3

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Is the Paleo Community in Agreement with Regard to the Etiology of Type-2 Diabetes?

Answered on August 19, 2014
Created September 23, 2011 at 12:11 AM

I'll post my current understanding of the processes involved and I'd appreciate any input you guys may have:

As far as I can tell, somewhere in our primate evolution, we lost the ability to synthesize vitamin C, and as a result, we also lost the ability to synthesize uricase, the enzyme that breaks down uric acid. 1 Why the former occurred, I couldn't tell you, but it was perhaps advantageous to a greater extent to preserve that glucose for a brain that was ever-increasing in size. The latter was likely lost in response to the former, since uric acid and vitamin c have overlapping roles as a sort of general purpose antioxidant. When vitamin C rises, uric acid falls. 2

The significance of this for us is that if we do something that spikes uric acid outside of its optimal range, like eat a lot of fructose, it will have too much of an antioxidant effect and will create a "reductive stress" if you will. Too much of an oxidant creates an oxidative stress, while too much of an antioxidant has the opposite effect. It exerts its effect where it shouldn't, so instead of effectively coping with the reactive oxygen species in our blood, uric acid oversteps its boundaries and reduces things that we don't want reduced, i.e. endothelial nitric oxide. Insulin resistance arises because insulin needs nitric oxide for glucose uptake. 3

So the question is, once a person has NIDDM, what do they do to correct it? They find themselves in a situation where glucose is pooling in the blood in response to a starchy meal, but is just sitting there because insulin can't shuttle it into the liver and muscle glycogen and activity isn't sufficient to oxidize all of it in muscle mitochondria. It seems to me that, at this stage at least, with regard to diet, any producer of uric acid should be eliminated or at least limited. Obviously fructose is non-essential so it gets pitched first. Any yeast needs to go as it spikes uric acid as well. Even purine-rich meat should probably be limited for a while until things get under control. Glucose is now becoming a fairly potent poison and glycating proteins as it pools in the blood, so low carb is the obvious choice. They then should be eating a diet that is high in fats that are readily converted into ketones like coconut oil along with a nominal amount of meat and some non-starchy vegetables if desired. That should take care of most of the diet end of things.

I would argue that if that's all you did, it would take much longer than necessary in order to bring about a full correction. The answer to this problem also happens to be the answer to the problem of lowering triglycerides (that are probably elevated here as well) and reducing fat mass (which is likely also elevated), namely a high volume of low intensity exercise that is performed in the fasted state. In practice, this means walking as much as possible before every meal. The glucose pool needs to be reduced rapidly via oxidation in the muscle mitochondria. I see no reason why walking in this way wouldn't be sufficient for correcting insulin sensitivity completely and thus reversing the disease. 4

If this continued, there should be an eventual adaptation back toward lipids as the primary energy substrate in muscle mitochondria, and thus no longer a need for starch avoidance, provided that 1) activity continued in the fasted state and 2) serum uric acid levels weren't allowed once again to climb and interfere with endothelial function as it relates to insulin sensitivity. When this insulin sensitivity is restored, the transient blood glucose spikes that would occur subsequent to a meal containing starch would be properly met with an insulin response that shuttled this glucose into liver and muscle glycogen. There would be a healing period that would clearly depend on the duration and severity of the disease, but I don't see why most cases couldn't be corrected in a matter of months if this protocol is followed. This is especially so since walking has been shown to increase mitochondrial density, and thus improve the capacity for the individual to oxidize fat or glucose as needed. 5

Where this would fail obviously is if individuals who have endured this disease are left with some kind of permanent inability to properly handle carbohydrates. I'm not familiar with any such thing, so if you are aware of a compelling reason why starch could never be added back into the diet if desired, I would be very interested to hear what that is.

Medium avatar

(39831)

on September 24, 2011
at 03:16 AM

Also, the fat storage for winter thing is pretty tenuous at best. It does little to explain the lack of C and uricase in frugivorous apes at tropical latitudes.

Medium avatar

(39831)

on September 23, 2011
at 05:26 PM

Yeah, I think there is some compelling evidence that mitochondrial dysfunction can arise as a result of magnesium and/or manganese deficiencies.

A968087cc1dd66d480749c02e4619ef4

(20436)

on September 23, 2011
at 01:56 PM

The double knockout for C & Uricase are possibly to allow for more storage of fat from eating fruit (for winter) and to increase blood pressure so that we don't pass out when we stand erect. Also, I'm not sure that T2 is really when the liver becomes IR or when the adipose tissue becomes IR (refuses to accept more fat). Walking has definitely been shown to lower IR in T2 diabetics. I seem to be able to handle more starch now that I have upped the magnesium significantly.

