Insulin Resistance

[xyzzy]

Been meaning to ask this for a while and has probably been asked somewhere before.

Although I understand what the effects of insulin resistance are and why its important to shift it can some one explain in layman's terms what goes on biologically speaking to cause resistance. Know its something to do with fat but that's about it.

 

[Defren]

Good question, it's something I too would like to know. Xyzzy wants laymen's terms, can I have it as if you were explaining to a three year old please?

 

[Pneu]

Right... I will try and explain as best I know!

Basically insulin resistance is linked in some part to the size of your fat cells... typically people that are overweight have 'larger' or 'inflamed' fat cells... now as these cells get larger they attract the attention of your immune system (inflammation is a natural low grade immune response).. typically a type of immune cell called 'macrophages'... basically these macrophages release chemicals as an immune response and its these chemicals that cause the insulin resistance. There appears to be some argument over what comes first the macrophages invasion of the fat cells or the inflammation of the cells.. i.e. does the invasion cause the weight gain and resistance or is it as a result of the weight gain and the resistance... but either way the result is an increase in insulin resistance.

 

[Defren]

Right... I will try and explain as best I know!

Basically insulin resistance is linked in some part to the size of your fat cells... typically people that are overweight have 'larger' or 'inflamed' fat cells... now as these cells get larger they attract the attention of your immune system (inflammation is a natural low grade immune response).. typically a type of immune cell called 'macrophages'... basically these macrophages release chemicals as an immune response and its these chemicals that cause the insulin resistance. There appears to be some argument over what comes first the macrophages invasion of the fat cells or the inflammation of the cells.. i.e. does the invasion cause the weight gain and resistance or is it as a result of the weight gain and the resistance... but either way the result is an increase in insulin resistance.

Thank you. So, if you are insulin resistant how would you know, and how does it effect T2's? Does it mean that insulin resistant T2's will likely end up on insulin, and as insulin resistant, how does this effect the injected insulin? Sorry If I sound a little dense, I blame the gin :lol:

 

[librarising]

Know its something to do with fat

"to simplify somewhat, fat in the blood feeding the liver causes insulin resistance, which causes elevated serum insulin levels, which cause the fat cells to build even more abdominal fat, which raises triglycerides in the liver's blood supply, which causes insulin levels to increase because of increased resistance to insulin.
If that sounds circular, it is. But note that the fat that is the culprit here is not dietary fat.
...
High glyceride levels are not so much the result of dietary fat as they are of carbohydrate consumption and existing body fat.
...
There are at least five causes of insulin resistance - inheritance, dehydration, infection, obesity, and high blood sugars.
This reduced efffectiveness of insulin, known as insulin resistance, has been attributed to a phenomenon called POST-RECEPTOR DEFECTS IN GLUCOSE UTILISATION."
(Dr Bernstein's Diabetes Solution)

Now if I only knew what that last bit meant :roll:
Dr B did only promise to simplify SOMEWHAT

Geoff

 

[phoenix]

Good explanation Pneu.
You might like to look at the two diagrams in this paper by Keith Frayn.
This model suggests that the fat cells either get overfull as in the case of obesity or alternatively there aren't enough of them as in the case of extreme thinness(anorexia) or lipodystrophy (no fat*) . Both can result in insulin resistance, a lipodystrophic diabetic may need insulin doses of thousands of units to keep glucose levels down, yet never puts on weight and never gets DKA.
This results in an overflow of fatty acids into the circulation. This is deposited as triglycerides in the liver and muscle cells interfering with the action of insulin.
http://journals.cambridge.org/download. ... 0d065b8fde
*edit that's adipose fat, they have 'invisible' fat around the organs.

There are a lot of papers about this. Haven't got time to look them all . Frayn, McGarry Schrauwen, Boden, are some of the researchers. Look up lipotoxicity
The big question is how much influence do dietary fats have on this process?
and just to get you thinking I'll post a couple of graphs of the OFTT of 2 people, after a long high fat diet and a return to a normal diet. The clue as to who they were is they ate nothing but meat for a year.... and yes the lack of glucose tolerance was temporary. What caused it is the contentious issue.

