Again from dissertante's query: How can chicken be found to raise blood glucose, acutely?
Many years ago, as a beginner at treating diabetic animals, I tried to balance insulin dose rate/timing against carbohydrate intake. Owners always asked if there was anything they could feed as treats etc. I used to suggest meat and fat as they shouldn't need insulin for processing.
This was a mistake. Dogs are, by the time we diagnose them, functionally type 1 diabetics. While fat is perfectly OK, protein certainly isn't.
Eating protein, for a type 1 diabetic, produces an immediate rise in blood glucose. This is nothing to do with gluconeogenic amino acids, the effect of which would expect to be delayed for several hours, if it occurs at all. While protein for an normal human being/animal is neutral on systemic blood glucose it never the less produces an immediate spike (by around 60 minutes) in blood insulin.
Dandona measured insulin and glucose, although not glucagon, after casein ingestion as we saw in the last post:
Eating 75g of casein protein more or less triples your blood insulin level but doesn't budge blood glucose down any more than cream does, which leaves insulin pretty well alone. Under normal conditions the casein induced spike in insulin is counterbalanced by a rise in glucagon. If the insulin rise does not occur (through beta cell failure) the glucagon will still rise and is unopposed, so hyperglycaemia is the net result, coming from a rise in hepatic glucose output.
This took me years to realise. Slow, I know but ah well.... It's now common knowledge and Dr Unger's glucagonocentric view of diabetic hyperglycaemia makes a great deal of sense.
So protein will provoke hyperglycaemia in the absence of an insulin response, via glucagon, in a type 1 diabetic. I would guess that the same would apply to an advanced type 2. It very recently occurred to me that an elevated blood glucose after protein intake might be a useful supplementary test for certain oddities in OGTTs.
I had an email a few weeks ago about OGTT results in long term, non diabetic low carb eaters. I don't know the exact details of duration of LC eating or the period of carb loading before the OGTT, but the end result after glucose ingestion was a sustained hyperglycaemia with profoundly depressed C-peptide levels.
The worry here is that long term LC might have led to endocrine pancreatic insufficiency. My initial thought was to wonder what the response to exogenous insulin might be, but this was probably the wrong line of thought.
What would be far more interesting would be to run an oral protein response test, looking at blood glucose, insulin, glucagon and C-peptide. Although, at a pinch, all you need is the blood glucose result. If a person has developed a significant loss of beta cells then the unopposed alpha cell glucagon response to this protein would produce hyperglycaemia. A normal insulin reaction in response to protein would produce normoglycaemia after said protein load.
We all know that after a month or two of LC eating that three days at 150g/d of carbs will restore a normal response to glucose. But the question is what time scale of carb loading is needed after several years of LC eating. The regulation of insulin secretion in response to glucose requires active glycolysis, regulated by glucokinase in the pancreas. Glucokinase gene expression is controlled by dietary glucose supply. If long term glucokinase down regulation takes longer than a few days of carbohydrate loading to reverse, this would produce intolerance to glucose but would have no effect on insulin secretion when driven by amino acids. It would be quite simple to differentiate between down regulation of the pancreatic glucose sensor from newly acquired type 1 diabetes during LC eating.
Summary: Elevated blood glucose after an oral protein load suggests genuine diabetes. Poor responsiveness to glucose after sustained LC eating simply reflects a mothballed glucose sensor, provided response to protein is normal.
Tuesday, February 02, 2016
Insulin glucagon and protein
Posted by Peter at Tuesday, February 02, 2016
Labels: Insulin glucagon and protein
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So the moral is, if long-term LC, avoid an OGTT (and any other alphabet soup), and other boluses (bowls) of glucose, and all will be well.
And why would you want an OGTT, if you were long-term LC?
I'm aware of Dr Kraft's work (via Ivor Cummins, at thefatemperor.com), but really, why bother, if LC, especially if HFLC?
Patrick, personally I wouldn't bother. Though I'm tempted to see what my HbA1c is occasionally. But what would you change on the basis of the result???? But how the physiology works is interesting in its own right, to me anyway.
So what is the effect of a fat only diet? Is it harmful over time? Could supplements be added to prevent negative effects?
Would protein would spike insulin/glucagon in a very low fat context?
