Thursday, September 23, 2010

von Gierke's disease

I'm just taking a quick break from packing boxes and trawling through hepatic insulin resistance related to metabolic syndrome because I got (as always) side tracked. By hepatic glycogen storage this time, rather than lipid storage.

You have to giggle about glycogen storage disease type Ia. It may not be much fun if you have it, but at least you are protected against premature cardiovascular disease.

About von Gierke's disease:

"Glycogen storage disease type Ia (GSD-Ia) is characterized by hypercholesterolemia, hypertriglyceridemia, decreased cholesterol in high density lipoprotein and increased cholesterol in low and very low density lipoprotein fractions."

Of course, with lipids like those, you should die of CVD at a very early age. But you don't.

As people may recall my current hypothesis for the cause of premature CVD is that it is triggered by Purple Spotted sdLDL, something which is NEVER measured by lipidologists. This is hardly surprising because I made it up. Taking a lesson from the lipid hypothesis founders there.

So folks with glycogen storage disease type Ia have the worst possible lipid profile you can imagine and no premature CVD.

To explain this paradox (gasp in awe at the explanations) you can look at antioxidants like uric acid or do very clever things with cholesterol efflux mediators or hypothesise about adiponectin. Take your pick.

Guess what. People with glycogen storage disease type Ia are virtually never hyperglycaemic or hyperinsulinaemic. In fact hypoglycaemia can be a serious problem for them. But they don't get heart disease. Funny that.

Oh, and they are told to avoid fructose too (haven't checked why, but it seems like a good idea)... Perhaps I'm wrong about Purple Spotted sdLDL, it could just be that it's made of fructose rather than sucrose!

Peter

34 comments:

Aaron Blaisdell said...

Have you considered that these folk are so enormously worried about their atrocious lipid profile that they are distracted by it while crossing the road and get killed by a bus instead? This premature death-due-to-distraction (DDtD syndrome) may not give the CAD enough time to reach deadly proportions.

Happy boxing!

Lynn said...

I realize you are trying to be entertaining, but as the parent of a 19 year old son woth GSD 1A, I can assure you there is absolutely nothing that is even remotely amusing about this disease. The avoidance of fructose is because it meatabolizes into sucrose at a point in its degradation and since the disease is characterized by glucose 6 phosphatase deficiency, simple sugar is stored as glycogen and the liver is unable to break it back down. Also, there is increasing concern about premature CVD as our kids approach a normal lifespan -- rarely achieved prior to cornstarch therapy. Both hyper and hypoglycemia are a problem, though hypo and subsequent lactic acidosis can be associated with seizure and death. I appreciate the impulse to lighten your studies by spoofing medical topics. I just hope by the time you might have occasion to treat someone with the disease that you have mastered your biochemistry. Lynn Nezin, NYC

Peter said...

Now I've been told

Peter

praguestepchild said...

Lynn,

Peter isn't mocking a disease or people afflicted with it. He's mocking the conventional wisdom about heart disease, cholesterol, fat and carbs.

If, say, the conventional wisdom was that CVD could be cured by bleeding someone with leeches (or, God forbid, giving them statins), and someone were to mock that with irony, that wouldn't mean that person thought heart attacks were hilarious.

On the contrary, it is gallows humor because people are keeling over in the thousands from silly notions about diet and health.

I'm very sorry for your son and I wish him a long and healthy life but you totally missed the point of this post.

Anand Srivastava said...

Thanks Peter, for the gem.
It will be an interesting thing to tell people.

J. A. Deep said...

Thanks for finding this. An ingenious way to approach the potential fructose causality, if that is where you might be going? I can't begin to imagine how your mind works!!! But so glad it does.

blogblog said...

Lynn,
the treatment recommended for your son shows the sheer ignorance of the medical profession with regard to diet.

Humans (except infants) require ZERO carbohydrate intake. They can produce any glucose, as required, from protein via gluconeogenesis.

Cornstarch is almost pure GLUCOSE. It is metabolised exactly the same way as regular glucose. The Glycemic Index is a nonsensical idea that has no connection to the real world.

The rational dietary treatment for von Gierke's would be be a high fat diet with severly restricted (<20g/day) carbohydrate intake.

Carol said...

Absolutely love your blog. You are a fun read and I learn a lot. Often times it's off to see what else I can find on your subject matter.

This is a very interesting disease. I've just done a bit of reading and my heart goes out to those people who have it and their families.

The treatment is lots of carbs
just to stay alive. There is a Springerlink article about the long term effects of using uncooked cornstarch.

There is also a very interesting article on gene therapy to cure this. It seems to have worked enough on the mice to believe it will one day be an option for humans.

http://www.ncbi.nlm.nih.gov/pubmed/10625614

Jenna said...