 

[librarising]

Now if I only knew what that last bit meant

"We conclude that the mechanisms of insulin resistance in patients with impaired glucose tolerance and in patients with Type II noninsulin-dependent diabetes are complex, and result from heterogeneous causes. (a) In the patients with the mildest disorders of carbohydrate homeostasis (patients with impaired glucose tolerance) the insulin resistance can be accounted for solely on the basis of decreased insulin receptors. (b) In patients with fasting hyperglycemia, insulin resistance is due to both decreased insulin receptors and postreceptor defect in the glucose mechanisms. (c) As the hyperglycemia worsens, the postreceptor defect in peripheral glucose disposal emerges and progressively increases. And (d) no postreceptor defect was detected in any of the patient groups when insulin's ability to suppress hepatic glucose output was measured."
(Receptor and postreceptor defects contribute to the insulin resistance in noninsulin-dependent diabetes mellitus.
O G Kolterman, R S Gray, J Griffin, P Burstein, J Insel, J A Scarlett, and J M Olefsky)

Knew there was a simpler way of putting it. This just isn't it :roll:

Geoff

 

[Defren]

Good explanation Pneu.

Phoenix, you seem to be very educated on this subject - thank goodness. So in very simple language could you answer the questions I posed? Are they answerable or am I completely on the wrong track here? I can't believe I did Biology as an option and extra curricular subject, yet am failing to grasp this. Thank you in advance.

 

[librarising]

Glucose tolerance after high fat and normal diet.JPG (52.59 KiB) Viewed 12 times

Phoenix I found the above graphs quite intriguing, as a high fat disciple. Was I on the wrong path ? Been lied to ?
Then I found this. Wouldn't advise anyone to have a high fat diet with 40% carbs :

In a randomized crossover study, we measured the effects of the HF diet [40% carbohydrate ...
(Effects of isoenergetic high-carbohydrate compared with high-fat diets ...)

Just leaves me wondering what were the constituent parts of the diets reflected in the graphs ?

Geoff

 

[borofergie]

Wouldn't advise anyone to have a high fat diet with 40% carbs

Yeah. Forget low-carb/high-fat vs low-fat/high-carb, high-fat/high-carb will kill you every time.

But I guess that's how some of us ended up here in the first place....

 

[phoenix]

Sorry to leave it like that, but dinner was on the table and then we went offline.
(the joys of living in rural France with overhead lines)
Ok the graph is of Steffanson and Andersons glucose tolerance after a year eating meat. They were not diabetic and after 2 and 4 weeks they were back to normal.

One suggestion is that they had to adapt back to be able to process carbs. The other is that circulating fats create insulin resistance at least temporarily.

It is certainly true that many long term low carbers suggest that you 'carb up' before a glucose tolerance test. There is one ketogenic low carber who suggests that as long as he keeps in the ketogenic zone it doesn't matter, he still keeps his blood glucose low. The fact that this temporary resistance happens certainly explains why some people who follow very low carb diets get very high rises if they eat quite small amounts of carbs.

I have read a lot but I'm not an expert, please take the next part as my understanding, or attempts at understanding so far.

Most of the researchers, rather than the populist writers believe that fat in some way is implicated in glucose tolerance/insulin resistance. What is not clear is how that fat gets there.
They are starting to track the different fats to see their fate in the body. You eat a fat and it might not end up as the same type of fat in the body. There are only a couple of fats that can't be created by the body in any case.
Some types of fat seem to be protective, others may not be so. (and some foods contain both types. (both protective and possibly harmful).
There is a medscape article Role of Different Dietary Saturated Fatty Acids for Cardiometabolic Risk: Future Perspective that tries to sort this out. (as we know today)

Carbs aren't exonerated either , glucose is used first as fuel but excess will be converted to fat. Normally converting glucose to fat isn't a major pathway in humans and it uses more energy than simply storing fat. However, it certainly occurs. It seems to happen more readily in those with insulin resistance why? (and what happens first is a genuine question)

Back to Frayn, why do some peoples fat cells overflow? , is it the mix of the easily assimilated high energy foods that are so available today, processed quickly by the body and thus causing 'overflow'? Is it that we really don't use as much energy as our ancestors so the cells simply have too much ?
Is it that some people are more susceptible as they have fewer fat cells or smaller ones that don't expand as much as others
It's obvious that some people can be very obese and not insulin resistant, others very thin and equally insulin resistant. Having smaller or fewer fat cells may be part of the explanation of why people who were conceived during famines have high rates of diabetes.


The answer is though that we don't know all the answers.
edit changed corrected error (carbs instead of glucose)

 

[xyzzy]

Right. All this biology was never my strong subject, if bodies were computers or physics it would be a lot simpler imo and I'd have a fighting chance.

