? What is happening? I am in deeper ketosis of course, I measure and confirm that, but still energy disappears somewhere somehow. What is your take on that?

Sorry for my English, it is my second language.
Thanks,
Victor

Monica Perry said...

Hello Peter!

I love your blog and discussions, it is so helpful to find a good blog where everybody has something interesting to share.
I want to bting my experience on lchf looking for some feedback or clues on the "problems" I faced. I was on a very low carb high fat diet for six months this year until mid september when I decided to stop for three reasons:
1. By the third month in the diet I started to have veru cold legs during the night and then all day long. In the beggining I thought it was some sort of temporary effect or adaptation but, it got worse over the last thre months.
3. I got amenorrhea right after the first month in the diet, of course tought it was an adaptation and it should resolve, after 7 months now it has not.
2. I got my blood work and my A1c went up to 5.6 and my liver enzymes went from 27's up to 44's.

Any ideas on what went wrong with the diet? May be it is not for every one?
I'd really like to continue lc as I felt great most of the time but, seems does not wrok for me.

Thank you a lot in advance
Mónica

Kevin FST said...

I am perplexed and wonder if anyone can make sense of this:
I have been LC-ishHF (50-100g carbs/day, usually about 75) for 4+ years.
FBG averages about 5 (actually 4.9).
A few months ago I thought it would be interesting to test my insulin levels.
First result was 20.4ùUI - seemed reasonable since it was 80-90min after lunch.
Last result was 19.5 - fasting (ca.14 hours) and it makes no sense to me.
Unusual circumstance - I had just come off a 5-day fast (completed 48 hrs before) and my intermediate FBG (24 hrs after end 5-day fast, 24 hrs before insulin measurement) was a very unusually high 6.3 (although previous time I did such a fast I got a 5.5 FBG 24 hrs after end of fast).
Comments welcome.

Peter said...

Hi Kevin, what's your BMI? if you are post obese, what was your peak BMI? Does fasting put you in to ketosis and at what time after staring the fast? How many +++ on morning urine testing?

Interesting.

Peter

Kevin FST said...

Hello Peter, thanks for responding.
BMI ca. 24 (range 25 trending down to 24- over past 3 years)
Peak was 36+ (4+ years ago)
Yes, fasting puts me in ketosis (48 hrs, maybe less) - FBG towards end of recent 5-day fast was 3.6 (112 hrs) & 3.7 (120 hrs).
Don't usually test with ketostix but when I have done it's usually been ++.

Peter said...

If you go to http://high-fat-nutrition.blogspot.co.uk/2011/05/fasting-insulin-and-weight-loss-on.html and scroll down to the third figure it's a graph of fasting insulin vs time in a group of people under an extended water fast. They are transitioning (quite rapidly) from obese to post-obese. Note that the insulin drops from 50 to 20 micro IU/ml at the start of the actual fast and stays there for the duration of the study, with almost no change. So this may be you.

The question is: Why is insulin 20 micro IU/ml on a water fast? The interesting parameter would be C peptide. This lets us decide whether this insulin is being secreted and used (which should be terminally hypoglycaemia inducing) or is it "old" insulin which is just not being metabolised. Insulin, as a general rule, has to attach to the insulin receptor (activating it) before it's degraded. If insulin is high and C peptide low I would go with this explanation. The fly in the ointment is that I've heard rumours that C peptide measurement is a bit hit and miss in terms of accuracy, don't really know. But that's the way I'm thinking.

Peter

Kevin FST said...

Thanks for that link (part of the gold mine that is your blog). I will definitely do some more testing.
On the face of it, it looks like I may have a fairly typical Joseph Kraft Pattern V (LowCarb rather than T1D) of flat line insulin values (fasting or any post prandial) <30ùIU.

Fur-Kids said...

Has anyone correlated blood type to food intake and resultant glucose levels post meal? Some blood types do better with low carb...

Ermias Giovanni said...

Hello Peter,

Thanks for all the work you do, more importantly documenting it all for us to read.

I may be misunderstanding the data or projecting my opinions on to it. My position seems to be leaning towards the fact that LCHF is more of a diagnostic tool / health improver that we should eventually transition out of.

I went from keto <30g/day to full on ZC (zero-carb) where I consume an average of ~5-8g per day and I am making great progress.

My thinking at the moment is that I should continue until I meet my health and physical goals after which I can reverse diet upwards, gradually increasing carbs and kcals to more balanced figures - whatever 'balanced' means? I'm thinking Perfect Health Diet macros (30C:15P:55F).

I'm looking forward to your opinion on this. If nothing else I want to avoid Steve Cooksey's unfortunate demise of never being able to have pizza again. :)


Katie Coleman said...

