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A Few More Thoughts on Diabetes

After reading some more hyperlipid I have begun to question whether it is the adipose tissue or the liver that goes first in the pathogenesis of diabetes. One way to imagine the progression of diabetes is that through heavy fructose consumption, the liver becomes damaged and stops being able to manage glucose in the blood thus leading to elevated blood glucose levels. The pancreas thus overproduces insulin in an attempt to compensate for this and this process, which is simultaneous with hyperphagia due to disruption to leptin by excess fructose and toxin exposure, leads to the insulin resistance of fat cells and thus elevated NEFAs in the blood.

I have heard that elevated NEFAs appear before elevated BG so I would guess that these processes happen simultaneously but that the adipose tissue fails first as a result of hyperphagia and that this causes the pancreas to overcompensate with insulin hastening the arrival of hepatic insulin resistance soon thereafter. In any case, the factors that cause this remain the same, fructose and other dietary toxins that promote hyperphagia. The question is whether fructose or the hyperphagia that high fructose consumption can induce is the primary factor in this process. If it is the former then hepatic insulin resistance should happen first, if it is the latter then adipose insulin resistance should happen first. These are likely simultaneous processes where one has more susceptibility to what is happening and becomes insulin resistant first.

EDIT: I think that perhaps the way it works is something like this. Fructose damages leptin and this causes hyperphagia. Hyperphagia forces the body to fatten to avoid lipotxicity. At some point, the body refuses to fatten any longer and so the fat cells become insulin resistant and elevated NEFAs is the consequence. The pancreas secretes more insulin in response to the elevated NEFAs. The liver, simultaneous with this, is getting damaged by fructose leading to non-alcoholic fatty liver disease and once the pancreas goes into overdrive to control the elevated NEFAs, hepatic insulin resistance occurs and the liver stops being able to ration out glucose and process fructose well. Now you also have elevated blood sugar levels and the pancreas is going nuts with insulin production. Now you have diabetes. So far this is what makes the most sense to me.

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Filed under: Diabetes, Hormones, Insulin, NEFAs, Obesity, Pathogenesis

Some Thoughts on the Pathogenesis of Diabetes

Let me preface this by saying that I am not a scientist at all. I was trained in semiotics and film/video production.

One of the things that I’ve been wondering about ever since I started looking at CarbSane‘s blog is where elevated non-esterified fatty acids (NEFAs) fit in in the grand scheme of things. Let me elaborate a little first so that this makes sense. The theory of fattening and insulin resistance that is usually given goes something like this: carbohydrates are the most insulinogenic macronutrient and the SAD (Standard American Diet) is a high carb diet and over time this leads to chronically elevated insulin levels, especially if you are snacking all the time which you are more likely to do on the SAD since you’re running on glucose (instead of fat) which your body has limited storage for. Additionally, insulin is the master hormone for fattening and if it’s always high then you are always accumulating fat rather than burning it. Of course, this has some truth to it but the picture is a bit more complicated than this and I’ve been looking for a way to reconcile this with some more nuanced descriptions of how fattening actually works.

Insulin is not the only hormone implicated in this process. There are, at the very least, two others: leptin and ASP. But anyway, that isn’t exactly my point. CarbSane mentions often how the one thing that bothers her the most about low carb is that it is necessarily a high fat diet and that elevated NEFAs in the blood appear connected to sudden cardiac death (SCD) as well as diabetes (that is, elevated NEFAs are supposed to happen before the elevated blood sugar happens). But looking more at her posts, it seems that the likely mechanism of fattening and eventually diabetes works something like this:

-One goes into caloric surplus in some way (for now, it is my belief that nutrient poor foods like most grain carbs combined with liquid calories and food toxins like fructose or those found in grain carbs induce hyperphagia over time either as a function of form (such as the difficulty of the body recognizing liquid calories) or damage to the leptin receptor (the possibility of wheat lectin binding leptin has been hypothesized by Stephan)).

-Now that you are in caloric surplus, you begin to store more and more fat. You begin to have chronically high levels of insulin to inhibit lipolysis of all that fat which is necessary to avoid elevated NEFAs and lipotoxicity in the body.

-Eventually, however, fat cells become insulin resistant and this leads to elevated NEFAs which continues to exasperate production of insulin in the body. Over time, the rest of you becomes insulin resistant and now you are diabetic.

-To summarize, it appears the problem is pathological overeating caused by some damage to leptin which eventually leads to fattening and chronically elevated insulin through insulin’s attempt to inhibit the lipolysis of all that fat tissue and this eventually leads to insulin resistance in fat cells, elevated NEFAs and, eventually, elevated blood sugar and diabetes.

The reason Paleo diets work, I believe, is because calorie intake is spontaneously reduced through the consumption of nutrient dense foods. This caloric deficit combined with the removal of the bulk of food toxins and the change from glucose to fat as the main fuel source makes it so that now those fats can actually be burned and used for energy and the hormonal system has a chance to heal. Hence, no macronutrient in particular is the culprit but food toxins and low-grade macronutrients (which are usually grain carbs) that lead to the initial caloric excess that changes the body’s fat setpoint. This is why this sort of thing doesn’t happen to the Kitavans. For someone who is metabolically healthy, it would seem that as long as the foods you eat are whole foods, macronutrient ratios don’t really matter that much.