Thanks for the write-up, Peter. If I recall correctly, diabetic subjects were not included in the Technion study. Are you suggesting that those who were eating moderate-high carb in the study and produced an acute glucose response to chicken are undiagnosed diabetics?
OldTech, again I wouldn't bother. You need some protein and eating carbs as part of real food simply leaves some level which might be open to discussion as to what is best. An open question...
Pass, yes, I would expect a normal response to amino acids under pretty well all circumstances. I also suspect different amino acids input in different ways to the the TCA and probably to the ETC, though I've not gone looking in detail. I'me expecting an FAD linked input at to CoQ couple to be involved in insulin secretion (as well as in insulin response).
dissertante, yes, I would be concerned along those lines. As Patrick commented, once you read Kraft the term "non diabetic" becomes very, very grey indeed. This is why T2's are so broken before their elevated FBG gets them the "label". They have been hyperinsulinaemic/glycaemic for years before FBG creeps up to pass the benchmark. T1s have no pre existing disease and it takes a year of hyperglycaemia on poor control to break them properly, unless they read Bernstein of course.
seems to have a lot of information
So it is a keto diet that is best for both us and our animals (at least dogs and cats) that have diabetes?
Do cats have the same problem as dogs (i.e., they are already functional type 1s)? BTW: how do you do a glucose test on dogs or cats?
What about chicken vs other meats and proteins?
Chicken has a lot more linoleic acid ?
Metformin seems to reverse the protein effect for me.
There are piles of papers trying to see linoleic acid as a health aid. Am I being paranoid thinking there is something sketchy going on with handing out the grant money?
Very interesting Peter.
Glucose rise after glucagon injection is due to glycogenolysis, as gluconeogenesis is too slow. (this when high-dose glucagon injection is used to reverse hypoglycaemia in T1D). So what is protein response if glycogen is depleted? Not that I think it will be in long-term LCHF case.
I don't know if you've seen this paper Ivor dug up, but seeing as it's from 2000 and by 2 anaesthetists is seems a safe bet that you have.
It's some of the loveliest writing I've read on this subject. I just long for it to be extended to cover lipolysis as well as proteolysis in the end discussion, and to describe mechanisms during a ketogenic diet as well as fasting and normal feeding.
I finally found a little explanation (below) of why a ketogenic diet controls proteolysis and lipolysis in the absence of an insulin response. (why a KD prevents DKA in decompensated diabetes). Basically we have the beginnings of an alternative, fat-responsive, homeostatic system in the absence of carbohydrate and glucose-forming protein levels; there may be a healthy underground economy on the other side of the High Fat Iron Curtain which no-one has bothered to map out yet.
Ach I'll put the niacin back on the shelf then and just cut back on the protein. Peter this is a very clear and useful blog post for me (distant sounds of pennies dropping) George also those links are good damnit. The hi-fat curtain? Reminiscent of the war when Au and Nz were shipping loads of butter off to the old country through hazardous waters. We need to put together a cargo of good suet and lard for the relief of those poor folks again. C.
Peter take this people failing your protein test and put them on a high fat diet and tell them to look 15 degrees away from the sun rise when it begins for as long as they can........then tell me what you notice about their insulin and glucogon status. You will see a big change. Sun exposure through the central retinal pathways have massive effects on beta cell regeneration and on lowering glucogon release. It also lowers the liver release of glycogen but this requires more sun in the AM.......based upon location to get this effect the regeneration cycle needs two specific frequencies that do not show up until later in the AM.
@ George Henderson
That paper is excellent --- I really liked this bit "...a 20 yr ‘black age’ of endocrinology"
In my quest to figure out 'what bit gets broken(tm)' that paper inspired me to think of the insulin to glucagon ratio - and I see others have thought of it also - as seen in this paper .
Then I looked at your other link - same issue -- this ratio. There is the bit "leptin and somatostatin" ( be aware somatostatin has many synonyms:
growth hormone–inhibiting hormone (GHIH)
growth hormone release–inhibiting hormone (GHRIH)
somatotropin release–inhibiting factor (SRIF)
somatotropin release–inhibiting hormone (SRIH)
somatostatin 28 inhibits lipolysis --
I did a search and this is one topic that petro hasn't written on yet that I can find - yet with all the synonyms I'm not sure.