Hi Peter. I have been doing LCHF for almost a year now. I did a GGT after weeks of LC I was in the pre diabetic range (not surprising from your research). My 2 hr pp levels are 100-110. My a1c levels have been 5.2, 5.4, and most recently 5.5. I am concerned that the a1c levels are slowly ticking up. Is it possible that from the LCHF diet (less than 50 g of carbs a day) that I have affected my a1c as well? Recently bloodwork showed my cholesterol was over 300 so I switched to a low carb lower fat diet (not fun). My cholesterol went down to 202 in 2 months but A1c remained about the same (5.5). I have also been feeling very fatigued lately. My issue now is keeping weight on. Wondering if I don't have enough to fat (either from diet or from storage) to burn, thus the fatigue?

Could I have some decreased insulin sensitivity from the low carb that takes effect even when I eat veggies or bigger high fat meals?

Hope I'm making sense. Have lots of questions around this issue and am having trouble finding answers. Thanks so much!!!

Katie Coleman said...

Hi Peter. I have been doing LCHF for almost a year now. I did a GGT after weeks of LC I was in the pre diabetic range (not surprising from your research). My 2 hr pp levels are 100-110. My a1c levels have been 5.2, 5.4, and most recently 5.5. I am concerned that the a1c levels are slowly ticking up. Is it possible that from the LCHF diet (less than 50 g of carbs a day) that I have affected my a1c as well? Recently bloodwork showed my cholesterol was over 300 so I switched to a low carb lower fat diet (not fun). My cholesterol went down to 202 in 2 months but A1c remained about the same (5.5). I have also been feeling very fatigued lately. My issue now is keeping weight on. Wondering if I don't have enough to fat (either from diet or from storage) to burn, thus the fatigue?

Could I have some decreased insulin sensitivity from the low carb that takes effect even when I eat veggies or bigger high fat meals?

Hope I'm making sense. Have lots of questions around this issue and am having trouble finding answers. Thanks so much!!!

Katie Coleman said...

Hi Peter. I have a question about possible insulin resistance with LC dieting. My blood sugar was high durning an ER visit where I had my appendix removed. This value was discredited due to infection. They did a1c at that point and it was 5.5. Later I did a GTT after being on a low carb diet and came back in the pre diabetic range (not surprising from your research). I have since lost 65 pounds and have been LC for almost a year. Fasting glucose is in the 85-90s typically. My 2 hr. PP blood sugar levels are 100-110. My recent a1C values have been 5.2, 5.4 and 5.5. I have been concerned they are ticking up. Could my LCHF diet be affecting the a1c levels as well? Wondering if the decreased insulin sensitivity can affect a1c too. Could decreased insulin sensitivity take place even when consuming vegetables and high fat meals? I am eating about 40-50 g of carbs a day. Wondering if I should add more?

About 6 months into the diet I realized my cholesterol was over 300 so I switched to a low carb low fat diet (not fun). Cholesterol went down to 202 in 2 months. My issue now is keeping weight on. I have been feeling fatigued lately. Wondering if I am not getting enough fat (from diet or storage) and is causing fatigue?

Hoping my questions make sense. I have a lot of questions in this area and am having trouble finding answers. Thank you so much for your time!!

Peter said...

Hi Katie, sorry for the delay, I'll try and get an answer sorted today

Peter

Peter said...

Hi Katie, I doubt you would raise HbA1c with physiological insulin resistance. What you have to differentiate between is a rising HbA1c from rising 24-7 BG levels vs increasing lifespan of red blood cells which will give Hb longer to accumulate glycation. You can check with fructosamine which looks at glycated plasma proteins rather than haemoglobin. You can check frequent BG readings, fasting, 1 and 2 h post prandial and some random post absorptive values away from dawn phenomenon.

You should absolutely increase your fat intake. I’m always amazed that people make life decisions based on a cholesterol number. The epidemiology suggests that a low, and especially a falling, total cholesterol value is associated with increased all cause mortality. Never, ever, work at dropping your cholesterol. Don’t be another victim of Ancel Keys.

If you are becoming diabetic, say you carry the gene for LADA, LC eating will not stop the underlying progression, though it will be part of management.

So check other aspects than HbA1c, eat lots of saturated fat and find out if you have a real problem.

Peter

drmjw18 said...

Hey Peter. This comment is a stretch for an "Insulin Resistance" blog, but I could stand getting some feedback and perspective right about now.

I started eating low carb around 10 years ago. My 'Restless Leg Syn" and morning sneezing fits went straight away. All good.