So while I try and digest (geddit) what you've all said and as usual Phoenix you've given me the lowest GI version that will take the longest to digest :lol: here's a very simple noddy question.

Get the macrophage immune response bit Pneu thanks, never knew that, but why does an immune response in fat cells effect insulin acting in blood cells? Aren't the two systems different? What I mean is fat as such actually surrounds organs etc I thought it was only temporaily circulating in the blood stream. Is it because the macrophages that are attacking the fat cells are constantly in the blood stream and stop insulin working by attacking it as well? I have no doubt I have got something with how the phsiology of all this works horribly wrong.

I've also read insulin helps with memory and cognition in the brain. Does insulin resistance make you stupid? (patently yes in my case as I stupidly let it give me T2D :lol: ). Will my IQ rise as I lose weight? That would be nice cos obviously if its fallen because of resistance over the past whenever I'd maybe be become too stupid to realise I had become stupid!

 

[librarising]

Ok the graph is of Steffanson and Andersons glucose tolerance after a year eating meat. They were not diabetic and after 2 and 4 weeks they were back to normal.

As a diabetic, and having read the study ...

http://www.jbc.org/content/83/3/747.full.pdf

... I'd conclude that I'd prefer a year eating meat, with its attendant absence of blood sugar problems, and an occasional surge on the odd celebratory occasion, than a diet of troublesome carbs.
What did the researchers conclude ? Interesting I thought :

"These data are of practical importance in pointing
out a probable fallacy in the interpretation of the glucose tolerance
test, when the factors here discussed are not considered."

Not an endorsement of a carbohydrate diet, nor a condemnation of a high fat diet. Simply an observation about a TEMPORARY effect (in normal people) :

"The explanation of this phenomenon is that the nor-
mal carbohydrate mechanism needs daily stimulation for good
function. Should that stimulus be lacking as is the case in low
carbohydrate, high fat diets, and in prolonged fasting, it is tem-
porarily incapable of handling large quantities of carbohydrate.
In normal human beings this mechanism recovers fully after a
general diet."

Something for me to chew on.
If only life (and diabetes) were simple.

Thanks for the further info, Phoenix.

Geoff

 

[claymic]

one thing i am confused with....does that mean that if you are eating a higher fat diet because you are doing low carbing it means the insulin resistance increases? or did i get the graphs wrong?

 

[borofergie]

one thing i am confused with....does that mean that if you are eating a higher fat diet because you are doing low carbing it means the insulin resistance increases? or did i get the graphs wrong?

No. They're not relevant.

(1) That (n=2) study deals with the transition between a high-fat/very low-carb diet and a regular "high-carb" diet. Your body does all sorts of funny things when you force it to switch fuel types. It takes about 2 weeks to move in the opposite direction (from being a sugar burner to a fat burner) so it's not unreasonable for the same thing to happen when you move back. As phoenix says, low-carbers often have to carb up for a few days before a glucose tolerance test. I think that this data is a good reason why you shouldn't dip in and out of ketosis by occaisionally binging on carbs, but it isn't any reason not to stay on a low-carb diet.

(2) When the "experts" say that a high-fat diet decreases insulin sensitivity, they usally mean one with 45-60% of the energy coming from fat, and studies involving those diets tell us nothing about what happens when your body is in ketosis. Ketogenic diets have around 65-80% of energy from fat and, by defintion, put your body into a different metabolic state. Steve Phinney says: "a well formulated ketogenic diet consistently makes insulin resistance better. This benefit isn't just limited to the early stage of a ketogenic diet, when energy intake is reduced, but persists for months and years into carbohydrate restriction when weight loss has stopped and most of your energy comes from injested fat."

(3) A low-carb diet will probably help you to lose weight. Easily the most significant thing that you can to to increase your insulin sensitivity is to lose weight (and add muscle mass).

(4) On a proper ketogenic diet, you're eating so few carbs that insulin sensitivity is pretty irrelevant. @30g my BG rarely goes above 6mmol/l at any time after I eat. Although as Phoenix says, if I make a mistake and accidently eat a few more carbs I'll see it on the meter.

When reading any of these studies always ask yourself "Is the diet described really a high-fat/low-carb diet?" (in this case yes) and "Does the study last long enough to account for changes due to adaption?" (this is a transition study, so it's not relevant).

Conclusion: "Don't flip flop in and out of ketosis".