I've started working on a diagram for adipose regulation - and I've had somewhat of a realization. I understand complex feedback loops fairly well - non linear/intergrating/differential/pulsatile etc.
In regards to my enigma "what bit gets broken(tm)", causing the obesity/T2D pandemic - a small 1% dis-regulation is all it takes. Once dis-regulation occurs lots of things get out of whack and we find correlations - but we have to be very careful about what is actually causative. I can think of dozens of plausible explanations. There is a real need for Ockhams Razor as we feel around for an answer.
But one thing is for sure - the signal that disrupts adipose regulation/appetite could be very small in amplitude - and the long term effects might have much larger amplitudes thus misleading us.
In control loops for automation - we use integral feed back to provide accuracy - the error is added up over time. This provides an accurate set point. One bit that acts sort of like that is leptin. (the opposite of this would be something like a post-synaptic receptor that gets desensitized(as in serotonin)). There likely is a SINGLE system that creates a precise set-point - as is the case in biology there are redundant systems that help prevent a single genetic error from being lethal - yet what controls the weight set-point with precision is likely singular.
What is so strange on this quest is as I go on, I learn more things yet what think I know for sure becomes less and less. (One of the tricks I use - comes from a friendship of a savant - is we would debate some issue - and then one or the other of use would agree and the debate would reverse - sometimes more than once - some level of debate helps find the holes in logic. So please feel free to disagree with anything I mention.)
the warning about synomyms is appreciated, and more searches will be done - however, there are 2 forms of somatostatin and SST 14, which is not diet-linked but seems to be an internal control, is usually the one used in experiments, because it's easier to make and a more potent glucagon antagonist (e.g. it is the version used by Unger). Because the hormone comes in 2 different lengths, it is necessary to differentiate, but SST 14 was originally considered the generic version.
When we only eat fat - and our small insectivore ancestors came close to this regularly when they devoured large grubs of the huhu type - insulin is left out of the loop, yet life goes on. (Huhu grubs are said to taste like peanut butter or butter chicken, but I can't find a nutrition breakdown.)
I didn't make this clear enough in the article, but the somatostatin 28 response to macros is pretty much the exact inverse of the insulin response. Full response to fat, half response to protein, no response to carbohydrate.
FFAs raise insulin but cream doesn't - even after several hours when FFAs rise significantly. This tells me that the FFA responses are largely irrelevant to discussions of diet - they are internal biostatic controls, and not analogous to fat feeding. Yet these FFA studies are trotted out whenever the harms of fat are discussed, and pure fat-feeding studies are not, because no-one bothers to conduct them. Even the cream studies, though marvelously useful, do not use a pure fat.
I am just curious. Peter, did you recommend any treats for dogs with diabetes?
OldTech, there is simply no choice. The core need is to supply exogenous insulin to the portal vein without having a high dose hit adipocytes. Ketosis minimises whole body insulin usage and allows systemic and portal concentrations to get as close as practical to equilibrium. I would suspect the concentration surrounding alpha cells would also equilibrate to systemic venous levels under deep ketosis. There is no choice.
No, cats are frequently more like type 2s, though there are multiple subtypes. Many cats will go in to remission with insulin therapy and stay there long term, certainly if you low carb them. This happened more when we had protamine zinc insulin, but that’s long gone.
OGTT, for a cat, I used to feed a decent meal of CIAB, carb based, and get a urine sample 3 hours later. We only deal in gross changes. I also routinely checked response to exogenous insulin to look for severe IR, in cats this is usually GH (brain tumour) related.
karl, some of the fiercest protein induced spikes I saw were following beef ingestion. I never looked in to it as to why. Paranoid about funding and research integrity, a low carber?????
George, yes I read Sonksen and Sonksen in the original (PAPER copy!!!) as I used to subscribe to BJA and I took that particular edition (July) on a camping holiday to the North Norfolk coast in August 2000 as a little light reading. How sad is that? I think it would bear re reading as many of the ideas are still quite current. I’ll have to read the link you sent as this whole concept of ketogenic diets controlling ketoacidosis seems rather important to me….
Pass, I’ve dealt with a lot of blind dogs over the years before enough pennies dropped!!