Over time I realized that if I'm going to eat low carb I have to come to terms with eating fat since too much protein isn't a viable long term nutritional strategy.I tend towards being lean, so I've learned to treasure avocado, all forms of coconut, butter, lard and so forth. I've been strong and def healthy, except for autoimmunity issues/toxic exposures (dissection classes in the 70's set me up for becoming chemically sensitive, but staying away from toxics would have been something I'd have gotten into in any case, so not a big deal). Till now.

In the last half year, though, I started having serious muscle spasming and muscular rigidity; a nerve conduction study was abnormal (agonist and antagonists fire simultaneously and continuously). The + GAD auto-Ab's finding led to a Moersch-Woltman (rare, autoimm n-muscular disorder) dx. The diagnosis means nothing to me, unless it can help me get a handle on how this has happened and what is going on with me. What I'm wondering is whether the biochemistry of my low carb diet could somehow be associated/utilized with this disorder- one way or the other.

In M-W syndrome, the GAD auto-Ab keeps me from making the GAD enzyme (which facilitates GABA formation). Indeed, I did a 23 and me genetic profile, and am homozygous for the GAD1 SNP.
M-W, being autoimmune, is assoc w multiple AI incidences, so I'm wondering whether my insulin resistance (along w Hashimoto's and IC) all dovetail, and whether going deeper into ketosis, or trying to incorporate starch can make a dent in the biochemistry of this condition.

Not sure if I've gone too far afield of your expertise, but any thoughts appreciated, Peter. I guess I'm asking more about the clinical biochemistry of ketosis, since it's a profound systemic fueling variation, and ketotic diets have been used for neuromuscular conditions for almost a hundred years now. If you see any connections or have ideas, lead on..

thanks,
Marshall

Brennan Lentz said...

If your fasting blood glucose is 5.5 (100 mg/dl), that would translate to an A1C of approximately 4.98%, which we will round to 5% for the sake of argument. That is using Richard K. Bernstein's equation. That A1C estimate is disingenuous because it has the big assumption built in that your glucose stays at 100 24/7, which is likely not the case. So the real question is, what is your blood sugar doing throughout the day, and what do you consider "fasting blood glucose"? If you are referring to your blood sugar right upon waking as being 100, then that means your blood sugar is likely staying at 100 for at least some duration of time during the night, which would have the affect of raising your overall A1C. Now, you also claim that your A1C is 4.4%, which translates to an average blood glucose of 80 mg/dl.

What I'm getting at here is that by definition, the only way you could possibly have an A1C that low with a fasting blood glucose that high, is that you have to be spending approximately equal time with LOW blood sugar, maybe in the range of 60-70 mg/dl (depending on duration). Or your numbers are wrong. Or possibly your A1C measurement was inaccurate (which can happen for a variety of reasons such as anemia or lab error). Otherwise you would be having multiple hypoglycemic episodes a day to balance the amount of time you have elevated blood sugar in the 100 range. I don't know how many carbs you eat, but it could be possible you experience rebounding hypoglycemia without realizing it, although if you're eating a VLC/high fat diet I highly doubt that is the case. More likely the case is that there is something about your numbers that don't add up. I highly recommend you wear a continuous glucose monitor if you want to see what your blood sugar is really doing, because these numbers don't make any sense.

This page happens to be one of the first articles/blogs/etc. that comes up when people google search "physiological insulin resistance" but your post is not really based on any good evidence. People link this article to me as a justification of their high blood sugar without understanding any of the science. You posted a study talking about the evolutionary need for insulin resistance to protect the fetus during pregnancy (agreed), and you posted a study talking about the OGTT and why it shouldn't be used in the context of pregnant women (fair enough), and you posted some tangential stuff about self-selection of diet in rats. I'm not seeing any evidence posted that attempts to show walking around with an elevated blood glucose is normal and safe. The elephant in the room is there is tons of evidence showing a 5.0% A1C and a glucose level of 100 mg/dl will cause all kinds of nasty side effects over time - all the microvascular and macrovascular symptoms of diabetes. There are plenty of cases of "mild" or "pre" diabetes that show diabetic complications in patients with an A1C of only 5%. Therefore the burden of proof is on you to show that walking around with an elevated glucose like that is somehow not dangerous, and yet all you can really fall back on is your supposed A1C of 4.4%, which I find questionable due to the reasons above.

There is a growing trend that I'm seeing among keto dieters on the internet that they believe blood sugar doesn't matter and insulin resistance doesn't matter, and I think it's hugely disingenuous to try and explain it away and claim that it's no big deal to be walking around with blood sugars that high, regardless of the diet. That's what people take away from this article, whether you realize it or not. I believe the keto diet is ultimately good, but in SPITE of the insulin resistance, and that keto dieters should do everything in their power to keep insulin sensitivity high. That means you have to maintain a low body fat, incorporate insulin-sensitizing exercise, and frequently keep tabs on your blood sugar, etc.

