If we look at the extremes of substrate source for the provision of bulk calories we have the choice of either fat or carbohydrate.
Under high carbohydrate intake we have high pancreatic insulin output and almost matched hepatic insulin extraction. Some insulin spills over in to the systemic circulation to facilitate bulk glucose utilisation but systemic hyperinsulinaemia and hyperglycaemia should be mild and within physiological limits (whatever they might actually be...). However there is a marked differential between portal vein insulin levels and systemic insulin levels, especially post prandially.
Under extreme ketogenic conditions energy is sourced almost exclusively from lipids. Insulin has minimal involvement with hepatic glucose uptake because almost zero hepatic glucose uptake is going on. Extreme hepatic insulin resistance leads to minimal extraction of what pittance of insulin the pancreas is producing and you end up with the minimal possible difference between portal vein insulin and systemic insulin concentrations.
What happens when someone needs to use insulin to maintain normal blood glucose levels?
If your only route in for exogenous insulin is via peripheral injection you can, with ketosis, put the body in to a state where insulin is relatively unimportant. You do not have to plan for one concentration of insulin to hit adipocytes and muscles while (impossibly) targeting a far higher concentration to hit the liver. Under ketogenic conditions the liver is no longer a sump for insulin usage. In fact there is almost no sump for insulin disposal as it's not being much used for anything. Peripheral and portal insulin requirements are similar and can be met by the peripheral route.
As you move from ketogenic eating to carbohydrate based eating the portal vein to systemic insulin difference has to increase and the problems of controlling hepatic glucose output while still allowing lipolysis to give access to adipose tissue calories becomes progressively more difficult.
It's notable that successful diabetes control, as promoted by people like Dr Bernstein, uses mildly ketogenic macronutrient ratios, ultra extreme ketosis does not appear to be needed. Humans are not mice.
Carbohydrate based diets would appear to lead to that wheelchair in the dialysis room and the incorrect impression that diabetes is an inexorably progressive condition.
Peter
This comment has been removed by the author.
ReplyDeleteI wish I could get my diabetic grandmother to go along with this advice. :( Unfortunately she lives off bread and potatos and insists that she "doesn't like fat."
ReplyDeleteWhen one aims at insulin one aims at the wrong target. That is precisely what my profession has done for 50 yrs. Insulin is not the issue. Its all about leptin. Insulin is just easier for the human mind to comprehend. But that does make it the correct target. The ACCORD trial shows that in spades. Dr. K
ReplyDeleteI'm one of those individuals that functions much better on a an extreme [<20g/day carbohydrate] ketogenic diet. In fact I function perfectly on zero carbohydrates. At only 50-100g/day I soon develop polydipsia, polyuria, reflux and irritable bowel disease.
ReplyDeleteThe intensive glucose-lowering therapy in ACCORD involved more aggressive use of conventional diabetes treatments to achieve the desired HbA1c with the result that mortality increased so much in the intensive group (54 extra people, about 25% more than in the standard treatment group) that part of the study was discontinued early. How does that show insulin is not the issue when using more insulin ended up killing more people?
ReplyDeleteFor reference, from p54 of the ACCORD protocol "within 6 months of randomization, most intensive group participants will likely be on 3 or more injections of insulin per day in addition to 2 or 3 oral agents. Conversely, standard therapy participants are less likely to be on insulin, will be on < 2 injections per day if insulin is used, and will be taking fewer oral agents."
Hi Peter,
ReplyDeleteI have T1 diabetes, have recently (2.5 weeks ago) switched to a low(ish) carb / high(ish) fat diet, and have been reading your archived entries with great interest.
I'm particularly interested in the issue of physiological insulin resistance, as I wonder if I'm experiencing that phenomenon. After roughly ten days of fantastic blood sugar readings (5-6 mmol for hours on end) and reduced insulin requirements (~16 units per day, down from ~25 units per day) at the start of my low-carb journey, I now find that my insulin needs are creeping up daily. For the past few days, my blood sugars have been stuck around 8-9 mmols, and each day I've inched up the basal rate on my pump. I know you're not in a position to make diagnoses or suggestions, but I'd be curious to know what you think might be going on in theory.
I've been testing for ketones, and they're showing up in "trace" to "moderate" amounts. Another interesting change is that I no longer seem to need extra carbs to fuel exercise. And the hunger reduction has been a great relief.
Anyway, thanks for all the fascinating topics. Great follow-up to my reading of Bernstein.
Peter, your ideas are outdated. Joel Fuhrman cures diabetes.
ReplyDeleteIs there more room for glucose with coconut oil? I think I remember Houssay getting good results with Alloxan (so type 1?) rats but no positive results with other fats; perhaps they had moderate carb intake, but I don't remember.
blogblog,
What's your vitamin A & D intake look like? ...You're northern European, correct?