Jack, I’m still just working with the high fat diet stage…
Galina, here in the UK we don't have any effective therapy for diabetes in dogs. There is one licensed insulin, it's utterly useless and the last CPD course I went to promoting its use suggested all dogs would be blind from cataracts with 1 year of diagnosis. I used to use protamine zinc, low dose, bid, as basal with neutral to cover meals. No chance to do this nowadays as the human insulins are 100iu/ml and vet insulin is 40iu/ml. I'm glad I'm no longer a clinician. So treats? Theoretically none but our control is so bad I doubt it makes much difference...
George witchetty grubs are very tasty. The title of this article is off-putting but the theme is good:
Some time soon this year our back verandah will be bombarded with giant rain moths, so-called because they appear in the first autumn rains. They are the adult stage of another type of witchetty grub and as thick as fingers. In Canberra they have Bardi grubs and Bardi moths which are full of fat. Beware of flying food!
Human beings are very creative in finding sources of intoxication. Even nowadays some primitive groups exict which members chew some starchy plants, spit it in a pot and wait till fermentation takes place. I sospect that our Neanderthal ancestors chew grains mostly for booze production. May be beer making was the first step in a grain consunption for humanity.
Just to throw in an n=1 as I have been low carbing since 2010 and currently have a continuous glucose monitor attached. I can eat low carb mixed meals and have no effect at all on blood glucose, this includes 70 and 150 gram portions of beef, 100g of salmon and a glass of white wine, Tesco's finest chorizo style pork burgers etc etc.
Give me a Diabetes UK meeting working lunch on the other hand and my BG goes up 4.5 to 8.5 :-(
Phil, T1 or T2? Exogenous insulin?
Thanks in advance
Galina, nice idea! I still miss beer, a glass of gin with a slice of lemon somehow never quite hits the spot! Though it's OK.
An old paper but interesting
@ George Henderson
One thing to keep in mind - there is archaeological evidence of some of the foods our ancestors ate - yet picking up a grub and popping it into ones mouth isn't going to leave any.
In some primitive tribes, you will see mothers picking out the lice - and instead of just smashing them - they eat them.
I did some searching on nutritional content of bugs a while back - there is a pretty wide range of they types of fatty acids depending on the bug.
My hunch is we are much more evolved to eat a fair amount of bugs (and even nematodes) than is currently accepted.
Re set points - when I think about it, it is amazing how accurate the food intake of a healthy person is - errors being too thin would be lethal during famines. In a lot of the world - being told you look fat is a compliment. Tiny errors matter.
Being overweight has to have it's own selection as well - too heavy and you can't run fast/long enough to survive battles? The appeal of a woman's subcutaneous fat suddenly disappears at some point of excess. ( Estrogen is involved in this layer - storage for gestation - is it possible that it is adjusting the set point system? )
That occurred to me too when I looked up the huhu grub - there would be no trace of this at a campsite, but grubs would be a major source of fat at some times.
For example, this Australian Hunter-Gatherer diet would not be so high in protein if grubs were available (and, perhaps, if they didn't have modern hunting equipment, in which case grubs would have been sought out when hunts failed. Maybe.)
Some bug fat data - bugs are pretty fatty and some have normal animal mixes of fats
"If the insulin rise does not occur (through beta cell failure) the glucagon will still rise and is unopposed, so hyperglycaemia is the net result, coming from a rise in hepatic glucose output."
Amylin plays an important role here too.
"Amylin is co-secreted with insulin, and its best known functions are reducing food intake and gastric emptying, and inhibiting pancreatic glucagon.."
I'd guess without these functionaing feed-back loops, the glucagon spike is highly exaggerated in the T1D and the advanced T2D..
Which leads to MORE insulin needed in meals with protein.. Bernstein (if I remember right) mainly attributes this need for dosing insulin for protein intake to gluconeogenis. And it clearly goes beyond that..
I wonder if Amylin therapy would reduce the need for exogenous Insulin, or at least cut back on the amount required? The less insulin needed the better.. trick stuff though, when you're talking about these complex feedback loops..
Peter said, "Poor responsiveness to glucose after sustained LC eating simply reflects a mothballed glucose sensor, provided response to protein is normal."