I would love to hear a response!

Peter said...

Hi Brennan,

Excellent comment. To question is imperative. Here are the pieces of information you lack:

The first thing you didn’t ask is what my post prandial glucose level is. This varies from 3.9mmol/l to 4.5mmol/l, 1-2 h after supper. By bed time it will be around 4.0mmol/l. Other meals are smaller and contain less carbohydrate, so I doubt they do more than supper.

The FBG I take in the morning is the one which is commonly over 5mmol/l and probably reflects the dawn phenomenon, which I consider to be triggered by growth hormone induced lipolysis.

The second piece of information you need is what my BG level is after exercise. I don’t go to a gym but I cycle a lot, walk a lot and paddle various small boats as much as I can now I’ve retired. An hour’s walk on a mid day empty stomach gives a BG of 3.3mmol/l. My first 45 mile cycle trip this Summer (after an overnight fast) gave a post-ride BG of 2.4mmol/l. (asymptomatic, except I was knackered, urinary acetoacetate dark purple). Next ride gave 2.6mmol/l. Two most recent ones have been 3.6 and 3.3mmol/l for 45 and 50 miles respectively. I think cutting the lawn one time last year gave a 3.3mmol/l.

Outside of exercise random BG levels are around 4.0mmol/l, sometimes below, sometimes above.

This is the information you lack, because I didn’t put it in to the blog post. What interested me, at the time, was what was happening to raise the BG without obvious reason. What I need is a physiological framework to explain waking up with an occasional BG of 5.5mmol/l or triggering a spike with a small glucose (or sucrose) load.

Or, of course, the lab work might be wrong (possible) or I might have made it, and all of this comment, up. How can you tell?

I have a number of generic points I could make about general approaches but you clearly do your own thinking and come to your own conclusions, not something I would consider trying to change.

BTW. Yes an asymptomatic BG of 2.4mmol/l is real and not made up. Within the limits of a Freestyle Lite glucometer and this being Tinternet. You probably need a few ketones and a lot of free fatty acids in your blood at the time.

Peter

I’m off for a cycle tour round the North of Scotland starting on Saturday for a week or so and I won’t be looking at the blog while I’m away. I don’t own that sort of phone.

Brennan Lentz said...

No, this was definitely very helpful and the extra context you provided makes perfect sense. The component that was missing in your post was the fact that you have low (or borderline low) blood sugars in certain parts of the day. I don't think it's typical for people (not children or pregnant women) to drop to 3.3 mmol like that in most cases, let alone 2.4, but that could definitely explain why your A1C is that low. Now I can believe the 4.4% A1C number with the extra puzzle pieces revealed.

I believe you 100% on the asymptomatic low blood sugar - the all-important George Cahill study has shown that artificially inducing low blood sugar in the fasted state (high blood ketones) does not necessarily create psychological/adrenaline affects and I've experienced that firsthand myself.

I guess my point in all of this is that I want people to understand what their blood sugar is doing at different times in the day if they are worried about it. I've seen overweight people on keto that have bad insulin resistance and a high A1C, and they try to justify this to themselves that there is nothing wrong, while in the mean time they are developing the same complications as type 2 diabetics.

Thanks for the response!

Peter said...

Yes, I think Cahill got that chap down to an asymptomatic 0.9mmol/l BG with ketones around 14mmol/l, using exogenous insulin. Without exogenous insulin the lowest BG I've come across was in my wife as she finished a 13h intern shift. The interns and nurses were playing with glucometers, as you do, and she came out at 1.9mmol/l. Politely refused the proffered emergency biscuits... Which the nurses tended to much on all night!

Peter

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Victor said...
This comment has been removed by the author.
Victor said...

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?
Anyway, I do not like these wild BG swings and wander if anyone has the same or can offer
any explanation to calm me down. You Peter seem to have a grasp on such phenomena, please comment. I have more data to provide if necessary.
Regards.
Victor.

Victor said...
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Victor said...
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Victor said...
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Unknown said...

This exact thing happened to me...i typically have fbg of 90...i started atkins and today my fbg is 115..i immediately went to internet.....well i know now this is completely a normal response from my body..thanks

Unknown said...

Sir I am 32 years old from pakistan last days I did my A1C which is 5.3 and OGTT is one is in fasting 108 but after intake of 75 grams gulucose 2 hours reading is 117 so I took 3 days fastening readings at my home that r 93,97,100 I mostly used fast food and chicken in my dinner My doctor declared me as prediabetic
Can u plz give me your opinion in my case
Thanks
Mubashar

Peter said...

Your Dr might be correct but you don't have enough information to know...

