We are told, ad-nauseam, that obesity is the main cause of type II diabetes. This, allegedly, follows a very simple causal chain.
Obesity > insulin resistance > raised blood sugar levels
For those not familiar with the term Insulin resistance, this is the condition whereby various organs in the body become gradually more insensitive to insulin, which forces insulin levels higher to keep the blood sugar levels down.
Eventually the resistance to insulin becomes so great that the blood sugar levels rise anyway – despite the high insulin levels. Alternatively, or in parallel, the pancreas gives up fighting against the resistance and insulin production becomes ‘burnt-out’. Whichever process is dominant, they both result in sugar levels become very high, and you will be diagnosed with type II diabetes.
At this point I have to state that I have always found it weird that a raised blood sugar level can be defined as a disease, when it is clearly nothing of the sort. In my world a ‘disease’ is the underlying malfunction which causes various signs and symptoms to occur (of which a raised blood sugar level would be one).
Everyone agrees that insulin resistance is the basic underlying cause of a raised blood sugar level a.k.a. type II diabetes. Despite this we define the blood sugar level itself as the disease.
‘A high blood sugar level is type II diabetes….end of.’
‘So, if we lower the sugar level, we have cured the disease?’
‘Yes. Now do shut up.’
Clearly bonkers, but let us not expect too much in the way of logic in medicine. Anyway, that is a slight distraction from the main theme here, which is the: obesity > insulin resistance > raised blood sugar levels discussion.
Now, for reasons that I am not going to fully bore you with here (but maybe at a later date), I have always had problems with this causal chain. Primarily, that it has never made much sense to me. Insulin resistance occurs almost exclusively in two tissues; the liver and skeletal muscle, and NOT in adipose tissue. So why would having too much adipose tissue make you insulin resistant? Answers on a post-card please*.
In order to pursue this thought further I started to look at evidence from Sumo Wrestlers. These are the most obese people on the planet. At least they are if you use BMI to define obesity. Yet, none of them have type II diabetes (at least not, whilst in training). For example:
‘Abnormally large waist circumferences, which were determined by the criteria established by the Japanese Society of Internal Medicine, were present in all Sumo wrestlers (100%), and fifteen Sumo wrestlers (83%) had high abdominal visceral fat areas (>100cm2). Only 2 subjects were categorized with high serum triglyceride levels, and 5 subjects were classified with low HDL-C levels by established criteria. None of the Sumo wrestlers had fasting hyperglycemia (high blood sugar levels) (0%)’1
Interesting, is it not, that the most obese people on the planet do not have type II diabetes (although some of them have a degree of insulin resistance – for reasons that I may explain at a later date). Yes, I know exactly what you are now thinking. They do not have diabetes because they exercise a lot. It’s true, they do. But does that not make it more likely that a lack of exercise is the true of cause of insulin resistance, rather than obesity….yes, of course it could certainly mean that.
In truth, finding very obese people without diabetes does not rule out obesity as the cause of diabetes. But it does rule out obesity as being both ‘necessary’ and ‘sufficient’. At this point I need to explain the concept of necessary and/or sufficient.
It was Koch who first tried to determine a process of logic to describe whether or not something may be a true cause of a disease, or just a chance association. He introduced us to Koch’s postulates, and also the concept of necessary and/or sufficient.
For example, it is known that the bacteria vibrio cholarea causes cholera. In order to get all the signs and symptoms of cholera it is ‘necessary’ to be infected with this organism. However, infection with vibrio cholarea does not cause cholera in everyone. If you are a fit and healthy adult you can shrug off the infection with only mild symptoms. Koch proved this by drinking a glass of water known to be infected with vibrio cholarea and developing only mild symptoms of the disease
Thus it can be stated therefore that infection with vibrio cholarea is ‘necessary’ to cause cholera. However it is not, on its own, ‘sufficient.’ Other factors are needed. On the other hand, if you could find people with cholera who had not been infected with vibrio cholarea, then you would have to declare that vibrio cholarea was neither necessary, nor sufficient, to cause cholera. So it could NOT be the cause of cholera.
This is obvious, and inarguable.
So, moving back to type II diabetes. Can you find people with type II diabetes who are of normal weight? Or, to stretch this concept to the limit, can you find people with type II diabetes who have no adipose tissue at all? Surely not, you say. Surely impossible.