And it makes sense, in a Nick Lane/Doug Wallace/Bio-Energetics point-of-view, that those sensors would be mothballed. There's some kind of energetic cost for maintaining those sensors. The body is thrifty and all that.. The important thing to remember is that this is transient, as the "carb-loading before OGTT" testing/discussions have shown us.
kelly, there was a discussion about 10 years ago about amylin interfering with alpha-beta cell communication. That might be important.
"The idea that amylin is a part of the beta-cell drive that normally limits glucagon secretion after meals fits with the observation that glucagon secretion is exaggerated in amylin-deficient states (diabetes characterized by beta-cell failure)."
So it's not only that glucagon is allowed to rise unopposed, it's that the secretion is exaggerated in the absence of amylin in T1D and advanced (beta cell missing) T2D..
Think about what that looks like, for example, in the case of my T1D boy..
Even when we strictly limit non-fiber carbs his BG spikes as if he's just downed a Snickers candy bar after eating a big juicy steak, for instance. Gluconeogenesis alone can't explain the BG spike but this glucagon secretion triggered by the amino acid plasma content certainly does....
We estimate his insulin needs and inject prior to meal.
He eats the protein and veggies.
Amino acid plasma concentration triggers glucagon reaction.
Lack of amylin allows for an exaggerated glucagon reaction.
Exaggerated glucagon secretion translates to exaggerated glucose production by liver.
Exaggerated glucose production translates to BG spike that is evident 1-2 hours after meal.
BG spike calls for extra insulin to be injected to bring it under control..
If the goal is to limit the amount of insulin injected, which I think is critical for long term health, then limiting protein to only what is needed is critical.
(this reply is in 2 parts)
thanks for that link about amylin. In T2DM amylin resistance lags behind insulin resistance - because of IR and high production of both hormones, the brain takes up 10x as much amylin as insulin; without enough insulin pancreatic amylin contributes to amyloid in the brain - which is probably (IMO) why T2DM have a high rate of Alzheimers and T1DM, for all the sugar stress on their brains, don't.
There is a glucagon response to carbohydrate as well as protein - this is brief if it induces insulin in alpha/beta cross-talk, but problematic in diabetes.
Somatostatin 28 is produced by gut delta cells in response to fat feeding and inhibits glucagon, insulin, and HGH. It inhibits proteolysis (muscle breakdown) and lipolysis, the latter by a direct effect on fat cells as well as the inhibition of glucagon.
When somatostatin  alone was infused there was no
significant change in either the plasma glucose concentration
or in the rate of glucose turnover. As a consequence,
the rate of glucose clearance also did not
change. The basal rate of glucose turnover in these studies
was 19.0 ± 3.6 ,umol/kg/min, and during somatostatin
infusion the value was 20.1 ± 3.2 ,umol/kg/min.
When somatostatin was infused in the TPN patients the
effect was similar; there was no significant change in the
plasma glucose level or in the rate ofglucose turnover or
glucose clearance (Fig. 1).
When both somatostatin and insulin were infused
there was a selective reduction in the plasma levels of
glucagon and HGH while the plasma insulin level did
not change significantly. In this setting the plasma glucose
level decreased from 6.9 ± 0.7 ,umol/mL to 4.8
,umol/mL (p < 0.05), and the rate of glucose turnover
decreased from 17.6 + 2.2 ,umol/kg/min to 11.1 ± 2.5
,umol/kg/min (p < 0.01). The rate of glucose clearance
also decreased from 2.7 ± 0.3 mL/kg/min to 2.3 ± 0.3
mL/kg/min (p < 0.04) (Fig. 1).
Somatostatin infusion resulted in a decrease in urea
turnover in each of the three protocols. When somatostatin
was infused alone, the rate of urea turnover decreased
from 13.4 ± 2.9 gmol/kg/min to 11.8 ± 2.0
,umol/kg/min (p < 0.002).
Now, the effect of somatostatin 28 (SST 28) above on urea turnover is a measure of its effect on glucagon. Look at the Table 17 in this old pre-insulin diabetes paper - feeding a huge dose of fat (273g) has a similar (but greater) effect on nitrogen excretion in diabetic subjects without insulin.
So, it seems, with a high-fat diet restricted in carbs and with protein at nitrogen balance you have an extra mechanism to restrain glucagon, directly related to dietary fat. If you limit protein to only what is needed, there is room for more fat in the diet.