Hi Heather,
ReplyDeleteYour quite correct that you cannot pin down exactly what might be going in an individual insulin dependent person at a distance. But one of two things has to be happening. You either need more insulin to maintain normoglycaemia (ie insulin resistance has increased) or you have an increased need for insulin to maintain a given level of insulin in the blood (ie greater insulin sensitivity, probably hepatic, allowing greater insulin breakdown). What has happened is hard to say and you realise that Dr B has a very hands on and detailed micro management system....... The other factor I have noticed in my diabetic dogs is that the glucagon spike after a protein/fat only meal requires a bolus of insulin to counterbalance it, and some protein sources spike glucagon more than others.
Hope that might give you some pointers, nothing works in isolation.
Peter
john, we'll have to have a look at what controls leptin sinsitivity next won't we...
ReplyDeleteand Chris, yes this round thing is a wheel, now, what colour should it be? (Ref Hitch Hiker's Guide to the Galaxy). No need to discuss the ACCORD study when Jenny Ruhl has done an excellent job.
other john,
Wow, he beat Dr Barnard to it then???? Hee hee, might post on that one some time. Without going back to dig out the full alloxan pdfs I have memories that the MCTs used protected the pancreas from alloxan damage rather than treating the type 1-ish diabetes which results from alloxan exposure if you are a chow fed rodent. Possibly through reduced PUFA free radical propagation or possibly through ketone-body protection of the beta cells.
Peter
Thanks, Peter — that's useful food for thought (low-carb, bien sûr!). Whatever's going on, it appears I need more insulin, which is a bummer as I attempt to shed post-sabbatical-in-France extra kilos (not the only reason for going low-carb, or the most important, but a consideration nonetheless).
ReplyDeleteHi Peter, can you tell us what protein sources spike glucagon more than others? I'm guessing casein is one of them...
ReplyDeleteI'm seconding gunther gatherer's request. What proteins spike glucagon? I'm just starting out following Dr. Bernstein's method (about halfway through the book, but I'm already seeing improvements). I found last week if I eat steak or ground beef and take the insulin I normally would with other proteins, my blood sugar drops to about 40 an hour later, even if I have a potato with the meal. I had thought it was the amount of fat slowing the digestion, but now I'm wondering if it's the type of protein affecting glucagon.
ReplyDelete@Gunther/Emily - this does not completely answer your question, but this is a partial response based on an exchange I had with Peter on another post-
ReplyDeleteAravind-Do you think the insulinogenic effects of milk are of limited concern if fasting insulin levels are low? I am trying to relate this to your potato post. Implicit in this question is the assumption that other agents of disease - fructose, gluten, vegetable oils - are eliminated from the diet and fasting levels can return to good levels even with consumption of things like milk.
Peter-I don't worry too much. First is the glucagon spike which accompanies the insulin spike. I haven't been able to follow up the effect of physiological glucagon on lipolysis but pharmacological doses certainly promote lipolysis. Second is the effect on fasting insulin. Post prandial insulin is possibly beneficial for anabolic effects, fasting insulin probably determines hunger...
Peter, thanks for the link.
ReplyDeleteSorry, if my question is naive,I have no medical background, but could you, please,explain, why does liver extracts almost all insulin output? What does it do with the insulin after the extraction?
ReplyDeletePeter my take is a bit more cutting to the bone for my profession. No matter what drugs you use.....you still die six years earlier. Bottom line is you can control blood sugar and HbA1c great......and it still does not confer health at all. The goal for patients and doctors are to eradicate type two DM with diet and lifestyle. That has been shown to work by Dr Fasano. I don't think the response you linked was good at all. It did not cut to where the rubber meets the road for physicians who are just practicing cookbook medicine that believes it as "evidence based medicine" Evidence based medicine is medicine based upon trials that are terrible in design and flawed and will guarrantee that pharma and hospital will benefit from the endpoints elucidated. So no, I disagree Jenny did well. She did not scratch the surface . Dr K
ReplyDelete"I don't think the response you linked was good at all. It did not cut to where the rubber meets the road for physicians who are just practicing cookbook medicine that believes it as "evidence based medicine" Evidence based medicine is medicine based upon trials that are terrible in design and flawed and will guarrantee that pharma and hospital will benefit from the endpoints elucidated."
ReplyDeleteDr K, I was under the impression that this is exactly what Jenny says. You are correct, she is correct. I'm puzzled.
Peter
Hi Galina,
ReplyDeleteInsulin doesn't just "work". It locks on to a receptor and is "used up" in the process. The process involves many things but a big use is the uptake of glucose. The liver should uptake almost all of your dietary glucose. The insulin needed to do this is broken down in the process, so relatively little insulin (or glucose) gets past the liver. Insulin is like money, when you use it, it's gone. It gets used in the liver... Does that help?