In relation to NEFAs there is another issue of interest. CarbSane is worried about the elevated NEFAs that seem to be produced in those on very low carb (VLC) diets, however, I believe this worry may be misplaced. The reason I believe it may be misplaced is because the phenomena of elevated NEFAs seems to be caused by very different things in diabetes than in a VLC diet and I do not believe elevated NEFAs are sufficient to produce diabetes in an individual outside of the context of elevated NEFAs in the pathogenesis of diabetes described above. On a VLC diet, insulin is being minimized and so lipolysis is encouraged and since virtually no carbs are being eaten this makes sense as lipids are the main fuel source. A normal person on the SAD would have a lower level of NEFAs but they are also running on a combination of lipids and glucose so this makes sense. On a VLC diet, the elevated NEFAs are also not occurring in defiance of insulin but because the diet is designed to produce little insulin in the body. Hormones are thus not being disturbed in the same way. Also, I wonder how rigorously “elevated” is being applied which is to say that if people on a VLC diet have elevated NEFAs relative to those on the SAD, I’m not sure if that really means anything. In the pathogenesis of diabetes it does since a diabetic on the SAD versus a “normal” person on the SAD can be compared to one another to see what difference the pathological state is having on that person. VLC is designed to elevate NEFAs so unless your body is trying to kill you, I find it hard to believe that elevated NEFAs in the context of normal functioning are a problem or that we would be designed in such a way that would put our lives in mortal danger if we were forced to survive on a VLC diet. Once again, I must say that I believe that any macronutrient ratio is perfectly fine so long as food toxins are not consumed and whole foods are consumed.

Looking through some posts at hyperlipid (this one in particular) it would seem that VLC produces a temporary physiological insulin resistance since the body is getting adapted to low carb intake but that this is not pathological and if one were to change to high carb the next day, the body would adapt to it and become insulin sensitive within a week. Thus, the carb loading that low carbers due before blood sugar tests are done because those tests are attempting to measure how insulin sensitive your tissues are in the context of a moderate to high carb diet. The low carbers thus make their diets temporarily moderate to high carb in order to get an accurate reading of insulin sensitivity.

In summary, I am coming to believe that this physiological insulin resistance and elevated NEFAs are nothing to worry about so long as they are not in a context that suggests that they are markers of a pathological state which I believe they are not in the context of a VLC diet. Now, I do not advocate a VLC diet for other reasons and if you do believe these things are to be worried about, the solution is simple. Instead of a very low carb, high fat diet eat a low to moderate carb, high fat diet and there you have it.

Filed under: ASP, Diabetes, Diet, Hormones, Insulin, Macronutrients, NEFAs, Obesity, Pathogenesis, VLC

Ever Heard of Diindolylmethane (DIM)?

I hadn’t heard of it at all until yesterday by chance on an acne forum where a woman had reported that her stubborn acne was greatly reduced after supplementing with DIM. I looked it up and DIM is something formed from indole 3-carbinol which is found in cruciferous vegetables like broccoli. If these websites are to be believed then DIM is perfectly safe in men and women and promotes healthy hormonal metabolism by essentially helping to metabolize bad estrogen in the body into good estrogen which in women helps to support healthy estrogen levels and in men helps to free bound testosterone so that in each gender a better hormonal balance is achieved. Hence the reason why it would seem this compound would help to clear up acne.

In any case, I am a man and am wondering if this might help me with mood stabilization and muscle synthesis so I may give this thing a try and see what happens. At the best, it would seem to simply free up my own testosterone and at the worst it would do nothing.

Now why might DIM be necessary or helpful? I am starting to think that maybe one of the reasons for the acne that prevails in the industrialized world and does not in hunter-gather groups is because of an excess of unnatural estrogen. First of all there is phytoestrogen which no hunter-gatherer groups would’ve consumed a huge amount of considering that the largest source of phytoestrogen that I know of is soy and that is a legume. Secondly, I remember reading somewhere that many of the pesticides that are used to grow produce can act as hormone disruptors in the body. Thirdly, apparently plastics have something called xenoestrogen which also acts as estrogen in the body. Fourthly, our water is contaminated with hormones I am sure from the waste products of contraceptives among other things. It would seem that all this would create an environment in which it would not be too difficult to produce hormonal imbalances in people. Use plastics, drink water, eat some soy, and eat some conventional produce and you probably have some of these fake estrogen compounds in your body. There is also the interesting point made by Don Matesz (in this post) that we probably are eating a lot less testosterone than we probably did historically. His argument is essentially that historically we likely ate a lot of bull meat since killing a bull would have very little effect of the fertility of a herd versus killing a cow. Nowadays, most of our meat comes from steers whose hormonal production is much less than that of bulls due to their castration. Add all this up and it seems like maybe DIM would be helpful to more people than just post-menopausal women and old men.

References:

http://www.wholeworldbotanicals.com/factsdimmen

http://www.dimfaq.com/site/toc.htm

Filed under: Acne, Diindolylmethane, DIM, Hormones, Strength training, Supplements