However, insulin is needed for growth and extra protein allows enough insulin for growth in kids - this is the thinking of Dr Bernstein, and the results of his higher-protein, very low carb diet speak for themselves.
However, in well-managed T1DM peripheral insulin will always be higher than needed to control proteolysis, because of the need for a high portal concentration to control gluconeogenesis. Less so on a very low carb diet, but still so.
"HbA1c is only a measure of recent glycaemic control; fortunately, however, in the vast majority of people with diabetes, if glycaemic control is good then so are other metabolic processes. Indeed, in patients with diabetes treated with insulin who have ‘tight glycaemic control’, there can be ‘over‐control’ of other metabolic processes. This is explained as follows. Exogenous insulin is given peripherally and the dose adjusted to control hepatic glucose production, not proteolysis. With subcutaneous or intravenous administration of insulin, the concentration in the portal circulation will always be less than in the systemic circulation. This is a reversal of the normal situation. Good glycaemic control thus invariably results in peripheral hyperinsulinaemia. Hence lipolysis and proteolysis are slightly ‘over‐controlled’ (protein synthesis is normal—insulin‐independent and regulated by growth hormone—but protein breakdown is reduced as a result of the ‘chalonic’ action of peripheral hyperinsulinaemia)."
So, beyond this over-control of proteolysis, what exactly are the factors required for growth which are likely to be under-supplied in T1DM, and what compensations are available?
In addition to what Karl pointed out about the dynamic nature of the way these things work together and possible sensitivity to small changes, more slowly changing inputs generally give rise to greater stability. It is possibly one of the few ways in which low GI theories of nutrition are plausible, you don't get such rapidly changing numbers even if the final setpoints end up too high or too low. Sometimes the peak values of a wildly oscillating quantity are more dangerous than the average value.
That's a distraction. What I'm thinking about is a person who is type 2 diabetic but weight stable. (moi?) Seemingly the catabolic action of glucagon doesn't overwhelm a setpoint which is locked in somewhere due to action of sufficient insulin? Or perhaps as George suggests, with sufficient fat intake somatostatin locks down the lipid stores acting similarly to insulin. Lower insulin from low carb eating is an effective weight loss method also suggesting unopposed glucagon might also be good for this, which suggests that at least temporarily a lower fat intake with low carbs---> lower somatostatin and higher glucagon etc.
But what about the protein?
Thank you! Good stuff.
"So, it seems, with a high-fat diet restricted in carbs and with protein at nitrogen balance you have an [b]extra mechanism to restrain glucagon[/b], directly related to dietary fat. If you limit protein to only what is needed, there is room for more fat in the diet."
Good deal. I'll work through all of these links today along with your post a few times to try to understand this mechanism..
RE: (part 2)
"So, beyond this over-control of proteolysis, what exactly are the factors required for growth which are likely to be under-supplied in T1DM, and what compensations are available?"
hmm.. Well, I'm a self-educated Dad who's first question upon hearing that his kid had T1D was, "HUH? What's insulin?" but..
Factors for growth: building blocks (appropriate protein/fats) and the correct signaling, I'd guess..
Under-supplied: There are definitely known common mineral and vitamin deficiencies in Diabetics..
Compensations: Supplementation for known deficiencies
It's the "correct signaling" that gets out of whack so easily in the T1D.. The periphery issue you mention, timing of insulin "spikes" vs timing of low-insulin states... All of that is wonderfully orchestrated by Mother Nature in the healthy, growing child..
We're replacing Mother Nature's perfectly orchestrated sense of timing and all of these signals and the cascading effects they have with a very imperfect/flawed, manual, test and inject process that I'd argue, even in the most tightly controlled individual will lead to less than optimal growth and development...
RE: " With subcutaneous or intravenous administration of insulin, the concentration in the portal circulation will always be less than in the systemic circulation. This is a reversal of the normal situation."
Just wondering/thinking out loud here. A lifetime of this "reversal of the normal situation" where peripheral insulin concentrations are always higher.. I'd think that would leads to less maintenance and repair in the peripheral tissues (autophagy, etc), as these processes are kicked off when the body senses that nutrients/energy in the environment is low and it's time to "conserve and repair and maintain"... Might explain the accelerated aging and some of the complications that diabetics (even tightly controlled) see.