Peter
Gunther and Emily, there is, somewhere, a paper listing glucagon effects of proteins which somebody linked to in the comments years ago. I can't find it on my hard drive or in pubmed. Plenty of papers on individual proteins. But a good rule of thumb is that insulinogenic proteins will also be glucagon-ogenic ones, assuming BG does not budge on ingestion....
ReplyDeletePeter
In "Fructose: Metabolic, Hedonic, and Societal Parallels with Ethanol" Lustig claims only about 20% of a glucose load is taken up by the liver, the rest being used up by other organs. If he's right, it wouldn't change anything you said, except for the bit about the liver uptaking all of the glucose (unless you meant it takes it all up and then releases 80% to the systemic circulation). Any comment either way?
ReplyDelete@ John,
ReplyDeleteblogblog,
What's your vitamin A & D intake look like? ...You're northern European, correct?
100% Northern European origin.
I live in the Australian subtropics and spend a fair bit of time outside so my vitamin D would be extremely high probably >10,000iu/day.
I eat a huge amount of pasture fed cream, butter and cheese equivalent to >300g of butterfat per day. So my Vitamin A would also be around be 10,000iu or 4x the RDI.
A high-fat breakfast of bacon and eggs may be the healthiest start to the day, report shows
ReplyDeleteSide note to Heather B: Peter knows vastly more about this than I, but some of what you're seeing may be a function of your body getting better at making glucose out of protein.
ReplyDeleteThe Eades have a quick weight-loss diet called The Six-Week Cure for the Middle-Aged Middle. It is heavy on whey-based shakes, especially in the first two weeks.
What was striking about that diet was how many diabetics (mostly T2s, I'd guess) reported large blood-sugar spikes a few days in, apparently from the whey protein. (Other people might experience the same effect. Hard to say, since non-diabetics don't measure their blood sugar.)
My point is that the volume and type of protein in the diet seem to have a strong effect on blood sugar in at least some people.
(I think that when some people go low-carb, they err on the side of excess protein because of lingering lipophobia. So I suspect there is a subpopulation who get very good at making sugar from excess protein.)
"Bottom line is you can control blood sugar and HbA1c great......you still die six years earlier."
ReplyDeleteNo, the ADA standard of an HgbA1C 7.0% is pathetic, and two thirds of Type 2s in the US never achieve that level of control.
I was diagnosed in March of 2000 and my doctor said try the Protein Power diet plan and see if it works for you. My A1C, at diagnosis, was 7.1% and three months later it had dropped to 4.8%. For the next 5 years I was able to stay in the low 5s by diet alone. When diet alone no longer sufficed and my A1C rose to 5.6, I went directly to insulin.
Other than two weeks on Metformin, which gave me terrible gastric distress I've never taken any oral diabetes meds. I read a great deal of diabetes research. There is not any research done on people like me.
The standard research template is to take patients who average around 10.0, treat them and get them down to around 7.0 and to call that tight control. The EPIC Norfolk study makes it clear that patients would do a lot better if doctors forgot about cholesterol and focused on keeping A1C below 5.0% and watched out for signs of hepatic insulin resistance.
In my thirties, 20 years before I was diagnosed, I ran 1600 miles a year and my BMI was 22.5. But my blood pressure was high, my triglycerides were over 250, and my HDL was 26. 10 years later I had a doctor who was concerned about my numbers. I was put on Questran and told to eat a low fat diet.
The medical profession has a lot of blood on its hands from all the bad advice given and inadequate treatment of disease.
The boardroom of MegaPharma.
ReplyDeleteHead of Research:
'I've got some terrible news on the latest XYZ100 clinical trial. It's the second worst outcome possible.'
CEO (horrified expression):
'Are you absolutely sure?'
Head of Research (shaking head):
'Yes. I'm afraid it's true! Unfortunately the patients were actually cured.'
A very old pharmaceutical industry joke. The worst possible outcome in a clinical trial is, of course, death.
@David Isaak,
ReplyDeleteIn nature milk is only intended for juveniles who need to be able to produce glucose easily for heat generation and brain function.
Wild mammals typically consume 3-5g protein per kg of body weight each day (including that produced by gut fermentation).
@Ken,
ReplyDeleteHGs eat generally eat very little breakfast or lunch and consume nearly all their food between mid-afternoon and late evening.
I never have any breakfast or lunch unless I'm socialising. The simple reason is that I'm never hungry before about mid afternoon. I then eat my 4000Cal of fat and protein over 3-5 hours.
Prior to the early 1800s in the Royal Navy "dinner" was a huge main meal served at around 2pm.
In Australia lunch was called dinner and the evening meal was known as tea until about 20 years ago.
