The initial cause of insulin resistance

[Burak]

Since I haven't seen it anywhere, I wanted to share my theory after couple of observations and skimming some PubMed studies:

 

First of all, we know that only carbs and protein causes insulin secretion but not fats. When the blood levels of some EAA and BCAAs increase, insulin levels also increase (most likely to send those AA to cells to protein synthesis, but the reason doesn't matter). However, at the same time, increased insulin levels also increase glucose transfer to the muscle cells with elevated rate. Without the excess protein, glucose metabolism would be perfect, but now body has more insulin to regulate glucose, and hence the roller coaster begins. Glucose lover brain doesn't like this of course, especially low glucose levels after insulin overshoot, so as a natural response muscles and liver become more resistance to insulin to absorb less glucose (in order to compensate of increased insulin levels). For example, this natural change also occurs in pregnant women in order to prevent muscles to suck up too much glucose so that baby's brain development doesn't hurt.

 

This process is also completely reversible, backing that it is just an adaptation for this new situation. For example, with plant based diet you normalize EAA intake to ust above RDA levels and eat plant protein to prevent rapid absorption. Pancreas starts to secretes less and less insulin ( and in a more balanced way, without roller coaster) and your muscles start to adapt these new insulin levels, and voalá in a couple of weeks you back to normal.  

 

Elevated free fatty acid levels (high insulin levels prevent to shift to fat oxidation) comes later, then hyperlipidemia, weight gain, and metabolic syndrome and so on.

 

I was lazy, I didn't make references, but what I present here is very basic that almost everyone who follows this forum should have the knowledge.

[Todd Allen]

Carbs and protein both provoke an insulin response.  Typically carbs produce a stronger response than protein, especially high glycemic ones though some amino acids such as BCAAs produce a strong response too.  Most people eat more grams of carbs than protein and considering there is no minimum requirement for carbohydrate but you absolutely need some protein it seems improper to single out excess protein as the problem.  I think it better to state it as excess carbs & protein, regardless of the balance struck between them.

[mccoy]

Like Todd says, whey proteins seem to be pretty insulin-stymulant, hence the known anabolic properties of milk and dairy products which contain whey, even if they exhibit a very small glycaemic load.

[Burak]

Thank you for your comments. The important point is that insulin both regulates and its level is affected by AA and glucose in the blood. I always questioned why they are regulated by a single hormone but I think the answer is clear now. We cannot separate protein from food, therefore whenever food comes it comes with some protein. To body, there is no need for additional hormone to regulate protein and carbs differently. We should also note that although we are omnivores, we descended from herbivore origins unlike i.e. dogs which have carnivore origins. We are not adapted to eat too much protein (especially high AA foods without fiber), we only eat them when we were able to find them and in small quantities, i.e. scavenging whatever left or catching small mammals. 

 

The problem begins when you ingest protein (animal protein- high AA without fiber - high insulin response) and carbs (sugar or refined carbs - faster absorption without fiber) separately without the perfect harmony like in plants, you destroy this finely balanced system. When you ingest easy protein (animal protein), it increases insulin levels more than to regulate what we eat as carbs, therefore the rate of glucose transfer to muscle is faster than desired (sudden drop of glucose levels are especially not wanted by brain). For carbohydrate case, you overshoot insulin because of glucose spike, and again this time you have more insulin than you actually need. As a response, muscles need to be less sensitive to onset this imbalance, then insulin roller coaster leads to less glucose fluctuations in the blood which actually is a good thing. However, if this insensitivity goes for a long time, then complications begin to occur (impaired glucose and lipid metabolism, inability to burn fat as fuel, wight gain etc.).

[Todd Allen]

Another aspect to consider is that many tissues respond to insulin such as liver, muscle, fat, nerves and bone.  The degree of insulin resistance can vary in these tissues and they seem to have differing triggers.  For example alcohol and fructose have both been implicated in hepatic insulin resistance.  It appears my disease first aggravates insulin resistance in skeletal muscle.  And genes play a role in adipose tissue retaining insulin sensitivity.  Apparently the healthy case is people who can very readily generate new fat cells and easily gain weight with rapid accumulation off subcutaneous fat which keeps viscceral fat low.  In this case their adipose tissue remains highly insulin sensitive protecting their liver and other organs allowing them to become quite obese with minimal health impact.