Completely random interjection, but did you ever find the solution to your wife's migraines? They seem to run in my family, and appear to be associated with hormonal changes, menopause being a major trigger. I see that you eat chocolate every day [at least as of 2013], and was wondering if your wife did as well. For me, chocolate causes some weird issues that are potentially neurological. However, the only time I've gotten a true migraine was after having some very cheap white wine :)
Hi Rattus, yes my wife still eats chocolate and drinks coffee. The migraines come and go and are also very stress related.
I hope you were all smiling while I painted myself into a nutritional corner there.
I had migraines as an adolescent, from about 15-21. They went away for 30 years when I became addicted to opiates and opioids. A few years ago I withdrew from methadone; last year I started getting scintillating scotoma again, but not the full-blown headache. Being low carb seems to protect me from pain (likely amylin is a factor in the pain) but not scotoma, weirdness, and subsequent dullness.
I traced the likely cause to coffee - it usually followed the excess cup. But occasionally chocolate or bacon seemed the triggers. Bad news I know.
So I stopped the coffee and cut back on the other two. Basically had a cup of coffee every other day instead of 3-4 a day, and stopped drinking the cheap instant brew I was drinking.
After a while I was able to re-introduce a better instant (Moccona) without problems, I use bacon sparingly now, and eat as much dark chocolate as I like. If it happened again I'd use the coffee washout - if you're a caffeine junkie I think it's a good idea to do a periodic washout, it didn't hurt at all.
So what was the trigger? My guess is a combination of tyramine and some serotonin analogue, histamine, or other neurotransmitter analogues, in these foods. No problem with cheese though.
I looked up factors for growth in T1DM and found that Growth Hormone and insulin-like growth factor 1 (IGF-1) are required, and somatostatin (SST) 14 inhibits GH, acting as an internal brake (SST 14 is not affected by diet like SST 28). SST 28 also inhibits GH, albeit less. All these hormones are produced outside beta-cells. So this (SST as GH inhibitor) might help explain why Inuit are short on natural diet and kids on ketogenic epilepsy diets have reduced growth in infancy, but not if placed on ketogenic diet later in childhood - the effect would only be significant in rapid growth phases - infancy and late puberty.
Ergo, if you really wanted to use a ketogenic diet in T1DM, the appropriate time to depart from this and replace some fat with protein, a la RK Bernstein's diet, would be during infancy and puberty, when growth is normally faster.
Based on some very simple understanding of these mechanisms and not intended as medical advice! Also, not taking into account what will be the most palatable very low carb diet, one the child will want to be consistent with. Which might well be the most important consideration here.
re: Dr Unger's glucagonocentric view of diabetic hyperglycaemia...
It Sure does make sense..
Unopposed glucagon whether it's caused by a lack of insulin in the T1D/Advanced T2D or caused by alpha-cell IR in the earlier-stage T2D explains a lot.
Looks like Unger is still blaming that evil Palmitic Acid for the IR @ the Alpha-Cell... "lipotoxin" I think is his word of choice.. You've written about that bad science before. He talks about T2D at about the 23 min mark in one of his latest lectures I could find: https://www.youtube.com/watch?v=VjQkqFSdDOc
Other than that (and that's a pretty big deal, as it reinforces the fat-phobic BS that has sent everyone down the carb road...) I like where he's coming from.
Yea I think both the chocolate and coffee are potentially migraine triggers. Both contain pretty high quantities of stimulants, both are seeds. Plants obviously want to protect their seeds, so it would make sense that they might cause issues in some people. Tea also contains stimulants, but is made from leaves so maybe less harmful.
Bacon would probably be a trigger because of the PUFA/MUFA content, but you probably already knew that. Pork in general is pretty weird. Even wild pigs usually have a high ratio of PUFA/MUFA, just because they aren't ruminants and their tissues pretty much directly reflect their diet.
@Peter I have impaired fasting blood glucose (6.8 or so, sometimes in the 7.x range). No exogenous insulin or diabetes meds. Using diet and having a go with a CGM to help - seems I have reasonable glucose tolerance in terms of bumps in BG coming back down, but my cumulative daily glucose account can get overfull leading to the higher fasting numbers.