Miriam Kalamian said...

Peter, I specialize in education in keto for cancer and my clients test BG often. Of course, FBG trending higher over time creates a lot of anxiety for them as they are very driven to keep glucose low and steady. I explain what I know and send them to your site but I would really like some peer-reviewed papers to cite in my writing and in presentations. Any suggestions beyond what you noted in your original post?
Thanks!
Miriam Kalamian

Peter said...

Hi Miriam,

I've not gone at this directly in any sort of sustained manner but as you think around electron transport chain function the role of FFAs and their derivatives (CoAs and carnitines) continue to support the concept. The exact site of action isn't clear but the CoQH2 docking site on complex III is suggested in one paper but I've gone through the authors subsequent publications and they made no follow up to this concept. The group is pretty awful (generally) but that one idea might be correct. After that it's the RET ideas from me (Protons) and from Dr Speijer in The Netherlands. But here we're more specifically relating to insulin signalling rather ETC control per se. It's self evident that FFAs MUST limit ATP generation, a health fasting human has FFAs at 2000micromol/l. You can't let that down beta oxidation/TCA/ETC without some sort of negative feedback. Just no one is looking at the mitochondrial level (that I've tripped over).

Peter

Itu Chaudhuri said...

Hi Peter, thanks for one of the best lchf++ resources on the web and the wicked humour, which might be curative by itself.

I'm trying to understand a relatively high 5.8 a1c after 6 months of pretty strict lc eating (<40g carbs, no sugars, 60g protein, 120g fats). I had good weight loss (bmi went from 23 to 90), FBG on the same draw was 99 mg/dl. I ate a very low glycemic load breakfast, eggs + coffee with coconut oil, ghee, and 2g honey + 2g xylitol. PP bg was 95. I asked a doc friend if I should eat a carby breakfast but he said "lets see what sugars you have with your normal bfast" He was also anti OGTT preferring to "wait for something abnormal first".

Background, I've been loosely lchf for about 3 years, with about a year off. My last bloodworm, about 4 yrs old had 5.7 a1c, and generally I've reported FBG in the 90s and th only OGTT I've done, in 2008, was in the low 110s (seems incredible with what I now read),

Is this physiological IR? My father was t2 diabetic, used insulin, well managed, and lived to 90. What should I do to find out if I am prediabetic, IR for sure etc. Should I ease up a bit on the keto diet, or continue to wait for stability. and should I get an OGTT with or without the 3 day loading?

Deeply thankful for your opinion, I realize this come close to asking you to practice medicine on the net.

Unknown said...

Mr Lenntz, this thread emphasizes, but not limited to, the issue of FBS being higher than pp results.
Peter has been a beacon in the wilderness of science that you talk about....there was time, when I was 20 that animal fat and eggs were poison and vegetable oil were great....I am a 63 year diabetic, and wAs on two types of meds twice a day....I water fasted for 7 days and started hflc diet....2 months later I am off all meds my results are way better,almost 'cured' without a single tablet...my only problem is the high FBS which is 120 and drops to, and remains sub 100 through the day....what should I do for this Mr. LENNTZ....I WOULD LOVE TO HEAR YOUR REPSONSE

Itu Chaudhuri said...

Hello again, Peter.
Still trying to wheedle a response:)

I suppose the issue I'm trying to understand is how to know if I'm prediabetic. I didn't mention that my fasting insulin came out at 14. My FBs is 99, lower than a1c of 5.8 might suggest (for example, does that imply a lot of hyperglycemia on a auc sort of basis.)All on the same draw. After 6 months of pretty compliant lc eating, a lot of it I suspect in some sort of keto state, with much reduced hunger, etc, weight loss At 19 Bmi starting out at already moderate 23.

This may be the opposite of what this thread is about but in a way apposite too.

The issue is in New Delhi, India, l can't find any physicians etc who get lc. Some few have heard of it and are noncommital or pronounce it faddish and dangerous; the majority are haven't -heards wh subdivide into uninterested and curious, the latter further into open an aghast.

Exception: My mother's cardio is a insulin theory believer, lipid hypothesis disbeleiver, who isnt aware of the popularity of this Line of thought, hasnt heard of Finney, volek, your blog, NUSI, nor anyhting on thr internet circles, which i trawl endlessly. he says he'd read abut of the Gary Taubes book which he thought was on the right track, and approved of the politics of it even more.

He is unwilling to label me prediabetic, being unconvinced by my sugar numbers which he says need too much interpretation which he admits he isn't up to. He relies on my 'ideal' hdl/tg ratio of 1.02, and the high LDL which he thinks may be protective if anything, and a little on a WHR of <0.5, and not so much my low BMI. He thinks there may be hood endocrine / metabolic researchers in india, but who will not engage with an individual case. Hence the help request as I try to learn my way through the issues and the red herrings.