 

In my case I believe I developed a high degree of insulin insensitivity while eating a very low fat, low protein diet having tried veganism for a few years and vegetarianism for more than 20.  I believe what did me in was too much sugar and starch, fruit juices, honey, maple syrup and lots of processed grains.  After regaining some degree of  insulin sensitivity by eliminating the problematic carbs I find I now benefit from intentionally spiking highly insulinogenic protein such as using BCAAs and whey protein concentrate which now produces a pronounced anabolic effect in muscle.

 

We can choose to use insulin to help us convert sugar into fat or to use insulin to help us build muscle from amino acids.  There are limits in each case and if we over do it we will get into trouble.  I suspect the government nutritional guidelines to minimize fat, the least problematic macro nutrient with respect to insulin, has contributed to the growing epidemic of diabesity and has brought us stores full of "heart healthy" frankenfoods such as power bars chock full of fast digesting sugars and protein.

[mccoy]

Todd, it must be said that, like everything else, it also depends upon people. Some guys like myself are apparently insulin sensitive. If I cut my significant daily quota of carbs I start loosing weight precipitously.

Also, the specific context is vital. In your case, for example, because of your condition you are trying to max up MPS and boosting the Leucine + amminos signal and that's probably a sensible strategy. The Insulin-IGF-1 signal is superseded by the mechanical stimulus, especially so after our 20's (at a younger age hormones apparently govern growth).

 

In a T2D context, people may want to avoid or strictly limit  fruit and its simple sugars.

 

In my personal context, no conditions, presence of exercise, no excess bodyweight, I thrive with abundant fruit.

[Burak]

This study supports my idea that it is protein (probably only animal protein or isolated&concentrated plant proteins) which is the major contributor rather than fats and carbs:

 

----------

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797984/

 

Dietary Intake of Total, Animal, and Vegetable Protein and Risk of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL Study

 

Abstract

OBJECTIVE

 

Dietary recommendations are focused mainly on relative dietary fat and carbohydrate content in relation to diabetes risk. Meanwhile, high-protein diets may contribute to disturbance of glucose metabolism, but evidence from prospective studies is scarce. We examined the association among dietary total, vegetable, and animal protein intake and diabetes incidence and whether consuming 5 energy % from protein at the expense of 5 energy % from either carbohydrates or fat was associated with diabetes risk.

 

RESEARCH DESIGN AND METHODS

 

A prospective cohort study was conducted among 38,094 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Dietary protein intake was measured with a validated food frequency questionnaire. Incident diabetes was verified against medical records.

 

RESULTS

 

During 10 years of follow-up, 918 incident cases of diabetes were documented. Diabetes risk increased with higher total protein (hazard ratio 2.15 [95% CI 1.77–2.60] highest vs. lowest quartile) and animal protein (2.18 [1.80–2.63]) intake. Adjustment for confounders did not materially change these results. Further adjustment for adiposity measures attenuated the associations. Vegetable protein was not related to diabetes. Consuming 5 energy % from total or animal protein at the expense of 5 energy % from carbohydrates or fat increased diabetes risk.

 

CONCLUSIONS

 

Diets high in animal protein are associated with an increased diabetes risk. Our findings also suggest a similar association for total protein itself instead of only animal sources. Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk. This finding indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful.

 

In this study, high total and animal protein intake, but not vegetable protein intake, was associated with increased diabetes risk. This relation was not explained by specific protein sources such as meat or by weight change during follow-up but was attenuated after adjustment for baseline adiposity measures. Consuming 5 energy % from protein at the expense of 5 energy % from carbohydrate or fat increased diabetes risk by ∼30%.

----------

 

 

30% is pretty high and this for diabetes risk. I assume that the risk for insulin resistance will be higher since it is much easier to develop by definition.

[Mechanism]

Edited

[Mechanism]

Edited

[Mechanism]

Edited

[Burak]

Here is Rosedale's opinion (thanks to mccoy for referencing him) on this issue, which is very similar to what I theorized here:

 

http://drrosedale.com/blog/2011/11/21/ron-rosedale-protein-the-good-the-bad-and-the-ugly/#ixzz3kqwMcoCJ

[mccoy]

Hi Burak, Ron Rosedale's stance on proteins caused a bit of a stir in the paleo world and a schism with the proponents of high protein, Taubes, Eades et al.

 

Actually, the quantities he proposes for healthy people are pretty low. 0.7 g d-1 kg-1 of lean body mass. It is a real protein restriction. But also pls note that his staff suggests 1 g d-1 kg-1, plus 5 to 10 extra grams to those who are physically active. It's confounding perhaps, but I think that they may be afraid of the legal consequences.

