Confused About Insulin Resistance

[Squire Fulwood]

I've been doing a lot of reading about insulin resistance. I'm not a scientist so it's hard going but I'm getting the gist. I think that IR underlies a lot of the weight issues in our society.

So do I.

 

[Brunneria]

Me too.

And I'm intimately acquainted with IR.

But (as I'm sure you have already read) there are other things that increase insulin resistance as well as a fatty liver. These include subcutaneous fat, hormone conditions (eg PCOS) and some drugs. There are probably more.

Plus there is also the question of scarring.

I was surprised to read this when I came across it, but now it seems perfectly obvious... A liver isn't designed to get fat and then defat. And rather like alcoholic cirrhosis of the liver, scars can develop in the liver. These scars can inhibit normal function.

So there is no guarantee that defattifying will restore normal liver function, or that it is even possible to get beneath the personal fat threshold, because the personal fat threshold changes over time, depending on many things, including age, liver scarring, fitness level, and all those other IR generating factors.

It's a hugely complex issue, and sadly it all boils down to the individual's body and lifestyle and environment, much of which is unquantifiable. Even if a person defats and 'reverses' their T2 at 40, and keeps the weight off, there is no guarantee they won't get the symptoms of D back, years later, as their PFT shifts downwards with age.

So it's unpredictable, variable and very frustrating!

 

[kesun]

But (as I'm sure you have already read) there are other things that increase insulin resistance as well as a fatty liver. These include subcutaneous fat, hormone conditions (eg PCOS) and some drugs. There are probably more.

Plus there is also the question of scarring.

That's very true. I don't normally have IR, and my insulin production is relatively mildly impaired, but in my last two pregnancies I developed IR. Both times once the pregnancy was over the IR apparently vanished, but I do wonder about scarring and whether I'm now more vulnerable to IR.

Unpredictable, variable and frustrating is about right!

Kate

 

[Miss_Dior]

Me too.

And I'm intimately acquainted with IR.

But (as I'm sure you have already read) there are other things that increase insulin resistance as well as a fatty liver. These include subcutaneous fat, hormone conditions (eg PCOS) and some drugs. There are probably more.

Plus there is also the question of scarring.

I was surprised to read this when I came across it, but now it seems perfectly obvious... A liver isn't designed to get fat and then defat. And rather like alcoholic cirrhosis of the liver, scars can develop in the liver. These scars can inhibit normal function.

So there is no guarantee that defattifying will restore normal liver function, or that it is even possible to get beneath the personal fat threshold, because the personal fat threshold changes over time, depending on many things, including age, liver scarring, fitness level, and all those other IR generating factors.

It's a hugely complex issue, and sadly it all boils down to the individual's body and lifestyle and environment, much of which is unquantifiable. Even if a person defats and 'reverses' their T2 at 40, and keeps the weight off, there is no guarantee they won't get the symptoms of D back, years later, as their PFT shifts downwards with age.

So it's unpredictable, variable and very frustrating!

Oh, absolutely, once you get the idea that you understand it all, you read something and, "it's complicated." My point is that learning about IR explained a lot.

For example, and I'm really ashamed to admit that, I used to scoff at people who said things like, "I only eat 1400 calories a day, and I gain weight." I would say, "that's not possible. You're undercounting. Most people have no idea how many calories they eat. What about the 400 extra calories in that peanut butter sandwich?" Like that.

Well, I've learned my less, it's true and I'm sorry for my former attitude. Yes, a lot of people really do eat minuscule amounts of calories and gain weight, or can't lose. Why? I'm convinced that it is IR.

What makes my former scoffing attitude really nuts is that I am one of those people who finds it difficult to lose on 1200 calories a day. I really have to cut my intake to semi-fasting. I don't maintain on 1400. So I began reflecting on my history. I started getting fat at age 10. I began to lean out by 14, but "stuff happened" and I weighed 186 by age 16.

I'll spare you the nasty details but as an adult I cycled between 140-150 and only by age 56 did I get a handle on this weight thing and go below 140. From 2012-2014 I was in the mid 130s. I had injuries...last winter was brutal. I backslid and my weight crept up to the low 140s. And I was almost totally sedentary. I realize this is not massively obese but given my lifetime of weight issues, it was enough to cause problems. (I had gone to 6.0 in January 2014 as well, but temporarily reversed it. Then back up again.)