Hello Peter,

Just slightly off topic: help! I have a cat with a skin allergy, I de-flee, so it must be nutritional, I guess, and the local vet has suggested that I change my cats food, from store bought to 'science plan' specially catered for cats! The vet has said that cats are not supposed to eat butchers raw scrap meats, but that they must be fed game/very low fat proteins? So, just wondered what your humble opinion would be! If you can point me in the direction of a good book, or your personal vet-like advice, would be much appreciated! Thanks X

Ned Kock said...

Fructose + glucose seem to provide a better fuel for glycogen synthesis than glucose alone. GSD I sufferers have a glycogen breakdown problem, which leads to excessive storage and enlargement of the liver.

Fructose from fruits is probably healthy if you are constantly depleting and replenishing your glycogen stores:

http://healthcorrelator.blogspot.com/2010/06/fructose-in-fruits-is-good-for-you.html

Peter, often the prescribed treatment for GSD I is continuous carb. feeding, to make up for the impaired hepatic glycogenolysis and gluconeogenesis. This might lead to high average glucose levels. So the glucose link with CVD (which definitely exists) may not be the main factor a play here. Perhaps the constant bouts of hypoglycemia would lead to low body fat levels, as it often does, lending some support to the adiponectin connection.

Anna said...

Jenna,

www.catnutrition.org
http://www.catinfo.org/
http://feline-nutrition.org/

All good starting points for learning more about what to feed/not feed a companion cat. There are other sites for whole prey models but I don't have those bookmarked, but they are easy to find if you decide to go that route.

But so far, with the notable exception of Peter, I haven't been impressed with vet recs regarding commercial (retail store OR vet Rx) cat food.

Since switching from commercial cat food to raw food about 4 year ago, I wouldn't consider any sort of cr*p in a bag or can for any reason, even if recommended by a vet.

Jenna said...

Anna,

Thanks so much! Great help.

Peter said...

Briefly, from a friend's computer,

Am I mocking GSD 1a? No.

The lipid hypothesis of heart disease? It's bollocks. Oops, I mean yes.

The idea of a ketogenic diet for a glycogen storage disease is quite interesting. You would need the maximum physiological insulin resistance and minimal glucose use, preferably from slow release sources. About as likely to be tried as a ketogenic diet for epilepsy. Oh, that has been tried and it works for epilepsy, hmmmmmm....

Jenna,

Follow Anna's links. My cat (down to one now, the youngster just never came home one day) eats raw pork mince and raw liver occasionally. Some cooked food as a treat. Well over 20 now and getting a little rickety but very happy.

Peter

blogblog said...

Hi Jenna,
many years ago my local vet advised me to feed my cat on an expensive dry "scientific diet". The result was eczema, asthma, IBS and neurosis. This was cured when I reverted to a good quality canned food.

blogblog said...

Peter,
our local TV news had a story on using of ketogenic diet for epilepsy a few weeks back. They explained it worked exceptionally well. Then the story degenerated into absolute nonsense about the diet being incredibly boring and exceptionally complex. They even claimed that all food needed to be weighed to the nearest gram and must be administered by a dietitian with specialist training.

I went to my supermarket the next day and saw half a dozen varieties of gluten-free gourmet sausages that had the exact protein/fat/carbohydrate balance required for a ketogenic diet.

David said...

Saw some links suggesting atherosclerosis is associated with GSD...

http://www.jpeds.com/article/S0022-3476(08)00957-8/abstract

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WHP-50RMPJK-1&_user=10&_coverDate=11%2F30%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=8286ec9eb57a29dbf5782e2d16c5e5f4&searchtype=a

http://www.invasivecardiology.com/articles/Premature-Coronary-Artery-Disease-a-Patient-with-Glycogen-Storage-Disease-III

Jenna said...

Peter, thanks! Just wondered though if your feeding your cat raw pork/raw liver occasionally/some cooked food as a treat; then what do you feed your cat the rest of the time (don't tell me, the vegans)?

blogblog, thanks! I would gladly buy good quality cat food, but I can't find any without additives that are inexpensive. Probably because I live in the UK?! Possibly. . . .

Thanks again all, I promise no more cat food divergences!

CarbSane said...

The idea of a ketogenic diet for a glycogen storage disease is quite interesting. You would need the maximum physiological insulin resistance and minimal glucose use, preferably from slow release sources. About as likely to be tried as a ketogenic diet for epilepsy. Oh, that has been tried and it works for epilepsy, hmmmmmm....

Since the enzyme that is deficient is also involved in gluconeogenesis, I don't think carbohydrate restriction to produce ketones would be advisable. Even the most keto-adapted person requires some glucose. Where would that come from?

blogblog said...

"The ketogenic diet is well established as therapy for intractable epilepsy. It should be considered first-line therapy in glucose transporter type 1 and pyruvate dehydrogenase deficiency."

Curr Treat Options Neurol. 2008 Nov;10(6):410-9.
The ketogenic diet: uses in epilepsy and other neurologic illnesses.

Barañano KW, Hartman AL.

julianne said...

