Etiology, the path to diabetes (T2DM) and heart failure

The etiology deals with the causes of diseases. It is not about risk factors, but about the real causes. If the cause is, the disease arises, if it is not, the disease does not arise. It is so simple as this, when the etiology of the disease is known.

Do we know the etiology of type 2 diabetes? The one you grow yourself?

In this picture, you can see how diabetes gradually develops from obesity (OB) through inconspicuous glucose intolerance (OB-GLUINTOL) to diabetes (OB-DIAB), first with high insulin and gradually with less and less insulin production. At the same time, you can see in the upper graph a gradually decreasing rate of glucose uptake from the blood, which is compensated by the increasing secretion of insulin, so you will not know anything with standard fasting blood glucose measurements. You can easily recognize it by the OGTT test in the chart below, but no one does it. So it continues farther until you reach the maximum insulin and then you gradually follow the path to more and more irreversible changes in the body. Then you suddenly want to start solving it? Really?

Your doctor will only identify the problem when the insulin curve is behind the peak. Only when the changes are almost irreversible. If you have at least a little common sense, don't let it go that far. And this is not about obesity. We will show that the production and storage of fats is just a rescue mechanism.

What you will not see in the picture above is the level of free fatty acids, which is essential for finding the causes, but unfortunately often neglected and not measured.

We must use rat model studies to truly assess the etiology.

The model has the advantage that changes take place quickly. Follow the ZDF curves. It's like in palm of your hand, within ten weeks, rats can get diabetes. But watch what precedes it. The first changes take place on the free fatty acids curve (middle graph) long before the glucose level changes. Free fatty acids (FFA, NEFA) are the fuel for mitochondria. ZDF mice are obese, so their adipose tissue releases more and more free fatty acids over time through lipolysis. However, the tissues cannot burn this amount, the supply exceeds the demand, so their level is gradually rising. Thus, free fatty acids must be repackaged in the liver in VLDL trucks and sent back to adipose tissue if everything is still working well.

However, it can happen that adipose tissues no longer absorb more fat, the level of free fatty acids rises permanently. It is then a vicious circle. Fat begins to accumulate even where it does not normally do so, eg in the cells of the liver or pancreas (islet TG in the lower graph). But we are still talking about intelligent rescue mechanisms. Nothing that the body does is wrong. If it can be gained on adipose tissue, that's fine (ask Asians who can't). If this did not work, the level of free fatty acids would increase even more and many more cells would die. That needs to be understood.

Similarly, the deposition of triglycerides in pancreatic beta cells is a rescue mechanism that prolongs cell life under conditions of high levels of free fatty acids. However, relatively soon it reaches the limit, the beta cell no longer takes more triglycerides and dies from the toxicity of high levels of free fatty acids. This lowers insulin production, raises glucose levels, and you have diabetes.

This process seems clear. Elevated levels of long free fatty acids are the etiological cause of diabetes, but also of high blood pressure, obesity, high insulin, high glycemia, vascular disorders, etc. High levels of free fatty acids are toxic to cells. But not all fatty acids are equally toxic. In its basic state, it doesn't have to be toxic at all. It depends on how stable each fatty acid is, whether it easily peroxidizes, whether it is converted to other toxins. Here it turns out that saturated fats are the most stable. The worst off are polyunsaturated fatty acids (PUFAs), which are subject to peroxidation and decomposition into toxic products. So it is not good to have too many in the body and they should not circulate at all in an endless cycle between the release from adipose tissue and re-deposition. Without increased levels of free fatty acids, diabetes will not develop.

When we examine when and under what conditions the free fatty acids are burned for energy, we find that they burn the most at rest or at low intensity of movement. At high intensity, muscle glycogen is burned and fats from adipose tissue are released but not burned. Only fats contained directly in muscle cells are burned. This may come as a surprise to you.

With advancing age and metabolic syndrome, burning of fat at rest decreases and is replaced by burning glucose. During feeding in normally healthy individuals, fat burning is suppressed, free fatty acids disappear from the blood and mainly glucose is burned directly from food. This suppression also weakens in the case of the metabolic syndrome, and free fatty acids do not disappear during and after meals. Fructose from food is converted into fat in the liver and stored in the same way as ingested fat. Only short and medium chain fats (C4:0 to C10:0) are not stored. These go directly from the digestive tract to the portal vein into the blood and liver. The other fats first break down into individual long-chain fatty acids in the digestive tract and are absorbed. Over time, they are reassembled into triglycerides, packed in trucks called chylomicrons, and sent for storage. That is a very complex process.

What is the reason for reducing fat burning at rest? Why suddenly free fatty acids cannot be burned even it was possible before? Why is valuable glucose burned instead? This is an absolutely crucial question. Fats should be burned for energy. A little of fat is used as a building material, but that's really very little.

If we look at the distribution of energy reserves, a person has orders of magnitude higher energy reserves in fat than in glycogen (stored glucose). Even in a thin person, it is about 30 times more energy in fats. Using fat stores as an almost infinite source of energy is vital to us. So where's the problem? Genetic modification of fat burning is performed in ZDF mice. This is not the case with humans.

