I have written about diabetes quite a few times. Thus far, I must admit, I have kept the discussion relatively conventional. Anyone who has read my previous blogs may not think so, but compared to what I really believe, everything has taken place close to the middle ground. Time, I believe, to start turning diabetes upside down, give it a good shake, and see what it looks like from a completely different angle.
Some of you may have watched Professor Unger’s fascinating YouTube lecture on type II diabetes. If not, here it is. I recommend it1. To keep things as simple as possible, his view is that the key hormone that drives diabetes is glucagon, not insulin. Indeed, by focussing almost entirely on insulin and sugar/glucose, we cannot understand what is going on with type 2 diabetes, as we are only looking at a small part of the picture. In addition, we are looking at it the wrong way round.
He is, of course right. Now, stop, stand on your head…
Ready, here we go. The critical requirement of human metabolism is to ensure that there is a high enough level of glucose to power the brain. Without sufficient glucose the brains shuts down and dies. Not all the cell types in the brain need glucose and all brain cells can also metabolise ketone bodies, to an extent. (Ketone bodies are synthesized in the liver from fatty acids). However, the bottom line is this. If your blood sugar level drops below about 2mmol/l, and stays there, you will enter a hypoglycaemic coma and die.
Which means that it is absolutely critical that this does not ever occur. In order to prevent this happening we have a hormone that keeps blood sugar from dropping this low. It is called Glucagon. It is produced in alpha-cells in the pancreas (right next to where insulin is produced). How does it work? Here is a short, standard, explanation from diabetes.co.uk:
Glucagon plays an active role in allowing the body to regulate the utilisation of glucose and fats.
Glucagon is released in response to low blood glucose levels and to events whereby the body needs additional glucose, such as in response to vigorous exercise.
When glucagon is released it can perform the following tasks:
- Stimulating the liver to break down glycogen to be released into the blood as glucose
- Activating gluconeogenesis, the conversion of amino acids into glucose
- Breaking down stored fat (triglycerides) into fatty acids for use as fuel by cell
Of course, this statement from diabetes.co.uk is true. However, I would ask you to review ten of the words again, and think about them for a moment or two. ‘Glucagon is released in response to low blood glucose levels.’
Now, you almost certainly do not recognise it, but here is the crux of the entire blood diabetes/insulin /glucose discussion. Those ten words, innocent thought they may seem, have been driven by upside down thinking, and represent the exact point where things go wrong.
This not deliberate, indeed the concept is so familiar, so unquestioned, that you almost certainly have no idea what I am talking about. At this point you are probably wondering, ‘what the hell is Kendrick on about here?’
Indulge me for a moment whilst I re-frame that statement.
As it stands, we are given to believe that glucagon is the reactive hormone, only produced when blood sugar levels drop. Insulin, on the other hand, is the key hormone, the controller of metabolism and blood sugar levels. Glucagon only activates to increase blood sugar after insulin (or exercise) has caused it to fall too far. Which is why we have these ten words: ‘Glucagon is released in response to low blood glucose levels’
You think this is not important, just playing with words. Then try this alterative statement on, and see how it fits. ‘Glucagon keeps the blood sugar level high enough to ensure that the brain has sufficient glucose to function. If, however, the glucose levels rise too high, the body produces insulin to counteract the effects Glucagon. This brings blood sugar back down.’
In one way, I am saying exactly the same thing as diabetes.co.uk said. Looked at in another way, however, and I have just changed everything. No longer is insulin the key hormone, it is now ‘merely’ the subservient hormone, produced to counter the effects of too much glucagon.
Once you have changed your thinking around this way, it should come as absolutely no surprise to find the following. If you have a mouse, and you destroy its beta-cells (insulin producing dells in the pancreas) it will become diabetic, and die. However if you get rid of the glucagon producing cells as well, the animal will not have a high sugar level and will not be diabetic – despite having no insulin at all. It will also appear to be completely healthy.
In addition, if you give such a mouse, that cannot produce either glucagon, or insulin, a glucose ‘meal’ the blood sugar level will rise, and then fall, in pretty much the same pattern as a ‘normal’ mouse. Ergo, the body does not need insulin to keep blood sugar levels down. There are other mechanisms that the body can use. I am sure that having insulin help to optimize blood sugar control, but it is far from essential.
Of course, this type of experiment has never been done in a human – for obvious reasons. However, I do not think there is any reason to doubt that the results would be pretty much the same. Which means that, crikey, insulin is not required for blood sugar control… If I tell my medical colleagues this they absolutely and completely refused to believe it. However, it is true. They choose not to believe it, because it undermines what they think is true.
In fact they think what almost everyone else things. Which is that the insulin/glucose: glucose/insulin model of diabetes is correct. It certainly appeared to explain what we saw in type I diabetes, whereby you gave insulin to those with high sugar levels [those who could not produce insulin, the underlying cause of type I diabetes] and they were ‘cured. Whilst the discovery of insulin and the treatment of type I diabetes was a medical triumph, it is also where the thinking went wrong.
It blinded everyone to fact that insulin is not the key hormone in glucose metabolism. It is simply there to act as a negative feedback mechanism to control glucagon. Unfortunately, since Banting Best and MacLeod, we have become stuck with the insulin/glucose paradigm.
If the blood sugar rises, whatever the underlying cause, we call it diabetes and drive it down…sigh. The more it rises the harder you drive it down….Sigh. The lower you get the blood sugar down the better…sigh. How do you do this? Mainly by giving drugs that force beta-cells to produce more insulin, or by adding in drugs that work with insulin to lower blood sugar levels, or by injecting additional insulin.
How well does this work? Some of you will have heard of the ACCORD study, others will not. In this study researchers, tried to force blood sugar levels down as far as possible using intensive treatment. They found the following:
‘Until last week, researchers, doctors and every medical professional has believed for decades that if people with diabetes lowered their blood sugars to normal levels, they could not only prevent the complications from diabetes, but also reduce the risk of dying from heart disease. But the Accord Study, (for Action to Control Cardiovascular Risk in Diabetes), a major NIH study of more than 10,000 older and middle-aged people with type 2 diabetes has found that lowering blood sugar actually increased their risk of death.2’
There is one other way of lowering blood glucose, by using insulin ‘sensitising’ drugs. In diabetes most doctors look at metformin as the wonder drug. This drug improves ‘insulin sensitivity’ i.e. it helps to reduce insulin resistance. It is the absolute mainstay of type 2 diabetes treatment. Once again, however, it is targeted at purely the insulin/glucose model:
‘Metformin has been the mainstay of treatment for type 2 diabetes since 1998 when the UK Prospective Diabetes Study showed reduced mortality with metformin use compared with diet alone. Recently a French meta-analysis of 13 random controlled trials questioned the central role of metformin in the care of patients with diabetes. In this meta-analysis, in which 9560 patients were given metformin and 3550 were given conventional treatment or placebo, metformin did not significantly affect the primary outcomes of all cause mortality or cardiovascular mortality. The secondary outcomes—myocardial infarction, stroke, heart failure, peripheral vascular disease, leg amputation, and microvascular complications—were also unaffected by treatment with metformin.’3
Today we have a virtually unquestioned model of diabetes that is very simple, and easy to understand. It should be simple to understand as it works like this. If the blood sugar goes up, the body produces insulin to lower it. If the blood sugar goes down, the body produces less insulin and the sugar level goes up.
This has meant that, if you find someone had high blood sugar levels, you basically hit them with insulin. I call insulin the ‘glucose hammer’ and, as a wise man once said. ‘If the only tool you have is a hammer, pretty soon everything starts to look like a nail’.
Reducing glucagon…. anybody?
Well, you’re a bit behind the times here, Malcolm as they’re hot on the tail of the glucagon hammer! Not here yet but I’ve read this stuff already, fairly recently. When insulin is released in the pancreas, a tiny squirt within the pancreas suppresses the glucagon. This is lost in diabetes…
A bit behind the times in blogging about it, for a very small group in the know. But for almost every single person I have spoken to, including all doctors, this is news.
The new result that “a tiny squirt within the pancreas suppresses the glucagon, which is lost in diabetes” makes sense in the reasoning framework here put forward by M. Kendrick. In fact does not make sense that Glucagon and Insulin are relaeased at the same time. This fact enlights the role of glucagon as the driver of glucose release, and the role of insulin as the “brake”. The “new result” does not invalidate the basic idea that is expressed in the post, on the contrary it contributes to its confirmation.
I wasn’t in the least being critical! Mind you, stuff that’s ten years old is news to most doctors! Keep up the good work. When you eventually get it all right, Carbsane will criticise you for being perfect!
As a new comer to this site I am amazed at just how much information & research has been done on the subject of Diabetes its causes and treatment!
I am a T2D or at least I used to be. However after years of Insulin therapy, metformin, statins etc…. It seems my once normal pancreas no longer produces any Insulin. Does that make me a T1D.
A few weeks ago I failed my Cardiac stress test & Angiography followed 3 minor coronary artery blockages & 80% RCA blockage with DE Stenting means I dodged a bullet or did I.
Hence I have been on a furious journey to learn how to try & turn all of this around.
Finding out that drug therapy & the Diabetic industry diet is a killer has made me so angry at their lies and betrayal that I find myself having to find out how to treat myself.
I found a Link to an Old 1927 Cookbook for the treatment of Diabetes before Insulin was available as a treatment for T1D and what was once considered old age diabetes. Insulin resistance or T2D today’s version of it.
What really amazes me is that the only real treatment was Nutrition as Medicine the only way it was treated. Under 40gms of Carbs per day. Bone broths – High Fat – Medium Protein – Low carbs. If one did not follow this protocol one would likely die.
Growing up I lived on farms in NZ. We had cows, chickens, beef, sheep. Eat local seafood we mostly caught ourselves. Grew every form of vegetable the only way to feed 14 children. Had our own fruit trees had our own walnut & almond trees eat our fresh eggs & fresh cream rich milk made our own butter! We were a healthy bunch of Kiwi kids.
However my Grandpa age 52 was Diabetic & died from complications of diabetes. Coronary artery disease.
Moving off the farm in the late 60,s early 70’s refined & commercially available foods lead to Diabetes & heart disease that killed my father aged 59 my uncle aged 42 with Cardiomyopathy & my younger uncle aged early 59’s & peter always Grandma. Of the 14 siblings I have three older ones T2D 1 of which died blind, strokes, liver & kidney failure age 57. Older sister coronary artery heart disease & only 1 functioning kidney.
1 younger brother is T1D living on his 1 donated kidney transplant.
2 younger siblings have Insulin resistance borderline diabetes and my 2 daughters have PCOS & Insulin resistance despite normal weight & athletic lifestyles.
So all this Hype by the Medical Profession and Big Pharma who have had more than enough time and money to provide value for money TRUTH and information to treat reverse or even cure Diabetes is all totally erroneous.
It’s all about making money getting rich off of the sick & dying. Producing chemically toxic poisons & drugs that ultimately kill us from the side effects alone need to be accountable & made to tell the TRUTH to those who are dying from their negligence. They educate and pay for the medical profession. Fund the food industry with its chemically & genetically modified hormonally force fed animals to make more money then feed the poor highly refined mass produced carb ladden foods with chemical enhancers to prolong shelf life antifungals corn syrup loaded low fat low taste high sugar foods then chemically artificially produce so called vitamin and mineral pills and potions in pill form to enhance or supplement the now defunct nutrition poor artificial substances that stock our supermarket shelves and have the cheek to call it food.
Then they charge the average person extortionary prices for fresh fruit veg & meats that are so chemically polluted & modified. This is total insanity at epic proportions.
We need to get back to nature growing harvesting and eating our own produce like mum & dad & Grandma used to do or our Grandkids & generations to come will be dying or dead from these chronic diseases at age 5-10 years old.
Most average everyday folk do not have the know how or knowledge that’s we here on this forum have or the scientific evidence based formation to tackle the epidemic of Diabetes, obesity, metabolic disease that is claiming our and our future generations. Unless something is done within the next decade to stop it.
We need to educate them from preschool nursery school through to college & university to get back to basic and eat real food produced by nature grown in good organically rich soils that provide & sustain good organic nutrition at economically affordable prices. Teaching them that good wholesome naturally produced foods are the only medicines they need ever take to heal the damage that modern Pharma. Big Business has and the money hungry greedy commercially based industry has done to them. Phew well that’s my say.
Thank you for this scientific information that is reinforcing my determination to fight on for health & healing through the education freedom of information and good old nutrition as medicine.
Exactly Malcom……..for every one person that reads your article, there are thousands who have not the foggiest about it. I welcome the repeats so that I can be reminded every day how lucky I am not to suffer this awful condition.
I’m reading this in November of 2017 and this is news to me–thank you, Dr. Kendrick.
“When insulin is released in the pancreas, a tiny squirt within the pancreas suppresses the glucagon. This is lost in diabetes…”
My personal theory is that it is lost because not all alpha-cells (glucagon producing) are in the pancreas, some are in the stomach. Visceral fat somehow blocks the insulin message to the alpha cells in the stomach which continue to secret glucagon. This is supported but the find that obese people with diabetes 2 that have had bariatric surgery, where they remove 90% of the stomach, have their blood sugar levels normalize within days—long before any weight loss has occurred.
“Patients can often stop taking their diabetes medication even before leaving the hospital. Traditionally, doctors recommend weight loss through dieting and exercise to improve blood sugar levels—but this surgery lowers blood sugar levels almost immediately.”
in 2014 I lost two stone weight and my type 2 Diabetes disappeared. also my allergies and addictions. I have no explanation for the weight loss. I have recovered one stone and my allergies and addictions have returned.
Possibly you didn’t notice that Dr Kendrick referenced Roger Unger’s lecture on the role of Glucagon in diabetes. It would seem that that work has been ongoing for some time.
Moreover, Wikipedia indicates that this hormone was known about way back. The real question is why medical science – at least in practice – chose to emphasise the simplest theory that only involved the hormone insulin.
Everyone thinks that no stone is left unturned to solve diseases like diabetes, but the frustrating reality seems to be that science just gets stuck in a rut!
Of course, perhaps it’s a good thing glucagon has been mostly ignored. Can you imagine what would happen if yet another block-buster drug were developed, this one to suppress glucagon?
Medicine hasn’t ignored Glucagon, but seems to view it as a break on insulin production, rather than a direct control of blood sugars.
Liraglutide(Victoza) is a long-acting glucagon-like peptide-1 receptor agonist, binding to the same receptors as does the endogenous metabolic hormone GLP-1 that stimulates insulin secretion.
Excessive hepatic glycogenolysis, stimulated by excessive glucagon, is the sine qua non of all diabetes. This is due to the normal paracrine hormonal crosstalk within the islets. Most of the “area-under-the-curve” excess BG is due to hyperglucagonemia in all forms of diabetes.
But the defect is in the beta-cell(s), inducing inadequate and faulty insulin secretion which the alpha cell is dependent upon for normal signaling and glucagon secretion — make no mistake about that.
I recommend Alan Cherrington’s work in addition to that of Unger and many others. Paracrine hormonal control of hepatic glucose/glycogen regulation has been largely recognized and understood since the 1970s.
The diabetes drug companies are well aware, and working on glucagon suppressors. But this is a very tricky, risky, and poorly understood area of research. Unger, IMO, is overly optimisitc about the potential for this type of intervention. Insulin remains as the safer and most potent hypoglycemic intervention for BG control in diabetics. Efficacy of metraleptin (for BG regulation) does not persist in the long term in animal models — this is not an optimistic sign.
As an HNF1a monogenetic diabetic myself, the ability of protein to cause hyperglycemia had initially required explanation. Inadequate PSIS (protein-stimulated insulin secretion) and excessive PSGS, which are coupled, is the cause (also demonstrated in ’70s). Also, diabetics with extreme insulinopenia (e.g. long-term T1Ds) lose the ability to sense BG in the alpha cells (similar to the progressive morphology of beta cells in T2Ds) and this causes problems of hypoglycemia. All of these phenomena have been well understood for decades within the research community.
Ken, thanks for your insights. I suppose my natural tendency is to think that pharmaceutical companies have little interest in finding cures for ‘diseases’ that can be then be treated lifelong with drugs. Diabetes is now, I believe, the single biggest money spinner for pharmaceutical companies. How much interest do they have in looking at glucagon suppressors, or any other alternative drugs? [Or, perish the thought, low carb diets]. Best thing is to advise people to eat carbs/suagar, then find ever more complex and costly ways of forcing blood sugar down using drugs such as rosiglitazone….ooops, increases the risk of dying of heart disease. My cynicism in this area is very high.
Exactly and thanks.
That Unger lecture turned my world upside down as well a while ago.
I have watched that video a number of times now and I learn something new every time and what he says make more and more sense.
What still remains as a riddle is the actual cause of the insulin resistance which seems to be at the bottom. My own guess is that too much fast acting carbs in our diet which causes insulin spikes may be a culprit.
Isn’t this pathway targeted by GLP-1 receptor agonists?
No, GLP-1 receptor agonists increase insulin release and inhibit glucagon release. Same old, same old.
Yes, the mechanism of action is supposedly that GLP-1 receptor agonists compete with glucagon by attaching to the same receptor. Less glucagon causes more Insulin release. But the Unger video makes me wonder. Have they actually measured increased insulin response directly or are they just assuming insulin is up because they see blood sugars go down? Because in the video Glucagon release causes insulin release and less Glucagon could be expected to lower both blood sugar and insulin. Two benefits of GLO-1 receptor agonists are fewer hypos and weight loss, both of which are consistent with lower insulin and not consistent with increased insulin release.
M. Kendrick reasoning is of scientific kind. It questions current paradigms in search for better explanations of current medical issues and better understanding of physiologic mechanisms behind health and disease,
Very different is the current medical/clinical approach: “evidence based medicine”, i.e. empirical practices and guidelines issued by committes of “experts”, are the rules to be followed by every practioner. Unorthodox opinions are not welcome, even if scientifically based. This creates a kind of totalitary thinking, that closes the eyes to the error, and and persecutes all dissenting views. This attitude causes much more harm to the patients than the scientific attitude, open-minded but responsible, and treats the doctors as little responsible people. I wish to greet once again M. Kendrick for his stance.
I support your view. Current medical thought seems to be of the closed kind. Conventional “beliefs” cannot and must not be challenged. Contrary research is flagrantly ignored. May be this is the major reason for decline described by Dr LeFanu in his book “The Rise and Fall…..
I would like to thank Dr Kendrick once again for raising this matter and to re-iterate his final question “Reducing glucagon…. anybody?”
re: Reducing glucagon…. anybody?
Definitely worth understanding.
But how about reducing glucose available to the bloodstream in the first place? Then no hammers of any kind are needed?
In my view T2D is no more a disease than ALD (Alcoholic Liver Disease). T2D is an almost predictable metabolic response to a full-time moderate to high glycemic diet. Any number of LC diets are having great success in making T2D simply cease to be an issue for the formerly diagnosed (if caught early enough).
T1D and LADA are another matter. I have no speculation on whether some glucagon intervention there might be worth a look.
Another “light bulb” moment! Amazing… and so simple.
Fascinating and intriguing! Please can we have more? For instance, how do statins interfere with the insulin/glucose/glucagon mechanism? Why are people on statins more likely to become diabetic than the lucky ones who never fell for the hype?
I explain the statin-diabetes connection here: http://www.tuitnutrition.com/2015/04/statins-and-diabetes.html
There are many competing explanations. I am not sure which one I favour. I don’t suppose it really matters. Statins increase the risk of diabetes, that is all that is important.
Thank you Amy. An excellent explanation, with humour/humor as well! I am coeliac/celiac and became diabetic while on simvastatin, having previously had no sign of it. I wish all doctors knew that statins are too big a risk for people such as me. People like you and Dr Kendrick are invaluable for spreading the message. I wonder if it will take 40 years, as with the saturated fat v. Carbs to realise the iatrogenic damage being perpetrated on so many people by the flogging of statins?
The insulinocentric model of diabetes is more akin to a heuristic which can be useful when intelligently applied. Regardless, it’s incomplete and more importantly leads conventional doctors down the wrong causal pathway (albeit the most dastardly consequence). I think Unger’s rat experiments are the best kind of provocative. Writing an essay on Diabetes for my Msc I made a point to include his piece on glucagon https://raphaels7.wordpress.com/2015/06/04/diabetes/. It is a rather long essay but feel free to skip to the part where I note the limitations of insulinocentrism and propose glucagon as a (the?) missing piece.
Malcolm, thank you for drawing our attention to this area again.
Raphaels7 that is an excellent piece of writing.
I don’t think anyone is ever going to work a miracle cure for diabetes by whacking the ‘insulin theory’ or whacking the ‘glucagon theory’ without trying to understanding the dynamics of the intertwined feedback loops of the endocrine and paracrine systems involved, the entanglements of glucagon/insulin/somatostatin/leptin etc
I appreciate your writing really very much. Being a diabetic myself I always knew the standard therapy was dead WRONG: Just instinct. Nobody ever measured my insulin levels, nobody ever cared about glucagon.
There is just too much money involved.
And what do you think about this: years ago I catched on the web (cannot find it anymore), that the parameters for “normal” sugar levels were “adjusted” from 120 to 100 JUST AS THE LANTUS & CO insulines were released. What a coincidence indeed. Giving Lantus you were supposed to reach “Normal” morning levels.
So what`s wrong with the “dawn syndrome”? What a terrible term – sounds really sick and it`s ment to sound sick.
The caveman and cavewoman had to be alert at dawn, because the BIG predators came at that time and you better jump before the sabletooth tiger jums at you.
Now BIG pharma jumps at us. We are all prey.
Do you have more information about this miraculous lowering of the morning sugar???
Best regards, Tuulikki KyytsÃ¶nen Medical translator
P.S. May I translate quota in my blogs? (Finnish & German)
I have always questioned the concept of the awfully named dawn phenomenon.
When I was a mother of 2 teenagers, juggling a full time, ward-based nursing job, I can tell you I needed that extra boost of glucose in my blood stream to get cracking every morning.It never caused me any problems in the least. But, once I was trapped in the spider’s web of NHS screening, ( so-called well women clinics), the elevated fasting glucose was translated as requiring aggressive drug treatment. The barmy glucose tollerance test, (whereby my alimentary canal was unnaturally plied with a bottle of yucky Lucozade) conveniently played into the hands of Big Pharma, as it goes without saying that such a high intake of instant glucose left my system reeling! Oh…another reason to eat yet more yummy, lucrative, anti-diabetic tablets.
So who measured my insulin levels? Who mentioned the role of my glucagon? Who bothered to question if I displayed any symptoms of type 2?
You’ve guessed, no one.
But, COMPUTER SAYS!
And who devised the computer programme?
I suspect…BIG PHARMA.
Oh, and as a fully fledged diabetic…computer says….add on statins…add on B/P meds….throw in something to settle the gut…..put her on the flu jab list….get her in every few weeks for yet more screening, tick, tick, lovely jubbly money quotas building up!
I am so annoyed, and very unforgiving of the system that got me caught up in this monumental fiasco. I truly believe that all of those awful medications mucked up my physiology to the point of inducing very poor health, when I had actually been a healthy specimen to begin with.
Fortunately, I gave up the well women clinic, ditched the tests and meds, and…hey presto….lucky me is back on track.
This is not the NHS that Aneurin Bevan ever envisaged, or that I started working in in 1965. But I do worry about the NHS I will die in..prematurely ushered towards the grim reaper if I fail to stop questioning the system.
Awesome comment, Jennifer!
