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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