Medium avatar

(39831)

on September 23, 2011
at 06:00 AM

I wonder if that surgery just greatly reduces the extent to which glucose can be absorbed in the intestine and lets it get deeper in to the gut where it's fermented.

3c6b4eed18dc57f746755b698426e7c8

(5147)

on September 23, 2011
at 04:30 AM

We still do not understand the pathogenesis of T2 diabetes and insulin resistance. Note that the above mechanism involves no exercise, just a physiological change. http://care.diabetesjournals.org/content/31/Supplement_2/S290.abstract?sid=122c854a-fc11-4c42-b60f-668ba0fab1e5

3c6b4eed18dc57f746755b698426e7c8

(5147)

on September 23, 2011
at 04:29 AM

And don't forget those obese T2 diabetics who undergo bariatric surgery often reverse their insulin resistance after surgery ... BEFORE they become thin. We see this in those who undergo "duodenal switch", which shrinks the size of the stomach and bypasses the duodenum in the small intestine. What's happening here? Well, this is the incretin theory of t2 diabetes. Incretins (GLP-1, GIP) tell pancreas to produce insulin until shut down by DPP-4. There is something going on in the small intestine which might be anti-incretin, and the bypass is making the t2 diabetic to avoid the incretin.

667f6c030b0245d71d8ef50c72b097dc

(15976)

on September 23, 2011
at 01:11 AM

Your zinc is really kicking in now eh

1a98a40ba8ffdc5aa28d1324d01c6c9f

(20378)

on September 23, 2011
at 01:09 AM

I like the idea of advancing the state of the art. I know PH can do it.

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1 Answers

2
3c6b4eed18dc57f746755b698426e7c8

on September 23, 2011
at 03:50 AM

I see no reason why walking in this way wouldn't be sufficient for correcting insulin sensitivity completely and thus reversing the disease. 4

Actually there was a study done this year in UK which showed that recently-diagnosed, obese T2 diabetics who went on a 1200 cal diet was able to reverse the disease (google UK t2 diabetes reversal). The study is controversial but the medical establishment seems to be accepting the position that T2 diabetes, in certain cases, can be reversed. The study has been excoriated since 1200 / day is at starvation-level: i.e., it would be de facto ketogenic even if not low carb. Those successful tend to lose weight rapidly (as you would if you stick to 1200 cals) and rid themselves of the fat in their pancreas (fatty pancreas) and liver (fatty liver). What's intriguing is the possibility that the pancreatic beta cells may not have actually "died" when "burnt out" but may be revived by "shocking them out of their dormancy." We still do not know whether these beta cells are dead or lost their functionality temporarily.

What's intriguing is that there are doctors in Asia and India and other countries who do not get published in medical journals ... who claim to have cured T2 diabetes by restoring insulin sensitivity this way: through an extreme diet and exercise... many believe in restricting animal fats (i.e., satruated fat), overall calories, and all sugary snacks. These are anecdotal accounts but I tend to believe them because I've been somewhat successful in restoring my own insulin sensitivity.

It's counterintuitive and finding a right metabolic pathway that induces insulin sensitivity might be within reach. The problem is that these pathways are black boxes and the only way to figure out is to reverse engineer: find someone who reversed his insulin resistance, study what he did, repeat in more T2s through clinical trials, see if you can repeat it, then theorize about what could be happening, and you still can't be sure that the mechanism is actually what happened, not something else.

3c6b4eed18dc57f746755b698426e7c8

(5147)

on September 23, 2011
at 04:30 AM

We still do not understand the pathogenesis of T2 diabetes and insulin resistance. Note that the above mechanism involves no exercise, just a physiological change. http://care.diabetesjournals.org/content/31/Supplement_2/S290.abstract?sid=122c854a-fc11-4c42-b60f-668ba0fab1e5

3c6b4eed18dc57f746755b698426e7c8

(5147)

on September 23, 2011
at 04:29 AM

And don't forget those obese T2 diabetics who undergo bariatric surgery often reverse their insulin resistance after surgery ... BEFORE they become thin. We see this in those who undergo "duodenal switch", which shrinks the size of the stomach and bypasses the duodenum in the small intestine. What's happening here? Well, this is the incretin theory of t2 diabetes. Incretins (GLP-1, GIP) tell pancreas to produce insulin until shut down by DPP-4. There is something going on in the small intestine which might be anti-incretin, and the bypass is making the t2 diabetic to avoid the incretin.

Medium avatar

(39831)

on September 23, 2011
at 06:00 AM

I wonder if that surgery just greatly reduces the extent to which glucose can be absorbed in the intestine and lets it get deeper in to the gut where it's fermented.

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