Studies have shown that kids who have weight problems are at high risk for developing metabolic problems later in life. I count myself very lucky that I didn't develop T2. I think I have incredibly strong genes (Eastern European peasant genes, which gave me short legs and big muscles, ) but I do think that this lifetime of putting on weight (and taking it off), gave me a mild, but persistent case of IR. Perhaps the IR is a bit genetic as well - my ancestors getting thru feast and famine? Who knows. But I hope to "cure" this by losing the excess weight once and for all, so that I can eat more, but I'll never be able to eat like my SO, who can down a quart of milk and eat slices of cake at 10 PM. (He's very lean, fit man. Crazy active.)

I think that every parent should be on the lookout for weight problems in their kids. Because of the future health problems. Not because of fashion or style. Health!

 

[Miss_Dior]

That's very true. I don't normally have IR, and my insulin production is relatively mildly impaired, but in my last two pregnancies I developed IR. Both times once the pregnancy was over the IR apparently vanished, but I do wonder about scarring and whether I'm now more vulnerable to IR.

Unpredictable, variable and frustrating is about right!

Kate

As I said, I am no scientist, nor do I play one on the internet, but according to my reading IR is a response to overfeeding. It's as if your cells are saying, "stop feeding me! I've had enough! I need a break!" Perhaps pregnancy IR is your thrifty and efficient genes kicking into hyper-gear, saying "I'm being overfed" at normal food intake levels.

Fasting seem to benefit everyone - except children, pregnant women and the already very thin. In the distant past, pregnant women fasted, not by choice, but by necessity. Our species had to find a way to survive. Your deep ancestors got through a lot of difficulties and hard times to produce you. Now you have their genes, in a massively easier environment. When you got pregnant, your metabolism became very efficient. That's how I think of IR. It's not essentially a defect but a bodily defense. What is the body defending against?

Just a thought.

 

[Brunneria]

I'm unconvinced about fasting.

There's a huge buzz about it at the moment, and it may be about to have its day. Fung's work is impressive, and the 5:2 diet has had a huge mainstream following. Nothing wrong with that.

But most historic reasons for fasting had absolutely nothing to do with the reasons used today. Crop and hunting failure, or religious abstention do not, in my mind, provide historic justification for me to treat my body to a series of fasts.

I've actually used fasts before. 24 hrs, 72 hrs, a week. Fruit fasts (before I knew I was pre-D). Water fasts. Herb.

The results were not favourable. I never achieved the fasting 'high', I never stopped being hungry, I never felt well, and I lost ridiculously tiny amounts of weight.

The only fast I might consider is a fat fast because it would avoid sending my body into starvation, and it would encourage ketosis. But it wouldn't be low calorie - which doesn't suit my body. Going low calorie and fasting taught my body to switch to starvation mode and hoard fat at the drop of a hat. I've been paying for that for over 20 years. And I'm not the only person whose body reacts like that.

My 'thrifty gene' behaves as if it is on steroids.

 

[Squire Fulwood]

What is the body defending against?Just a thought.

It is probably not so much a defense but more a coping mechanism. Our ancestor was in dire straits when reduced to eating only leaves and roots so the body evolved an efficient process for using the carbs in them and saving any spare as fat. Since then we have learned to squeeze the essence out of leaves and roots and sell it in packets called flour and sugar. Bit of a shock for a coping mechanism.

Coupled with that is the foods on sale. Now I know that prepared foods have flour to bulk them and sugar to give them taste, walking round a supermarket is a whole new experience. The only stuff not made of flour and sugar seems to be the fresh meat aisle, the vegetable aisle and the hardware department.

All the fish cakes and fingers, kievs, goujons, nuggets, dippers, pizzas, bread, cakes and hundreds of other products of strange, non natural shapes and covered in breadcrumbs.

This is a personal view I have slowly come to after reading people like Briffa and Kendrick and many others.