I was told by the Trust that insulin was not measured because “the treatment was the same whether insulin was high or low”. I wrote to the company making gliclazide requesting information on the kinetics of the drug and its effect on insulin level. Apparently never done.
I asked the same question and got the same but more detailed reply, they would put me on drugs and keep increasing the dose until at some point they would give up and prescribe insulin. One might of thought that greater curiosity might be of long term benefit in understanding the disease – if that actually concerned them.
I love this type of article. “We” have a ‘crank’ here called Ray Peat who I also love because everything we were always taught was true, he says isn’t. [I love cranks, they are so often smarter than, and ahead of, those who comprise the establishment in any arena]. Cranks are able to think outside the box, because they were born outside of it, and are not allowed to come in, while the Establishment types who set the rules have never even seen outside the box, let alone thought outside of it, because the box is the known world as far as they are concerned.
So, now for my particular peeve: Parkinsonism. I’m coming to believe that much of what passes for Idiopathic Parkinsonism, is actually Iatrogenic Parkinsonism. Since I have it, apparently a weird type, I was told that there was no alternative to the dopamine approach to treatment. Then, just yesterday, in passing, I saw that some group is beginning to study the neurotransmitter Glutamate as a treatment for PD because it will circumvent all the problems (side effects/adverse effects) associated with dopamine +/- analogue/receptor based treatments….Hmmm….
Whatever happened to the idea of intellectual humility among our intellectuals?
Lyn, I have read a lot of Ray Peat….sorry for your iatrogenic Parkinsonism. If u have not already done so, since posted 10 months ago, please investigate B12…..Could It Be B12:an epidemic of misdiagnosis by Sally Pacholok, RN, BSN and her Osteopath husband. Then join the private Pernicious Anemia/B12 Deficiency FB page. All the best!!!!
Yes, Bev. Pernicious anemia / B12 deficiency can be diagnosed as all sorts of things before the correct diagnosis is made. A dear friend of mine made a miraculous and complete recovery once the correct diagnosis and correct treatment were in place.
If you want to read more on history of glucagon and the complexity of diabetes;
Another point of view on the Accord study;
Theory on diabetes;
While reading your thoughtful article I was thinking about metformin and then surprisingly you started getting onto that as well. In some people, metformin lowers both insulin and fasting blood sugar. In my case, where I take it to assist with weight loss with a “functional medicine” doctor (East coast US), it lowers fasting insulin nicely but leaves my fasting blood sugar untouched. According to your model, assuming it is applicable, if blood sugar is lowered while insulin is lowered, then the glucagon must be lowered as well. Glucagon must have been lowered to an effectively greater extent than the insulin, in fact. But in my case the 2 effects must cancel each other out apparently, in order to see no effect on fasting blood sugar, which is very slightly elevated but not to diabetic levels. Although my fasting blood sugar and insulin levels get tested, I don’t believe I’ve ever had my glucagon levels tested assuming such a blood test is available.
“Reducing glucagon…anyone?” …. I guess I don’t get it. For those with high blood sugar (lots of people), wouldn’t reducing glucagon have little or no effect? And for those with normal blood sugar (most of the rest), wouldn’t reducing glucagon make them tired?
I am halfway through “Doctoring Data” and now I question everything. Citation no. 3 in this article mentions the 1998 UK Prospective Diabetes Study which showed reduced mortality with metformin use compared to diet alone, yet in the French meta-analysis metformin did not significantly affect all cause mortality. Can you tell me what was different in these studies to make the conclusions different.
No, I cannot, sorry. But I am going to have a look.
I think you have well put Unger’s view in a broader clinical context and without violating his basics.
With one anecdotal reference, my wife severely diabetic tyoe 2, cutting the carbs made wonders to her health. Restored vision, regression of severe peripheral neuropathy as well as other health benefits but problems returning when ‘cheating’ again with the carbs. Then it is easy start thinking in terms of cause and effect with the carbs as the cause and the health problems as effect.
Is it possible to think along other lines?
I don’t know as much as most of the people who write on here, but even I saw as I read this article that it was a ‘light bulb moment’. Even with my limited knowledge, and though I don’t understand it all, it sounds logical to me. One thing though – how does one reduce glucagon. Two things actually, does this mean that anyone whose blood sugar is elevated needs to reduce their glucagon?
Excellent post as usual Dr Kendrick.
There is a connection between glucagon and counterregulatory hormones in diabetics.
But, but, but.. Why then do low-carb diets work so well (to normalise blood glucose in people with type 2 diabetes)?
Isn’t it because low carb diets stimulate the release of glucagon, because blood sugars from dietary sources are lowered? This happens at the same time as insulin production is also suppressed again because there is very little need for it because so little glucose is being consumed.
IT is my understanding that the diet changes how one metabolizes food in general and assists the body such that these hormones are released time wise more efficiently. I do not have diabetes, but I can tell if I do eat even something high carb just once or twice in one day. I start feeling awful. That is why it must be done rarely particularly as you age and if you are not active. I find this explanation fascinating once again. I often wonder why (despite all our efforts to control diabetes with both medications and diet) we have seen a huge surge in the incidence of pancreatic cancer.
In response to someone who talked about the sleep cycles, after I stopped (actually weaned off) B/P meds, sometimes I would awaken early hearing my heart beat and wanting to hit the ground running. It felt odd. I thought “Wow, am I having a heart attack?” My B/P was normal or within normal range. When you body starts to work more efficiently, it feels odd at first. We are so accustomed to being medicated that we forget what “normal” feels like. Ha.
Dr. Kendrick’s blog is fascinating once again. I want to take some time to read this again and again to understand better. Thanks Dr. Kendrick!
Hi, do you mind telling how you weaned yourself of BP meds. Did you find your BP was all over the place whilst you were doing this. I am on two BP meds. Tried breaking one in half which was fine. When I stopped one it made my BP go all high so I started taking it again. Do you take any supplements. Thanks.
On lowcarb, glucagon remains the same but the glycogen content of the liver falls. The liver likes to keep some glycogen around in case of emergencies, so it does less glycogenolysis when stimulated by glucagon, and releases less sugar into the bloodstream so the elevated fasting blood sugar which characterizes diabetes miraculously becomes normal. Read this study: http://www.ncbi.nlm.nih.gov/pubmed/15579777 (sorry, don’t know how to get a link into the message!)
Intesting. I hadn’t thought of that. Thanks for the link.
If glycogen levels determine glucose release in response to glucagon, and glucagon is stuck on “high” in diabetes, then … that actually works pretty well! It explains why fasting works, why exercise helps, and why low-carb diets are so effective. Thanks again.
Missing piece of the puzzle, isn’t it!?! This team also looked at healthy men and found the same thing: “dietary carbohydrate content affects the rate of postabsorptive glucose production mainly by modulation of glycogenolysis. In contrast, dietary carbohydrate content affects the postabsorptive rate of gluconeogenesis minimally” http://www.ncbi.nlm.nih.gov/pubmed/10843182 Extinguishes all doubt over what a diabetic should eat …
Please explain this comment for idiots. I didn’t understand the study you linked to here either.
Jonathan, can you put your comments into a more understandable form, please. Or, maybe provide an English translation of the link, as I am surely not the only layman flummoxed by it. I am sure you are well intentioned…..but….
@thelastfurlong – most agree that glucagon is high in diabetes, insulin resistance and metabolic syndrome, and that high glucagon indicates we’re starving so the liver breaks down stored glycogen to give us glucose. Insulin inhibits glucagon release, but in Type I diabetes insulin is injected peripherally so the liver sees little of it and in Type II diabetes, the liver is insensitive to insulin’s message. The two studies I cited ( http://www.ncbi.nlm.nih.gov/pubmed/10843182 and http://www.ncbi.nlm.nih.gov/pubmed/15579777) show that in both normal people and diabetics, reducing carbohydrate intake reduces the amount of glycogen stored in the liver, and this reduces the amount of glucose released by glycogenolysis in the liver when glucagon is high. This is why lowcarb is so effective and diabetics eating lowcarb do not suffer suffer the high fasting blood sugars characteristic of diabetes. I’m insulin-dependent yet my HbA1c is 5.1% on lowcarb, and although 75% of my calories have come from fat for 15 years my calcium score is zero – I’m the proof not eating the pudding, so to speak. Until these studies, no one could explain why lowcarb normalized blood sugar in diabetics, they leave no doubt that lowcarb is the way to go for diabetics in spite of the drivel from the ADA. Is this clearer? It’s so hard to find the line between TL-DR and cryptically baffling …
I’ll give it a go. If you eat carbs, your liver turns glycogen into glucose for fuel. Severly restrict carbs and you’ll make what little glucose you need from scratch and leave your glycogen stores alone.
@imnoclue Yes, admirably put, that’s exactly how I think it works – you get all the glucose you need from protein via gluconeogenesis
@Jennifer That’s exactly what my wife always says!
Loving all the glucagon talk around the traps recently, been going on about it for ages and dismayed how folk are so obsessed with insulin alone…
Thank you! Totally new to me and totally fascinating.
Thank you, Dr. K. The conventional way of looking at diabetes now seems upside down!
It makes sense to see it as the body PRIMARILY being designed to keep blood glucose levels UP (glucagon) in order to keep itself alive, and SECONDARILY to protect it from too much glucose (insulin) because the latter situation is less of an acute threat to death than the former.
A definite penny drop moment for me!
I googled glucagon blood test to see if it’s even possible, and found this interesting statement (at this link http://www.healthline.com/health/glucagon#Purpose2):
“The glucagon test may also be used to measure glucose control in patients who have developed type 2 diabetes or in patients who may be insulin resistant. In these patients glucagon levels are typically high. Effective control of blood sugar levels will help the patient to maintain normal levels of glucagon.”
If glucagon levels are typically high in T2D, wouldn’t that be the CAUSE of their condition? Why/how would controlling blood sugar levels result in lowering glucagon levels? I don’t understand that logic.
I think many people, due to improper diet, first get excessive spikes in insulin, followed by the necessary excessive spikes in glucagon. Wish I could figure out where I read this.
That is a wonderfully clear description of your alternative theory – and very plausible – theory!
I am beginning to realise that so much in medicine is counter-intuitive because the body is crammed with negative feedback mechanisms of various sorts. For example, only recently is it accepted officially that eating food rich in cholesterol doesn’t affect cholesterol levels, because the liver operates to synthesise extra to cover any shortfall so as to keep the level constant. Maybe medical science could benefit from an influx of control theory experts.
Does anyone know if people can get into a situation in which both glucagon and insulin are circulating at the same time. If this can happen, I guess you could end up with a simultaneous rise in both hormones – even if only temporarily.
I wonder about the mice that lack both alpha and beta cells. Do they suffer any other defect. One might expect that they would be less able to put on a burst of speed – which could be fatal if cats are about!
Do you think people with severe diabetes would benefit from surgical removal of some or all of their alpha cells?
“Reducing glucagon…anybody ?”
Doesn’t fat dampen gluconeogenisis ? Doesn’t too much protein stimulate glucagon and hence gluconeogenisis ? Therefore, how’s about a diet of high fat and low carb with moderate protein ?
I mean doesn’t fat reduce glucagon ? (Can’t correct typos after posting).
Anne…..yes, perfect, I say, because I did, and my health has improved dramatically since introducing it in February 2013.
Removing the majority of carbs of all descriptions is not as easy as saying it though! There are times I have struggled with it, especially when having family get-togethers. It is so easy to revert to what was the norm of years ago.
But the outcome is so beneficial, I say it is the path to tread for all type 2s, all the obese and, in fact, anyone who wants to improve their overall health. The svelt people need not think they will be reduced to skinny rakes by relinquishing most carbs, but their health will certainly improve…..even thin people have health issues…..and these will be minimised by low-carbing.
Oh….have I been bannished to the naughty corner for promoting my anecdotal, low carb solution?
as my 9:41am comment seems not to be allowed today.
Jennifer – I’m actually “Type 2” though always thin and not insulin resistant (most likely I am a monogenic type diabetic but NHS likes it simple with 1 and 2). I’ve been eating extremely low carb for nearly eight years now and really enjoy it. Never miss the carbs. The only carbs I get are those in leafy green veggies (very few carbs in those), the milk I have in tea and coffee, and the carbs in the glass of wine I have every evening. Diet is meat of various kinds with fat (including sausages and bacon), oily fish, eggs, almonds (oh some carbs in those), lots of green veg cooked in oil, coconut oil, sometimes olive oil, butter, sometimes cheese. I’m never hungry, I eat very well 🙂
Stop the Press!
A huge study in China, involving thousands of participants (well it is China), has announced its findings. The daily consumtion of fresh chilis reduces rik of cancer, ischemic heart disease and, wait for it….., diabetes. The study finds that their is conclusive proof that there is a 14% reduction in death rates.
Does this indicate that the lucky 14% live forever?
How soon before Big Pharma catches on and announces a new drug called ‘Chiliverstatin’?
When will prescription vouchers be issued from your pharmacy, redeemable at Tesco for red chilis?
And will the popular press urge their diabetic readers to stuff their pockets and purses with red chilis in case of diabetic coma?
As an aside, the red chili peeking (pun not intended for their Chinese readers) out of their top jacket pocket, will be a dead giveaway that the wearer is diabetic.
This really warmed my heart – because I really like chillis!
For ‘their’ read ‘there’. For ‘rik’ read ‘risk’
In a rush to buy me some red chilis
I’m wondering what causes glucagon to over produce glucose? Why is it sensing there isn’t enough glucose in the presence of so much carbs in the diet? Could there be somethung called glucagon resistance? But what is driving it?
I recently spent some time with someone who has type II diabetes (she said), but her problem seems to be continually low blood sugar and she was constantly eating snacks to try and get her blood sugar up. (In fact I think her diet was appalling, but that’s beside the point.) Presumably the issue here is that her body isn’t producing enough glucagon?
As an interesting aside, that experiment with mice would suggest that someone could possibly have their pancreas removed and still live a relatively normal life. Given that pancreatic cancer is so aggressive, has anyone tried it?
Google “living without pancreas.” These people develop diabetes and take insulin shots. They can lead fairly normal lives, but it’s not a cure for diabetes.
“(…) in fact a rise in glucagon is the first step in the insulin production cascade. Glucagon stimulates its counter-hormone insulin, which then suppresses glucagon.”
I’ll admit, I’m confused. I thought releasing glucagon & glycogenesis was a good thing?
To lose weight (and achieve a whole host of other benefits) I eat a high fat, low carb, medium protein diet. I thought the reason this worked so well was because a low carbohydrate diet included a reduction in the circulating levels of insulin along with increased levels of glucagon. This in turn helped to increase the mobilisation of fatty acids from adipose tissues and the liver starts to produce ketone bodies for the body to be utilised instead of glucose. The small amount of glucose needed by the brain, is made from the protein consumed. In a worst case scenario (starvation), the body starts to catabalise its own muscles. I know there are steps missed out here, but I’m trying not to be too complicated about it. In this instance, eating the way humans probably evolved to eat, why would I want to reduce glucagon levels?
Surely, the problem still remains that humans are stuffing way to much carbs / sugar down their gullets, which stimulates vast amounts of insulin to be secreted and glucagon barely gets a look in for those people, as their blood sugar is permanently high?
When I was Dx’d with type 2 in 1996, I read everything I could find, including Unger’s chapter in Ellenberg & Rifkin’s “Diabetes Mellitus.” I was struck by the comments about “normal BG” when both alpha and beta cells were removed and wondered why no one was following up on it. It seems that the important factor is not insulin or glucagon levels but the insulin:glucagon ratio, IOW, high glucagon is fine if you’re also able to produce high insulin.
I tried to follow up on this and found that there are people who lack a pancreas because of cancer, so they lack both alpha and beta cells, and they don’t have normal BG levels, as far as I remember. I think the “normal BG” levels reported for the animals was fasting levels, and when they ate, BG went up, but I haven’t looked at this for a long time and might be misremembering.
Maybe you could look into this.
The GLP-1 inhibitors do reduce glucagon levels and I think people are looking into other inhibitors. I corresponded with some Japanese researchers working on glucagon a few years ago, and we agreed that there’s not enough emphasis on glucagon. Unfortunately, I have no idea where I put their article.
“I tried to follow up on this and found that there are people who lack a pancreas because of cancer, so they lack both alpha and beta cells, and they don’t have normal BG levels, as far as I remember.”
In the video lecture (link posted by Dr Kendrick), from what I understood, Dr Unger says they found alpha cells in the stomach which, he said, explains why people who have had their pancreas removed get high BG levels due to those glucagon alpha cells.
Malcolm I’m sure you’ve seen this paper but others may not, it cites the maurine studies you mention and is focused on T1dm.
A question Dr. Kendrick. In the pantheon of degenerative disease and its treatment which specialties benefit from conventional medical wisdom which is on the mark in your opinion?
I just listened to Unger’s talk and most of it makes sense, but I disagree with two of his pieces of evidence.
He says people with type 1 can’t achieve anywhere near normal BG levels throughout the day with insulin alone, and showed a graph of BG levels going from very low to very high. This used to be true when we didn’t have pumps and BG meters and continuous glucose monitors. But today some type 1s get BGs in fairly normal ranges when using this technology and LC diets. Control might be better without glucagon, but it’s OK without.
The second is the controversial ACCORD trial, which people cite to prove that higher BG levels are better in elderly patients. There are many problems with that trial.
How does one lower glucagon?
I had seen the Glucagon video before and thought it was interesting.
If you affect insulin and insulin resistance, do you then affect glucagon to the same degree? For instance, Dr. Fung has theories about insulin resistance and feedback mechanisms that cause the same:
He believes that T2DM is a disease of high insulin resistance (not necessarily high blood sugar). He believes that intermittent fasting affects insulin resistance and can cure T2DM (along with a low carb diet). I recommend watching the lectures, if you have time.
I have been performing intermittent fasting, and it has done wonders for me. (I am not a type 2 diabetic, though, at least not by the “classical” definitions of these, although I would call myself insulin resistant). If I improve my insulin resistance using intermittent fasting, how does that affect my glucagon (resistance?)? Am I really improving my glucagon “resistance” only or am I improving both glucagon and insulin resistance? Dr. Fung believes intermittent fasting affects the pancreas (aka “fatty” pancreas), which is where some improvement in insulin resistance comes from (as the pancreas gets less fatty). I assume reducing fatty pancreas affects glucagon, too.
Sorry BobM. I meant to hit the thumbs up and missed and hit the thumbs down instead. I can’t seem to undo it. Consider the thumbs down as a thumbs UP.
What about type 1?
Paragraph 16: “In one way, I am saying […] to counter the effects of too much glucagon.”
Should that be “glucose” rather than “glucagon”?
(Also, next para, should that be “cell” rather than “dell”?)
Will look at it this evening
The problem with referencing the ACCORD study is that its data did NOT show that keeping blood sugar down increased or had no effect on risk of death.
Jenny Ruhl at Diabetes Update argues that people in the intervention group were put on Avandia and Actos, both drugs known to increase the risk of heart failure. In addition, this group’s increased deaths were from people who consistently had higher A1c’s — people in the group who had lower A1c’s did not have a higher death rate than the control group. In other words, taking drugs to lower blood sugar and actually lowering your blood sugar are not necessarily the same thing. She shows that later studies published in the Lancet and Diabetes Care studied the data and came to much different conclusions than the people who wrote up the original ACCORD summary:
It never ceases to amaze me how people can ‘immunize’ data they don’t much like the look of. Try finding out the impact of using a sulphonylurea and metformin in combination. Scary.
“The most difficult subjects can be explained to the most slow-
witted man if he has not formed any idea of them already; but the
simplest thing cannot be made clear to the most intelligent man if
he is firmly persuaded that he knows already, without a shadow of
doubt, what is laid before him.” Leo Tolstoy
Sulfonylureas and beta blockers. Scary.
Well I’ve seen it all now!
As you suggested, I am reading up on the problems of combining metformin with a sulphonylurea, and came across a diabetic blog where the patient was poorly for some weeks with a BG of 3. So….the nurse advised patient to stop finger pricks, and just eat more carbs. (sure, it would help the immediate crisis….., no mention of changing the medication)
Talk about burying your head in the sand….
In the bad old days, pre February 2013, I too was prescribed a sulphonylurea to add to my hefty 2g metformin……along with the sitagliptin and pioglitazone, until one afternoon my husband found me crawling around the lounge floor, unable to stand up. I thought my end had come, and that was probably the trigger that made me look deeper into the spiral of prescribing that I was experiencing.
Yes…..you did read me correctly….the diabetic nurse on the blog advised the diabetic patient to stop finger pricking and just eat more carbs to avoid going hypo. Well….if that is the standard of diabetic care in UK today, God help us.
What about the effect of Adiponectin on the whole process?
Dr. K, you said “In addition, if you give such a mouse, that cannot produce either glucagon, or insulin, a glucose ‘meal’ the blood sugar level will rise, and then fall, in pretty much the same pattern as a ‘normal’ mouse. Ergo, the body does not need insulin to keep blood sugar levels down. There are other mechanisms that the body can use. I am sure that having insulin help to optimize blood sugar control, but it is far from essential.”
So this is a bit confusing. I thought that insulin is required to bring glucose into muscle and other cells. Isn’t insulin required for the brain to use glucose? What happens to the glucose in the circulation if it is not being used by any of the body cells?
Can’t recommend high-fat-nutrition enough. Insulin to “use” glucose is a fairytale simplification from diabetes industry.
There is an osmotic way (by gradient) and many types of cells do not care about insulin signals.
Insulin does make most cells take up nutritients faster but its main role is not to “use” the glucose, it is to get it out of the bloodstream. Kill the storage tissues (muscle, liver, fatpads) or make them insulin-resistant and you got serious hyperglycemia.
I think the amount of glucose that is “used” by insulin spike should thus be rather small.
As to the poor mice without any of glucagon or insulin, I cannot quite believe that. Maybe it is the amount of glucose they were fed, which would be rather small, that ensures equilibrium. Sorta like DM1 patients with LC and 2 g glucose per hour snacks.
Little bit different than the main topic, but saw this type 2 diabetes prevention articles in my email box today. Haven’t looked at the study, but the write up for it mentions a testing level above 40ng/ml was nicely beneficial at preventing diabetes.
“…Our latest paper, just published with YOUR Data, shows a full 60% lower rate of incidence of type 2 diabetes with our median serum level of 41 ng/ml vs.the NHANES median of 22 ng/ml. Another very significant finding was that the data were consistent with previous data we have published showing a sigmoidal response curve with the serum level, and not a straight line:
there is a flat (no) response for people under 10 ng/ml
between 10 ng/ml and 30-35 ng/ml, there is a very definite positive clinical response and
no additional effect above 30-35 ng/ml…”
Ok, if I bite a mouthful of a butter stick, Will that reduce or increase my glucagon production?
Perhaps lactose is problematic, let’s try with ghee.
I have to confess two things. Ever since I’ve been eating eggs cooked in lard at low temperature (takes more time to cook), I feel that I’m better than anybody else, and I don’t like that. But when I ate my stupid 0% fat milk and corn flakes (with some sugar because, well, low fat milk tastes pretty bad, and corn flakes are disgusting, so sugar is needed in order to trick the palate and swallow that), I felt I was a stupid and hopeless as every one else. I don’t miss my 30 pounds of fat, but I miss the warmth of the losers wagon.