At this point I shall introduce you to ‘Berardinelli-Seip Congenital Lipodystrophy’. This condition affects about one in ten million people. So it is hardly common, but that is not the point. The point is that the primary abnormality in Berardinelli-Seip Congenital Lipodystrophy is a lack of functional adipocytes – which means that those who suffer from this condition do not have fat cells, and cannot store fat. Ergo, that they are extremely lean. The leanest of the lean, the least obese of the least obese.
From time to time I describe this condition to doctors. At which point I somewhat cheekily ask them to guess what percentage of people with Berardinelli-Seip Congenital Lipodystrophy have type II diabetes. I say cheekily, because they inevitably get the answer wrong. They always, without exception, answer pretty much as follows:
‘Obviously, none of them.’
The correct answer is, of course, ‘Every… single…one…of…them.’ [Gasp, sounds of people collapsing to the floor in shock etc.]
Now, if you can understand why this is true, you are at least one step on the road to understanding type II diabetes. Or to be more accurate, what is the true underlying cause of insulin resistance and high blood sugar levels. You will also understand that obesity has only a small and indirect part to play in this process; that BMI has no relevance to the issue, and that the simple causal chain: Obesity > insulin resistance > raised blood sugar level……is wrong.
Of course obesity is closely associated with diabetes – to state otherwise would be nuts. However it is not the cause of type II diabetes. It is caused by it. By which I mean that obesity is (in major part) caused by that the underlying process that also leads to insulin resistance and high sugar levels. There is a causal chain here, but it is not Obesity>insulin resistance>raised blood sugar levels.
More on this later, once your brain has become unscrambled.
*Yes, for those who know about this area, you can talk about visceral fat, but this is another more interesting and completely different discussion. I am also only discussion type II diabetes, not type I (which is a completely different condition altogether).
How good to hear someone talking commonsense. I always did wonder why my slim and petite sister might have type 2 diabetes. I’m not sure though that she has absolutely no fat cells, but she has certainly never been overweight.
Incidentally, I was somewhat bemused by the latest research from Taiwan purporting to claim that high doses of statins protect against altzeimers. I imagine it must have been mere coincidence that my memory problems resolved within 2 weeks of giving up statins. Ah well, I’m sure I’m just a little eccentric, because it sure doesn’t make sense to me.
When my wife read out the headline from the paper, I suggested that if you are a muddle-headed codger on statins, it’s diagnosed as caused by statins, but if you are not on statins it’s diagnosed as Alzheimer’s.
My husband has Type 2 and he has always struggled to keep his weight up. But he has been a high consumer of sugar all his life. So he is a good example of what you are talking about here Malcom. I always put it the simple way, its the diet that causes the Type 2, which CAN lead to Obesity, but not in everyone. Therefore whether you have a weight problem or not, you need to avoid sugar.
Heh. When I read your challenge to guess the percentage of those poor BSCL sufferers who have type 2 diabetes, I thought to myself “How the hell could they avoid it? They have almost no buffers!”
Does this make me more endocrinologically perspicacious than those doctors to whom you refer? 😉 Not as comforting a thought as my ego would imagine!
You have done well, young grasshopper.
Of course, doctors are all pretty well brainwashed….obesity causes type II diabetes, obesity causes type II diabetes…exterminate, exterminate, resistance is useless etc.
However, almost everyone gets that wrong. Once you have decided on a causal chain, it is remarkably difficult to think outside that box
On Wed, 4 Sep 2013 16:02:05 +0000
So, is it possible that increased adiposity aka obesity (horrible term) is an adaptive process by which the body deals with raised the blood sugar that is consequent to insulin resistance? The fact that all the B-S folks have Type II diabetes supports this possibility, because they are physiologically unable to adapt by increasing adiposity.
If this is so then it seems that by the time high blood sugar persists, the underlying disease of insulin resistance (or should I say the factor or mechanism that causes the liver and the muscle cells to become resistant to insulin) is well advanced.
Are there tests that can direct our attention and intervention towards the problem before persistently high blood sugar becomes an issue needing drug intervention.
Yes, there are. Triglycerides HDL ratio is good
I’m interested in your comment that adipose tissue does not become insulin resistant. There’s plenty of disagreement to be found on that point.