There's a study in here showing lower post-prandial glucose when carbs ingested 1x daily than when spread out over 3 meals.
In addition to modifications to carbohydrate amount, carbohydrate distribution may be another important nutritional consideration for altering diurnal blood glucose response and GV. In a randomized crossover study, Pearce et al. (176) examined 23 adults with poorly controlled T2DM (mean HbA1c 8.6%) and compared the effects of consuming an energy-balanced,moderate-carbohydrate (40% energy) diet with either an even carbohydrate distribution across three meals (70 g carbohydrate/meal) or carbohydrate loading (125 g) at breakfast, lunch, or dinner and assessed PPG (PPG peak, time spent>12 mmol/L, and glucose AUC) from three-day CGMS. This study showed that an even carbohydrate distribution did not optimize bloodglucose control, whereas carbohydrate loading at lunch provided the most favorable PPG profile. Furthermore, carbohydrate amount and GL at each meal were only weakly related to PPG peak, accounting for 16–17% of the variance in PPG peak. Because insulin resistance causes impaired suppression of gluconeogenesis and excessive glucose production in T2DM (38, 150), repeated carbohydrate exposure may potentiate sustained increases in PPG.
In other words, a layering effect of insulin exposure is what generates pathological IR and results in inappropriate gluconeogenesis and glyconenolysis. Widely separating carb intake and/or insulin responses through some kind of intermittent fasting (or indeed fasting) makes sense here.
Peter, I guess there is no reason to think that those on a low carb diet would also have a mothballed PROTEIN sensor. Clinically I often need to differentiate between physiologic IR and those truly diabetic with burnt out beta cells. The clinical presentation is always helpful. I don't know of any standardization for a protein challenge, but it's an interesting idea. Thanks again.
You mentioned being curious about your HbA1c and I'm wondering if you've ever tested it while you are eating low carb. There seems to be some debate over the idea that blood cells may survive longer and therefore be more glycated which would produce a HbA1c that may not be as accurate as it would be for someone who is eating a SAD. In my case my HbA1c is normal (5) but seems to me that it is higher than it should be for someone who is very low carb. When I look at the average blood sugar that 5% represents, it seems that it can't possibly be an accurate representation of my blood sugar. Any thoughts from Peter or other readers?
@George thanks for your thoughts and the download link. Have been restricting eating hours to have a longer overnight fast.
Hi Peter. Very interesting. What kind of an insulin response can be expected, from someone who stays pretty close to ketosis for years, when eating protein? Do you still get the insulin spike one hour after eating if there is little to no glycogen stored in the liver?
Hi Olga, the insulin secretion in response to protein is triggered by certain specific amino acids, which also trigger glucagon secretion. There is no reason why the ability to metabolise these amino acids should be down regulated on a LC adequate protein diet, so I would expect zero hyperglycaemic response to an oral protein load. A minor fall is quite common but we are sonly taking 5 point something to 4 point something in Dandona's study. Diabetics should acutely spike. How high depends on the protein amount and composition.
If protein stimulates both insulin and glucagon, and they cancel each other out, what purpose does it serve? Is it just to exercise the alpha and beta cells?
Hi Rpbert, they might cancel out on BG levels but I doubt there is a complete cancelling out on the ton of things we know insulin does. To me, BG control is an "add on" to insulin's job. Goodness knows what glucagon does, beyond raising BG...
I did this test myself a while back. I am a T2D and I compared myself to a friend who is not. We were both LCHF at the time (many months in his case and over a year in my case). His blood sugar went down 20-30 points and mine went up 20 points over a couple of hours. I documented it here.
I do consider it a good test of the "fixedness" of my T2D. If my blood sugar response matched his then I'd think about considering myself as fixed. Since it doesn't even though I have an HbA1C of 5.2 and no symptoms (due to LCHF), I still don't consider myself fixed.
Hi Doug, still working through your links, not ignored. Interesting. One of the things that also interests me (among others) is what breaks in DMT2? Shrinkage of adipocytes and side stepping glucose intolerance is absolutely the way to go. But you will never eat another pizza and have the BG of a 15 year old.... As some trivial consolation; I think most of us, if we live long enough, will join you there!
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