Why I ate bad tasting milk and bad tasting cereals? Because I was afraid that if I ate even one egg I would wind up in an ambulance. Such stupid was my fear. Marketing can be pure evil: Don’t eat what tastes good because you will die a terrible death, but eat what tastes bad and leaves you hungry, and you will live a long, sad and paranoic life. Well, not so long, after all. Do this because is good for us, the big-agra and big-pharma. Forget the fact that your ancestors ate lots of fats, and very few sugars, and they were stronger than you, and smarter than you, and happier than you. They were unlearned, unscientific, and therefore they were criminals, because not giving sugar coated cereals to children is a crime. Don’t even think that politicians want peoples that are undernourished, weak, incapable of thinking most of the time, or hooked up on some substance to feel happiness. That never happened, anywhere, ever.
Perhaps I missed something. Is there anything actionable here? What can I do different/better?
Just wondering what implications this has for treatment and prevention.
Interesting. The role of glucagon in maintaining normal blood glucose was apparent to me when looking at the insulin response to ingesting protein. Insulin leaps up but BG stays the same – as glucagon turns up the liver’s glucose release. So it clearly is not just the “low level alarm” of blood glucose control, but a primary actor. Perhaps the protein actually stimulates glucagon which causes sugar release and hence the insulin response to bring it down – chicken vs egg. I’m sure someone will have infused glucagon and observed the results….
Personally I have a stake in this as I eat low carb but have a fasting blood sugar and HbA1c in the pre-diabetic range (I could easily get a diagnosis of T2D on WHO criteria). Less hepatic glucose output would be great for me.
and me too….until Dr K’s excellent explanation of glucagon this week, I think many of us have thought type 2 must surely be far more complicated than merely lowering blood glucose levels with low carb diet and/or medications, but we just couldn’t figure out why.
This discussion about glucagon must be an important part of the puzzle.
We are now convinced that 40 years of low fat intake has driven the obesity epidemic. Well…..
I think we are just a midges’ d..k away from showing that 40 years of anti-diabetic medications have failed type 2 sufferers, because the end stage type 2 problems are expanding exponentially. Maybe no medications could not be any worse than the buckets full we have been prescribed, because, as Dr K suggests, we have been looking at the problem from the wrong angle.
PhilT, try eating fewer meals per day (the so-called intermittent fasting), such as not eating breakfast or not eating breakfast or lunch a few times per week. This supposedly helps reduce fat in the liver and pancreas, both of which increase insulin sensitivity. Also, fasting lowers blood insulin levels, which also helps reduce hunger (and longer term fasting such as 24 hours can increase growth hormone and norepinephrine levels). As you change your insulin sensitivity, your blood sugar levels also change. I was on low carb for a while and still had fasting blood glucose over 100 mg/dL (US units) and a relatively high HbA1c level. I started intermittent fasting, and my fasting blood sugar level dropped (oddly, the HbA1c level stayed constant, but I changed blood testing facilities, so I think that caused a different result).
You may be able to achieve similar results with low carb, but I think you have to up your fat content and it’s going to take longer than intermittent fasting (IF). For me, IF worked much faster than did low carb, especially for weight loss. (Note: I still eat low carb, but just added IF on top of that; I’ve also attempted to increase the fat content in my diet.) As always, your response and experience my be different.
Bob, Professor Thomas Seyfried also advocates intermittent fasting and a low carb diet in relation to cancer prevention and treatment. Apparently cancer cells feed on glucose. He has some intriguing talks on Youtube.
Now, having watched professor Unger’s lecture which is the foundation of this article I think the role of insulin has been hugely underplayed in this article from the point of view of what causes the problem in the first place. The malfunction in a-cells takes place when they become disobedient to their boss, insulin, which tells them when to stop sending signals to the liver for glucose production. Problem starts when glucagon producing cells become resistant to insulin due to lipid accumulation in them. We know insulin is the main driver in fat accumulation. Im not interested in what insulin does to blood glucose after too much of it is being produced, Im interested in why in the first place too much of it is being produced: glucagon cells become resistant to insulin. According to professor Unger’s causal pathway chain for a-cells’ resistance to insulin, the first step is caloric excess where he completely gets it wrong because caloric excess is an effect of metabolic disregulation and when we did deeper for the causes of caloric excess again insulin comes out as a main culprit…most of the time at least.
Once the problem has occured, do we treat it by suppressing glucagon? Dr Kendrick might come up with part 2 of this article.
The purpose fo the blog was simply to try and get people to look at the entire glucose/insuin/sugar/diabetes problem from a different angle. Only then can the debate move into more interesting areas. The entire issue of what causes insulin diabetes is fascinating. You clearly cannot understand it by focussing purely on insulin. My next blog will probably to make the point that type II diabetes is not a disease anyway. it is just a blood sugar measurement
“My next blog will probably to make the point that type II diabetes is not a disease anyway. it is just a blood sugar measurement”
In my eyes this is ‘great’ thinking.
It reminds me of what the worlds most famous physiologist all time (?), the French nineteen century Claude Bernard, had to say about our homeostasis. On top of my head I can now not remember that he dwelled to any extent on any diseases but rather discussed different physiological states, homeostasis, of our bodies in terms of the scientific notion of cause and effect. To me his thinking is clearly scientific although he seems to have been a horrific person from any animal ethic perspective – his wife actually left him because of that. (I guess that Bernard had not been impressed by what another favourite of mine, as well as Bernard’s contemporary, the philosopher, Schopenhauer, had to say about the ‘feelings’ of animals.)
Today, in the medical circles, it seems like the actual diagnosis is the Holy Grail. Arriving at THE diagnosis is the crucial point and arriving at ANY is a true relief for everyone involved and no more questions really need to be asked except perhaps of how much of the prescribe medicine could be appropriate. That about half the number of diagnosis are found to be “wrong” upon autopsy is something that is not very much discussed and this lack of self reflection, in the present dogmatic medical world, is quite understandable, at least to me.
It may not be a disease but it certainly is a big industry.
“… is not a disease anyway. it is just a blood sugar measurement…
Gadzooks ! is there no end to this man and his Heresies ?
If insulin and glucagon are two different sides of the same coin, then how does one know the “insulin” resistance is caused by too much blood sugar/insulin (Dr. Fung’s theory) or too many calories (Dr. Unger’s theory)? Personally, I think it’s the former (too much blood sugar/insulin), as it’s difficult to overeat protein and fat (especially fat), but it’s quite easy to overeat carbs. If I ask my kids if they want another pork chop/more cheese/more bacon/more meat, they’ll say they’re full; if I subsequently ask them if they want some type of sugared dessert, they suddenly become less full. Granted overeating carbs means overeating calories, but it seems to me the culprit is the carbs and their effects.
I think the glucagon theory is very interesting, but it won’t change my current diet at all, and it won’t change that I can’t really measure glucagon; I can only measure blood sugar and insulin. It’s difficult enough to know if what you’re doing affects “insulin resistance”, as there are few tests for this and none I can find to have done on me. There are tests they do in studies to measure insulin resistance, but I can’t find the same tests I can actually order for myself. And most other tests (fasting blood glucose, glucose tolerance test, etc.) imply insulin resistance but don’t quantify it.
You need to go back to basic anatomy Bob, most people know that children and a lot of ladies have two stomachs, the standard stomach and the pudding stomach.
I think Dr. Unger is brilliant on Glucagon. That doesn’t mean he’s great when it comes caloric imbalance. I don’t think there’s anything in Unger’s findings that is inconsistent with the idea that dietary carbohydrate causes hyperinsulinemia. It just does so indirectly by driving Glucagon up.
I agree that Unger is still trapped in certain ways of thinking.
Ofcourse, pure focus on insulin is no good. My point was that we cannot ignore its role either. In the context of Professor Unger’s lecture in my view hyperinsulinemia and insulin resistance come out as very significant, if not core, issues with regards to causing problems with glucagon.
Of course, I agree. Hyperinsulinaemia and insulin resistance are highly significant. Quite what insulin resistance may be caused by, exactly, that is far more tricky. Equally, one cannot ignore insulin (just look at type I diabetics, for example). What I am trying to do, for myself, and encourage everyone else to do, is to try to smash the current thinking to pieces and see what actually remains. Personally I find this quite exciting and I hope that others do as well.
I would argue that there are at least two types of insulin resistance: pathological insulin resistance and physiological insulin resistance.
Pathological insulin resistance is found in newly diagnosed type II diabetics and seems to be related to too much insulin over a long period when the body is running on a glucose based metabolism.
Physiological insulin resistance is found in in people on a low carb or ketogentic diet and is related to the body running on a fat base metabolism. One manifestation of physiological insulin resistance shows up as a false positive when patents on a ketogentic diet fail a glucose tolerance test.
Peter at Hyperlipid has an interesting post on physiological insulin resistance and insulin resistance in general. See http://high-fat-nutrition.blogspot.com/2013/07/physiological-insulin-resistance-again.html.
OldTech: I hear about pathological vs. physiological insulin resistance all the time, and it always makes me wonder, if the high circulating glucose is what causes the damage to the various body parts, what difference does it make whether the high glucose is caused by one or the other mechanism. It’s still high and still circulating around wreaking its havoc.
Guess I’ll go read Hyperlipid and see if it answers my question.
In so-called physiological insulin resistance glucose isn’t “high” though, compared to your average SAD grazer.
90-110 is common for long-term strict ketards/carnivores, but the kicker is it rarely strays from there, very well balanced homeostasis. “Paleo” ketards (carb-whateverBS-protocol) generally have much lower fasting BG (60-80) and never revert fully to their natural state of PIR – or better put as Glucose Sparing.
Average pre-diabetic SAD’er has fasting 90-100, but spends majority of their day 130-190 in spikes and troughs – that’s just asking for sticky blood in the long term, even if you’re eating donuts and staying skinny.
Tricky? You bet. Try “insulin resistance does not exist. ” The medical literature (mainly from Asia) documents about three forms of abnormally formed insulin present at birth. These malformed insulins cannot facilitate the passage of glucose into the cell. Result: All these babies die shortly after birth. There is no model in biology which supports the notion that if you are born with a normal functioning hormone, like insulin, then years later… you wake up one morning and that insulin has stopped working. Really? This is “Tooth Fairy” thinking. Get a grip folks! If you bought into “insulin resistance” you should not be taking care of patients. (“People believe what the want to believe.” Ralph Waldo Emerson).
Roberto Illa, M.D.
Is there a need to make either insulin or glucagon the boss? I think most things in nature are about balance.
True, but medical thinking has made insulin the ‘boss’ to end all bosses. I am just trying to redress that balance somewhat.
Insulin resistance does not exist. The “clamp studies” miss the fact that human blood sugar changes every 60 seconds approximately. Even the Dexcom continuous glucose meter misses about 30% of all hypoglycemic episodes. Testing intervals for glucose in clamp studies is about 5 minutes; not sufficient to find hypoglycemic episodes in a significant number of patients. C-Peptide always shows a low value in Type 1 patients (insufficient insulin production). Other patients (non-Type 1) have to be sorted out into their respective groups by the various means outlined in my book (Dexcom CGM testing, modified 4 hr GTT with direct insulin and glucagon testing, non-contrast brain MRI for evidence of hypoglycemic infarcts.)
The myth of insulin resistance began in 1932. The ACCORD trial *NEJM 2008) which was prematurely stopped because 257 deaths resulted from “intensive insulin therapy”….dramatically showed that there was no insulin resistance among “Type 2” diabetics. This intensive (3x per day mealtime insulin) tripled the hypoglycemia rate (See ADA minutes 2008 San Francisco meeting). However, it must be stated that since the authors did not screen for Nesidioblastosis or “spontaneous” hypoglycemia (two primary hypoglycemic disorders which are not diabetes and found in high frequency) they gave insulin to patients already suffering from random hypoglycemia…thus precipitating the deaths. No retractions or apologies were given by the ADA. Misguided recommendations (glycemic testing only) continued to be issued by ADA and other national endocrine societies. Shameful.
Roberto Illa, M.D.
Thank you for that post. Now we are really getting somewhere.
Well – it seems like another ‘religious’ dogm is about to be destroyed for me. This is though quite enjoyable since for each one of these destructions my research heart is being refreshed.
Goran. Smash everything to bits, see what is left when the rubble settles. It is the only scientific way to think. Insulin resistance…. Once your liver and skeletal muscles are full of glycogen (about 1,500 calories worth), you cannot store any more. So, both organs will be entirely resistant to the effects of insulin. Insomuch as they cannot store any more ‘sugar.’ Eat carbs for a week, take no exercise, and every person on the planet would be ‘insulin resistant.’ Clearly, however, they would not all have type 2 diabetes. Clearly, therefore, insulin resistance is not the underlying cause of type 2 diabetes. It is something else.
To get type 2 diabetes, you need *both* insulin resistance and beta cell defects that don’t allow the beta cells to secrete enough insulin to overcome the IR. The IR is actually protective, as it keeps muscle cells from taking up so much glucose that they’re harmed. One problem is that not all cells need insulin to take up glucose, for example, endothelial cells, so they lack the protection of IR and high BG levels can harm them.
We didn’t evolve in an environment with too many calories, so our bodies aren’t equipped to deal with this situation.
If you like turning things upside down, I’ve often wondered if diabetes doesn’t cause heart disease but heart disease causes diabetes.
I think we have an awful lot of un-learning to do.
I look forward to the day when we have a better understanding of the glucose/ glycogen/glucagon/insulin interconnections. And of course it will need to be properly researched and confirmed by honest scientists, rather than the charlatans of yesteryear.
“Goran. Smash everything to bits, see what is left when the rubble settles. ”
Well – I have heard about AGE (Advanced Glycemic Endproducts I think it was) which as far as I have understood it are ‘caramelised’ proteins which have to stuck together and that the enzyme that is meant to untangle these proteins should be the same that is taking care of the insulin and that there is some kind of competition about this enzyme.
So what may be left among the rubble just now for me seems to be that high blood sugar levels are not good for my ‘health’.
That’s fascinating, and makes me wonder what type 2 diabetes, with it’s reported additional effects, is. And the cure could be making things worse! Will be fun to read what you likely mention in a future post.
It is a interesting, to me at least, when looking at the mention of disease. Here in America we have an outbreak of legionnaires disease. It seems to have some frightened. I’m somewhat familiar with the politics of that disease bacteria, created or most would say noticed first in Philadelphia in 1976, possibly coincidently after a fight between city politicians and the CDC.
Physiologic insulin resistance is quite interesting and perhaps one of the grey and least known areas of low carb dieting. Peter at Hyperlipid has done a nice series on it but I still wonder whether it is a healthy state to be in long term as glucose tolerance does get impaired in this state which is restored after eating higher carbs for couple of days. Not everybody experiences it though. This is what Jeff Volek said about it:
“When one is properly keto-adapted there is a dramatic shift to near exclusive reliance on fatty acids and ketones for fuel, and a substantial reduction in the need for insulin-mediated glucose uptake. Fats don’t require insulin to be transported or oxidized. That’s why a ketogenic diet works so well, even in individuals who are profoundly insulin resistant.
Evaluating a keto-adapted individual with an OGTT would be like testing how a Tesla runs on high octane fuel.”
My cocaine tolerance gets impaired after a while without a hit.
I am getting lost in some of the blogs this week.
Maybe I am just thick.
I don’t know the answer, but for me I see little choice since I am a type II diabetic. I have been on my keto diet for over a year and half and I am feeling good. Even better my A1c has fallen to 4.5%. And I hear of reports that others have been in ketosis for years without apparent ill effects.
I will say that you do need to make sure that you are getting adequate electrolytes and nutrition if you go on a ketogentic diet. For me, that means eggs, fatty meat, hard cheeses, cream and a variety of fresh leafy greens. I also eat a variety of salted nuts along with liberal use of the salt shaker at meals. Finally I take a variety of supplements including calcium and magnesium.
I have been saying this for years, and even more radical things. See my website at http://www.chicodiabetesdoctor.com. See my YouTube presentations and my 4th Edition Textbook (self-published) “Disorders of Blood Sugar”. Over the past 8 years we have found that Nesidioblastosis and “Spontaneous Hypoglycemia” cases outnumber Type 2 diabetes by far. (If you test your patients correctly: C-Peptide, direct insulin assay ( modified 4 hr GTT with insulin and glucagon assays, Dexcom continuous glucose meter).
I wish we had some kind of forum here instead of comments : just because that programme “Trust me I’m a doctor” was on and they are harping on about cholesterol as if LDL and HDL are understood and have clear causative effects.
It just bugs me, and is related … to this topic.
Not all of us are as academically astute as some of the brilliant authors of papers on this blog, and we may struggle to understand their train of thought. However, others of us have simple examples of our own day to day experiences, and I feel that we have a part to play in deciphering the problem.
There is room for both.
“I hear about pathological vs. physiological insulin resistance all the time, and it always makes me wonder, if the high circulating glucose is what causes the damage to the various body parts, what difference does it make whether the high glucose is caused by one or the other mechanism. It’s still high and still circulating around wreaking its havoc.
Guess I’ll go read Hyperlipid and see if it answers my question.”
Keto adapted individuals with physiological insulin resistance generally have normal blood glucose, so there is no damage occurring.
I am on a ketogentic diet and am physiological insulin resistant, yet my last A1c was 4.5% and my fasting and post postprandial readings are in the normal range (less than 100 mg/dl or 5.5 mmol/l). However, I have no doubt that I would fail a glucose tolerance test especially since I am still a type 2 diabetic.
Note if you are diabetic and go on a ketogentic diet you still need to control your blood glucose. For me, I still take metformin and do not need any other drugs. If you are on other drugs or insulin then it would be important to work with your doctor on doses. If you are type 1 recommend that you look up Dr Bernstein and follow his advice. His 6-12-12 diet is likely ketogentic for most people.
Thanks for the input.
I guess what I was mostly curious about was the so-called “dawn phenomenon” wherein my blood glucose rises in the early morning, even though I’m eating a good low carb diet and haven’t eaten for several hours. I’ve read many times that it just doesn’t matter because the raised glucose levels are “physiologic” rather than “pathologic”. But, again, it seems like if the glucose levels are raised, through whatever mechanism, it isn’t doing the body any good.
As for my own health, although my morning glucose levels can sometimes be over 100, thus far I’ve managed to avoid an official diagnosis of T2 diabetes, by hook or by crook, simply because I’d rather manage it myself than start on the downhill slide of relying on ever increasing medication use. Some might say that’s not a good plan, but that’s my story and I’m sticking to it.
Peter at Hyperlipid has also reported that his fasting numbers are up, but that his A1c has remained in the 4s so it may not be something to worry about. I would rely more on your A1c to determine this since it is an index into how damaging your higher fasting levels are from glycation.
Re your mention of “dawn phenomenon”, I just came across the following in the Comment section of Dr. Richard Feinman’s latest blog. http://feinmantheother.com/2015/08/12/meta-analysis-is-to-analysis/
“I started to realize last fall I may be stable because I am controlling my fasting blood glucose… it turns out peripheral clocks can become misaligned and desynchronous with central circadian clocks. My regimen may align peripheral clocks, to allow fasting BG to be normalized as a symptom of enough clock synchrony to slow or prevent metabolic disease progression. Glycemic control during the day reinforces circadian controls, with in turn, reinforce the next days glycemic control.”
Dr. Feinman replies with a link which is way beyond me but may be of interest to some on this blog.
Click to access nihms225004.pdf
I have understood for sometime that glucagon is the main driver of T2D’s high blood glucose. My diabetic wife has now been low carb for about a month. In the first couple weeks her fasting blood glucose remained nailed to 230 mg/dL. I was surprised that it varied by only 5 or 10 mg. After a month I got one reading of 185 but not sure if it’s a freak. I fear she’s perhaps bordering on T1D. I have no idea what changes I can suggest in her diet to bring down the glucagon which, I assume is what is driving her glucose levels so high. I wonder if any one has any suggestions?
One thing I can suggest is to have your wife join the long distance program here:
They treat type 2 diabetes with intermittent fasting (and also low carb). They have experience with people like your wife. They do, however, believe in the “insulin is bad” theory and don’t take into account glucagon. They use intermittent fasting to dramatically reduce insulin resistance. It does seem to work, at least for me, but I’m not a type 2 diabetic (but am insulin resistant or perhaps glucagon resistant or both).
It is not just the insulin, nor the glucagon nor the diet. Yes, our perspectives need to be turned upside down. To correctly categorize and treat your patients in a safe manner you need to throw the conventional paradigms overboard. That’s right. No more HgbA1c thinking. (You will miss the short periods of hypoglycemia that kill brain, pancreas and kidney). No more making a diagnosis and planning treatment using glycemic indices alone (A1c, FBS, 2 hr PP, plain 4 hr GTT). In Nesdioblastosis A1c may vary between 5 and 10.5 (unpublished data from my office.) These old paradigms and tools are misleading and will harm you patients (See ACCORD trial 2008 NEJM and other published studies showing the failure of the “insulin resistance” theory. )
When you have a new patient with a blood sugar disorder you must first document the C-Peptide level (introduced in 1972). All your Type 1’s will have low values. So….you must treat them with some insulin. All other patients need further evaluation. Nesidioblastosis can be present if you have normal or high C-Peptide (the insulin is being released randomly). At this point you cannot distinguish Nesidioblastosis from an insulinoma (or other abdominal tumors making insulin). They can coexist (published).
In summary here is the breakdown of blood sugar disorders. a) Type 1 DM, b)Type 2 DM (normal insulin levels. No hypoglycemia. Normal glucagon), c) Nesidioblastosis (High insulin levels on GTTIDG, may see high Glucagons which elevate when hypoglycemia occurs), d) Hypothalamic Hypoglycemia. Normal insulin levels. May see high glucagon levels. May see glucose levels under 70 mg%. Human glucose levels in the healthy individual range between 70 mg% and 140 mg% (convert to metric in UK). These levels are maintained by the CNS (hypothalamus. See Puglianiello and Cianfiari 2006. The Review of Diabetic Studies).
For more detail see my book, Disorders of Blood Sugar, available for most online booksellers. Or view my YouTube presentations. The Gestational DM has the method of classification.
Roberto Illa, M.D.
Roberto. I like you stuff, but I edited your post.
Unfortunately, I have a very busy weekend planned and don’t have the time to read and watch all of that this post makes available. But I am super pumped about this. Yesterday, I watched Dr. Fung’s excellent lecture from South Africa about the 2 lies about T2. His conclusions: Its the insulin, stupid. Yes, we can cure T2.
So now, I’m naturally wondering is it the insulin or glucagon? It’s like when I started watching the twin evils of our diet get discussed, sugar and wheat (grains). I was wondering which is the most evil. But, now, is it glucagon or insulin? I am excited as I normally get before a Ronda Rousey fight.
Well, thing is, blood sugar we can readily test and modify by habit patterns, and we have a relatively well established causation/correlation paradigm with insulin.
Squeaky wheel gets the grease…
Hepatic-directed vesicle (HDV) insulin has more realistic potential as a fundamental improvement upon interventions for diabetics than glucagon suppression IMO. In an engineered way it gets around the inability of injected insulin to achieve physiological levels of hormone in the portal vein and recovers much or most of the postprandial capacity of the liver to store meal-absorbed carbohydrate as glycogen. This is enormously important.
Fixing the islets, where hormone levels are yet higher by another order of magnitude, still seems only possible by beta-cell recovery.