 

[Indy51]

I posted this on another thread, but it definitely relates to this one too as it investigates why different people respond differently to fasting/calorie reduction: http://www.sciencedaily.com/releases/2015/05/150511162918.htm

I really think a lifetime of yo-yo dieting can screw up our metabolism big time

 

[Miss_Dior]

I've never had an easy time fasting either. I don't lose a lot of weight, but it's the only way that I do lose it. I try to do it only for 18 hours - eat a meal in the middle of the day, and it's 2 18 hour fasts. Yes, I'm hungry. But since I regulated my blood sugars, I'm mentally clear. My mental fog happens when my BGs are high, not when they're low. So it's a trade off. I'm hungry but alert, and I try to keep my eyes on the prize.

 

[Miss_Dior]

I posted this on another thread, but it definitely relates to this one too as it investigates why different people respond differently to fasting/calorie reduction: http://www.sciencedaily.com/releases/2015/05/150511162918.htm

I really think a lifetime of yo-yo dieting can screw up our metabolism big time

I've seen things like that. I came across a metabolic ward study that showed no weight loss in obese subjects. It was very depressing...I didn't bookmark it.

I think one of the mysteries is what really happens to insulin levels when BG rises. We take a rise in BG as a proxy/clue for insulin levels but who knows what's really going on? The models are based on "normal" people. (and mice.) They make it sound as if the body works brilliantly - you eat something and the body produces just the right amount of insulin and it all works perfectly. So you "should" be able to lose weight if you cut calories. Well, why do the experts think that people with metabolic issues follow their models?

Suppose as a result of eating sugary type carbs my body produces MORE insulin than it needs to clear the BG. Then I'm hungry again very quickly. Or, maybe my IR is preventing the glucose from getting into the cells...still hungry.

So many unknowns.

 

[Squire Fulwood]

I think one of the mysteries is what really happens to insulin levels when BG rises. We take a rise in BG as a proxy/clue for insulin levels but who knows what's really going on? The models are based on "normal" people. (and mice.) They make it sound as if the body works brilliantly - you eat something and the body produces just the right amount of insulin and it all works perfectly. So you "should" be able to lose weight if you cut calories. Well, why do the experts think that people with metabolic issues follow their models?

Suppose as a result of eating sugary type carbs my body produces MORE insulin than it needs to clear the BG. Then I'm hungry again very quickly. Or, maybe my IR is preventing the glucose from getting into the cells...still hungry.

So many unknowns.

Kendrick again.

"insulin makes you fat? Well who’d a thunk? Well, lots and lots of people actually. At which point, let me introduce you to the Pima Indians of North America. This race has an almost unbelievably high rate of type II diabetes. It is greater than 50%. Perhaps more. Are they obese, yes? Of course. However, of greater interest is that Pima Indians, long before they become obese and/or diabetic, produce far, far, more insulin than any other race"

Here is the full article.

http://drmalcolmkendrick.org/2015/01/23/thinking-about-obesity-and-diabetes/

 

[phoenix]

re the Kendrick article
The reasons why the Pima in the US have high rates of diabetes and obesity have been the subject of study for decades.
Importantly, the Pima as a "race" do not have high rates of diabetes, only those that are in the reservations of the US.
Their genetically identical cousins in the Sierra Mardre mountains in Mexico are not overweight and don't have a diabetes problem. They continue to eat nearer to their traditional diet (which was very high carb/fibre and much lower in fat) The diet eaten in the US reservations was very different, energy dense and nutrient poor.
There are other factors involved Far too much to go into here but this website gives a lot of information http://diabetes.niddk.nih.gov/dm/pubs/pima/obesity/obesity.htm
traditional diet of the Pima ie in the 19th century pre diabetes

We estimated that the traditional Pima diet, although seasonably variable, was ∼ 70–80% carbohydrate, 8–12% fat, and 12–18% protein

http://care.diabetesjournals.org/content/16/1/369.abstract

re fat cells and people who don't have any.ie generalised lipodystrophy’

. The current hypothesis accepted by many researchers is similar to Dr Kendrick's explanation. The difference as he says is in the order but there is a lot more to it than he suggests.

Fat is meant to stay in adipose cells ie fat cells. That's what they are for. That's the case with the very fat Sumo or even the many people who are overweight but not diabetic.
It's when they overspill that problems arrive
Rather than explain I will quote because it's hard to summarise any more than this.