Hopeful, and in advance, thankful if you can get around to it one of these days. Your reading, and a pointer to how to think further.

Thanks ever so much

Itu

Peter said...

Hi Itu, I think if you suspect you are diabetic and really wish to know i’d point you towards Kraft’s book. You would need to be glucose adapted to do an accurate OGTT with insulin. The usual advice is 150g/d carbs for three days pre test but a bit more for a bit longer might be best if you are going to spend a great deal of money on insulin assays.

Obviously, you can do Kraft’s OGTT protocol without the insulin measurements but you cannot assume a “normal” glucose response means you have normal insulin response. A “good” glucose response means you need to do the same test but with the insulin measurements added in. But a failed glucose response, using Kraft’s criteria, is convincing that you have the problem. Assuming you are carbohydrate adapted. The book is here:

https://www.amazon.co.uk/Diabetes-Epidemic-You-Joseph-Kraft/dp/1425168094

Ivor has lots of information on Kraft’s approach over at http://www.thefatemperor.com/blog/2017/2/21/dr-joseph-kraft-passed-away-today-rest-in-peace

Hope that helps

Peter

Itu Chaudhuri said...

Peter, thanks ever so much for your comment. I had heard of Kraft, via Ivor too, but also from Ted Naiman's talks.

It's strange that the stringency of my diet fails to at least 'mask' IR. Scores like HOMA and QUICKI point to IR. Fasting insulin of 14 is the smoking gun for those scores. The TG/HDL ratio of 1 points the other way, and the use of the ratio seems useful for IR for Asian men. Maybe not this one!

From your article, it would appear that physiological IR is a possibility, or do I have it wrong?

Will follow up on Kraft, buy the book, and read Ivors artfile, but meanwhile, what insulin measurements, other than the (carb adapted) OGTT? Euglycaemic clamp? Horrors. Meanwhile good to know that the Kraft protocol is specific.

Yes, every word helps. Thanks again, and I'm continually amazed at the way you put yourelf out for others.

Itu

biochemistry in the next life. but trying hard to follow it in this one .

Peter said...

I think really you need the dynamic test to find out what level of insulin/glucose you are likely to be exposed to. The other thing well worth considering, after a "Kraft Test", would be to look at your glucose/insulin exposure after a typical meal i.e. an extended set of insulin/glucose measurements after a typical LC meal when you are back to carb adapted eating. Then you are in a position to decide if you need to change more lifestyle factors or even consider metformin etc. But you need the data...

Peter

Itu Chaudhuri said...

Peter, thanks for the response.

So the steps.1 Carb adapt for 3+ days.2 Kraft test. 3. Repeat after lc meal.

Or dud you mean:
1.stay ketodiet. 2.Kraft test. 3.carb adapt. 4.Kraft after lc meal.

I'm assuming 'extended set of insulin/glucose measurements' means a Kraft or like protocol. Pls correct me.

Thanks a megamol.

Itu

Victor said...

It is very easy to test yourself for PIR. Measure you FBG first thing in the morning, lets
assume it is 100 mg/dl. Move around, walk, waive your hands, do a light exersise (sit ups, stairs etc) for 15-20 minutes. If you have PIR, your muscles will eat up all extra sugar quickly, indicating that insulin resistance is not real, but physiological and thus,temporary. Remeasure BG, it should drop by at least 10 points, likely more (like 15-20 points).
PIR just temporarily raises your BG while you are not active (sleeping, resting, not thinking etc). Of course, all this valid only for low carb/low glycogen dieters in fasted state in the morning, when nothing comes from the food. I am making this conclusion on N=4 experiment.
Victor

Peter said...

Itu,

Carb adapt. OGTT as per Kraft, keto re-adapt, follow glucose insulin after a normal LC meal.

Victor, and the other option would seem to be an oral protein load then follow BG (+/- insulin). If you have non functional beta cells protein = hyperglycaemia as the alpha cells will secrete un-opposed glucagon. But I still feel Kraft's approach is probably the gold standard.

Peter

Itu Chaudhuri said...
This comment has been removed by the author.
Itu Chaudhuri said...

Peter, the debt of gratitude continues to rise.

It appears to neophyte me that teasing out IR is science and art, let's call it Kraft. I have the book and will also do as you say.

Just before I do, given the (not insurmountable, but still) difficulty of conducting a 5 hr test with lots of draws, might a standard OGTT test, post carb adaptation, that gives, say >140, be treated as a true positive for treatment, while accepting the caution that a just sub 140 score does not rule out a failure by one of Kraft's curves and thus calls for the 5 hr thing. Have I over-simplified or misunderstood?