You are focusing on the “trees” and not seeing the “forest”. Our scientific literature is flooded with these “micro-studies”, most done on mice. Note that in the study cited it is not related to diabetes but was done on ” in healthy subjects” and would be to a large degree in contradiction to the mass of data that shows that human blood sugar is controlled by the hypothalamus. Just do a Google search to prove this. CNS control of blood sugar was first noted by Claude Bernard (1848).See my textbook for excerpts from his animal studies. Most studies on Type 2 diabetes over the past 40 years must be thrown out, as their “Type 2 diabetics” when subjected to more rigorous testing turn out to be made up of several groups. Glycemic testing for diagnosis is worthless. We have all been duped. (See recent British Medical Jo. article on link between drug company financing and our “thought leaders”).
To review what we are told to consider as “type 2 DM” breaks down into the following on closer inspection:
1. True Type 2 diabetics (no elevation of C-Peptide, no increase in insulin with direct assay, normal glucagon levels on multi-hour testing. See my last post.
2. Nesidioblastosis (normal or usually high C-Peptide. multiple samples of insulin 5 approx show elevation of insulin. This is random.
3. Insulinomas and other insulin producing solid tumors.
4. Hypothalamic (“Spontaneous”) Hypoglycemia. (normal C-Peptide, normal direct insulin assays, low sugars on Dexcom CGM (may have to test more than once), usually high glucagons…depends on lab you use.
So…over the years they have mixed “apples, oranges” and drawn conclusions as to how we should diagnose and treat “Type 2 diabetes”.
“The Emperor has no clothes”.
Roberto Illa, M.D.
Hi Dr Roberto,
What is your take on low carb eating approach, does it have any role to play in terms of improving diabetes?
Dr Roberto, what is your take on what the hyperglycemic clamp and hyperinsulinemic-euglycemic clamp measure?
re: “… most done on mice.”
Speaking of that, this recent paper raises serious questions about all rodent trials:
PLOS|ONE: Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests
And that’s the “control” diet. Rodent trials with high fat or keto cohorts are even more screwed up. Off-the-shelf lab keto feed is often basically Crisco, or other high-inflammatory PUFA, if not outright trans fat. The only papers I’ve seen where care was used in formulating the rodent keto diet are those by Dominic D’Agostino.
I am afraid the main line of thinking that needs to be turned around is that insulin’s primary action is to enable cells to take up glucose. It is by far not the case and it should be obvious from Prof. Unger’s and others’ work. A glucagon knockout mice in which also T1 diabetes is induced ends up being completely healthy. In humans the difference seems to be that on top of the pancreas the gastric wall contains alpha cells as well and for some reason (visceral fat?) these cells become resistant to insulin while the pancreas still overproduces the latter hormon in T2 diabetics, this way presenting the typical condition of simultaneous hyperinsulinemia and hyperglycemia. In fact hyperinsulinemia precedes hyperglycemia by years or even decades (!) causing most of the harm through inflammation known as modern diseases of civilization. Please read: http://profgrant.com/2013/08/16/joseph-kraft-why-hyperinsulinemia-matters/
TL-DR, insulin is mainly an inhibitor for other hormones of metabolism and insulin resistance means not properly controlled, hyperacting hormones, principally glucagon and its effect on liver and subsequently BG regulation.
Good summary about the modern view on the actions of insulin:
Click to access 69.full.pdf
A relative recent publication in PLOS – open access
Int. J. Environ. Res. Public Health 2014, 11, 2092-2107; doi:10.3390/ijerph110202092
Nutrition & Metabolism 2004, 1:15doi:10.1186/1743-7075-1-15 Received: 20 October 2004 Accepted
Both open access.
Thank you for an interesting publication on the benefits of ketogenic diets.
Since I am often in a ketogenic state with our strict LCHF lifestyle I believe that the benefits are greater than any harms inflicted. My experience is though that it is very hard to stay constantly in such a state since it does not take much of any carbs to leave it. Happens all to often in my opinion.
I thought this a curiosity. Maybe helpful, maybe not. It’s out of the box and easy to do, so if possibly a part of the diabetes puzzle thought to mention.
I was thinking about the two study mentioned above in which lowering blood sugar intensively (with medications I believe), and the use of Metformin “did not significantly affect the primary outcomes of all cause mortality or cardiovascular mortality. The secondary outcomes—myocardial infarction, stroke, heart failure, peripheral vascular disease, leg amputation, and microvascular complications—were also unaffected by treatment with metformin.’3”
Reading some of the other writings on diabetes, I noticed a mention on sumo wrestlers tending to not develop type 2 diabetes despite being morbidly obese. I remembered that the diet sumo’s ate was called chankonabe – which is high in vegetables, meats, and some white rice.
Looking at the chankonabe being prepared,sumo wresters training, and their fights I noticed that sumo wresters walk around barefoot all day. I was thinking it might be one of the few sports if not the only where participants are barefoot.
It reminded me of Dr. Sinatra’s writings on earthing, barefoot walking and diabetes. Dr. Sinatra is one of the cardiologists that was seen in that Australian TV show about statin mediations that caused an uproar with statin promoters.
Dr. Sinatra noticed that people that walk barefoot develop thinner blood. He has a test for it called zeta potential.
He has mentioned that patients that ground, and are on blood thinners such as coumadin will often need lower doses of the medication or to stop taking the blood thinner all together. I’ve found it mentioned that those with diabetes tend to have thicker, clumping blood.
I noticed in the 2nd updated book earthing with Dr. Sintra as an author, observations are made of improvements seen with secondary conditions associated with diabetes. He wrote about those observations also on spacedoc sight, Dr. Duane Graveline.
“Earthing – Observations on Diabetes from Other Doctors”
Snippet from the article:
“In my more than thirty years as a general practitioner, I’ve never had anything to offer patients for diabetes neuropathy. No doctor really has anything. All we can do is try to optimize blood sugar and control it. But that doesn’t fix the problem of numb feet. Earthing has changed this dilemma altogether. …”
The Australian doctor then goes into examples of how barefoot walking, or grounding on a mat helped patients, with numbness, stabilized some patients renal function, improved eye sight, etc.
another article where Dr. Sinatra makes his case:
“Is Mother Earth a Remedy for Diabetes?”
I think what Ash meant (or at least this is my take on it) is that the phenomenon of physiologic insulin resistance might be just a normal adaptation to a period of time without much stimulus from sugars. Not something to worry about.
Dr. K, this is a bit tangential, but still on the matter of hypoglycemia:
Hello, Dr. Roberto,
As a long-time MSer, I found your YouTube presentation, “Dementia/Alzheimer’s and Multiple Sclerosis. The underlying cause” to be of interest. If, as you suggest, these and other neurological conditions are associated with repeated hypoglycemic episodes, it might explain why ketogenic diets seem to be neuroprotective — they provide nutrients if/when glucose is low, and thus prevent damage.
Over the two decades that I’ve been researching MS, I’ve encountered a boatload of ideas about the causes of MS, and ways to fix it. A number of these ideas are well thought-out and worthy of consideration, though I always keep in mind that it would be pretty hard to prove any of them.
Keep up your good work, but keep an open mind. Those lesions on the MRI of the brain — though they are associated with hypoglycemia — might be due to hypoglycemia, or they might be due to a virus, or too much or too little of this or that, or something else no one has thought of yet. We really don’t know for sure.
Read this: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154031/
This sort of reminds me of Otto Warburg’s description on cancer. Does anyone know if diabetes is correlated in any direction with any cancer?
Yes, dIabetes is strongly linked to increased cancer risk.
Insulin resistance (which some believe causes diabetes; I’ll forgo discussion of glucagon) is associated with many diseases: heart diseases, cardiomyopathy, cancer, overactive bladder, tinnitus, skin tags, cataracts, just to name a few. These are only correlations, however. Some of these have plausible mechanisms for operation, and a few have studies where they try to reduce insulin resistance and the result is a benefit in symptoms. Tinnitus, for instance. However, there’s not a lot of money for non-drug techniques for reducing insulin resistance, such as low carb diets or intermittent fasting. I’m still researching this area, but it seems that once someone has a study indicating there’s a correlation between a disease and insulin resistance, that’s basically it. Nothing else happens. (Perhaps if you believe high carb diets are good, and low carb diets are bad, there’s not a lot of incentive to put people on low carb diets.)
Amazing revelation about statin!!
I suppose this ought to be blog transferred to the ‘Cholesterol Con’, but as there would appear to be an obvious connection between type 2 diabetes and statins, this blog is just as valid. Here goes:- The BBC News Magazine headlines a report by the well-known Dr Michael Moseley (he of the 5-2 diet etc etc). His report researches whether medical screening tests have any value. So he visits prominent cardiologist Dr Duncan Diamond for a CT scan, whereupon he is told he has an ominous dark shadown on one of the main coronary arteries, the proximal left anterior descending (LAD). Dr Diamond explains “The reason it’s dark is because of soft cholesterol-rich plaque on the wall of the artery. These are known in trade as ‘widow makers’, so I advise statins. Soft plaques treated with statins metaphorically have the cholesterol sucked out of them”
Michael Moseley leaves the esteemed cardiologist a worried man, presumably concerned what ‘metaphorically’ has to do with sucked cholesterol?
I think I’d be more concerned about the cardiologist’s ability to bring on a premature heart attack by his ever-so-gentle ‘bedside’ manner. NOT.
Widow-maker? He’s obviously mastered the art!
Any thoughts Dr K?
“There are roughly 900 calories in a litre of blood, making it much more calorific than beer. Donating blood is a good way to lose weight.”
The amount of calories in a litre of blood do not matter so much because to a large extent they only become freely available under the influence of vital co-factors
The blood is a highway. Well more dual carriageway really. In terms of energetics the flow has aspects that are bi-directional. In the first lane energy is being conveyed from the digestive track to all the cells of the body; a process that must arise around the clock or cells will be starved of essential metabolites and die.
However the way we feed does not always supply energy in absolute accord with the demand created by our cells needs. Just after eating surplus energy enters the blood from the digestive track. The surplus is conveyed in lane 2 where it can be converted to gycogen, and when the glycogen stores are full surplus energy arising after a meal enters lane 3 where the energy is converted to fat to be distributed about the body for storage.
But after the passing of time, and as we go hungry, glycogen gets released back into the blood to find its way back into lane 1 where it can energise cells. Think of it like this: Immediately after a meal energy supply is in surplus, and the surplus must be managed. But with the passing of time energy supplied by the last meal turns to deficit. Re-release of energy from reserves of glycogen then finds it’s way back into the blood to compensate for the deficit. Then when glycogen reserves are running low fats are dispatched from adipose sites back into blood to maintain the feed of energy cells need.
Together cells burn energy at the rate of roughly 100 calories per hour. That blood contains about 900 cals/litre is interesting — but it informs little about the direction of flow of the energy within it. And in any case a large proportion of those 900 cals only become freely available for cells to burn when they have been subjected to the right process in the presence of the appropriate metabolic co-factors.
Genius. You’ll lose about 900g instantly. That’s almost a kilo! Do it every day. Slow and steady wins the race.
I meant instantly lose a kilo. l liter of blood weighing near exactly kilo.
No doubt Dr K does have thoughts on that Magazine article regarding Dr M Moseley….along with many more of us in UK.
For those who have followed my story over the last couple of years, I have told the tale whereby my GP sent me off home with the threat that if I stopped ANY of my medications, I would likely suffer a “cardiac event”.
I felt I had to follow my instincts ( shown to be correct) to rid myself of all my medications. But, believe me, the GP’s words have resonated in my head ever since, and the unsaid threat that I would be a “widower maker” has caused me much consternation.
BUT…..look on the bright side, Dr. Moselely forked out £1000 for his advice….whereas mine was on the “free at the point of need” NHS!
GPs, unfortunately, like John Snow ‘know nothing.’ but what they are told, based on evidence from clincial studies bought and paid for by the pharmaceutical industry. I usually ask my colleagues to introduce me to a patient who is still alive, who would now be dead had they not taken their ‘preventative’ medication. Of course, no such person exists.
Dr K. I am obviously just a bloody awkward customer, because not only am I still alive, I am in far better fettle than my peers who have continued taking their preventative meds as prescribed. Of course, my GP could not introduce me to anyone today, because we are no longer in contact.
So should we reassess the notion of insulin resistance and wonder if a notion of chronic hyper-glucagon-emia explains early stage T2DM and apparent insulin resistance better? Then in turn are there other endocrinological and environmental factors orchestrating hyper-glucagon-emia?
Please bear with me as I try and understand the hypothesis being proposed.
Glucagon drives the production of glucose to maintain sufficient levels of glucose to enable the brain to function correctly (blood glucose levels > 3.5). If left to its own devices glucogenesis continues to produce glucose effectively indefinitely. The negative feedback for this is insulin.
If I understand what is being hypothesised is that Type 2 DM is out of control glucogenesis, rather than failure of the feedback path, whereas type 1 DM is failure of the feedback controller. However, Insulin is still required to transfer glucose into cells for use during respiration.
Does this also explain gestational diabetes? The foetus making demands on the mother requiring higher levels of glucose production that eventually overwhelms the feedback from insulin.
Could this explain the development of certain dementias, with consistently high glucose levels having a debilitating effect on brain cells?
If I now consider the development of DKA in compliant type 1 DM patients and type 2 DM patients, e.g. through infection. Glucose production is increased as a response to infection due to the increased metabolism associated with pyrexia, tachycardia and tachypnoea (sepsis), driven by glucagon.
In type 1 DM the lack of insulin means that cells cannot respire and have to switch to reversionary metabolic pathways, whereas in type 2 DM, because the person is already in a hyperglucagonaemic state there is a pre-existing relative deficiency of insulin, therefore cells are unable to follow normal metabolic pathways and also switch to reversionary pathways.
In normal euglycaemic patients that become septic, glucose production increases, and can overwhelm insulin production leading to a relative hyperglycaemic state, such that a BM of > 7.7 is considered a sign of sepsis.
Does this new model have any impact on the flow of electrolytes into and out of cells?
I like your thinking here. Adding flesh to the bones. I like the concept of ‘out of control glucogenesis.’ This is clearly what happens in type I diabetes. Also, you get out of control ketone production as fatty acids exit adipose tissue and are transported to the liver where they are converted to ketones.
I know It is horribly complicated but it would be interesting to hammer down on what really starts the process of brake free glucose production especially from the point of view of preventative measures. Why does glucagon stop responding to insulin? It is lipotoxicity according to Prof Unger but what causes this? Too many calories? Which calories? If too many calories then why are too many caloris coming in? Or is it High insulin? What is causing high Insulin? Why some people secrete lot more insulin than others? Could it be a defect in mitochondria? Could it be flooding of high glucose levels to the cells that they decide at some point, no more? What is the role of glucokinase, has it given up? Is it hyperinsulinemia that does the damage initially or hyperglycemia? How effective low carb is? Is it really protective/therapeutic or only masking the damage that is going on?
Apologies, I know I’m probably asking a really stupid question – but with regard to this statement: “If left to its own devices glucogenesis continues to produce glucose effectively indefinitely. The negative feedback for this is insulin.” – is that really the case? How does that work with ketogenic diets? If you are barely eating carbs & fairly low protein, with the majority of your food intake as fat, how is the glucogenesis kept in check, given that you won’t be stimulating much insulin production?
Glucose control has nothing to do with diets, ketogenic or otherwise. Think of the hypothalamus as a “room thermostat”. It senses, at intervals of seconds, if the blood sugar is too low or too high….and takes steps to control the blood sugar between 70 mg% and 140 mg% .(See “circuit diagram in paper by Puglianiello and Cianfiari, Review of Diabetes Studies 2006. Editorial). So glucose maintenance of “blood glucose homeostasis” is under the control of the central nervous system. You can access the many papers that confirm this through Google or http://www.pubmed.com. Search Hypothalamus and blood glucose or similar wording. This may hurt the diet and food scammers, but help you treat your patients.
Roberto Illa, M.D.
Not stupid, source of confusion for many! On lowcarb, glucagon remains the same but the glycogen content of the liver falls. The liver likes to keep some glycogen around in case of emergencies, so it does less glycogenolysis when stimulated by glucagon, and releases less sugar into the bloodstream so the elevated fasting blood sugar which characterizes diabetes miraculously becomes normal. Read this study: http://www.ncbi.nlm.nih.gov/pubmed/15579777 Imnoclue translated this into English: If you eat carbs, your liver turns glycogen into glucose for fuel. Severly restrict carbs and you’ll make what little glucose you need from scratch and leave your glycogen stores alone.
Jonathan, but does glucagon actually remain the same? All forms of diabetes are characterized by hyperglucagonemia. If low carb diets lead to normalized blood sugars, and they do, then Glucagon levels would fall to normal as well, no?
Unger’s work suggests that if insulin levels are low it is because glucagon levels are low.
Robert, Why does the fact that the body tries to maintain homeostasis mediated by the hypothalamus necessarily mean that diet has no effect? It’s pretty clear that a big dose of glucose can swamp the body’s ability to maintain equilibrium. There’s no reason to think chronic exposure is benign and T2 diabetics who switch to low carb eating routinely show tighter blood glucose control.
Imnoclue, Allick 2004 measured glucagon in their type II diabetics but didn’t mention it in the Results section – I took that to mean glucagon didn’t change between the low- and high carb arms. My takeaway is: low-carb -> lower gluconeogenesis -> normal fasting blood sugar. Priceless info for diabetics whatever their glucagon is doing
I guess no one is reading my posts. Food does not control human blood sugar. The homeostatic range of blood sugar (70 to 140 mg%) is under control of the hypothalamus. See numerous papers on this subject. You can find them through Google.
Roberto. You just have to keep banging away to break through. I keep on banging away, but one of my techniques is to keep switching the point of attack.
Thanks Malcolm. This food idea is so deeply ingrained but the data showing CNS control of blood sugar is huge (vagus nerve to liver, autonomic nervous system to pancreatic alpha and beta cells). Claude Bernard (1848) was the first to discover this connection. The food idea of control is not based on science but is supported by the food and diet book industry. Oprah’s book on controlling “diabetes” through diet far outsells my referenced textbook.
“the data showing CNS control of blood sugar is huge ”
Can you explain what this means at a practical level? If I eat a slab of cake my blood sugar spikes which causes damage. If a non diabetic eats the same cake their blood sugar is properly controlled. So how is blood sugar control not related to food? If I could press a button and stimulate my vagus nerve, for example, would my blood sugar be normal?
Good question. I will try to summarize, as it is a complex answer. (See Diagram of CNS control mechanism in the Puglianiello and Cianfiari editorial, Review of Diabetic Studies 2006).
Let me digress before I address the core of your question. See 2006 Jo. of Nutrition article
on rate of absorption of carbohydrates. I have this paper at the office and if you e-mail or post me again I will give the specific citation. Radioactively labelled glucose was given too 50 men and the time it took to get to the blood was noted. You can check this out but it was about 40 minutes. So, first of all, the notion that you “spike” or that orange juice or glucose pills can be given to treat hypoglycemia has been debunked.
As the Puglianiello editorial points out it appears that even “Type 2” diabetes has some element of defective hypothalamic control. The DCCT study of 1993 (Type 1 diabetics) supports this notion, as the duration of hypoglycemia varied in these young people. The greater their number of previous hypoglycemic episodes the more sluggish their “glucagon rescue” response. The worst cases requiring third party assistance. From my case experience some element of defective hypothalamic regulation is the rule in blood sugar disorders (Type 1, Type 2, Nesidioblastosis, Hypothalamic Hypoglycemia ).
Sadly 99 % of publications in the medical literature purportedly dealing with “Type 2” diabetes must be thrown in the trash heap. Not even in the massive (10,000+ patients) ACCORD trial of 2008 July NEJM did any one check the C-Peptide or do a direct insulin assay (my GTTIDG test for example) to rule out the primary hypoglycemic disorders (Nesidioblastosis, Hypothalamic (Spontaneous) Hypoglycemia, Insulinoma or other solid tumors fabricating insulin). As a result of this lack of caution 257 patients died and the study was stopped 17 months early.
To convince yourself of the lack of correspondence between ingested food and blood sugar you must do what I do at my office. You must place a Dexcom continuous glucose meter on your patient and try to correlate the blood glucose changes with meals. This is the best meter on the market (Do not use a Medtronics meter. Data is “massaged” in their “cloud” and not truthfully reported to the doctor.) It will miss about 25% of hypoglycemic episodes because it averages five one minute readings into a single point. As human blood sugar oscillates every 60 seconds approximately, many low readings will be “averaged out”. (The company refuses to discuss this …but this is another long story involving “tampering” by FDA with scientific instrumentation). .
I know this is a long-winded response but the complexity of the topic requires it. My advice is do a Dexcom study on all your patients and see what you get.
“To convince yourself of the lack of correspondence between ingested food and blood sugar you must do what I do at my office.”
Actually I just use my meter and the correspondence between ingested food and blood sugar is as obvious as the sunrise. There’s also a correspondence between the levels and the amount of sugar in what was eaten. Also, what is the practical implication of what you are saying? You seem to be saying what you eat doesn’t matter, which seems quite counter to experience.
I’m on HFLC Primal. Permanent ketosis. Sugar perfect. Of course food affects blood sugar. Millions of us are proving it. Avoid doctors. “Why” is not helpful to Type 11. We need actual understandable actions WE can do without going near them.
I understand your cynicism. However, just like other professionals, pilots, engineers etc….not all are alike. I wish patients could control their “diabetes” by themselves with “diet and exercise” and popular books….but it is not possible. The misunderstanding here arises from 1) inadequate classification of the blood sugar disorder (see previous posts). 2) The fact that blood sugar oscillates very rapidly….so a home meter cannot detect these changes reliably. 3) Inaccurate home meters. 4) Years of overwhelming misinformation given to doctors and patients.
I am also an insulin-requiring diabetic for the past 16 years, so I see things from both points of view. Even though the Dexcom CGM is not perfect…however,it is a step in the right direction. Although I encourage all patients to own their own Dexcom CGM… insurance companies will not always reimburse the patient. For example…Medicare will pay NONE of the $ 1400 cost. If managing blood sugar were that simple so that a patient could do this at home without a medical education (The “I know my body” syndrome)…then I could have spared myself 11 years of expensive education (and stress) after college.
Roberto Illa, M.D.
So you’re insulin-dependent. Yet you say “Glucose control has nothing to do with diets, ketogenic or otherwise.” I infer that you haven’t actually tried Dr Richard Bernstein’s very low carbohydrate diet to discover its effect on your blood sugar levels. Am I right?
You are right. I have not tried any diet plan. However, I have recently brought my blood sugar from over 400 mg% to 170 mg% and reduced my Lantus dose from 70 units per day to 8 units per day on the following: Pioglitazone 30 mg daily, Tradjenta 5 mg per day, Trulicity 1.5 mg sc per week. This new class of agents..GLP 1 agonists are great for true Type 2’s (no hyperinsulinmia. no random hypoglycemia) I use it in a few other settings but it is approved for Type 2 DM This group includes (U.S. available)
1. Byetta (older agent. higher rate of nausea etc.) Twice per day sc injection.
2. Byudureon once per week sc injection. Lower side effect rate than Byetta. Approved by almost all insurance companies.
3. Victoza . Once per day. About as effective as Bydureon but most patients prefer weekly injections.
4. Tanzeum 30 mg once weekly.
5. Trulicity 0.75 mg/0.5 ml and 0.5 mg/0.5 mg formulations. This is the most recent and most expensive. However, it appears to the most consistently effective and has the easiest to use pen device.
I have not had a great deal of luck with inhaled insulin (Afrezza) but it may have a place. It is a pre-meal short-acting insulin with a more rapid onset of action and a shorter duration of action.