"When the cells become full of as much fat they can hold, and there is obviously an upper limit for the cells, they become dysfunctional. When fatty acids cannot be easily used as fuel in the body and in the metabolism, or be deposited as reserve energy and triglyceride in the fat cells ,the accumulation of free fatty acids and also, mono and diglyceride takes place.
These compounds are toxic and the so called state of lipotoxicity develops. This initiates inflammatory signaling from the cells as if they were foreign bodies They may die so called apoptosis and they made they initiate local inflammation and the formation of collagen networks around the cells, like the fibrosis occurring in other inflamed tissues.
The state of lipotoxicity and inflammatory process and signals make tthe cells insulin resistant, which in this context may be seen as a defense mechanism since insulin blocks the release of fat from the cells"

The body doesn't want that fat to overflow and be deposited elsewhere in the liver or around the pancreas because that leads to further problems .

The process may also effect the beta cells in the pancreatic islets, and thereby impede their ability to respond to increase needs of insulin to overcome the insulin resistance and to maintain glucose homeostasis. Assuming this theory to be true, it nicely explains how diabetes is related to overweight and obesity. To apply this theory however, we need to assume that there are considerable individual differences in the fat storage capacity.
That greater BMI is associated with increased risk of diabetes is explained by the increasing likelihood that the greater the fat mass, the more people have used those capacity for storage of fat. Thus paving the way to insulin resistance by continuous fat overloading. It also explains why only some of the people with high BMI get diabetes. Those who don't get diabetes are not filled their fat depots up to the limits and hence have not reached the step that elicit the processes that induce insulin resistance..................... On the other hand, the theory explains why some people with normal or even low BMI may run an increased risk of diabetes. They have a small capacity to store fat, they may essentially fill up the stores and initiate the processes leading to insulin resistance. In the most extreme cases, this is seen in patients with lipodystrophy, where the adipose tissue does not work properly for various reasons, such as genetic disorders or side effects to some drugs

Thorkild I A Sorensen, Professor of Metabolic and Clinical Epidemiology Faculty of Health and Medical Sciences, University of Copenhagen.( part of lecture from Coursera Global diabetes course)

This is very much the theory behind Dr Taylors research. He has been able to produce images of fat deposited around the liver and pancreas. When this is reduced and fat is back to where it should be in the fat cells then people become less insulin resistant.Just as above he suggests that people have their own individual fat thresholds.

Primer on fat storage http://science.howstuffworks.com/life/cellular-microscopic/fat-cell2.htm

 

[Miss_Dior]

re the Kendrick article
The reasons why the Pima in the US have high rates of diabetes and obesity have been the subject of study for decades.
Importantly, the Pima as a "race" do not have high rates of diabetes, only those that are in the reservations of the US.
Their genetically identical cousins in the Sierra Mardre mountains in Mexico are not overweight and don't have a diabetes problem. They continue to eat nearer to their traditional diet (which was very high carb/fibre and much lower in fat) The diet eaten in the US reservations was very different, energy dense and nutrient poor.
There are other factors involved Far too much to go into here but this website gives a lot of information http://diabetes.niddk.nih.gov/dm/pubs/pima/obesity/obesity.htm
traditional diet of the Pima ie in the 19th century pre diabetes

http://care.diabetesjournals.org/content/16/1/369.abstract

re fat cells and people who don't have any.ie generalised lipodystrophy’

. The current hypothesis accepted by many researchers is similar to Dr Kendrick's explanation. The difference as he says is in the order but there is a lot more to it than he suggests.

Fat is meant to stay in adipose cells ie fat cells. That's what they are for. That's the case with the very fat Sumo or even the many people who are overweight but not diabetic.
It's when they overspill that problems arrive
Rather than explain I will quote because it's hard to summarise any more than this.



The body doesn't want that fat to overflow and be deposited elsewhere in the liver or around the pancreas because that leads to further problems .



Thorkild I A Sorensen, Professor of Metabolic and Clinical Epidemiology Faculty of Health and Medical Sciences, University of Copenhagen.( part of lecture from Coursera Global diabetes course)

This is very much the theory behind Dr Taylors research. He has been able to produce images of fat deposited around the liver and pancreas. When this is reduced and fat is back to where it should be in the fat cells then people become less insulin resistant.Just as above he suggests that people have their own individual fat thresholds.

