Our food should be our medicine. Our medicine should be our food. But to eat when you are sick, is to feed your sickness. Hippocrates

The best of all medicines are rest and fasting Benjamin Franklin

In the article, insulin resistance is defined as:

, and contextually as:

In the first quote, the actual definition is always in the context of glucose-preferred-fuel, i.e. the standard test for insulin resistance is oral glucose tolerance (OGTT). From the result of this test - blood glucose level at a point in time post-test - insulin resistance is assessed by proxy, not directly, through the assumption that since glucose is the preferred fuel, and since blood glucose is not "cleared" quickly enough, and since insulin is the hormone that "pushes" glucose inside cells, then cells must be resistant to insulin. The term "cells" refers generally to all cells, not specific cells.

A more appropriate definition of insulin resistance needs a few corrections. For example, the bulk of glucose from the gut is "cleared" by the liver itself. This is done primarily through insulin, the bulk of which is also cleared (not in quotes here, because insulin is actually cleared by degradation, unlike glucose which is merely stored by conversion to glycogen) by the liver with insulin-degrading enzyme. This means that it's not all cells that are insulin resistant, as the case may be, it's just the liver cells. When that happens, the liver doesn't do its job, blood glucose lingers, until blood glucose is cleared by other organs like the brain for example.

But there's a big problem with the whole idea. The liver does not actually resist insulin at any point. On the contrary, even in the most extreme cases of diabetes type 2, the liver will continue to normally receive - and respond to - insulin, which will inhibit ketogenesis as its first act. Proof is in the blood - zero ketones. If the liver was truly resistant to insulin, there would be lots of ketones. In fact, "insulin resistance" is deemed to be akin to absence of insulin, and in this case - diabetes type 1 - there is no insulin, and there's tons of ketones.

Furthermore, an obscure experiment with dogs and insulin shows insulin causes atherosclerosis directly. We could be dealing with some misunderstood insulin resistance, but we're certainly dealing with hyperinsulinemia. This means the conclusion "there is not enough insulin" is patently false.

The point is there is an obvious lack of genuine expertise in the field when it comes to insulin, the liver and their interaction, and the effect of insulin on heart disease itself. I certainly agree that the standard model is horribly flawed, but I also question vague alternative hypotheses even when they come from respected people.

This suggests that it is the inflammatory effects of insulin which create the poor health outcomes?

I don't know if insulin causes inflammation, or if the disease process of atherosclerosis involves inflammation. I think it's possible that inflammation is not an a priori, but once it's there the disease accelerates, i.e. an infection for example.

Inflammation is not a disease in and of itself, but a response to disease, particularly acute conditions, i.e. injury. Atherosclerosis can be seen as an injury of the arterial wall, so inflammation would occur as a response to this injury. If the injury is chronic through hyperinsulinemia (or through some other chronic cause like a bacteria or something), then inflammation would also be chronic. So in that sense insulin causes injury to the arterial wall, but I don't know the specific mechanism.

In my understanding of the actions of insulin, I think the mechanism is deregulation of various cellular processes, most importantly fuel and enzymes, specifically with hyperinsulinemia, normal insulin level shouldn't cause disease since it regulates processes normally. Just like in liver cells, insulin shuts down ketogenesis in all cells, but I think I don't have to invoke this, since the lack of ketogenesis in the liver alone is enough to explain fuel deregulation in all cells that require ketones.

In the other extreme - diabetes type 1 where there's no insulin - there's no synthesis of various things essential to cellular functions like enzymes and protein for example, yet there's tons of fuel as glucose and ketones. And apparently, there's no atherosclerosis either. We could conclude that glucose itself is not the agent that causes the injury to the arterial wall, but merely the trigger. With a high-carb diet, there's lots of glucose coming in, so there's lots of insulin produced to handle that, and we now have a better overall picture of the sequence.

But it's not a complete picture. A high-carb diet is not the only cause, it's just the primary cause. This is in line with the idea that going low-carb can be used as a diagnostic tool to expose underlying conditions that also act the same way as a high-carb diet, i.e. causes hyperinsulinemia. So now we look at the PPAR-x pathways in the liver, where insulin-degrading enzyme does its thing to degrade insulin. When there's no IDE, insulin rises. However, this means BG should go down, but it doesn't, so when IDE is intefered with, there must some parallel effect on glycogenolysis or glucogenesis going on, maybe glucagon or other hormones that stimulates glucose release and/or production from the liver.

But again it's not a complete picture. I don't see how insulin causes injury, there must be something else going on. I bet on some pathogen. All bacteria - all pathogens - are opportunistic in nature, they will do what they do the instant the opportunity presents itself. Well, when cellular processes are disrupted all over the place, that's the opportunity. It's a bit like a supermarket that loses its doors so it remains open at night but doesn't have anybody working there at that time, so even people who are not bad just walk in and take whatever they want, rather than just the really bad people who would otherwise break in. See? Opportunistic pathogens will take over once there's hyperinsulinemia to deregulate standard cellular defenses.

We have all kinds of pathogens all the time, but they never bother us normally because we can handle them just fine when everything's working right. On the skin, tons of them, no problem. In the gut, tons of them, no problem. Tonsils, appendix, tons of them, no problem.

Pathogens are living things, they evolve and adapt. It's likely that some have adapted to at least maintain their preferred environent, once this environment has been established a priori, if they haven't developed a means to create this environment in the first place. In there somewhere, it's possible that those pathogens have the ability to deregulate the PPAR-x pathways and IDE so that insulin is not degraded, so that the cellular processes that normally handle those pathogens don't work properly.

Throughout all this, inflammation will invariably come into play (because we're talking injury), but not necessarily as an initial causal factor.

Don't take any of this too seriously, I just thought this up in a few minutes. Anyways, any of this make sense to you?

Well, for mainstream nutritionists, most doctors and the media they're not.

Still, the common denominator among centenarians is low insulin levels. Insulin resistance leads to the opposite.

I was following you until here ...

I agree insulin inhibits ketogenesis.


No, because there is alot of insulin around.
Anything but low insulin = No ketogenesis.

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In fact, "insulin resistance" is deemed to be akin to absence relative deficiency of insulin, and in this case - diabetes type 1 - there is no insulin, and there's tons of ketones.
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There is excess of insulin in Type 2 diabetes.
Anything but low insulin = No ketogenesis.

Feel free to ask questions.

FWIW, the idea that "type 2 is like type 1 because of a "relative lack" of insulin" .... is a misleading line of thinking. It explains the hyperglycemia but ignores insulin and insulin resistance.
Type 2 and 1 one are entirely different diseases and one of them should be renamed to highlight this. While discussing Diabetes Type II, there should be no references to Type I (to avoid needless confusion, simple is good) They are different diseases and the audiences dont really overlap. The overlap (MODY etc) is acceptable in professional discussion but

Type 2 = super high insulin, sugars high, insulin resistance high
Type 1 = no insulin, sugars high, insulin resistance low (until you start injecting insulin). Type 1 can have high insulin resistance if they become obese eating carbs. They usually are super skinny to start ... as they haven't had insulin for a while ... as their beta cells were being killed by their immune systems.

Hope that helps.

Feel free to ask questions.

Have you ever seen a chubby 100 year old ?