For patients on Coumadin, or who have bleeding disorders, it may be possible to replace all their daily injected insulin with three times daily with inhaled insulin (4 unit and 8 unit doses available) and put them on a once per week GLP-1 agonist like 1-5 above. These most recent additions may completely change how we treat Type 2 and maybe Type 1 diabetes. Regrettably the company making the new inhaled insulin has not yet published Dexcom CGM studies on this agent in Type 2 or Type 1 patients. This is essential as a guide to making the switch, especially for Type 1 patients…..the most difficult of all.
Roberto Illa, M.D.
Dr Illa, you owe it to the people you advise to make a trial of a ketogenic diet.
To declare such diets ineffective spreads fear, uncertainty and doubt, and is, in any case, wrong
I have no C-peptide, I take 30 units of insulin per day and my HbA1c is 5.1%. If your fasting blood sugar is 170, your HbA1c must be near 8% – the DCCT follow-up http://tinyurl.com/q2n95yf suggests my risk of heart disease, stroke and cardiovascular death is at least 57% lower than yours, and my calcium score is zero …
I urge your to read Dr Bernstein’s Diabetes Diet http://www.diabetes-book.com/diabetes-diet/ On this diet, Ketostix suggest I make low to moderate ketones
Ketones have been repeatedly demonstrated to protect brain cells in hypoglycemic episodes since 1978 http://www.ncbi.nlm.nih.gov/pubmed/720768, and this article’s title “Protective Effects of Ketogenic Diets on Signs of Hypoglycemia” makes it clear that the rats exhibited far less hypoglycemic behavior when ketotic. I’m sure I lost many brain cells eating the absurd ADA diet (when my HbA1c was, like yours, near 8%), but since I started Dr Bernstein’s diet 17 years ago, I have not had a single hypoglycemic episode. Ketosis has restored my “hypoglycemic awareness”
These advantages make nonsense of your statement “Glucose control has nothing to do with diets, ketogenic or otherwise” It’s bombastic. You have made the extremely astute observation that 50% of Type II diabetics have been misdiagnosed and are suffering iatrogenic injury, you have absolutely no need to resort to hyperbole
My opinion regarding diets is not simply based on a personal experience but extensive reading and experience with more than 1200 patients. My “bombastic” statements and “hyperbole” comes from someone who assumes responsibility for the lives of others. An HgbA1c of 5.1 suggests that you are experiencing hypoglycemic episodes. The Taiwanese study done on 36,000 civil servants showed that “low” HgbA1c’s at that level was associated with an increase in mortality. As I recall this article appeared in Diabetes Care. A Type 1 diabetic without their own Dexcom CGM is like driving blindfolded.
1. . Prescrire Int. 2013 Jan;22(134):23.
Type 2 diabetes: increased mortality with low HbA1c.
Five-year follow-up data from the Accord trial once again confirm that it is
better to target an HbAlc level between 7% and 7.5% rather than a lower value, in
patients with type 2 diabetes and a high risk of cardiovascular events.
PMID: 23373083 [PubMed – indexed for MEDLINE]
2. Diabetes Care. 2012 Oct;35(10):2055-60. Epub 2012 Aug 1.
Low hemoglobin A(1c) in nondiabetic adults: an elevated risk state?
Aggarwal V(1), Schneider AL, Selvin E.
(1)Department of Medicine, Division of Cardiology, University of Colorado
(Anschutz Medical Campus), Aurora, Colorado, USA.
OBJECTIVE: To identify predictors of low hemoglobin A(1c) (HbA(1c)) (<5.0%) and
to investigate the association of low HbA(1c) with cause-specific mortality and
risk of liver disease hospitalization.
RESEARCH DESIGN AND METHODS: Prospective cohort study of 13,288 participants in
the Atherosclerosis Risk in Communities Study. Logistic regression was used to
identify cross-sectional correlates of low HbA(1c), and Cox proportional hazards
models were used to estimate the association of low HbA(1c) with cause-specific
RESULTS: Compared with participants with HbA(1c) in the normal range (5.0 to
<5.7%), participants with low HbA(1c) were younger, less likely to smoke, had
lower BMI, lower white cell count and fibrinogen levels, and lower prevalence of
hypercholesterolemia and history of coronary heart disease. However, this group
was more likely to have anemia and had a higher mean corpuscular volume. In
adjusted Cox models with HbA(1c) of 5.0 to <5.7% as the reference group, HbA(1c)
<5.0% was associated with a significantly increased risk of all-cause mortality
(hazard ratio [HR]: 1.32, 95% CI: 1.13-1.55) and of cancer death (1.47, 95% CI:
1.16-1.84). We also noted nonsignificant trends toward increased risk of death
from cardiovascular causes (1.27, 95% CI: 0.93-1.75) and respiratory causes
(1.42, 95% CI: 0.78-2.56). There was a J-shaped association between HbA(1c) and
risk of liver disease hospitalization.
CONCLUSIONS: No single cause of death appeared to drive the association between
low HbA(1c) and total mortality. These results add to evidence that low HbA(1c)
values may be a generalized marker of mortality risk in the general population.
3. Circ Cardiovasc Qual Outcomes. 2010 Nov;3(6):661-7. doi:
10.1161/CIRCOUTCOMES.110.957936. Epub 2010 Oct 5.
Low hemoglobin A1c and risk of all-cause mortality among US adults without
Carson AP(1), Fox CS, McGuire DK, Levitan EB, Laclaustra M, Mann DM, Muntner P.
(1)Department of Epidemiology, University of Alabama at Birmingham, 35294-0022,
BACKGROUND: Among individuals without diabetes, elevated hemoglobin A1c (HbA1c)
has been associated with increased morbidity and mortality, but the literature is
sparse regarding the prognostic importance of low HbA1c.
METHODS AND RESULTS: National Health and Nutrition Examination Survey III (NHANES
III) participants, 20 years and older, were followed up to 12 years (median
follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards
regression was used to calculate hazard ratios (HR) and 95% confidence intervals
(CI) for the association between HbA1c levels and all-cause mortality for 14 099
participants without diabetes. There were 1825 deaths during the follow-up
period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red
blood cell volume, ferritin, and liver enzymes and the lowest levels of mean
total cholesterol and diastolic blood pressure compared with their counterparts
with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was
associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45
to 9.63) after adjustment for age, race-ethnicity, and sex. This association was
attenuated but remained statistically significant after further multivariable
adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood
cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI,
1.25 to 6.76).
CONCLUSIONS: In this nationally representative cohort, low HbA1c was associated
with increased all-cause mortality among US adults without diabetes. Additional
research is needed to confirm these results and identify potential mechanisms
that may be underlying this association.
4. Diabetes Care 2005 Wen et al
Increased Mortality Risks of Pre-Diabetes (Impaired Fasting Glucose) in Taiwan
Chi Pang Wen, MD, DRPH1, Ting Yuan David Cheng, MS2, Shan Pou Tsai, PHD3, Hui Ling Hsu, MS1 and Shu Li Wang, PHD4 +
Author Affiliations 1Division of Health Policy Research, National Health Research Institutes, Taiwan, Republic of China 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 3University of Texas, Health Science Center at Houston, Houston, Texas 4Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan, Republic of China
See J shaped graph in paper showing that low HgbA1c's are associated with increased mortality.
Roberto Illa, M.D.
None of the studies you cite are of low-carbohydrate dieters.
A low HbA1c is the kiss of death if the diet contains much carbohydrate, remember that the tight control arm of the DCCT was littered with dead bodies – but ketosis preserves brain cells during hypoglycemia. If my blood sugar goes low (rare), I do not have the nightmare hypoglycemic symptoms I remember from when I was eating carbohydrates freely.
Gannon and Nuttall compared a low carbohydrate diet with a low fat diet in Type II diabetics and found greatly improved blood sugars: http://www.nutritionandmetabolism.com/content/3/1/16
You really should read Bernstein – please! Bernstein, by the way, is also a Type I diabetic and still a practicing physician at 81 years of age.
Thank you for responding to my cynicism. It arises from watching my husband’s journey through the NHS – our National Health Service. He is so full of pills and insulin and statins and diuretics for his diabetes and now heart condition, I truly wonder what led to what! His diabetes has been a real eye opener for me. The doctors are not curing it! Some years ago I was told I was pre-diabetic and put on the diabetic register. I don’t mind that – I get useful tests. But I control my sugar as I said with diet (and fasting which I forgot to add). My husband never gets hypos. Or hypers. But he is constantly at a high reading. After a heart incident, he got even more medication – for high blood pressure (which he doesn’t have) and cholesterol (which he doesn’t have). In the UK, on the NHS whatever happens to you, doctors have a “list” of things they have to do – EVERYONE gets the same treatment whatever your circumstances. That makes me avoid doctors thinking they might “treat” me from a “list” at all costs. That is not treatment, its mindless (supposedly science led) just ticking boxes for which they get paid. None of them are free from this thought-numbing control. They just follow the “list” and collect the cheque.
There is no diabetes in my husband’s family. But when he was younger he worked with Catalised Furniture Spray Paint in Africa that was banned in other countries because of the formaldehyde. It was after that he was diagnosed “diabetic”. But his diabetes has always seemed strange to me – not “normal” diabetes. If he mentions the formaldehyde to doctors here, they say “It doesn’t matter how you got diabetes – you just have it” . But if there are different kinds of diabetics as you point out on your website – then the treatment actually matters!
Dear Last Furlong:
I could not agree with you more. Here in the U.S. they are continuing to do “cookie cutter”
diagnosis and treatment. I just read a BBC article which says diabetes in the UK has increased 60 % in the last decade! See: http://www.bbc.com/news/health-33932930
The same thing is occurring in the U.S. But has your head of the National Health Service maintains ” it is eminently avoidable” (Dr. St. Johns). In other words its your fault, your husband’s fault, my fault (I am diabetic). Governments all over the world have been chanting the same mantra for decades instead of looking at the published scientific data. I have spent the last 15 years of my life reading the world literature from 1848 on. (See my textbook “Disorders of Blood Sugar” available from most online bookseller in the world, including amazon.uk). What emerges is a very different picture from what the NHS, ADA and pharmaceutical companies have been telling all of us.
1. “Diabetes” in its various forms (Type 1, Type 2, Nesidioblastosis, Hypothalamic Hypoglycemia) is most likely caused by a virus. It is NOT inherited. See Lancet studies from previous decade showing similar incidence in SE Asia as U.S. etc. even with people eating two bowls of rice per day…who are very skinny. British researches were the first to show that when families moved from Malaysia to the UK the incidence of Diabetes increased markedly in family.
2. You can’t control “diabetes” with diet and exercise. This is in every drug company package insert “as an adjunct to diet and exercise”. This is utter rot. There is an inexpensive novel (with references) about the early days of diet and fasting treatment of diabetes in children (“Breakthrough”) It is a true story. It shows that children treated at Dr. James’ clinic in New Jersey and Dr. Oschner’s (sp?) clinic in Boston uniformly died. There is NO ;published study ever, supporting the “life style” modification theory of Type 2 diabetes control.
3. Virtually no doctors in the US or UK do proper initial screening of “diabetics”….so most Type 2 patients are not Type 2 patients. If you doubt this look at their published data. The largest trial was the ACCORD trial. Published July 8, 2008 in the New England Journal of Medicine. They did not screen for Nesidioblastosis or “Spontaneous” Hypoglycemia (as you term it in Europe) but went ahead with “intensive insulin” treatment of presumed Type 2 patients. They did not even do a C-Peptide to determine if there might have been insulin overproduction (Insulinoma, Nesidioblastosis). Result: 257 patients (study size about 10,000 at 300 centers) were killed by their therapy with insulin. The study was stopped 17 months early because of the high death rate. The Rury Holman, M.D. et al study (Oxford) had a less dramatic but similarly bad outcome. Poor initial classification of the blood sugar disorder leads to disastrous outcomes ….like your husband’s and all the study participants.
As you can tell this is a scientifically and politically complex subject. Again, British researches have twice documented (Briish Medical Journal) the financial ties between our “thought leaders” and the Big Money from Pharmaceutical firms (and probably here in the U.S. ….the “evil” insurance companies……No exaggeration.)
Is Telemedicine legal in the UK yet? I recently added this feature to my practice so I can consult with patients over the internet. Works well. California law changed in November 2014 permitting diagnosis and treatment over the internet. (Reason: The government botched the new health care plan (ObamaCare) and there are not enough doctors. Doctors are underpaid and are quitting private practice etc 85% of private doctors in my county have closed their offices). Long-winded answer but see documentation in my book and in my YouTube presentations.
Roberto Illa, M.D.
Dear Last Furlong:
By the way, the last time I checked your National Health Service bans (=will not pay for) the use of newer and more effective medicines for “diabetes”. What diabetics are allowed to receive is decided by a national pharmacy committee and, as with insurance companies in the U.S., the determining factor is MONEY, not the patient’s health. During the BBC presentation I viewed today the woman interviewed was using an older insulin, as I recall. The following insulin types should NEVER be used: NPH, Humulin. Mixed insulins (say 70/30). See my book. NPH insulin levels rise, peak and fall off later in the day. This results in uneven blood sugar control. The only safe long acting insulin types are 1. Lantus (Toujeo the new branded form) 2. Levemir insulin. If there is reduction in kidney function (eGFR under 60) you must start with Levemir.
Oral agents to avoid like the plague: Metformin, All sulfonylureas (Glipizide etc. Many in this class in Europe). These pose a huge risk for hypoglycemia ….which you cannot always catch on your home meter, as human sugar changes every 60 seconds. To make matters worse 50% of all hypoglycemic episodes occur during sleep. If you are in REM sleep you can’t wake up.
Roberto Illa, M.D.
Forgive me, all of you knowledgeable people. It is not that I’m not reading what you post – just trying to understand. I read history, work in PR & am a mum! Anything I know about human body functions is through slow & painstaking research of my own. Every time I research something, I find there are arguments, counter arguments & a warren of rabbit holes that you can disappear down forever. I love Dr K’s blog and realise I am incredibly ignorant, so please bear with me & don’t assume I’m not reading what you say.
Dr Roberto – I have indeed read your posts, and Puglianiello and Cianfiari 2006, absolutely fascinating but I am insulin-dependent so sadly the strategy you propose is irrevelevant for me. Worse, carbohydrate intake beyond 30 g per day produces loss of glycemic control and vulnerability to acute hypoglycemic episodes. I I realise Type I is only about 10% of diabetics and the proportion of Type IIs who respond to your strategy may be quite high (I for one would be very interested to know how high) but my blood sugar is normal on Dr Bernstein’s low carb diet, which is to say it cannot be further improved. Horses for courses.
Each type of blood sugar disorder has its own therapy. (In the middle of my Gestational Diabetes YouTube presentation you will find the “key” I use.).
I would agree that you are a Type 1 diabetic if you have a very low (or undetectable) C-Peptide. I trust this test has already been done. I do not discontinue insulin on those patients (Type 1) who do not make insulin.
CNS control of blood sugar is not a debatable point. However, one needs all four parts of the mechanism for it to function. 1. Hypothalamus 2. Beta cells 3. Alpha cells 4. Liver.
I think we would all agree that in Type 1 DM ….beta cells are very few in number ….essentially absent. My observation (and that of Philip Cryer, M.D. See his book ” Hypoglycemia in Diabetes”.) is that recurrent hypoglycemia not only damages the autonomic nervous system (leading to “hypoglycemia unawareness”) but also damages brain, kidney, and pancreas. Thus, one must be very cautious in treating Type 1 patients to avoid hypoglycemia.
The main issue that, I believe, is overlooked in management is that the “Type 2” category is not entirely made up of Type 2’s (see table in YouTube presentation above). What is happening worldwide is that “Type 2” treatment is initiated (including sulfonylureas and insulin) on patients who have, on detailed testing, Nesidioblastosis or Hypothalamic (Spohtaneous) hypoglycemia. I have seen well over 300 patients of each these in my practice in the last 6 years. Together they (primary hypoglycemic disorders) outnumber the Type 2 diabetics. The C-peptide level is normal or high in these disorders.
Roberto Illa, M.D.
Thanks for that Dr Roberto – more than half Type II diabetics aren’t, now that’s really interesting!
BTW you say “Thus, one must be very cautious in treating Type 1 patients to avoid hypoglycemia” – when I ate the ADA way, I’d stall crash and burn below about 60 but on Dr Bernstein’s low-carb approach, my bg can go much lower without me losing my marbles – last low was 38 without loss of function, just a sense of ‘something’s wrong.’ Apparently, ketones spare blood sugar – I don’t know if I’ve still got all my white matter, but life is infinitely easier on very low carb, well worth giving up the croissants.
I have a diabetic friend who was ‘released’ from the hospital today after a ‘suspect’ stroke and to my astonishment, to say the least, I noticed that he had been given statins for ‘preventive purposes’. Some years ago I convinced him to keep away from those statins he was prescribed at that time and he has been very fit without medication on a LCHF regime.
So now again I tried to convince him to keep away from the stuff he was given and finally on the paper that came along with the statins he actually read: “Not for diabetics and not for people with high blood pressure.” This is exactly what he is suffering from so hopefully he will not touch that bottle of ‘medicine’.
Funny. Years ago, when my diabetic husband was prescribed the latest, greatest new statin, Crestor, by the nurse practitioner at his endocrinologist’s office, I questioned whether it was a good idea since Crestor had been shown to increase the incidence of diabetes. She looked at me like I was stupid and said, “what difference could it make? He’s already diabetic.”
I got the same reaction from my GP just after I was diagnosed with type 2 and he wanted me to go on statins.
This is typical of the horrible dilemmas that bad medical science create. Do you object and point out that being diabetic is an arbitrary point on a blood glucose scale, or do you sink back into the comforting fiction that the medical people know best (as I am sure they do in many areas), and are caring for your relative/friend in the best way possible?
I hope your husband doesn’t take statins..
Well, being a good obedient patient, he did take the Crestor samples she gave him, despite my advice to the contrary. But since I pretty much took over his medication regimen about that time, filling his multiple daily pill boxes for him each week, he didn’t notice when I quietly stopped giving them to him.
He’s now in a nursing home, and thank goodness, even though he clearly has the xanthelasma deposits on his eyelids, his doctors have not started him on any statins. He’s 77 years old and has multiple medical problems, so I keep an eye on what they prescribe and will raise holy heck should they decide they need to give him statins to “save him from an early demise.”
Dear Dr. Sjoberg:
I have found that most “strokes” and “TIA’s” are not the result of clot of embolization. In my experience these turn out to be “hypoglycemic” in over 90% of cases. See my YouTube presentations through my web site; http://www.chicodiabetesdoctor.com. A non-contrast brain MRI
will usually reveal “white matter lesions”. (These result for loss of brain cells due to low glucose or low oxygen. See papers by Mak Dulatzai, U. of Melboure. ) A Dexcom continuous glucose meter would be mandatory in addition to the non-contrast brain MRI. I agree with being suspicious of statin therapy.
Roberto Illa, M.D.
I saw your YouTube presentation on the connection between ‘neurological’ hypoglycemic events and brain lesions. Really food for thoughts especially considering my friend!
To get involved with such ideas at hand is though to start a fight against medical windmills to my experience. Anything outside the ‘consensus’ box is a red blanket for most practitioners.
Dear Dr. Sjoberg:
I hope you can arrange a non-contrast brain MRI and Dexcom continuous glucose monitor for your friend. I think you will be surprised by the results. Over the past 8 years we have accumulated about 1000 brain MRI’s showing “white matter lesions” which are the result of hypoglycemic events. One case presented on one of my YouTube presentations shows a woman under 40 yrs of age with about 40 % of her cerebrum damaged by hypoglycemia. She recovered. The very impressive brain MRI is shown.
Roberto Illa, M.D.
Hi are you saying if you have high blood pressure you shouldn’t take statins
A recent study (6 yrs?) from the U. of Texas showed a marked increase in diabetes in patients on statins. Besides, contrary to common belief (promoted by cardiologists and vascular specialists), most “TIA’s” and “strokes” are the result of hypoglycemic episodes and are not vascular or embolic in nature. Correct procedure: non-contrast brain MRI to find the “white matter lesions” caused by hypoglycemia (<55 mg%=neuroglycopenia) and do a Dexcom continuous blood glucose study.
Great article on the importance of glucagon in diabetes and the incredible work of Dr Unger, a friend just forwarded to me. I would only like to add that proof of this concept was in fact done in humans with type 1 diabetes by Dr Unger and Dr Philip Raskin and published in the 1970s. They used the hormone somatostatin to suppress glucagon and normalized glucose without insulin in type 1 diabetes. I had the great honor of working with Dr Unger for several years (I am a physician, researcher, and devoted to type 1 diabetes as I have lived with it for 33 years). I worked with many of the mouse models of type 1 diabetes that were suggested and when glucagon is taken out of the equation, the animals in fact do not have diabetes! (models include glucagon receptor knock out mice and diabetic animals treated with the fat derived hormone leptin to suppress glucagon-although leptin does more than just suppress glucagon). I even had the opportunity of translating the mouse leptin work into humans with type 1 and have personally given leptin to a dozen adults with type 1, the results of which are not yet publicly available. God bless Dr Unger! He has contributed more than any other to our understanding of glucagon physiology (and perhaps to all of metabolism with his contributions in the field of lipotoxicity).
Would the suppression of glucagon with somatostatin have been a good long term treatment for T1 (and maybe T2) without serious side effects?
I presume someone, somewhere, may have given this a bash. Not sure if it worked.
Certainly a lot of comment here to stimulate discussion, here are my ramblings.
Somatostatin vs glucagon links (at George’s Blog)
Somatostatin suppresses both insulin production from beta cells and glucagon from alphas so if you have fewer beta cells or none at all then somatostatin would lower glucagon relatively. Evidently it has some rather serious side effects.
And notice that a high fat diet > increased somatostatin. This too:
At diapedia, we read that T2DM is characterised by a relative lack of beta cells:
And interestingly in there “By the 1960s glucagon staining techniques and radioimmunoassay became available, showing that type 2 diabetes was characterized by glucagon excess as well as reduced insulin action, and leading to the bihormonal hypothesis” ie fifty years ago. Everyone seems to be a bit slow catching up with this idea.
Metformin is also now believed to suppress glucagon as much as anything else it does.
In Unger’s article
We see a good summary of same material covered in the video you linked and as has been pointed out here already, insulin plus a glucagon suppressor such as leptin normalises the ratio of glucagon/insulin and consequently blood sugar levels. The catch might be — how siginificant it is that eg per his fig 5, the actual levels of both are significantly lower in the pancreas than in a healthy individual? Assuming that they both have a job to do and an optimum concentration then perhaps it is still not a perfect solution ???.
Malcolm, where you say that this idea is new to many doctors, I think it might be helpful to emphasise the General part of the phrase “General Practitioner”. It seems more like a paramedical profession & definitely not a science based one. Jack of all trades, master of none. I hope that a good Endocrinologist would be more attuned to the issues involved.
Hi Dr Roberto Illa,
To quote from your previous comment:
“Glucose control has nothing to do with diets, ketogenic or otherwise. Think of the hypothalamus as a “room thermostat”. It senses, at intervals of seconds, if the blood sugar is too low or too high….and takes steps to control the blood sugar between 70 mg% and 140 mg%.”
1. Would it be correct to say that “room thermostat” is being dictated by what is going on in the body and the tools it uses to control blood sugar can become malfunctioned due to various factors?
2. In the “for patients” section on your website, it states:
“you will be requested to be moderate and sensible in the ingestion of carbohydrates.”
If diet has nothing to do with blood glucose then why is there advice to be moderate and sensible about carbohydrates?