Primer on fat storage http://science.howstuffworks.com/life/cellular-microscopic/fat-cell2.htm

Thanks for posting those links. Right, the Pima in Mexico (which is also North America) are not fat. Nor were the US Pima historically, and they certainly did eat a carb-heavy diet.

The Kendrick article made my blood boil. I know he's a hero to a lot of people but tough, it was fallaciously argued and sloppily reasoned. He left out facts that didn't suit his agenda.

The Pima of "North America" are obese and diabetic. Wrong. The Mexican Pima are fine.

Sumo wrestlers have a zero incidence of diabetes. Wrong, as an easy check of Pubmed shows:

The incidence of diabetes mellitus, gout, and hypertension in wrestlers was 5.2, 6.3, and 8.3%, respectively, all values being considerably higher than in controls.

He scoffed at scientific work in a university "You made a breakthrough discovery of the absolute bleeding obvious." No, they demonstrated how an observed pathway functions on a metabolic level. That's science.

"The reason why you die in type I diabetes has little to do with blood sugar levels." Um, no one ever said it did.

" Yes, carbohydrates would cause the greatest rise in insulin levels." Not so simple. Has Kendrick ever heard of the insulin index?

Kendrick is the only guy who notices that there's a difference between insulin response and BG. From the previous link: "Thus, postprandial insulin responses are not always proportional to blood glucose concentrations or to a meal's total carbohydrate content."

Last but not least, he's tilting at a windmill that's already been demolished (obesity=T2D), and offering an explanation that based on incomplete or distorted facts.

Gary Taubes also got the Pima wrong. He also wants you to think that carbs = insulin = diabesity. This isn't a political forum so I'll keep my opinions to myself, but I think it's relevant to point out that after their land was stolen and they were dispossessed, the government kindly sent them rations, made up of what we would call "junk food" today. Still, their diabetes rates only shot up after WWII. Why? Maybe they just weren't eating that much, even of the junk. They were still scrubbing out a living in a nearly waterless part of the desert, their carefully tended water resources having been taken by the US Government to give to white farmers. In the Pima, obesity and diabetes are almost a match, which is not so with South Indians, whose "personal fat threshold" (Prof. Taylor's phrase) appears to be much lower. They weren't fat, so they didn't get diabetes. What about their insulin levels then? I don't know.

Also, I think their prolonged period of starvation in the late 19th century might have done something epigenetically. The children of survivors of the Dutch famine were noted to have higher rates of diabetes than other kids of same cohort. Sorry, don't have time to cite - google it. They had undergone periods of scarcity historically, but not prolonged famine.

Anyway the Pima story story to me is that there are good carbs and bad carbs. And prolonged starvation is deeply damaging to the genome. Who'da thunk?

 

[Miss_Dior]

re the Kendrick article
The reasons why the Pima in the US have high rates of diabetes and obesity have been the subject of study for decades.
Importantly, the Pima as a "race" do not have high rates of diabetes, only those that are in the reservations of the US.
Their genetically identical cousins in the Sierra Mardre mountains in Mexico are not overweight and don't have a diabetes problem. They continue to eat nearer to their traditional diet (which was very high carb/fibre and much lower in fat) The diet eaten in the US reservations was very different, energy dense and nutrient poor.
There are other factors involved Far too much to go into here but this website gives a lot of information http://diabetes.niddk.nih.gov/dm/pubs/pima/obesity/obesity.htm
traditional diet of the Pima ie in the 19th century pre diabetes

http://care.diabetesjournals.org/content/16/1/369.abstract

re fat cells and people who don't have any.ie generalised lipodystrophy’

. The current hypothesis accepted by many researchers is similar to Dr Kendrick's explanation. The difference as he says is in the order but there is a lot more to it than he suggests.

Fat is meant to stay in adipose cells ie fat cells. That's what they are for. That's the case with the very fat Sumo or even the many people who are overweight but not diabetic.
It's when they overspill that problems arrive
Rather than explain I will quote because it's hard to summarise any more than this.



The body doesn't want that fat to overflow and be deposited elsewhere in the liver or around the pancreas because that leads to further problems .