After reading about high protein/high fat/zero carbohydrate, I decided to try it. Unfortunately, I am one of those rare people that are truly hypoglycemic (probably due to some genetic problem). After two weeks on zero carbs, I had several hypoglycemic episodes which came on very quickly. I could taste and smell acetone. Mouth, lips and nose were tingling. Had nausea, headache, dizziness, and light-headedness. Luckily, I was sitting at the time, and did have some carbs that I slowly ate.
ReplyDeleteI would have to say that high protein/high fat/zero carbohydrates is definitely a way to get your sugar to plummet. My husband is diabetic, and has avoided having to go to insulin for the last dozen years by eating correctly. And I have now discovered, through my small mishap, some more information about my own medical conditions. I am now trying to keep my carbs up at about 65%, and actually feel pretty good.
http://www.ajcn.org/content/66/5/1264.short?rss=1&ssource=mfr
ReplyDeleteThe insulin index might be worth looking at, so far as protein and blood glucose goes.
Among proteins, the insulin area under the curve vs the glucose area under the curve was particularly high in this study.
Maybe fast food has taught our bodies to associate beef with crappy carbs?
Much is made of the cephalic response to sweet tastes, but it probably goes far beyond that.
I've been a type 1 diabetic for forty years and going to a low-carbohydrate, high-fat diet has resulted in much lower A1c readings (a little over 6, after many years of work to bring them down to around 8 from decades around 10). Cholesterol and triglycerides are much improved as well. I still need surprisingly much insulin, so I suspect that insulin resistance is a problem. For the first few months on the reduced-carbohydrate diet my insulin needs kept dropping and I kept cutting back on the insulin doses to ward off hypoglycemic episodes, but after that I've had to raise insulin doses a bit to keep the sugars in check. I exercise little and perhaps exercise would overcome some of the insulin resistance.
ReplyDeleteI wonder why you ignore the possibility that protein could be the macro providing most calories in a diet?
ReplyDeleteHi alan, people eating at either 90% protein or 0% protein are likley to end up very dead. It's a non starter.
ReplyDeleteHi gooley, (and Heather??) (and David Isaak??? Interesting observation!) one aspect which has crossed my mind id that at some point a LC diabetic will stop losing weight. They will then have a higher insulin requirement to stop the loss which is common with LC tight control. As you stop losing weight while not using glucose perhaps you need higher FFAs and so have higher FFA (palmitate) induced insulin resistance? Does this even happen??? Would it be pathological? I have no idea, I'm just guessing here, and why should dietary FFAs have any differing effect than adipose FFAs????? Is it a pain? Probably so.
donny, I'm looking at my type 1 diabetic patients and I'm getting the feel that protein spikes glucagon which the pancreas preempts with insulin, unless it is broken. I need to go through your link as one of them spikes far less with chicken than it does with beef. To which my response is "Damn!" Is hyperglycaemia worse than omega 6 PUFA long term???? Maybe lean chicken served cooked in butter might work, but you don't get that as canned cat food!
Stuart, "The medical profession has a lot of blood on its hands from all the bad advice given and inadequate treatment of disease." Amen.
Ken, amen too.
Poisonguy, I think fructose and the liver is probably VERY context specific. Moderate doses of fructose with some glucose on a glycogen depleted liver is probably the fastest way to replete glycogen possible. Three Big Gulps (buy one, get two free, drink all, mistake) in the aftermath of two giant sized potato pizzas with potatoes, chips (french fries) and garlic bread (without the butter of course) on the side will get you fatty liver faster than a Fois Gras goose... I think ethanol is probably a lot more fun than fructose if you want to destroy your own liver! Certainly in the early stages. Makes me think of George Best...
Peter
The Eades have a quick weight-loss diet called The Six-Week Cure for the Middle-Aged Middle. It is heavy on whey-based shakes, especially in the first two weeks.
ReplyDeleteRule No 1:
One of my university physiology lecturers used to say any book on diet or exercise written by an MD is usually complete nonsense.
A whey shake is a soluble protein solution which is digested very quickly.
HGs swallow large chunks of meat which take many hours to digest.
Peter, maybe the ketogenic amino acids would not spike insulin.
ReplyDeletehttp://en.wikipedia.org/wiki/Ketogenic_amino_acid
Hi Richard,
ReplyDeleteProbably it goes along those lines...
Peter
Over on the Bernstein forum, there are T1's that report a gradual rise in BG (over the course of a week) after reintroducing casein.
ReplyDeleteLet's not be forgetting that the Insulin Receptor in all its actions is a fabulously complicated piece of machinery which incorporates a great many of the micronutrients that might well be lacking in today's diet. Chromium and biotin seem to be particularly critical. Brewer's yeast and egg yolk/probiotics are good sources.
ReplyDeleteWithout doubt there is a form of insulin resistance caused by micronutrient deficiency (think: gluten, phytates, etc), as well as those due to rogue macronutrients and their ratios.