Your last comment about the ‘impossible’ situation of the GPs triggered my philosophic mind while now looking out into the very inviting late sunny summer weather.
As far as I understand it as an ‘outsider’, but well acquainted with research in the basic natural science I think you put i well in this way.
” It seems more like a paramedical profession & definitely not a science based one. Jack of all trades, master of none.”
To me, today, I though see a tremendous amount of systematic research fraud, well buried in the medical dogma about diseases and their treatments which has been established by the medical corporate industry and today in an escalating and a very elaborate fashion. All this fraud is evidently set in the practice in the health care system with almost the sole purpose of maximising the profits for this industry.
It is evident to me that the GPs and most of the rest of us are severely trapped in this very sophisticated system and can not possibly escape from it without at the same time loosing our fundamental faith in this very system. Of course some GP’s may then turn cynics with the insight and just ‘follow the guidelines’ well knowing that the medication is doing more harm than good and thus violating their Hippocratic oath they once pronounce when they left the medical school if that still is the practice among the Anglo-Saxons.
So much for my morning philosophising – now to the practical side of life with todays toil in the garden in order to strengthen the parasympathetic part of my autonomous nerve system and then feel well to the best of my ability.
“To me, today, I though see a tremendous amount of systematic research fraud, well buried in the medical dogma about diseases and their treatments which has been established by the medical corporate industry and today in an escalating and a very elaborate fashion. ”
As I have said before, I think that is now sadly typical of a great deal of science.
I don’t think most of those involved are deliberately malicious, but the problem is that very few people are as knowledgeable as they like to pretend they are – there are things they know really well, and other things that know more hazily, and probably yet other ‘facts’ which are intrinsically hazy because they don’t really make sense. If you want to pretend you understand things better than you do, the best strategy is to tow the official line. So you see something that doesn’t seem to fit – say the advice to diabetics to eat mainly carbs – and you simply assume it does fit somehow. It is then nice to find a comforting explanation of some sort – such as the notion that complex carbs deliver the glucose at a more steady rate – and leave it at that.
This is backed up by a science establishment that has become increasingly hostile to those who are willing to poke with sharp sticks. You don’t go into science to be brave, and making a stand is dangerous to your career and reputation.
All this has made modern science very malleable to outside interests, such as Big Pharma, the radical Green movement and others with an axe to grind. The really cynical manipulators know how much of modern science is bluff and mere belief and hearsay. Giving out the odd knighthood, and organising a conference in an exotic setting can change important people’s minds more effectively than mere experimental facts!
Dear Dr Bailey:
How comforting to read your insightful comments. Simply as a result of making observations supported by published medical reports I have suffered slander from colleagues who believe they are following the correct guidelines (telling my patients not to return to me etc) and, even by the California Medical Board, which seems to have ties to some very powerful corporate elements (for example the sham peer review board of Blue Shield). For criticizing the use of HgbA1c (useless in diagnosis and follow up of “diabetics”) MIEC malpractice insurance company of California cancelled my insurance policy in the middle of a malpractice suit (which I won handily…. as it was a fraud). This is but a small fraction of what I have endured.
If a doctor dares to question these powerful financial and political entities in service of their patients and scientific truth, he/she, puts their career and reputation in danger. The people who control medicine now will stop at nothing. They are in state and federal government, run the health insurance industry and malpractice insurance companies. I have been in medicine now almost 50 years, and I have never such ruthlessness in the effort of keeping doctors in the dark.
Roberto Illa, M.D.
Roberto. Sadly, the ruthlessness continues.
You are correct. Few us seem to admit to this massive corporate mind control. Most follow the ADA guidelines like sheep.Those who dare say “The Emperor has no clothes” (=the published literature does not support the dogma put forth by our “thought leaders”) are vilified. For the past two years the British Medical Journal has published the corporate financial connections of the powerful among us (leaders of the ADA etc) and how they prevent authors with challenging opinions from being published. Last year myself and my colleague (M.D. & PhD) submitted a paper to a Clinical Diabetes journal. Only R.N.s reviewed our paper and rejected it. They did not believe hypoglycemia was important.
Roberto Illa, M.D.
I’m getting a bit confused. Dr K you’ve certainly begun a meaningful discussion here, and there are some very very interesting comments forthcoming. But can you, or anyone else put something short and sweet (ok not necessarily short) in layman’s terms as to what it all might mean if you are a pre-diabetic (possibly) and want to know what to actually do about it all, apart from LCHF etc. I don’t understand all the ins and outs of the medical side of things, which I would imagine not many patients (apart from the people who write on this blog) do. Thanks in advance. It’s a tall order I know to put all these insights into layman’s terms, but if anyone can do it, someone on this blog can!
Well, ‘apart from LCHF’ I really don’t know.
For me there is a logic in avoiding food that is increasing the blood sugar and insulin levels which are both attributed to the, HC ,High Carb recommendations which are current. If you are healthy I don’t think there is a big problem with any carbs in your diet but if you are stuck in a pre-diabetic state you are most probably very vulnerable to these carbs,
Plenty of options for treating diabetes apart from LCHF: foot amputation; drugs; constant monitoring; etc…
I’m so fascinated by this but I have to say I’ve got a bit lost too. I always thought one of the advantages of eating low-carb was that you didn’t get the insulin surges that you would if you ate high-carb. However, Dr Illa’s research seems to suggest that this insulin surge is nonsense and that actually the food you eat has nothing to do with blood glucose control.
I definitely need the dummies guide to this way of looking at it all!
I feel really crumby eating high-carb. I get spots, my skin dries out, I bloat, I get afternoon tiredness, headaches etc. Surely, this has to be somehow related to insulin highs & lows?
Your spots etc are the result of the power of suggestion. The only way to put an end to your doubt and confusion is to do a Dexcom study on yourself and your patients and note the relationship to meals. I have done this with my staff and patients. We have done over 1200 Dexcom CGM studies. Commonly patients come back to the office with the comment “I ate and my blood sugar actually came down”. Even with its limitations (missing about 35% of significant hypoglycemic episodes….it is the best meter….perhaps the only meter that will “tell the truth”. Because human blood sugar (under the influence of the hypothalamus) oscillates every 60 seconds approximately you absolutely cannot get accurate data from your home glucose meter. If a patient has no blood sugar disorder of any type the readings will always stay between 70 and 140 mg%. Someone with say, Hypothalamic (Spontaneous) Hypoglycemia may only show “spikes” above 140 mg% several times per week. This is because the meter has “missed” the brief low (may be 60 seconds or less) and what we see is the Somogyi rebound (Michael Somogyi c. 1938. Proceedings of the St. Louis Medical Society.) So the spikes are signs that a low sugar (under 70 mg% has occurred).You can often verify this by assaying for glucagon at the same time. Depending on how good you lab is the glucagon elevation may be apparent. Of course it is occurring in response to a low sugar (the release triggered by the hypothalamus….which monitors your sugar every few seconds). So, it acts like a “smoking gun”. You may have missed the actually low sugar but glucagon is usually elevated after the event, and being a large molecule like insulin will be in the circulation up to an hour later. This is why I designed the GTTIDG test (Fasting, 1/2 hr, 1,2,3,4 hrs) sampling glucose, insulin and glucagon. It is a modified Glucose tolerance test. No glucola administration is necessary. I asked the lab to let the patient eat whatever they would like. A measured carb load is worthless and inconvenient (=glucola). People sick with some form of blood sugar disorder are not sick because they are consuming glucola at home. In addition the ADA guidelines for diagnosing diabetes, once you understand “homeostatic” control (like your serum sodium and potassium) are complete idiocy.
Hello Roberto. I am reading all the responses, and struggling to understand it all. You keep referring to some calibrator and saying it out performs the typical glucometer that us mere mortals have to hand in order to check our glucose levels. Some of us have forked out to buy our own, others get them supplied for free from the surgery, some, like myself have been gifted them for free from the manufacture because they know we are going to pester our GPs for scripts to get the strips from the pharmacy. Ching ching.
So, my question is….what practical advice do you have for those of us who cannot access the ‘better’ calibrator, in order to monitor, and thus manage, our type 2 to the best of our ability, with the limited resources we have? Thankyou for your great articles, and I look forward to your answer.
Fortunately I don’t have diabetes, nor even raised blood sugar (once I gave up the statins), but I certainly found all the details in the discussion of this topic very confusing – so I agree, it would be extremely useful if Dr Kendrick could add a summary of it all and what in means in practice.
Thank you very much indeed Dr Kendrick and Dr Illa and bloggers for this fascinating post and responses. It seems we are beginning to understand a little more especially that so called diabetes is much a more complicated beast than we ever thought. Like David Bailey I too would be grateful for a summary in English to help understanding the issues. It is good to struggle to understand things but some help to aid digestion without resorting to pills is even better.
I am very grateful to you for bearing the pain from your peers and colleagues. You are putting patients first. Blanket computerized solutions operated by zombies are not acceptable. Thank you.
Sue, I feel a bit like you at the moment, and earlier on this week I requested one of the excellent bloggers to try to simplify all of this amazing information for those of us struggling with these concepts.
In the main I think I am following the theme, but I am rather fearful that this ‘new’ knowledge is tending to show that the medical profession has been working on an incorrect understanding of diabetes type 2 for many decades. What a revelation.
The truth is….some of these credible explanations are far from ‘new’, but have been brushed under the carpet in order for Big Pharma to continue in their lucrative ways, via our Medical and Nursing schools regurgitating the old status quo ad infinitum. I include my own learning throughout my Nursing career…..I did try to question the way we managed type 2, but found my questions fell on deaf ears, and much of the terminology was unfamiliar to my peers, and, indeed, difficult for me to understand. Anyway, who has the time to question what has been accepted as gospel….there’s the daily chores to do, admissions, discharges, theatre schedules to meet….beds to make….food to serve up, the medicine rounds to do etc etc. It is just so much easier to say….”well that’s what we have always done” …no one got/gets disciplined for following policy, but questioners are quickly vilified for daring to interogate the norm.
That is why I follow this blog….I may not understand all that these generous people are sharing with us, but I support their brave actions in attempting to show that there may actually be a better way of managing type 2.
I pray that their messages will be heard and acted on. That in itself is a very tall order.
The BBC today reports that Diabetes UK have issued warnings of a 60% increase in diabetes in the past decade. They say it has ‘soared’, and their ‘expert’ claims 90% of the increase is due to obesity. That same ‘expert’ is unable to account why there has also been an increase in type 1 diabetes, presumably amounting to 10% of the surge. Hmmm, it couldn’t be statins could it? Oh no! Heaven forfend!
Sherlock Holmes would have said to Dr John Watson when an ‘expert’ doesn’t have an answer ‘When you have eliminated the impossible, whatever remains, however improbable, must be the truth’.
Is Inspector Lestrade the expert from Diabetes UK?
Or Dr Moriarty, perhaps?
I’m glad to read that I’m not the only one struggling with this. I am reading all the posts too – but I am finding some way beyond me. I read somewhere once, that if you can put something you have read into your own words, it means you’ve understood it. I haven’t quite managed to do that here yet! 😳. Keep blogging away, bloggers.
FYI. Another report linking Type 1 diabetes to viral infection.
Semin Immunopathol. 2011 Jan;33(1):45-55. doi: 10.1007/s00281-010-0207-y. Epub
2010 Apr 28.
Enteroviruses in the pathogenesis of type 1 diabetes.
Tauriainen S(1), Oikarinen S, Oikarinen M, Hyöty H.
(1)Department of Virology, Medical School, University of Tampere, Biokatu 10,
FIN-33520, Tampere, Finland.
The question if enteroviruses could cause beta-cell damage and type 1 diabetes
has become more and more relevant when recent studies have provided new evidence
supporting this scenario. One important observation is the recent discovery of
IFIH1 as a risk gene for type 1 diabetes. This gene is an innate immune system
receptor for enteroviruses offering one possible mechanism for the diabetogenic
effect of enteroviruses. This is further emphasized by the observations
suggesting that the innate immune system is activated in the pancreatic islets of
type 1 diabetic patients and that the innate immune system is important for the
defense against the virus and for the regulation of adaptive immune system.
Important progress has also been gained in studies analyzing pancreas tissue for
possible presence of enteroviruses. Several studies have found enteroviruses in
the pancreatic islets of type 1 diabetic patients using various methods. The
virus seems to be located in the islets while exocrine pancreas is mostly
uninfected. One recent study found the virus in the intestinal mucosa in the
majority of diabetic patients. Enteroviruses can also infect cultured human
pancreatic islets causing either rapid cell destruction or a persistent-like
noncytolytic infection. Combined with all previous, epidemiological findings
indicating the risk effect of enteroviruses in cross-sectional and prospective
studies, these observations fit to a scenario where certain diabetogenic
enterovirus variants establish persistent infection in gut mucosa and in the
pancreatic islets. This in turn could lead to a local inflammation and the
breakdown of tolerance in genetically susceptible individuals. This is also
supported by mouse experiments showing that enteroviruses can establish prolonged
infection in the pancreas and intestine, and some virus strains cause beta-cell
damage and diabetes. In conclusion, recent studies have strengthened the
hypothesis that enteroviruses play a role in the pathogenesis of type 1 diabetes.
These findings open also new opportunities to explore the underlying mechanism
and get closer to causal relationship.
PMID: 20424841 [PubMed – indexed for MEDLINE]
Roberto. Thank you for taking the time to provide all of this information and provide a very interesting discussion. I have not said anything much, as I do not want to distort what is being said. I think it would be good for me to communicate separately with you to try and put your ideas and thinking into a blog that looks at ‘alternative’ ideas in diabetes. I am not sure, for certain, what is going on in this area – but I do know that he current model is failing almost entirely.
Dr Illa, I like people who think outside the box, and your idea that people have hypoglycemia episodes so short that they don’t show with CGMs is interesting. However, when you say IR doesn’t exist and blood sugar has nothing to do with food, I question the rest of your statements. Of course the CNS is important in controlling BG, but that doesn’t mean IR doesn’t exist and food isn’t important. Diabetes is complex, and many factors are involved.
Can’t remember if someone else posted this link, but it seems germane to the glucagon topic of this post.
Hi Dr Roberto Illa,
None of my previous questions has caught your attention. Here is another one.
You stated in your comment:
“CNS control of blood sugar is not a debatable point. However, one needs all four parts of the mechanism for it to function. 1. Hypothalamus 2. Beta cells 3. Alpha cells 4. Liver.”
If I understood it correctly CNS DOES need functional beta cells, alpha cells and liver to control blood sugar. Do you think diet has no imapct on the function of alpha cells, beta cells and liver? As I understand alcohol and sugar has quite a bit of effect on the liver.
Yes. An engineer patient of mind describes the system as having four “servomechanisms”. In a healthy individual with all parts working the control is smooth and the blood sugar never goes below 70 mg% or above 140 mg%. To prove this to yourself connect a Dexcom continuous glucose meter to a perfectly healthy patient. You will note that day and night….the readings never exit this homeostatic range. Thus, if you get an “abnormal” Dexcom report….readings too high or too low…..homeostasis (imposed by the hypothalamus) has failed. This is the constant principle you see with other electrolytes or minerals; viz Na+, K+, Ca++ etc. Why should the main food source for cells (besides oxygen) be any different? Seen in this light “food/diet control of blood sugar” is a bizarre idea. Diet and exercise as treatment for “diabetes” has never worked in 100 years. (See the referenced novel “Breakthrough” $9 on amazon.com etc. Children treated at Dr. James’s clinic in N,J. and by Dr. Joslin in Boston by calorie restriction died.) What makes diagnosis and treatment of blood sugar disorders challenging is not only the misinformation put forward by the ADA, FDA and all the university professors but the fact that hypothalamic injury, liver injury, pancreatic and renal injury are present to varying degrees in most patients. If you think it is as simple as “Type 1 DM, Type 2 DM” you are dreaming or are not doing the required testing to properly define your patients problem(s)
I will take this opportunity. to list the references I promised to the readers:
“The Rate of Intestinal Glucose Absorption Is Correlated with Plasma Glucose-Dependent Insuinotropic Polypeptide Concentrations in Healthy Men. Wachters-Hagedoorn et al. The Journal of Nutrition June 2006 Vol 136. no 6: 1511-1516.
“Hypothalamic glucose sensing: making ends meet . Routh VH et al. Frontiers in Systemss Neuroscience December 2014. Vol 8. Article 236. Review article.
“Central control of glucose homeostasis” Puglianiello A. Cianfarani S. The Review of Diabetic Studies. Editorial 2006 3:54-60
” Approach to the patient with spontaneous hypoglycemia” Martens P and Tits J European Journal of Internal Medicine 2014 June 25(5): 415-21.
See my textbook Chapter 8. The Role of the Central nervous system in glucose control
“Disorders of Blood Sugar”.
Roberto Illa, M.D.
Dr. Kendrick, I don’t blame you at all for the cynicism. But the older forms of (i.e. human, Regular and NPH) insulin are actually the cheapest of all hypoglycemic agents by far, and also the most effective and physiologic. For diabetics the name of the game is to prevent or reverse diabetic complications — neural and vascular damage. For T1DM and T2DM it is sometimes possible to reverse the condition itself by beta-cell recovery, using the proper methods.
Meanwhile, there is nothing so non-physiologic as a diabetic animal with glucagon suppressed. Blood glucose regulation enhancement is transient even under artificially constrained conditions. The brain, and hence life, is partially dependent upon proper function of alpha cells and hepatic signaling in the very short term — hence, the efficacy of the “liver shot” as the pugilist Hail Mary.
Drug companies also get sued regularly. Their caution in this case is prudent for all.
For something much more practical and exciting in actual clinical potential, check out “hepatic-directed vesicle” (HDV) insulin. This at least offers an avenue to restore the role of postprandial clearance of BG from portal vein to liver in diabetics. It is an enhancement of the efficacy of exogenous insulin, extending it from peripheral-tissues-only to liver. A small (family-run) biotech company is attempting to bring it to market:
Anyone truly interested in understanding of diabetes would do well to follow this carefully.
I might add that, even in T2DM, muscle-tissue insulin resistance is not universal and never exhibits any progression with that of hyperglycemia — it is a constant. It is genetic, and generally stable from age 20 (or younger) onward. IR is not a driver in any form of diabetes — the basic research community has long recognized this. Diabetes in all known forms is a condition of abnormality in beta cells — insufficient population due to autoimmune attack in T1DM, progressively abnormal morphology and apoptosis in T2DM, and genetic abnormality affecting beta-cell function in MODY. IR is a red herring.
“For T1DM and T2DM it is sometimes possible to reverse the condition itself by beta-cell recovery, using the proper methods.” So what are the proper methods, Ken?
I will reply to your post first. I am happy this site has so much activity. We have to “turn diabetes on its head”. You are correct. There has been massive misinformation given the public. “Follow the money”. It is supported by the food/diet industry and Big Pharma. Two articles in the last year published in the British Medical Journal show the financial links between our “thought leaders” and the Big Money.
About the meter problem. This is a big one. So Medicare and the insurance companies as of three years ago began pushing patients to buy foreign made meters. We have used Accu-chek for 10 years. It is accurate. This week we compared Accu-chek with two newer meters (cheaper and pushed by insurance companies). The Accu-chek read 96 mg%. The newest meter read 151 mg% and another read 155 mg%. ALL ON THE SAME DROP OF BLOOD at exactly the same time.
Yes, that’s right…..your insurance company promoted home meters are garbage. Or so it seems. Maybe occasionally they will get it right, …..not likely. Whenever you seen Washington or for profit companies enforcing the use of a product, glucose meters or electronic health records….beware and get ready to be ripped off….or worse.
So….if, as I have discovered human blood sugar oscillates every 60 seconds….that means your home meter will not even remotely reflect how you are doing with control. Sad but true.
(See numerous case studies on my YouTube presentations or in my textbook.).
The people who you consider “mainstream” have got it so wrong and will lie to keep their rice bowl full.
Hypoglycemia (not hyperglycemia) is the main cause of renal failure among those considered “diabetics”. They are not 50% of the people being dialyzed. Almost 50% of these “type 2” patients are NOT. They have Nesidioblasosis and Hypothalamic Hypoglycemia. The low sugars they experience are frequently hard to find….but dangerous. This is why you need a Dexcom CGM study in your patients. The low sugars may occur as infrequently has once per week. I have a retired faculty member at the local university as a patient. It took two Dexcom studies to find the sudden (and infrequent) hypoglycemic episodes that caused him to feel faint and fall.
Unpublished data: We have been treating renal insufficency with DPPIV- inhibitors at high dose for about 5 years and have been able to reverse renal insufficiency and hypoglycema in HH patients with these agents. (No they are not just for DM….they are nuclear ligands.) See my textbook for case report on “David” who week took off of dialysis. eGFR from 3 to 60 (norma) in 1 1/2 years. Tough case as he had Type 1 DM also and suffered from mental retardation (birth injury?) We have reversed about 100 cases of milder renal insufficiency with this oral medication. Exciting stuff.
Roberto Illa, M.D.
Roberto, it is very kind of you to respond to me in such detail.
How about me recalling what I was taught many years ago, which I think has a significant co-relation to these topics of glucagon and hyper/hypo glycaemic attacks, and at a time when we did not have access to instant read-outs from the magic glucometers!
In a medical emergency, whereby a known diabetic was very unwell, but still conscious, one had to presume they were having a hypo, and to get glucose into them asap.
Now, in these days of sophistocated toys, the management would be to question the patient if they were type 1 or 2, if they had eaten recently, if they had taken or skipped insulin etc then….prick their finger., and no doubt give glucose, or in the ward setting, glucagon if unable to consume food.
However…. I was taught that the main objective was to avoid hypos at all costs….mainly to minimise brain damage. By giving glucose to someone who was possibly hypo, you would be helping them, but to give someone who was possibly hyper, some extra glucose would not cause much harm, because in either case they would be transported to a clinical setting, whereby a hyper would be dealt with. By faffing on wondering whether to give a diabetic extra glucose whilst experiencing a hypo, the damage is irreversible to the knocked out brain cells.
I now think the damage to many cells in the body, in particular the kidney and pancreas, ought to have been considered.
We have become obsessed with high levels of blood glucose, with its serious, life changing consequences, whilst simultaneously relegating the dreadful effects of hypos, and their serious life changing consequences.
Hypos = a real medical emergency, maybe irreversible.
Hypers = a chronic situation with long term serious consequences.
I understand from your answers that diabetics are experiencing many instances of hypos which go unrecorded, and are causing very serious consequences, but are being blaimed on hypers.
Is that a fair assement, and if so, what are we to do about it?
Yes, you understand what is going on. It sounds like you have a medical education. Hyperglycemia is bad (cataracts, increase in tendon problems …arthritis) but hypoglycemia by depriving cells of one of the essential nutrients (glucose) kills cells rapidly. Brain cells need oxygen and glucose. It is interesting that the brain MRI of a drowning victim with its multiple white matter lesions resembles that of someone who has undergone severe hypoglycemia. Younger patients can experience multiple hypoglycemic episodes without showing the white matter lesions……most of the time. However, if the episode lasts long enough you will see the lesions on the MRI.
To fix these misconceptions about diagnosis and management of blood sugar disorders I have written (self-published) several textbooks (“Disorders of Blood Sugar”….4th Ed being the most recent.) In addition I have prepared several YouTube presentations which present cases and literature data. See my website: http://www.chicodiabetesdoctor.com.