Thorkild I A Sorensen, Professor of Metabolic and Clinical Epidemiology Faculty of Health and Medical Sciences, University of Copenhagen.( part of lecture from Coursera Global diabetes course)

This is very much the theory behind Dr Taylors research. He has been able to produce images of fat deposited around the liver and pancreas. When this is reduced and fat is back to where it should be in the fat cells then people become less insulin resistant.Just as above he suggests that people have their own individual fat thresholds.

Primer on fat storage http://science.howstuffworks.com/life/cellular-microscopic/fat-cell2.htm

Another thought about the Tohono O'odham people*. Their traditional diet is very low in fat. And they were quite active, desert adapted people. Taubes stated in his book that anthropologists did not note a high level of activity. My response to that is the anthropologists he is quoting saw them in the 1890s, when they were defeated, depressed and living on government rations. They were NOT living their traditional lifestyle. I invite anyone to visit the Sonoran Desert, imagine what it was like to farm there, and conclude that these people were not getting loads of exercise. They just didn't run around the place looking for it. Anthropologists have been known to get things badly wrong.

This is just an observation, but I wonder whether a people who adapted nicely to an extremely low-fat diet have problems metabolizing fat. Especially in the context of a lard-white flour diet. Going from an active lifestyle, eating healthy fruits and vegetables and grains (nixtamalized maize) to government ration slop? No wonder they became diabetic!

*I'm the last person in the world to be politically correct, but I think people should be called by the name that they choose. Pima is an outmoded word that the Spaniards stuck on them. They call themselves the Tohono O'odham (pronounced oh-oh-tham). Being gracious people they don't mind if you refer to them as "T.O."s. I'm getting off my soapbox now.

 

[Jaylee]

This is a realy interesting thread... Are there any accounts regarding India's high number of Diabetics.??

 

[Roytaylorjasonfunglover]

This is a realy interesting thread... Are there any accounts regarding India's high number of Diabetics.??

Bmi is not really a good indicator of diabetes risk, it is what kind of fat that you have, how much of it, and where it is stored that is important.
This article explains it very nicely, and may give a clue why indians are particulary at risk.
http://www.nature.com/nm/journal/v10/n4/full/nm0404-325.html

Here is a picture that explains the article, the one the left has bodyfat of 9.1% the one the right has 21.2 %, and their bmi is the same!
http://www.nature.com/nm/journal/v10/n4/images/nm0404-325-I2.jpg

Genetics matter, and if you are of asian or black ethnicity, your diabetes risk is totally different from somebody caucasian, and that is because these groups store fat differently.

 

[phoenix]

This is a realy interesting thread... Are there any accounts regarding India's high number of Diabetics.??

The fat overspill theory is a simple answer that accounts for this ; groups with certain genetics have fewer fat cells but you probably have to go beyond genetics. There are many factors that may play a part.Heres one researches ideas http://www.hindawi.com/journals/ije/2014/593982/



I find epigenetics to be fascinating and it's the 'hot' area of research. Genes get passed on from parents but DNA is bound up in coils and around spindles (it has to be or it wouldn't fit in the nucleus) The way it is bound up alters which genes are able to be read If a gene isn't accessible for reading then it can't be expressed . Epigenetic modifications can occur during life but these only affect individual cells (which can then be replicated but not every cell will be affected.) Much more important are epigentic changes in Utero when there are far less cells and these will then be replicated to form the trillions in the body. See the 'epigenetics mechanisms diagram on this wiki page (the article is complicated)
Children of mothers that were malnourished during the Dutch Hunger winter are believed to have suffered epigentic changes that predisposed themto type 2. Similarly, in Cambodia, where there was almost no diabetes before ,it rose 30 years after the end of the Pol Pot regime . In SE Asia as a whole , , mothers who were undernourished during pregnancy have small birth weight babies who have a greater risk of T2 in later life. Malnutrition may though not always include undernourishment , it may be that nutrient poor high calories also have epigenetic effects
Unfortunately it seems that these epigenetic changes may be passed to the next generation. (and fathers may have an influence too!)
epigenetics and diet
http://learn.genetics.utah.edu/content/epigenetics/nutrition/
also
http://www.naturalhistorymag.com/features/142195/beyond-dna-epigenetics

 

[Miss_Dior]

Yes, epigenetics may be one of the reasons the TO's have such a high diabetes rate.