Mark. Of course there is. There is also almost unanimous consensus that raised LDL levels cause CHD too. It is possible to muddy the waters of scientific discourse almost ad-infinitum. However, on a more scientific point. There are clearly two forms of adipose tissue, subcutaneous and visceral. These are, basically, two different organs. To conflate the two is to deliberately ensure that no sense can be made of anything. Remove visceral fat from diabetic ob-ob, mice, and their insulin resistance instantly disappears. This, however, has nothing to do with their subcutaneous fat stores.
Well actually there’s three, let’s not forget brown fat! 🙂
Are you saying that visceral fat does not become insulin resistant, or at least meaningfully so? If that’s the case Glut4 is working fine in visceral to help provide glycerol for TAG synthesis?
It does stand to reason based on basic understanding that glucose uptake is primarily in tissues other than adipose (muscle) but is it clear that resistance doesn’t happen there (adipose) as well? All serious questions and would enjoy seeing that evidence if you have it handy. Thanks!
Ah, the plot thickens. Of course, this stuff is complicated. I was partly teasing with my article. Glad to see a good debate can ensue. The problem we have, primarily, is that a raised blood sugar level can be caused by many things. Whatever causes it we call it one thing… type II diabetes (ignoring type I for the moment).
The Inuit have many different words for snow – so I am told. We have only one term for a high blood sugar level….type II diabetes. Which causes everyone to force causation into a single Procrustean bed where nothing can be made to fit.
Insulin resistance, also, is one term we use to describe a series of different abnormalities.
We need a different lexicon.
So, I thought that the Sumos had both excessive sub-cutaneous and visceral fat stores. Yet, they are not necessarily developing insulin resistance, at least as far as elevated blood sugar is concerned.
Do we exhaust our capacity for sub-cutaneous fat storage and go to visceral fat storage?
Yet, I note what you reported that two Sumos had high triglycerides, low HDL-c’s and absent abnormal fasting blood glucose.
So, is the development of visceral fat stores and adaptive process, given that when they are active they do not demonstrate TTD?
Of course, we do need to consider their diet. Is it low carb, high protein/fat?
So, I’m not getting it. You said that good triglycerides and HDLs are indicative of normal insulin/glucose metabolism. Even these Sumos who did not demonstrate such ‘normality” did not show abnormal blood glucose and therefore did not demonstrate abnormal insulin metabolism–assuming we can extrapolate to this conclusion. What is going on?
If you do an enormous amount of exercise, you will burn off glycogen stores. So, skeletal muscle and liver will be able to absorb glucose (up to a point). As an aside, Sumo wrestlers eat a high carb diet – as they know this is what makes them fat.
The point is that insulin resistance is also one of the wishy-washy terms where the context is essential to comprehension.
Liver, muscle and fat tissues develop resistance at different rates. When liver and muscle resist the uptake of nutrients (probably because they’re already full) the adipose tissues still can and will take up the excess. It will do it up to a point. When the adipose tissues are IR, then you will get the other symptoms of DM-II.
Insulin resistance is also a natural phenomenon in fasting (ketotic) state. When fasting or being on highly ketogenic diet, there’s a glucose sparing effect in place, to avoid dropping blood sugar levels. This state, that some bloggers (Peter @ hyperlipid.com) call physiological insulin resistance is essential to survival and can not be compared to the DM II “insulin resistance”, yet a lot of research papers do conflate and mix them up.
There’s also much evidence that this uptake resistance is a product of the state of the mithochondria in the cell, which can btw also explain the higher cancer risk associated with obesity if one follows Warburg’s hypothesis of the metabolic origin of some cancers.
Since “risk factor” merely means positive correlate, then if obesity is a risk factor for T2D, then inevitably T2D is a risk factor for obesity.
Words are as wind. In order to have a proper scientific discourse one must, of course, ensure that everyone accepts that the words they use have a clear and universally accepted meaning. In general, I find that language is often the greatest barrier to understanding. ‘Risk factor’… what does it mean? Different things to different people. My view is that a risk factor must be proved (according to Hills Canons of Causation) to be causal, not merely an association.
That was rather my point. And even Hill’s rules don’t provide proof, they only add to plausibility. Proof requires doing experiments capable of falsifying the theory in question.
The causes of type 2 diabetes can be genetic/epigenetic. One example is the Agouti mouse, a lab animal bred to be obese with tendencies to diabetes. It is possible for Agouti mouse identical twins to appear different, one fat and yellow, the other small and brown (http://www.nature.com/scitable/topicpage/obesity-epigenetics-and-gene-regulation-927).