Victor, thanks for weighing in. After my FBG 99 reading, I ate a breakfast of eggs in butter and coffee with lots of superfluous fats (aka bulletproof coffee). Strictly non glycemic except for a 2-3 g of honey and 2 g of xylitol. I then climbed stairs and lectured with lots of hand waving, and intense discussion for an hour. The 2 hr reading was 99 mg/dl. This is all in my old post, sorry to repeat.

Does this qualify as close to your criterion and also Peter, your protein load.

Thanks in advance

Itu

Tim Foxon said...

Wow lots of comments.

I was wondering if there may be an alternative explanation for the outsize glucose reaction on LCHF. What concerns me is it may be fat accumulation in the pancreas.

This might arise under the following conditions.

1. The fat content of a LCHF diet may be too large, in this case after a high fat meal some fat spills over to liver which exports it to other tissues, including pancreas.
2. Pancreas is known to accumulate trigs "avidly" but to disperse them less enthusiastically.
3. This may occur even in energy balanced conditions, the only prerequisite would be that the fat content of the diet was too high.
4. It has been shown that pancreatic fat can be reversed under CR but this occurs less so than in liver and I haven't seen anything in energy balanced conditions.
5. When pancreas sees too much fat insulin production gets shut down as it goes into "survival mode".

So I am concerned that an LCHF weight stable individual may be headed for diabetes if the fat macro is somewhat out of balance.

Apologies if this has already been covered.
Would appreciate your comments.

References for the above statements.

http://www.rcpe.ac.uk/sites/default/files/jrcpe_47_2_taylor.pdf

http://sci-hub.bz/10.1007/s00125-011-2204-7 (May have to supply Kaptcha).

Cheers.

Anne said...

Hi Peter, So glad to find this blog but still very concerned for my own situation. I started LCHF in October 2015 because of a pre-diabetes diagnosis of FBG of 5.7 mmol/l (57-year-old woman with BMI back than of 24, but two 9+lb babies and polycystic ovarian syndrome - lean);
First two years was great - lost 17 lbs, FBG went down to 4.7 BMI now 22.5, feel great.
Have charted BG with a home monitor.
Last three months FBG going up. Usually now 5.9 to 6.1, the other morning it was 6.9, the day after heavy HIIT exercise for 90 minutes. If I move around - running on the spot, climb the stairs a couple of times after testing, the FBG is a few points higher! If i exercise in a fasted state, my BG will be much higher after exercise.
I have been in ketosis pretty much for 2.5 years.
I worry I am developing LADA.
My doc wants a FBG and HbA1C but she is not fan of LCHF -- although she was happy with my results for first two years. I am worried I will be diagnosed as diabetic.
What should I do?

jon w said...

Hi Peter

You stated that omega 3 fats (fish oil) are known to cause insulin resistance. I started on a KD to increase my insulin sensitivity.
Further, I had just started taking 3 fish oil capsules per day based on that was the amount given the subjects in this study:

Paoli, Antonio, et al. “Effects of n-3 Polyunsaturated Fatty Acids (ω-3) Supplementation on Some Cardiovascular Risk Factors with a Ketogenic Mediterranean Diet.” Marine drugs 13.2 (2015): 996-1009.

The result for insulin proved particularly interesting. The subjects who consumed the ketogenic diet alone went from an average insulin concentration of 9.3 nIU/mL to an average insulin concentration of 7.4 nIU/mL of insulin. [11] This represents a 20.4% average decrease. In contrast, the subjects who consumed the ketogenic diet along with omega-3 fatty acid supplementation decreased their average insulin concentration from 11.1 nIU/mL to 6.3 nIU/mL. [11] This represents a 43% decrease in average insulin concentration- more than twice the decrease seen in the ketogenic diet alone. Additionally, subjects who took omega-3 fatty acid supplements experienced greater decreases in triglycerides and inflammation markers such as adiponectin and interleukin 1 beta (IL-1B). [11]

https://cdn4.ruled.me/wp-content/uploads/2015/10/ketographs2-01.png

Could you please source your data on fish oil and insulin resistance?

jon w said...

Victor
Regarding your post on high fasting blood glucose on waking and lowered by moving around, raised again by sitting, etc.

I am beginning to believe that people on a keto diet who have high BG may have less to do with ketosis and its affect on body metabolism- and more to do with inactivity. Not a period of exercise, such as walking a mile or working out with weights, but regular and frequent interrupting of sitting with standing and/or walking.