As with others, I have become increasing disturbed with this discussion. For example, comments like food (carbs) do not matter just do not match my own experience and those of others who successfully managed their diabetes with low carb or ketogenic diets. So I got Dr. Illa’s book and started digging. Here is what I found compared with Dr. Bernstein’s approach.
Dr. Bernstein: Goal is to minimize medication by eating his 6-12-12 diet (low carb high protein) where the numbers refer to the number of carbs per meal. Insulin, if needed, generally consists of a long acting basal dose and a per meal dose matched and timed to the number of carbs and protein in the meal.
Dr. Illa: Goal is to optimized medication using a step-wise process based on lab tests and then on the patient’s home glucose readings. Dosages are not dependent upon activity or food and patients should eat normally with a sensible choice of carbs.
Dr. Bernstein: Primary medications prescribed: metformin and insulin. Other oral agents are generally avoided especially the agents that increase insulin production.
Dr. Illa: Medication prescribed: all agents (some exceptions) and especially agents that that increase insulin production.
Dr. Bernstein: Glucose targets – blood glucose 83 mg/dl (4.6 mmol/l) and HbA1c between 4.2 and 4.6. In particular he emphasizes that blood glucose should not be allowed to vary much from 83 mg/dl. In other words it should be mostly constant. No spikes.
Dr. Illa: Glucose targets – blood glucose between 70 mg/dl and 140 mg/dl (3.9 mmol.l to 7.8 mmol/l). HbA1c not relevant.
Based on what I have read I can see how both their prescriptions could be better than the ADA approach and perhaps in some cases even overlap in terms of results.
That said I am still far more comfortable with Dr. Bernstein’s more conservative approach especially when it comes to longer term treatment and the avoidance of diabetic complications.
OldTech, please do not become disturbed with any conversation. Disagree, argue your case….please do. My hope, at least in part, was that this blog could become a place where people felt free to put forward new ideas, different thinking, and be ready argue back and forth. A researcher who I communicate with regularly feels that science should be about playing tennis, where ‘opponents’ batter ideas back and forward. However, most of science has become like golf, where people play their own ball and do not engage with other ‘players.’ One of the rules of scientific tennis, however, is that you must play the ball – not the man.
Perhaps I used the wrong word, but for those of us who are also patients the reaction on a personal level is OMG. Have I made the wrong decision? So far my data tell me no. Still I now have to ask the question.
On an academic level I also had a similar reaction since the data seems to conflict. Saying that “Glucose control has nothing to do with diets, ketogenic or otherwise” seems way too strong a statement for the evidence.
I do agree that the statement should be true for people who have a ‘normal’ metabolic system. And I also agree that glucose homeostasis still has an impact on blood glucose levels regardless of diet. However, the evidence also seems to show that for people with damaged metabolic systems, diet can have an significant impact on glucose control and resulting damage to the body from high glucose.
The lack of correlation of food intake to serum glucose is more striking in those patients with diabetes and related disorders (Diabetes Types 1 and 2, Nesidioblastosis, Hypothalamic Hypoglycemia, Insulinoma and other solid tumors fabricating insulin or insulin-like molecules).
Those of you who cling fervently to the food theory need only watch the readings on the Dexcom CGM after you or your patient ingest food. (See http://www.dexcom.com). You will lose your “religion” promptly. There have been no published studies in 100 years that show that “diabetics” (or those classes or patients who appear to have diabetes) uniformly improved with diet and exercise. In the largest study I have seen some patients improved temporarily (for a year or so) then relapsed to worse sugar control. For the past 8 years I have kept records of patients with blood sugar disorders in a relational database and my office has done over 1000 Dexcom CGM studies. You must do the study. An exchange of words will not do. In my community (Butte and Shasta Counties, California) I have not seen a single Internist, GP, NP or PA perform a C-Peptide study in 8 years. This would be the most basic test to rule out or in the diagnosis of Type 1 diabetes. Neither have any of the 50 or so doctors, or mid-levels in the community done timed insulin/glucose/glucagon assays. Nor have they done any Dexcom CGM studies. (available since 2006). If your community is like mine, none of the universities (UCSF, UCDavis, Stanford U.) or HMO’s (Kaiser, Sutter, Ampla) done any relevant work on patient to correctly define their status. “People believe what they want to believe” Emerson. So, if you don’t look……you won’t see a problem (See documentation in my textbook and YouTube presentations).
Roberto Illa, M.D.
Dr. Illa thanks for taking the time to reply. After thinking about what you are saying I now think that your view that food (carbs) do not matter is a semantic difference. So I would expect you to argue that a GTT that results in a rising blood glucose response due to ingesting 100 g of glucose is because that is what the CNS ‘ordered’ and that the glucose did not directly cause the response.
From this perspective I would have to agree that you are technically correct. However, if the patient does not take the GTT then there will be no rising blood glucose response. It is in that perspective that we are arguing that food does matter. We are carb intolerant and if we avoid carbs we can better manage our blood glucose.
This is a common problem in analysis when we can only measure some variables and the behavior is not fully understood. One common solution to this problem is for the analyst to infer the existence of hidden variables and give them names. You say it is the CNS and we say it is the food, but in reality it is the same phenomenon with different emphasis and different names.
This, for example, is what insulin resistance is all about. It is a name of a hidden variable that helps to explain why a patient would have both high blood glucose and high insulin levels. So yes, you could argue that insulin resistance does not exist, but then you will need another name to explain why a patient would have both high blood glucose and high insulin levels.
Dear Old Tech:
See my last response to your post. You state…..” It is a name of a hidden variable that helps to explain why a patient would have both high blood glucose and high insulin levels.”
There is no insulin “resistance”. The “clamp studies” on which this concept is based (1976 onward) used glucose testing intervals of about 5 minutes. I have found that human blood sugar oscillates every 60 seconds. High insulin levels and, apparently concurrent high glucose levels are routinely seen with home glucose meters and the 4 hour modified Glucose Tolerance Test. If you add Glucagon assays to the GTT you will find in 90+ percent of the time high Glucagon levels which indicate that hypoglycemia has occurred. This is what I call the “smoking gun”. If you then do a non-contrast MRI you will find “white matter lesions” in most older patients. These are the result of the hypoglycemic infarcts that have occurred (in your “insulin resistant” patients). Add a Dexcom CGM and you will find that the blood sugars are not in the homeostatic range but “bouncing” (“Somogyi rebounds”).
I am not surprised that none of the doctors that are on this blog go through this testing of their patients but blithely accept “Tooth Fairy” theories of “insulin resistance” and “food control” of blood glucose. The Big Money controls all news outlets, most university authors (See BMJ articles on this topic.)
Roberto Illa, M.D.
OldTech, you took the thoughts right out of my head! I’m with Bernstein, I have no beta cells, Illa’s plan can’t work for me. But if I was Type II and deteriorating, I’d be over in Choico like a shot because what Illa’s come up with is that half Type IIs aren’t Type II at all but rather overproduce insulin unpredictably and are better treated by avoiding brief hypoglycemic episodes and supporting the re-growth of beta cells. It’s a breakthrough which could be life-saving forr about half of all diabetics. I’m not one of them, and I think IIlla’s credibility would be greatly enhanced if he didn’t dismiss diet as unumportant – it’s of paramount importance for the other half. Like moi.
You are correct about Type 1’s. I do not have a “solution” for Type 1 diabetes. No one has. The first thing I order on a patient is a C-Peptide. If this shows a very low endogenous insulin production….they are Type 1. I do not stop their insulin. How do I proceed? I always use a Dexcom CGM to detect any lows. It is easy to miss the Somogyi episodes (low followed by rebound) with a Type 1 patient. If at all possible I insist the Type 1 patients have their own Dexcom device for their own safety. No Type 1 is safe without their own Dexcom device.Most non-Medicare, non-Medicaid plans will buy one for you. Over the past decade I have found that Type 1’s coming to my office were taking too much insulin in just about every case. I have managed to reduce their total daily insulin in all cases. A study from the U.of Texas showed that Victoza (approved for Type 2’s) was helpful in decreasing insulin need in Type 1’s. I have started using this and found it useful in about 50% of my Type 1 patients. Following Dr. Donald Bell’s paper of 2004 (U. of Alabama) I have been trying Pioglitazone in Type 1’s (for beta cell regeneration). I have found success in only about 1/3 of patients. (By the way, a 10 yr follow up showed no bladder cancer association with pioglitazone. This was just lawyers looking for money). As for diet in Type 1’s…..I don’t believe the contribution is significant…….except that…..I urge my Type 1’s to eat on a regular basis. If the liver is depleted of glycogen and you have an episode of hypoglycemia this is dangerous, and the episode will last longer with attendant damage to brain, kidney and pancreas (the threat here for Type1’s is loss of glucagon-producing alpha cells….with loss of ability to rebound from hypoglycemia. See Dr. Philip Cryer’s book “Hypoglycemia in Diabetes” and the 1993 DCCT study on Type1 diabetics using short-acting insulin preparations in the New England Jo of Medicine).
Roberto Illa, M.D.
Thank you for your reply to Jennifer and also to NY on 18 Aug at 5.24pm. These are very interesting to me. Sorry to be slow in the uptake I have to look up some medical words.
Very occasionally I go low but my GP insisted that this could not happen since I was not on any drugs apart from the odd painkiller. I was told plainly I was cheating. When I asked about the accuracy of the monitors they laughed at me. This happened at several diabetic reviews.
In order to get a handle on accuracy of meters I ran two monitors side by side for three months using the same blood drop at the same time (at my expense). I was surprised to discover that one meter was consistently higher than the other by one mmol on average but the range of the difference in readings was between zero and two mmols – far too high for comfort.
I ended up using the monitor where the results over 8 weeks and 12 weeks before my HBA1c was the closer to my HBA1c results. This comforted me at the time. Alas if you are right, and I suspect you may well be, I consoled myself with two lots of rubbish results.
Thank you for your explanation about the different versions of T2 diabetes. This is very helpful.
You have explained what you have found is going on and it is scary. Rest assured I shall read your references. I am not too happy about what I am learning but it is better to know what is going on and make an informed decision.
Thank you Dr K for this blog and especially for Diabetes is not a disease but a symptom. I registered that the first time I read it!
Hi Malcolm – Like a couple of people (maybe more!?) here I have read all the comments and am a little confused. Are you able to revisit this in a detailed comment or follow up blog. I find Dr Illa’s comments insightful and provoking but am struggling to understand overall. Thanks so much. Claire D.
Hi Dr Roberto Illa,
Thanks for your response and the references.
I think when the homeostatic mechanism breaks then many factors come into play when it comes to treating a condition. Diet might not be a treatment for diabetes but there is a significant number of people who have clearly demonstrated that restricting carbohydrates greatly helps in managing their diabetes and avoiding/reversing its complications, it has also been shown in many studies.
When one becomes allergic to some foods they do much better if they avoid those foods. Similarly, if the body can’t handle glucose properly, where is the logic in carrying on pumping it with carbohyderates? It reminds me of Dr Malcolm Kendrick’s comment:
“On a certain level this is just common sense. You have problems controlling blood sugar levels. Well STOP eating so much sugar. By sugar I mean all carbohyderates. How hard can this be to understand, exactly.” (July 19 at 2.35pm)
Your website also states that you expect your patients to refrain from alcohol and be sensible about carbohydrates, surely there must be a good reason for this. How can it be possible that the food we eat can have no effect on various mechanisms in our body? I think promoting the idea that diet has nothing to do with blood sugar might do more harm than good as we have already seen the damage by promoting the idea that all calories are same.
Dr Joseoh Kraft in his book “Diabetes Epidemic and You” has documented that from his rigorous tests run on thousands of his patients he saw different patterns where lots of people despite having normal blood sugar released high levels of insulin for a long time which he refers to as “diabetes in situ” and suggests that it is hyperinsulinemia that does a lot of vascular damage way before than hyperglycemia kicks in. So, normal bloos sugars might not tell the whole story.
If diet and exercise helps people manage their disease then why not use it also as part of the overall treatment strategy?
Just to stir the pot a bit, here’s a YouTube presentation by Denise Minger, discussing Walter Kempner’s Rice Diet. The Rice Diet used massive amounts of refined carbohydrates, but as close to zero fat as possible. And, apparently no medications except supplements. Kempner claimed to have treated diabetes so successfully, that in some cases, some people could gradually go off the diet and remain free of diabetes.
Her discussion of the Rice Diet begins at about 4:35, with the results discussed at 6:50.
Let us see if anyone else can replicate this work.
I don’t know that anyone is trying to replicate it, but the whole thing is being kept very much alive by the “plant based diet” people. I can’t imagine people adhering to the diet wouldn’t eventually have massive deficiency problems. Talk about “cutting out whole food groups”!
I’m like a dog with a bone – I keep coming back to this with more questions!
My next question is, why do we have increasing diabetes levels? I appreciate that doctors are better at diagnosing the unwell than they were 100 years ago but the rise in diabetes in the last 40 years would seem higher than just better diagnosis.
My research to date leads me to believe that diabetes is increasing because of dietary changes. The dietary changes I believe that have led to this are the vast increase in the consumption of sugars & carbohydrates following the change in nutritional guidance to a low-fat diet.
Surely, this food change has an effect on our bodies that is detrimental to our ability to control our blood sugar levels or glucagon levels?
I also absolutely know that my spots / dry skin / slower healing / dips in energy levels, bloating, weight gain etc on a high carb diet are not somatised either!
The bihormonal hypothesis of diabetes is of course 50 years old. It is correct almost by definition, given the very strong interactions between blood sugar, insulin and glucagon. Yet as we all know, the pharmaceutical industry and its “sponsored research” isn’t really interested in solving a disease, but only in treating it. The insulin dogma has served that purpose well.
Yet even in a bihormonal framework, the key to diabetes remains the same: fructose. Fructose no only induces insulin resistance, but also interferes with glucagon thresholds. Besides, of course, it drives overconsumption, mutes satiety, boosts hepatic gluconeogenesis and de novo lipogensis, raises sLDL and endothelial inflammation, etc.
And fructose consumption has exploded during the 20th century, due to sucrose, HFCS and fruit juices.
This also explains why “low-carb” misses the point somewhat: As long as you keep fructose/sugar consumption low, you can eat as many carbs as you like. As many traditional diets of course do: Japanese rice, Indian rice, Arab bread, African couscous, Mexican tortilla, Bolivian quinoa etc. Only once you go high-fructose and thereby block insulin sensitivity, carbs may become a problem. But even then, there is no need to skip carbs. Just quit sugar.
Simple, isn’t it?
Andrew, I thought carbs were converted into glucose by the body? Surely if you are trying to cut sugar, you need to cut carbs too?
Nigella, carbs (starches) may be converted into glucose, glycogen or triglycerides (fat). But the important point is that sugar (sucrose, or HFCS) consists of glucose and *fructose*, and fructose is not glucose. Fructose has a vastly different and, at today’s consumption, hugely detrimental effect on our body.
That’s why you see so many indigenous cultures with diets high in carbs but extremely low in sugar/fructose. They are perfectly healthy.
The “low carb, high fat” approach essentially is a luxury fad. If populations in Asia, Africa or Latin America would convert to LCHF, our ecology would collapse tomorrow. Plus, it isn’t even healthier than simply quitting sugar.
No, HFLC eating is not a fad. it’s the result of Science. High fat is the essential part in a HFLC diet. If you go further into it, especially by fasting to, you can go into ketosis. The brain and body functions well on ketones, skipping the “sugar” part completely for fuel. The switch to ketones is physically palpable. Clearer thought, more energy, better mood – altogether altered person. It’s only a luxuary because we can do it on purpose without entering into malnutrition.
Many indigenous cultures (like the San in Namibia) eat very little. Even though it night be carbs, but mostly it’s meat. They are probably often in a state of fasting – and ketosis.
I only know about Africa where people live on a high carb (adopted) diet of mealies (corn) and bread – health not fantastic at all.
Whilst your brain can use Ketone bodies for energy, in part, if your blood sugar drops below about 2, you will enter a coma and then die. Your brain cannot skip the sugar part. That, I am afraid, is a fact. One of the few that I am absolutely certain is true. This does not mean I do not believe the HFLC can be a very good thing (for many people). In fact I actively promote it, and advised my daughter to use HFLC to lose weight – which she has successfully done. My son, however, remains a stick insect on an HC diet. HC being both high calorie and high carb. Ah, for the physiology of a 21 year old.
Well, I wouldn’t suggest such an eating plan to Type1 diabetics. I think you are talking about ketoacidosis? Even in a HFLC diet, something will turn into sugar – even protein does. But it’s normal in fasting, as we do anyway overnight, to switch into using ketones. I’m not sure, as someone else said in another comment that ketosis is not “normal”. In evolutionary terms, food wasn’t as abundant as it is now. We fasted a lot!
Simply put – we eat too much.
“Fructose has a vastly different and, at today’s consumption, hugely detrimental effect on our body.”
I wonder if fructose isn’t being falsely accused in much of what is written today. Here is what Dr. Richard D. Fienman commented on one of Tom Naughton’s blogs:
“Lustig’s biochemistry is convincing because of his excellent style, but it is not correct. In many details but, more important in general understanding. Fructose is not a toxin. Fructose is a normal part of metabolism. If nothing else, fructose and glucose are interconvertible. That’s why the glycemic index of fructose is 20 and not zero.
“More important, the metabolism of the two sugars comes together at the level of the triose-phosphates (three carbon products of the lysis in glycolysis). At that point, they are indistinguishable and both can contribute to fat storage (by providing glycerol-phosphate).”
Full comment at:
Dr. Georgia Ede has a three-part series on fructose in which, among other things, she points out how the studies that put fructose in a bad light are flawed in several ways.
The bad breath in (strong) ketosis alone indicates that this was meant to be an emergency mode. An efficient one, to be sure.
Sure you can “lose weight” by cutting carbs. But “losing weight” is a modern problem! All those traditional high-carb cultures have no issues with weight whatsoever – until they introduce sugar/fructose.
Hey, the whole point about fructose in evolution has been to add fat prior to winter or dry season! By driving up insulin, glucagon and blood sugar for a limited time.
Low carb is a “luxury fad” because it’s usually high in animal products and high-fat products in general. If several billion people on this planet started to skip their high carb basic foods (rice etc.) and switch to luxurious steaks, our agriculture and ecology would collapse rapidly. It only works as long as a few rich Westerners are doing it.
So, if we want to solve our “Western” health problems, let us please keep the rice, but ditch the Coke, candy, and all the hidden sugar in our food.
I don’t think it is just a matter of reducing sugar and processed food (although that would be a step in the right direction). Look back to what happen to native people when they first started adopting our western diet in the last two centuries. They fairly quickly got obesity, diabetes, heart disease and cancer and that was long before coke and modern processed foods were available to them. They just started with the basic white commodities.
I do agree with you that LCHF is a luxury diet for those who can afford it and that currently we could not feed the world on it. This might be solvable with tech, but first we need to understand what is essential to good health and we are a long way from having any consensus on that.
Andrew I so agree with you… I believe that removing high carb staples from the diet should be the last stage of a LCHF regime.Most people will benefit tremendously by firstly just eliminating SUGAR and other rubbish processed carbs. Their health will probably improve to such an extent, that removal of unadulterated, natural carbs will not be that necessary.
By the way…..in the last months I have noticed that the lower-end discount shops are being piled high with breakfast cereals, sugar and bread, all going at low prices….has the message got through to some folks who normally use the big supermarkets? Consequently, the processed food manufacturers are needing to find new outlets ( and generally those being used by people with little money), in which to offload the excess production of their unhealthy, food-like substances.
Just a thought, and not research-based….but merely observed by myself.
“In this article I explore how advocates of low-carb diets (such as Paleo, Primal, and Atkins-type diets) have grossly misrepresented the medical literature and the diets of healthy traditional populations in Asia. I also examine how advocates of fad diets have unfairly demonized wheat, which has been used as a staple by many healthy populations throughout the world.” : https://www.drmcdougall.com/misc/2013nl/aug/travis.htm
“How does the average person living in, say, Japan stay leaner and healthier than the average American while still consuming >70% of their caloric intake in the form of carbohydrates? ” : http://eatingacademy.com/nutrition/how-do-some-cultures-stay-lean-while-still-consuming-high-amounts-of-carbohydrates
@thelastfurlong: “Simply put – we eat too much.” Problem is, a healthy human feels satiated after a normal amount of food (leptin, ghrelin, insulin all play a role here). What has upset this key regulatory system? Fructose. It bypasses and mutes satiety, in fact it makes you even more hungry than you were before (there is excellent research on this effect). Why does fructose do that? Because evolutionarily, it was meant to help you add fat. Today it helps food and drink companies sell more of their stuff.
Also, recall that leptin (and insulin) is a key suppressor of glucacon, but fructose induces both leptin and insulin resistance, in fact after less than 2 weeks. (http://www.ncbi.nlm.nih.gov/pubmed/18703413)
@Oldtech: A Western diet is a high sugar diet. It’s not the bread or potatoes, which the Europeans adopted from other (healthy) cultures anyway and consumed for centuries without any health problems. But when natives adopted a modern post-1600 and especially post-1800/1900 “Western diet”, their sugar consumption multiplied. So did modern Western disease. Why? Because sugar contains fructose. Bread does not. (Although they often add sugar even to bread and everything else nowadays).
FYI: Dr. Illo, the 2005 paper you referenced that showed higher risk with low HbA1c has a follow up 2015 paper that claims that the risk is not due to the low HbA1c, but due to a confounder. See http://www.ncbi.nlm.nih.gov/pubmed/26236548. From the abstract:
“Diabetes mellitus is increasingly becoming an older person disease due to the increased survival and aging of the population. Previous studies which showed benefits of tight glycemic control and a linear relationship between HbA1c and mortality have largely included younger patients newly diagnosed with diabetes and with less comorbidities. Recent studies, which included older population with diabetes, have shown a U-shaped relationship of increased mortality associated with low HbA1c. The mechanism of such relationship is unclear. There was no direct causal link between low HbA1c and mortality. It appears that malnutrition, inflammation and functional decline are characteristics shared by the populations that showed increased mortality and low HbA1c. In these studies functional status, disability or frailty was not routinely measured. Therefore, although adjustment for comorbidities was made there may be a residual confounding by unmeasured factors such as frailty. Thus, frailty or decline in functional reserve may be the main confounding factor explaining the relationship between increased mortality risk and low HbA1c.”
I can’t find the reference right now but I also saw a paper that showed that HbA1c is inversely related to all cause mortality.
A lower HbA1c makes sense to me since HbA1c is measuring ‘glycated’ hemoglobin due to high blood glucose and that it is glycated proteins and lipid molecules that cause damage from diabetes. I think of HbA1c as an index into the damage that high blood glucose is doing.
I must disagree with the interpretation provided for the few “low HgbA1c/higher mortality” papers. These authors are speculating. “There was no direct causal link between low HbA1c and mortality.” These papers were not designed to find a “causal link”….simply to make the observation.
However, if you have been reading my previous posts and the other papers I have cited it becomes eminently clear why low HgbA1c is associated with higher mortality.
As you know HgbA1c is the average of three months of blood sugar readings. The more hypoglycemic episodes the individual has….the lower the HgbA1c.. Hypoglycemic episodes are correlated with higher mortality. See the “infamous” 10000 patient ACCORD trail of July 2008 (New England Jo. of Medicine). See also the follow up meeting minutes of the American Diabetes Association in San Francisco in 2008 during which it was admitted the intensive insulin group with the high mortality had three times the rate of hypoglycemia.
See also the example in my textbook which showed a case in which I eliminated the damaging hypoglycemia in the patient and the HgbA1c rose! I have seen hundreds of such cases in my practice over the past 10 years.