Another example is the Dutch “Hongerwinter” of 1944-1945. Babies from this time that had experienced caloric deprivation during the third trimester were born with low birth weight but subsequently grew to normal size in childhood. However they suffered from high rates of diabetes as adults.
what happens to people with Berardinelli-Seip Congenital Lipodystrophy if they eat a ketogenic or simply low-carb diet? Does their glycemia normalise?
These people can be helped by giving them leptin – which reduces their appetite (most of the time they are starving hungry, because their brain is being told they are thin). I do not know what happens to them if given a ketogenic diet. The problem is that, with nowhere to store energy other than the liver and muscle – almost whatever they eat is going to cause overload of storage systems.
I found this article on WebMD informative about fat: http://www.webmd.com/diet/features/the-truth-about-fat
Thanks for this. I have been looking at obesity for many years now, and it is extremely clear that it is all complicated.
If you take steroids, for example, you will lose subcutaneous/peripheral fat, and gain visceral fat. You will also develop the metabolic syndrome/diabets, due to increased insulin resitance. Steroids are derived from cortisol – which is a direct antagonist of insulin at most sites of the body etc.
My view on visceral fat is that it represents a rapid access energy store, and it is highly metabolically active. Subcutaneous fat is a ‘deep’ energy store that is only accessed once glycoge/glucose has been depleted and energy is primarily being derived from visceral fat. [look up the futile cycle].
Fat/triglycerides are always shuttling from visceral to subcutaneous fat and back again. The shuttle back from visceral to subcutaneous stops when insulin levels drop, and you enter a fat burning state. This is when you can, for example, lose weight.
I could go on. But it gets more complex
On Thu, 5 Sep 2013 12:56:35 +0000
Interesting. Do you have LADA?
After rereading the WebMD article I realized that the hormone adiponectin is an important player in diabetes because it makes the muscles and liver sensitive to insulin. It’s produced by adipose tissue, but the fatter one gets the less adiponectin is made and the more insulin resistant one becomes. This seems to be a feedback mechanism where the adipose tissue is signalling it has enough fat stored and it doesn’t want the liver making more fat.
Of course, if you have B-S syndrome, then you don’t have the adipose tissue to make any adiponectin , so you are insulin resistant. It would be hard to supplement with the hormone as a therapy because it’s a protein, so couldn’t be taken orally.
I have Type 2 diabetes but I am slim, verging underweight, always have been – though I don’t have that syndrome you mention Dr Kendrick. I am also NOT insulin resistant ! The edocrinologist I see thinks I have one of the rarer genetic variants of Type 2 – I’ve not had the test to findout which one as the treament for me is the same whatever: an extremely low carbohydrate diet, between 30 and 50g per day (mostly what’s called Paleo diet – I eat very well). My HbA1c stays around 5.4% and my cholesterol profile is very protective: Total 9, HDL 3.8, trigs 0.4, and LDL is calculated and completely inaccurate with Freidewald with my high HDL and low trigs so let’s not bother about it.
I haven’t got LADA. I don’t know which type it is, some type of “monogenic” diabetes. I once had a link to the various types, of which I might be one, but I can’t find it as it was a few years ago. I believe Exeter university medical school is studying this.
I once went to a diabetes meeting organised to find out what kind of support Type 2 diabetics in my area got, and of the 18 or so people there, 5 were very thin like me (my BMI: 18.2). A couple of those were insulin resistant despite being thin. Another had partial damage to her pancreas, probably caused by a virus, and she wasn’t insulin resistant and was classed as Type 2. There there was me and another, not insulin resistant, but Type 2. Quite astonishing that nearly a third of the people there were thin considering the public perception of overweight and obesity being linked with Type 2.
A few years ago I attended a cardiovascular exercise. There were far more thinnies than fatties.
My father had diabetes type 2. He has been very thin all his life.
And what do you do if you are a type 2, highly affected by carbs (so I eat very few of them) but start to gain weight after entering menopause? I’m told that to help with the symptoms, I should lose weight. But my body is gaining weight no matter how much I eat. I exercise regularly, both weight training and lots of physical activity. How can I ascertain what is causing the weight gain, or should I just accept that I am going to be a woman mountain again?
Get your metabolism measured using indirect calorimetry (looking at Respiratory Quotient), to find out if you are fat, or carb burning – to start with.