 

[Grazer]

Mi 'ead 'urts......... :crazy: :***: :***:

 

[phoenix]

one thing i am confused with....does that mean that if you are eating a higher fat diet because you are doing low carbing it means the insulin resistance increases? or did i get the graphs wrong?

No not necessarily. The Graphs were from non diabetics after a very extreme diet. They do illustrate that after a very high fat diet that you may temporarily not be able to process carbs . (just seen Borofergies answer though there are bits I don't agree with, I think that its best to move on so I scrubbed my answer
I'll move on)

Last night I tried to give a very simple explanation at the cell level. Only it ended up not so simple and I also missed out a huge amount in trying to simplify it. It's also just one part of a big picture with lots of other bits: the influence of hormones (and insulin is one of them), You know the story of the blind man and the elephant all describing different bits but not giving a whole picture.

Lat night I was mulling over all the factors I know about, there are a lot... but I'm still absolutely certain my understanding is limited and no-one has all the answers in any case. My writing skills also aren't up to it , confusing rather than helping.


My solution (get out of jail card) is to direct people to the series on insulin resistance on Stephan Guyanets blog.
To put it into context Stephan Guyanet had a confrontation at a conference with Gary Taubes last year. One of the results was that Stephan wrote this and a series on obesity. He is a mainstream lipid researcher(but not one of the 'top' guys, they probably wouldn't blog )
It's in several parts and lays out his views as a mainstream researcher on what causes insulin resistance.
There are of cause those that disagree with his interpretations and they have a full reign in the comment sections of his blog.
http://wholehealthsource.blogspot.fr/20 ... ch-results

What is important to remember is that in many cases insulin resistance does vary according to weight. There is lots of evidence that if a person is overweight then losing quite a small percentage, by whatever diet, reduces insulin resistance

Phew . That post has taken 2 hours to write :crazy:

 

[borofergie]

Last night I tried to give a very simple explanation at the cell level. Only it ended up not so simple and I also missed out a huge amount in trying to simplify it. It's also just one part of a big picture with lots of other bits: the influence of hormones (and insulin is one of them), You know the story of the blind man and the elephant all describing different bits but not giving a whole picture.

I think that's the perfect description of the whole field at the moment, which is why the debate get polarised into of factions based on part of the story(Taubes being the most prominent example).

Lat night I was mulling over all the factors I know about, there are a lot... and I'm absolutely certain my understanding is limited and no-one has all the answers in any case. My writing skills also aren't up to it , confusing rather than helping.

I don't think that's true, but even if it is, you're easily the best that we've got...

My solution (get out of jail card) is to direct people to the series on insulin resistance on Stephan Guyanets blog.
To put it into context Stephan Guyanet had a confrontation at a conference with Gary Taubes last year. One of the results was that Stephan this and a series on obesity. He is a mainstream lipid researcher(but not one of the 'top' guys, they probably wouldn't blog )
It's in several parts and lays out his views as a mainstream researcher on what causes insulin resistance.
There are of cause those that disagree with his interpretations and they have a full reign in the comment sections of his blog.
http://wholehealthsource.blogspot.fr/20 ... ch-results

+1 on that. Guyanet's stuff is very good, but highly technical. It's worth sticking at it though.

 

[viviennem]

Mi 'ead 'urts......... :crazy: :***: :***:

Mine too! :crazy:

The "Noddy" way I understand it - probably culled from 'populist' writers, I admit, - is:

Insulin resistance happens when the receptor cells on the muscle cells 'resist' the activity of insulin - ie, stop accepting as much glucose from the bloodstream. The pancreas pumps out even more insulin in an attempt to get that glucose out of the blood. The muscles cells still aren't playing, and the blood glucose is still high, so the insulin (or something!) converts the glucose into fats, mainly triglycerides, and stuffs that into the fat cells. This results in an overworked pancreas, which leads to diabetes Type II.

It shows how insulin resistance can cause obesity.

Now, I know that is very simplistic, and definitely incomplete! It doesn't address how obesity causes insulin resistance. But it is at a suitable level for an idiiot (me. in this case :wink: ) and I'd be grateful if anyone can tell me that it's even a little bit correct.

Viv 8)

 

[xyzzy]

Thank you Viv. You've taken it back to a level that mere mortals (and sheep I suspect) can understand. So based on my original question have you got any idea how what you say which makes sense links with Pneus macrophage stuff which also made sense but is different and also the question in my second post about insulin resistance making you stupid?