Here are some excepts from 3 individuals supporting that proposition:

Marc Hamilton, an inactivity researcher at the Pennington Biomedical Research Center:

This is your body on chairs: Electrical activity in the muscles drops — “the muscles go as silent as those of a dead horse,” Hamilton says — leading to a cascade of harmful metabolic effects. Your calorie-burning rate immediately plunges to about one per minute, a third of what it would be if you got up and walked. Insulin effectiveness drops within a single day, and the risk of developing Type 2 diabetes rises. So does the risk of being obese. The enzymes responsible for breaking down lipids and triglycerides — for “vacuuming up fat out of the bloodstream,” as Hamilton puts it — plunge, which in turn causes the levels of good (HDL) cholesterol to fall.

Hamilton’s most recent work has examined how rapidly inactivity can cause harm. In studies of rats who were forced to be inactive, for example, he discovered that the leg muscles responsible for standing almost immediately lost more than 75 percent of their ability to remove harmful lipo-proteins from the blood. To show that the ill effects of sitting could have a rapid onset in humans too, Hamilton recruited 14 young, fit and thin volunteers and recorded a 40 percent reduction in insulin’s ability to uptake glucose in the subjects — after 24 hours of being sedentary.

jon w said...

More on inactivity:

Dr. James Levine, author of the book Get Up!: Why Your Chair Is Killing You and What You Can Do About It.

It’s the hours of inactivity that are associated with the molecular mechanisms at the cellular level that are associated with causality for diabetes, hypertension, and even potentially cancer and other deleterious effects.”
According to Dr. Levine, there are at least 24 different chronic diseases and conditions associated with excess sitting. When you have been sitting for a long period of time and then get up, at a molecular level, within 90 seconds of getting off your bottom, the muscular and cellular systems that process blood sugar, triglycerides, and cholesterol—which are mediated by insulin—are activated. 
As soon as you stand up, a series of molecular mechanisms at the cell level set off a cascade of activities that impact the cellular functioning of your muscles. The way your body handles blood sugar is beneficially impacted, for example. Therefore, the disease prevention for diabetes comes into play. All of these molecular effects are activated simply by weight-bearing; by carrying your bodyweight upon your legs. Those cellular mechanisms are also responsible for pushing fuels into your cells.
Dr. Levine recommends sitting no more than 50 minutes out of every hour.

jon w said...

More on inactivity:

Dr. Joan Vernikos, former director of NASA’s Life Sciences Division and author of Sitting Kills, Moving Heals

In order to determine why regular exercise does not appear to compensate for the negative effects of prolonged sitting, some of her research focused on finding out what type of movement is withdrawn by sitting. What she discovered was as revolutionary as it was counterintuitive. Not only did she discover that the act of standing up is more effective than walking for counteracting the ill effects of sitting, the key is how many times you stand up.

It’s actually the change in posture that is the most powerful signal, in terms of having a beneficial impact on your health, not the act of standing in and of itself. Put another way, the key to counteract the ill effects of sitting is to repeatedly interrupt your sitting. The key is frequent intermittent interactions with gravity. Standing up 35 times at once will provide only a small percent of the benefit of standing up once every 20 minutes.

When it comes to interrupting your sitting, you want to stand up around 35 times a day or so to counteract the cardiovascular health risks associated with sitting. This is based on double-blind research where volunteers would spend four days in bed to induce detrimental changes. She then tested two groups to see which was more effective, walking or standing, and how long would you have to walk or how many times do you have to stand up to get better again?
Standing up once every hour was more effective than walking on a treadmill for 15 minutes for cardiovascular and metabolic changes
Sitting down and standing up repeatedly for 32 minutes does NOT have the same effect as standing up once, 32 times over the course of a day. To get the benefit, the stimulus must be spread throughout the day

Interestingly, lipoprotein lipase is dramatically reduced during inactivity, and increases with activity, the most effective activity being, you guessed it, standing up from a seated position. Lipoprotein lipase is an enzyme that attaches to fat in your bloodstream and transports it into your muscles to be used as fuel. So essentially, simply by standing up, you are actively helping your body to burn fat for fuel. But what is it about the mechanism of standing up that would account for this?

“These are all movements, almost below-threshold kind of movements, that do not burn up a lot of calories, as we know them, but that are designed to work against gravity,” Dr. Vernikos explains.

Dr. Vernikos views gravity a bit differently from the norm. She thinks of gravity as a virtual rod that runs through your body when you’re standing up; down to the center of the Earth. This virtual rod acts as a stimulus for your body, or put another way, gravity is a source of stimulation to your body. When you use it; when you challenge its downward force, you get a sense of acceleration and a sense of fun. Examples include jumping, skipping rope, cycling, downhill skiing, snow- or bodyboarding...

Unknown said...

The body heat and tiredness is exactly what should happen when you carb load after eating low carb. Completely normal!