You will note that there are papers cited showing an increase in mortality among “non-diabetics” who have low HgbA1c’s. These, strongly believe, correspond to the categories
of patients in my book listed as a) Nesidioblastosis and b) Hypothalamic Hypoglycemia (Spontaneous Hypoglycemia in Europe). These two categories a + b outnumber the cases of true Type 2 cases seen in my office. (700 over the past 8 years). If the testing techniques I recommend (C-Peptide, Dexcom CGM etc) are followed you will identify these patients.
HgbA1c in the Nesidioblastosis patients (unpublished study from our office) varies between 5.0 and 10.5. Thus it can not be used as a diagnostic criterion for “diabetes” as the American Diabetes Association, the NHS and others contend.
Yes, it is time for the public to panic. This is not my intent, but it appears thaT all of us are being marched slowly “off the cliff”. Even the NHS (see BBC clip) admits there has been a 60% increase in “diabetes” in the past decade in the U.K. Similar figures are being released by the Center for Disease Control (with the U. of Colorado) in the United States. And I am being accused of causing panic? Really? Is the data from our governments and medical journals not enough cause for serious concern? The highly profitable diet book/exercise plans have not stopped the epidemic and there is no published evidence that this approach can. The NHS restricts access to the more useful drugs (as does the U.S. insurance industry). Individual practitioners are not allowed to make vital clinical decisions for the patient’s welfare in either country without personal risk. In December of 2013 Blue Shield of California discontinued me as a preferred provider because I made the diagnosis of Nesidioblastosis (you can find the diagnosis on Wikipedia and other sites and 60+ scientific papers) in one of their insureds. I had been with them for over 35 years. They have also started a “narrow network” policy to increase profit. (You pay them every month as usual but you no longer have access to specialists.)
Roberto Illa, M.D.
This has turned into a very interesting debate and seems to have done just what the Doctor intended it to. Dr Illa has introduced an entirely new line of thinking, and stirred up a hornets nest, and to be quite honest I don’t understand a large chunk of what he says. It isn’t possible for me because I haven’t the education, or the medical knowledge to fathom it all out. He may be absolutely right, he may have most of it right – he may not, but I do see one thing, he has challenged the accepted view – and that’s truly scientific thinking.
But to counter that, it also seems incontrovertible that whatever ultimately turns out to be the root cause of diabetes itself, the food we put into our mouths does have an effect on our bodies. I certainly hope that scientific minds like Dr Kendrick and others, will continue to ferret away until the root cause of diabetes is dug out. Perhaps diet has nothing to do with it, but until we know for sure, we as individuals have to do the best we can with the knowledge we have. People on this blog and others, have proved conclusively to themselves that diet has an effect on their health, and their diabetes, and that this can be achieved without medication. The way we eat may not be a cure for diabetes, but if a LCHF diet etc makes us feel well again – isn’t that enough to be going on with? It may not be scientific, but what we want – until something better comes along is to feel as fit and healthy as we can without pumping ourselves full of drugs.
Dr. Illo I think I may owe you an apology. I have been reading more about HbA1c and hypoglycemia and especially papers on silent hypoglycemia. I was quite aware of hypoglycemia, but only vaguely aware of silent hypoglycemia so I had not spent any time researching either since I did not think they applied to me.
Now, I am not so confident after reading some of the papers on silent hypoglycemia and I do agree with you that the only way to know for sure is to get a continuous glucose meter and test. The problem with the general studies on HbA1c and hypoglycemia is just that; they are general and don’t seem adequate to judge risk for individual cases.
Dr. Illo a question. Why are you so confident that a patient with a low normal HbA1c is likely having silent hypoglycemia?
Just to add my share into HbA1c discussion, HbA1c is not written in stone and does not always correlate with blood levels due to the life span of red blood cells, thyroid status and iron stautus in the body. It is no more than an estimate. CBGM is definitely a far better way to find out blood glucose levels over time….if you can afford one. Dexcom costs around £1000 here in the UK.
Diet helped this guy
Health Central, for which I was blogging, has decided to pare down its staff, and I was among those dumped, which means I’ll have time to get back to my own blog, which I’ve neglected for several years.
Coincidentally, when reviewing the site, I discovered my last post was on glucagon.
It was in 2011, so no links to anything newer.
So glad that this thread is returning to a discussion of glucagon and the Bihormonal hypothesis that Dr Unger put forth 50 years ago and whose illustrious research career continues to support and develop. Here are some additional considerations:
Glucagon levels are elevated in both type 1 and type 2 diabetes as a result of insulin deficiency (type 1 and advanced type 2) or loss of first phase insulin secretion and insulin resistance (type 2). The important thing to understand here is that the alpha cell, which makes glucagon, is a glucose-responsive cell type, meaning it senses and responds to glucose concentration. In normal individuals, after a meal as blood glucose levels begin to rise, the alpha cell senses this even before the insulin producing beta cell and releases a tiny amount of glucagon, not to raise blood glucose but rather to prime the beta cell to release insulin (keep in mind that the alpha cell and beta cell exist next to one another in the islets within the pancreas and the communication between them is exquisite, they even have gap junctions, essentially small connections that allow them to communicate back and forth). So, in a normal individual, food increases glucose, glucagon primes the beta cell and then when the beta cell registers the increase in blood glucose it releases a large amount of insulin that shuts down any further release of glucagon. Both hormones travel from the pancreas directly to the liver and after a meal a high insulin/low glucagon concentration signals to the liver that it no longer needs to release glucose.
In diabetes, especially in type 1 diabetes and late stage type 2 diabetes, the glucagon level goes up after the meal but the alpha cell never sees the high concentration of insulin coming from the beta cell and so the alpha cell never stops its release of glucagon that is meant to prime the beta cell (there is no beta cell and insulin injected under the skin does not reach the alpha cell in high enough concentration). And so, at exactly the time that you would not want glucagon levels to be elevated because glucose is going up due to food consumed, glucagon levels continue to increase and signal the liver to continue to dump glucose into the blood stream. This is why glucose levels are so high after meals, its not only the food but also an inappropriately increased release of glucagon after meals. The important take away for me and my patients with diabetes is to be sure the blood glucose is normal before eating. The higher the blood glucose, the higher the glucagon release and the more this drives/maintains blood glucose elevation. I teach my patients, especially with type 1, to give insulin in advance of the meal, timing depending upon degree of blood glucose elevation, to counter this phenomenon. Low carbohydrate diets are also helpful in this regard as the avoidance of carbohydrates helps to avoid the post meal glucose spike which also helps to minimize the inappropriate glucagon hypersecretion. However, proteins do contribute to blood glucose increase and many amino acids directly stimulate glucagon release and so even with low carb diets it is helpful to normalize glucose before eating.
I would also like to weigh in on the observed association between increased mortality (higher death rate) and the low HbA1c levels. There continues to be much debate in the scientific literature as to what is going on. An increased occurrence of low blood glucose is one possible cause. Low blood glucose is not good! The question remains, is it possible to achieve a low A1c, in the 4 to 5 range, and not succumb to whatever it is that is causing the increased mortality observed in type 1 and type 2 diabetes? Those of us adhering to a low carb diet certainly hope so. Type 1 diabetes is a volatile disease in terms of blood glucose, owing to a complete lack of regulated insulin release but also due to abnormally regulated release of excess glucagon. Many of us (myself included) eating a low carb diet can maintain blood glucose levels in a normal non diabetic range (confirmed by the use of Dexcom CGM) and so we remain hopeful that by maintaining glucose in a normal range without an increase occurrence of low blood glucose that we will avoid the complications associated with both highs and lows and live a long and happy life! People like Dr Bernstein certainly give us hope!
Greg. Thank you, that was all very clear – to me at least. My own view is that trying to maintain A1c in the 4 – 5 range (in the UK we now use completely different units, the International Federation of Clinical Chemistry reference measurement procedure of mmol/mol. 5% = 31mmol/mol 6% = 42mmol/mol) is that there is too much danger of hypos. In my elderly patients when they start running 4- 5 I see too many hypos. I think if you are highly motivated, eat the right diet, use insulin before eating etc. etc. you can avoid problems. But not many people are that well organised.
P.S. What do you find works best for ‘brittle’ type 1 diabetics?
Malcolm, I agree that in most, trying to achieve an A1c in the 4 to 5 range, balancing rapid insulin analogs to carbohydrates consumed, causes way too many lows. It is only those who can strictly adhere to a low carb diet, reduce the dependence on rapid insulin who can avoid the lows and safely achieve the “normal” A1c levels.
In terms of what works best for “brittle” type 1 diabetes, the answer is education, education, education. I only see 2 patients per day, one in the morning and one in the afternoon, visits last 2 to 4 hours. I utilize continuous glucose monitors, download them at every visit as well as insulin pumps (in patients who want them, I personally do not use one) and then I take the time to educate my patients about every singe variable that impacts blood glucose. Very few understand how rapid insulin analogs work over time, that they do close to nothing in the first 20 minutes after injection, peak in glucose lowering action after 1 to 2 hours and taper off after 4 hours. Very few understand that proteins and fats impact blood glucose or how to give insulin for them. Very few understand that there are different types of exercise that can be used to raise or lower blood glucose. The number of variables that need to be considered, that few are considering, is great. In my mind nothing in diabetes is good or bad, everything just has an effect and our job is to understand all of these things first and then practice practice practice the exquisite balancing act. If a patient loves fruit or other carbs and does not want to cut carbs from the diet, ok, it is harder to do but can be done by understanding how the insulin and carbs work over time and then balance them as best as one can. I also use agents from type 2 diabetes in type 1 with great success, glucagon suppressing agents are a particular favorite but I also frequently use metformin to block the effects of glucagon on the livers release of glucose. SGLT2 inhibitors are also an interesting new addition to the tool box but are not without significant risk. Obviously it requires a very motivated patient to engage in this type of approach. I also make myself available to my patients between visits. My patients often send me dexcom downloads on a weekly basis. Type 1 diabetes requires constant vigilance and adjustment and learning. And, we balance all of this with burnout. We do all that we can without going crazy, not easy to do! Sadly, my type of approach is not one that other docs can adopt given the constraints of our health care systems/insurance reimbursement practices.
Diabetes and Diet
In http://www.ncbi.nlm.nih.gov/pubmed/11185712 ‘Effect of exogenous insulin and glucagon on exocrine pancreatic secretion in rats in vivo.’ it is noted that the effect of intravenous infusion of insulin or glucagon is to decrease amylase production
“Results: In the insulin group, the secreted volume of pancreatic juice increases with the maximum dose. All insulin doses results in amylase and lipase decreased activity. When submaximum and maximum insulin doses are administered, the trypsin activity also decreases. In the glucagon group, the activity of lipase and trypsin decreases regardless the dose, whereas the amylase activity decreases with submaximum and supramaximum doses.”
In the light of the recent research into the number of copies of the AMY1 (AMY2?) gene in the human genome that suggests that low AMY1 count correlates with a propensity to become ‘obese’, is there a possible link between the use of insulin and obesity?
In http://onlinelibrary.wiley.com/doi/10.1111/dme.12808/abstract ‘Association between salivary amylase (AMY1) gene copy numbers and insulin resistance in asymptomatic Korean men’ there is raised a probable link between low AMY1 count and ‘Insulin resistance’.
Some further reading
This is a good discussion but the issues are complex, and the reality is that “Diabetes” may mean different things (and different symptoms) to different people. T1 is not the same as T2. T2 seems to be a problem with excessive blood sugar and insulin resistance. In the long term it is not effectively treated with drugs.
From what I have seen the spiking and different levels in different places and different times described by Dr. Unger in his youtube lecture fits perfectly with the “pulses” described by Dr. Fung AND the need to avoid constant insulin exposure (and possibly similarly constant glucagon exposure). That constant insulin exposure is dealt with by the body through adaptation, and the body gradually becomes resistant to insulin, leading to higher and higher doses being required.
In this context the increased/excess weight and waist size are a result of diabetes, not a cause of diabetes, thus a symptom, not something to be cured by eating less. The essential “problem” or cause of the diabetes is constant or almost constant food consumption, with the resultant constant production of insulin and, for that matter, probably glucagon, rather than the body producing, and the tissues being exposed to, PULSES of Insulin. The cure is based somewhat on carbohydrate control and some reduction in food consumption, but MAINLY based on not eating all the time. Thus, intermittent fasting aka IF. It seems to work.
The IF program has the benefit of NOT requiring any expensive drugs and of being easy for almost any individual to manage. The simplest program is simply to push breakfast back about six hours and avoid snacks. Don’t eat between meals or after dinner. Break your fast about noon. Avoid “starchy” foods. Avoid sugar and sugary foods.
Hello Dr. Kendrick;
This upside down view of Diabetes gives many millions of us a great deal of hope. Before reading your blog I thought the miracle cure or the silver bullet to end DM was to go under the knife and have a Bariatric surgery. From many studies I understand that this surgery has a 90% cure for those suffering the effect of DT2 as I.
Do you think there is a link between what Professor Unger has found with glucagon being the primary driver and the loss of the alpha-cells in the stomach after the surgery takes place.
Dr. Unger has tested his theory in the lap using the mouse, while the rest of society may have proven him right by performing his theory on humans. Society has found one way of suppressing the production of this hormone. Has anyone made this connection?
Many see bariatric surgery leading to reduction of caloric intake with stomach size shrunk. I would like to suggest the reduction of the alpha-cells inside the stomach is leading our bodies to produce less glucagon, therefore lessens its role. With the body left only with the alpha-cells in the pancreas, the glucagon isn’t able to overproduce and run havoc.
Shall we all go under the knife then? Or wait for glucagon suppressor? What are your thoughts?
Thank you for this blog and helping to turn this debate upside down.
I think that the evidence on bariatric surgery would certainly suggest that ‘something’ happens immediately, long before weight loss could possibly explain the significant blood sugar lowering. It is probably something to do with reduced glucagon secretion. I have not looked deeply into this area, but it would certainly be interesting to do so. As to your question ‘should we all go under the knife?’ Until we have more data on the long-term effects, I would strongly urge NO.
In a YouTube presentation, “The Two Big Lies of Type 2 Diabetes” (posted by Cstckdvd in the replies to your “Tranny Fats Ha Ha Ha” article), Dr. Jason Fung quoted two excerpts from an article by Joslin in a 1916 medical journal.
For those who might be interested, two contemporary books describing diabetic diet can be found complete online — the first by Joslin himself, and a second by R. W. Oppenheimer:
Elliott Proctor Joslin, “A Diabetic Manual for the Doctor and Patient” (1918)
Rebecca Wolff Oppenheimer, “Diabetic Cookery” (1917)
In the preface to the Oppenheimer book, we read: “Because of her own need, the author became interested in diabetic foods given to patients in the highly successful treatments at Carlsbad and Neuenahr, where she spent her summers for eight years.”
In the section on “Typical Dietaries” (pp. 146-7), she writes, “The work done on these dietaries is typical of that which must be done for the diabetic as soon as his carbohydrate tolerance is determined by the physican. . .When the carbohydrate tolerance is only 40 grams, a small allowance, it becomes necessary to raise the proportion of protein above 100 grams, approaching 140, and to keep the fat above 200 grams to produce the energy requirements of 2500 calories. . . ” (LCHF in 1917)
Although the book doesn’t mention fasting, it does mention (p. 156) an “Abstinence Day” in which all carbohydrate foods are eliminated. A suggested substitute menu for people who are away from home contains 20 grams of carbohydrate, and bears much resemblance to the 1972 Atkins Induction.
Years ago sugar was detected in my urine for a flight medical exam. The GTT was nearly normal , the final reading was 5.1 and not 5.0 as per the guideline at that stage. I must add that I had a wild party the previous evening. The flight surgeon told me I was a class 2 diabetic ,although all the follow up GTT’s showed non diabetic. His advice was to eat more carbs to release more insulin . I questioned the reasoning as flawed as common sense indicated eating LESS carbs should be the way to go. His answer ‘The medical protocol is to eat MORE carbs’ ,I was stunned at the shear stupidity of the so called medical councils that determine these protocols. Lately during a flight medical , the cardiologists stated a ldl of 2.4 is too high as the latest guidelines by the american heart foundation / cardiologist panel was to lower it to under 2.0 (when are they going for 0).
Fortunately I had read the books by Doctor Kendrick and articles in Spacedoc.com. I told the cardiologist he was crazy and that they were killing people. Off course that did not go down well.
I had a 6 heart bypass with cholesterol of 4.0 in 2006. The cardiologist and surgeon could not explain why I needed a 6 heart bypass with cholesterol of 4. As Dr. Kendrick very clearly states , IT IS NOT CHOLESTEROL.
It is inflammation caused by either, viral, bacterial or excess carbohydrates( insulin).
I have since started a company that produces natural products that targets inflammation with fantastic results.
I have gone off statins completely after very unpleasant side effects.
The very disturbing aspect is doctors blindly following the garbage proclaimed as the truth by the pharmaceutical companies. Any doctor who dares to disagree ,with solid evidence ,is immediately branded a quack , as in the case of Dr. Kendrick.
One important aspect is that doctors ,hospitals and pharmaceutical companies without sick people will soon be out of of business.
Healthy people are a threat to their existence.
Keep up the fantastic work. I forward all your articles to my friends and advise as many people as possible to visit your website.
My very old book (1968) by a certain JH Green, merely “An Introduction to Human Physiology” states:
“The physiological importance of a second hormone glucagon produced by the alpha cells of the islet tissue has yet to be evaluated. It raises the blood glucose level probably by mobilizing the liver glycogen IN MUCH THE SAME WAY AS DOES ADRENALINE.” (My capitals)
Stress? HPA axis?
If this hasn’t already been viewed, I think it’s worth a read – and its Fig 1 is worth looking at too:
Here is a very interesting link:
“Glucagon is traditionally thought of as an antihypoglycemic hormone, for example in response to starvation. However, it actually increases energy expenditure and has other actions not in line with protection from hypoglycemia. Furthermore, it is often found to be elevated when glucose is also raised, for example in circumstances of psychological and metabolic stress. These findings seem more in keeping with glucagon having some role as a hormone enhancing the response to stress.”
(Minireview: Glucagon in Stress and Energy Homeostasis
B. J. Jones, T. Tan, and S. R. Bloom)
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 the video you link…
Other than that (and that’s a pretty big deal, as it reinforces the fat-phobic BS that has sent everyone down the high-carb road because people don’t know about “WHAT HAPPENS TO THE CARBS”…) I like where he’s coming from.
So do we ditch the carbs or not? As usual with a lot of MK’s ‘jargon free’ writing there is no simplified conclusion.
I don’t do simplified conclusions – sorry.
The simplified conclusion, and the answer to your question about carbs is simple to find if you take the time to read the various posts.
First of all, I am not diabetic and I do not suffer from anything like those issues. I am 71 years old and in good shape, and by that I mean I lift weights and exercise regularly and generally move around quickly. I still want to do better. So I have researched the issues as best I can.
What I haver found is the website (IDM, or intensive dietary management) of Dr. Jason Fung, a Canadian MD and Nephrologist. The “cause” of diabetes turns out to be…as I understand it…Insulin. Excessive or undesirable continual high levels of Insulin. Caused buy continuous eating.
It’s not that your body fails to make too little, the problem is that your body is making what it needs to make to cope with the food you eat (your individual diet), and when you eat it, coupled with the fat storage your body (already) maintains. The solution is to fast (reduce calories consumed to zero), for either a minimum of 16-20 hours or so per day, on a regular basis, or fast for daily periods, or even longer. The key is to stop eating all the time. Thus one would eat one or two meals a day, and NOTHING in between: No snacks. No treats. Yes, you will want to moderate, or minimize carbohydrates, but that is not the keystone to the program. The key is to avoid eating between meals.
Visit the website. Do it now.
Thanks Richard. I’ve saved the website and will read it.
I didn’t read all the comments here, but I want to say I agree with M. Yusuf (above), that I watched a lecture last year of a scientist (possibly Unger, but I can’t find the video now) who said that alpha cells exist in two places in the human body, the pancreas and the stomach. It occurred to me then that it is the reason so many people are cured immediately (not slowly over time) of diabetes just from having gastric bypass surgery or sleeve gastrectomy. I suffer from dawn phenom and T2D and have considered the procedure as an alternative to what I saw my mother go through over the course of 25 years of bad treatment. I’ve done so much research and found if I follow an incredibly strict keto diet with supplements, I can get my numbers into normal range, but its grueling and succumbing to any carbohydrate craving throws me out of ketosis, as does stress. The struggle is real.
Maybe I have misunderstood but there seem to be two different claims in your post:
(1) The key to reducing blood sugar levels is blocking glucagon production rather than injecting insulin or increasing insulin sensitivity. (Evidence: mice with no insulin but also no glucagon do not become hyperglycaemic)
(2) Reducing blood sugar levels does not improve health outcomes for people with diabetes. (Evidence: the Accord study and the meta-analysis of metformin studies – it being assumed taht metformin does reduce blood sugar levels)
The second of these claims contradicts everything we are taught about diabetes. In particular if it is true then it seems that the first claim becomes redundant.
By the way, with regard to the evidence for the first claim, I assume you are referring to the studies that used mice with their beta-cells destroyed by streptozotocin (STZ). This evidence is undermined by a study published in April 2016 which used a more powerful way of eliminating beta-cells and found that then glucagon blocking did not prevent diabetes. The authors conclude that the mice in the previous studies had some residual insulin production. In their words:
“we show that near-total β-cell loss triggers severe hyperglycemia and all the metabolic features of type 1 diabetes (cachexia, glucose intolerance, and death) in mice with constitutive or induced glucagon signaling deficiency. We report that the absence of hyperglycemia observed in glucagon-deficient mice after STZ treatment can be explained through the persistence of a residual β-cell mass, which ensures a low level of insulin action”
Damond et al (2016) ‘Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist’, https://elifesciences.org/content/5/e13828
I’d be interested in your comments.
From what I understand the ACCORD study was flawed. It only used insulin as the means to lower glucose and in many cases it resulted in the patients getting too much insulin. Thus the adverse results for diabetics with insulin resistance.
Hope someone is still watching this blog 🙂 My Experiment: I am an obese T2 with dawn phenomenon (25-50 mmol/l higher in the morning) trying to stay off Big Pharma medications (intestinal intolerance to Metformin). After taking a Small Intestinal Bacterial Overgrowth test, my fasting sugars increased from 130 to 230 mmol/l after the lactulose portion. After (mis)reading Kempner’s rice diet (didn’t see it was also supposed to be a low calorie diet), and eating a very high starch/low fat diet (a la McDougall), I worsened my diabetes to near coma range- my glucose meter only said HIGH (over 500). My A1C went to 13 after that several month experiment.
Reducing carbs slowly has lowered my fasting glucose to 300-350. (A1C now 8). I’ve tried taking Levemir, but interestingly it seems to not make any difference. If my sugar was up to 450 by bedtime, it would come down to 325-350 whether I took the insulin or not. If I was at 300-350 at bedtime, I would still be 350 in the morning, not a 250.
I did a fasting insulin test, expecting it to be high and indicating IR, but it read on the low end of normal. I’ve read Jason Fung(Low carb with Fasting), and Ray Peat (High sugar Low PUFA). I am intrigued by this post and would like to know more on how to reduce Glucagon as this may help me more.
I’ve just seen this and remembered your article above. Perhaps it’s of interest?
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The story of the man who has overcome diabetes – Patreon.com/VeteranVS