 

Dr Rosedale thinks that insulin resistance (and leptin resistance) is caused by an elevated amount of protein, by the illustrated mechanisms. The noxious effects of high protein and its link with obesity have been suggested by other medical doctors (for example, Dr Garth Davis of 'proteaholic').

 

Fat is the only good guy, which is the opposite of what Dr Neil Barnard contends, with his IML theory.

 

I tried a vegetarian version of Dr. Rosedale's diet but I was really loosing weight and muscle mass. If rigorously applied, it might cause starvation to lean individuals, since protein is little, carbs is low and you really get fed up with unlimited fat. It is really never unlimited, since eating much fat without carbs is difficult.

 

All in all, I believe that Rosedale's approach is the healthiest in the paleo world. It's very good for overweight people, since they benefit from loosing weight plus hae teh health benefits of inhibiting mTOR.

But in some people, like my wife, who followed Rosedale's suggestions, weightloss is limited, so fats, especially saturated fats, must have probably a role after all.

 

Most probably, the initial cause of insulin resistance is a very complex issue. Stephen Guyenet tackles this issue in his blog, attributing IR to cellular energy excess. It's a different angle but it captures the complexity of the mechanisms involved.

 

So far we have the following proposals:

 

• chronically high carbs
• chronically high proteins
• chronically high fats
• chronically high energy (blood glucose+fatty acids)

[Sibiriak]

 

Dietary Intake of Total, Animal, and Vegetable Protein and Risk of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL Study

 

"Further adjustment for adiposity measures attenuated the associations"

 

How critical is that qualification?

[Sibiriak]

 

Mechanism:

 

In high-carb Blue Zones such as Okinawa the rate of dementia is still exceedingly low ( 1/4 rate of US), again begging the question why go ketogenic if you can have a healthy low GI plant based Whole Foods diet, given the mice and other data suggesting optimized longevity and health for higher carbohydrate and moderate fat intake...

 

I came to the conclusion that Ron Rosedale was a diet dogmatist,  not a critical thinker,  after watching the "Safe Starches" panel discussion:

 

 

I was particularly struck by his terse, total denial that the Okinawan diet was in fact high-carbohydrate--a topic raised by Chris Kresser.   (There were many other problems with his arguments as well, but I won't go into them.)

 

Cate Shanahan also rejected the claim that the Okinawan diet was high-carb based on her experiences with Okinawans living in Hawaii.   Her argument is strikingly illogical, imo.

 

If you want to watch the exchange, I'd start with Cris Kresser at 24 minutes into the video approximately.   It's really quite revealing.

[mccoy]

I came to the conclusion that Ron Rosedale was a diet dogmatist,  not a critical thinker...

 

 

Yes, he's too much into denial, maybe prompted by professional bias (he's been curing patients affected by diabetes and metabolyc syndrome for a long time).

 

The Okinawans eating lots of fish? What's his source? Of course they don't eat only red potatoes and eat lots of vegetables, but apparently many families eat fish very rarely, notwithstanding they are amidst the ocean. And their diet is most surely very, very different from the Rosedale's ketogenic diet.

 

His objections on the kitavans are also a little off-kilter. They are not renowned for their longevity, rather for the fact that they are metabolically very healthy, and this according to his theory should not turn out to be true, in a population living mainly off starches, fruit, coconut.

 

Also, insisting on our metabolic commonalities is biased, since it is all too evident that there are commonalities and a large variability inside the commonality.

 

I admire him for his innovative ideas and the fact that he rigthly underlined the dangers of too many protein. But some other times he just drifts away, carried by his one-sidedness.

[mccoy]

 

 

Dietary Intake of Total, Animal, and Vegetable Protein and Risk of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL Study

 

"Further adjustment for adiposity measures attenuated the associations"

 

How critical is that qualification?

 

 

In table 2, model 4, corrected for WC and BMI (indexes of adiposity) we see that the increased HR between 4th and 1st quantile is no more statistically significant, not even at the p<0.05 level. That means that we cannot draw statistical conclusions from a model adjusted for those markers of adiposity. I daresay that the qualification may be pretty critical, because a normalization for adiposity ceases to support the main thesis of the authors, hence such variable may account for a significant quota of correlation.

[Sibiriak]

@mccoy

 

Thanks for the insightful responses.

[mccoy]

You are welcome Sibiriak, it should be noticed that the authors have been honest including that clarification more than once and this adds to their credibility. Sometimes such details, are just concealed.