Our factory for ATP fuel, a system of incredibly complex nanomachines (mitochondrial complexes I to V) placed in a mitochondrial membrane, basically a production line. CL = cardiolipin

We can show it on another model, again on laboratory rats. These researchers hypothesized that polyunsaturated fatty acids protect cells from death by a mechanism of apoptosis. This is the mechanism by which the cell is specifically disassembled and recycled.

Thus, they used two groups of rats, one fed a standard diet and the other a diet enriched with vegetable fats with omega-6 (20% sunflower oil). After four weeks of this diet, they caused diabetes by damaging the pancreas with streptozotocin. So there was a rapid increase in blood sugar. After four days of elevated glycemia in diabetes, they examined the condition of the heart cells and their mitochondria. The result is that while cell death by apoptosis is reduced, cells die by necrosis, which is uncontrolled cell death. The result did not mean improvement, but deterioration. The results show that PUFA omega-6 in the diet reduced the level of reduced glutathione (GSH). Cardiac muscle cells are specific in that they gain most of their energy by burning fat. However, when glutathione levels are reduced, the maximum rate of fat burning is limited. It's just that with a light load the difference is almost not apparent, but with a heavier load the heart cannot increase performance, this is a serious finding. Does this also apply to people?

Most likely yes, we have mitochondria in common. Although oils containing n-6 PUFAs are touted as beneficial, they disrupt mitochondrial complexes, thereby reducing the possibility of fat burning and consequently causing insulin resistance, metabolic syndrome, obesity, and ultimately diabetes. Consequently, they may accelerate myocardial abnormalities in diabetic patients. Nevertheless, they are still listed as beneficial on official dietary recommendations for diabetics. It is almost to be said that it is the production of patients.

We have already shown these images, demonstrating the effect of omega-6 on cardiolipin and glutathione (GSH) in the mitochondria of the heart muscles in experimental rats. You just don't want this to happen to you.

And now another important question. Can this process be reversed? Is it possible to proceed in the opposite direction from diabetes to health? Take a look at these charts.

Yes, studies show it. If there is no significant damage to the beta cells of the pancreas, remission can be achieved by increasing fat burning. One way is baryatric surgery, which is likely to increase the production of short-chain fatty acids, the other way is a significant reduction in daily calorie intake, which will allow cleansing (autophagy), burning triglycerides from the liver and pancreas. And what may surprise you the most is that an improvement in blood can be expected in as little as a week and a reduction in the triglyceride content in the pancreas in two months. It is enough to ensure the conditions for sufficient burning of free fatty acids.

There is another possibility. The current recommended diet does not contain any short and medium saturated fats (MCT). Our health experts spilled the baby with a bathtub. When looking for the causes, they correctly identified the problem of excessive fat. However, they have formed the wrong hypothesis, and it is already indefensibly wrong today. If you reduce the intake of saturated fats, you will completely reduce the intake of short and medium fats, without which we will almost not be able to burn fats properly. Subsequent recommendations to eat polyunsaturated fats catastrophically reduced the amount of glutathione and further reduced the ability to burn fat. Substitution for fats in the form of carbohydrates increased our own production of saturated fats and burdened the liver, thus reducing our immunity. Toxic products as a result of the breakdown of polyunsaturated fats have further reduced our immunity and weaken us overall. Unreasonably low recommendations for the intake of antioxidants do not make it possible to improve the situation by supplementing with vitamin C. The use of antibiotics has deprived us of bacteria that produce short fatty acids from resistant starches for us. Well, we know the result. See here what to eat and what to supplement and how to check the progress. Metabolic syndrome can be eliminated unexpectedly quickly and easily when one knows how.

Thus, it is absolutely essential to limit the intake of polyunsaturated fats to a maximum of 4 % of daily energy, to ensure sufficient levels of glutathione, to ensure sufficient stimulation of mitochondrial complexes by intake of medium saturated fatty acids (MCT) or short fatty acids produced by intestinal bacteria.

Resistant starches (RS), not fiber (RSF), correct the metabolism of fat burning compared to digestible starches (DS).

So can we say that we know the etiology of type 2 diabetes? I think yes. It is a limited burning of long fatty acids caused by a lack of short and medium saturated fats from food or produced by intestinal bacteria. If they are missing, the disease will show up, if they are, the disease will disappear. This corresponds to the definition of the etiological cause, just as a lack of vitamin C causes scurvy and with its supplementation the disease disappears.

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References:

Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease

Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes

Inverse Relationship Between Cytotoxicity of Free Fatty Acids in Pancreatic Islet Cells and Cellular Triglyceride Accumulation

http://yelling-stop.blogspot.com/

Carbohydrate and fat utilization during rest and physical activity

Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease

Medium-chain fatty acids: Functional lipids for the prevention and treatment of the metabolic syndrome

Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione

The In Vivo Net Energy Content of Resistant Starch and Its Effect on Macronutrient Oxidation in Healthy Adults