Here is a link to an NZ vet site with articles on feeding for pets
http://www.rawessentials.co.nz/content/page38/Articles.html

Tom Lonsdale is a well known expert in Australia

http://www.rawmeatybones.com

blogblog said...

Hi CarbSane,
there is no need at all for glucose. The CNS actually functions far better in the absence of glucose (after a few weeks adaptation).

Walter said...

@ Carbsane - Gluconeogenesis

from wikipedia

Gluconeogenesis (abbreviated GNG) is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids.
It is one of the two main mechanisms humans and many other animals use to keep blood glucose levels from dropping too low (hypoglycemia). The other means of maintaining blood glucose levels is through the degradation of glycogen (glycogenolysis). [1]

CarbSane said...

@blogblog: C'mon. Without glucose you die. Even zero carbers have glucose in their blood. Their bodies don't make it for the fun of it.

Jeffrey said...

Thanks Peter for this article. we can now share people about this. You have a good insight..

Check out Denver Chiropractor for our healthy tips and wellness.

donny said...

Hi all.

http://www.jpeds.com/article/S0022-3476(73)80531-1/abstract

Just an abstract, but it doesn't look promising...
---------------------------------

On fasting, subjects with Type I glycogenosis had lower concentrations of β-hydroxybutyrate than did control patients matched for age and degree of hypoglycemia. Also a ketogenic diet provoked less ketosis and the disposal of a standard intravenous load of β-hydroxybutrate was slower than in normal children. These findings indicate that, contrary to what has been widely believed, patients with Type I glycogenosis are less prone to ketosis than are normal children.
--------------------------------

So I wonder is glucose 6 phosphatase deficiency is causative?

Hepatic over-sensitivity to insulin might explain hypoglycemia, poor access to glycogen stores, failure to go into ketosis. Perhaps low insulin levels, caused by the poor release of glucose by the liver, is what inhibits ketone use in other tissues?


http://www.museumstuff.com/learn/topics/Von_Gierke_disease::sub::Metabolic_Pathophysiology

-------------------------------
Chronic hypoglycemia produces secondary metabolic adaptations, including chronically low insulin levels and high levels of glucagon and cortisol.
---------------------------------

Huh.

john said...

Hi donny,

So, you are saying because liver glycogen is high, ketone production is decreased?

Why would low insulin & blood glucose inhibit ketone use though?

...good to see you back around...

donny said...

Hi John. I just read up a bit more on this. The hepatic insulin sensitivity I was talking about looks sort of wrong. Adding a phosphate to glucose keeps it in the liver cell, removing the phosphate is necessary for the glucose to leave the liver. But it isn't necessary for the liver itself to metabolize the glucose. So it looks like the liver overfeeds itself glucose, and that's maybe all you need to increase triglyceride production, lower fatty acid oxidation and shut down ketone production.

For insulin increasing ketone utilization there's this;

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC291994/

"Evidence for an effect of insulin on the peripheral utilization of ketone bodies in dogs"

Okay, it's in dogs. But it's sort of my bedtime. :)

David said...

Hi Peter,

Off topic, but you've discussed several times here that high fat diets cause physiological (reversible) insulin resistance... wonder what you make of the following:

http://ajpendo.physiology.org/cgi/content/abstract/297/1/E236

Thx, David

Bushrat said...

CarbSane said:

"Since the enzyme that is deficient is also involved in gluconeogenesis, I don't think carbohydrate restriction to produce ketones would be advisable. Even the most keto-adapted person requires some glucose. Where would that come from?"

"@blogblog: C'mon. Without glucose you die. Even zero carbers have glucose in their blood. Their bodies don't make it for the fun of it."


In answer to your first post, I don't know where the glucose comes from but if ZCers have glucose in their blood than obvious carbs are not necessary even if glucose is necessary, which I doubt....

Bushrat said...

@ blogblog:

Do you have research citations on ketosis, ketoadaption, and the fact that we don't need glucose for survival?


@ Peter: You should allow people to leave random comments. Your lack of anonymous commenting has discouraged me (and probably others) from commenting in the past.

blogblog said...

Hi David,
Andersen and Stefansson were tested for glucose tolerance at the completion of their year long met only diet in 1928. Andersen was so insulin resistant that glucose was detected in his urine.

john said...

blogblog,

The glucose intolerance was reversed after two weeks of "normal" eating (maybe sooner, but they tested after two weeks).

blogblog said...

john,
The interesting fact was that they became insulin resistant even if it was reversible.

mnature said...

As far as I can tell, the reason for using an uncooked cornstarch with von Gierke's disease, is to have a constant source of glucose that will last for about four hours. Most foods digest so quickly that you would have to keep eating nearly every hour to prevent severe hypoglycemia. The uncooked cornstarch digests very slowly over the course of four hours, thus allowing a more normal lifestyle. The uncooked cornstarch also allows for a more normal sleep pattern, which would otherwise be disrupted by the hypoglycemia.

There are some people on high fat and protein diets that can eat once per day. Someone with von Gierke's disease does not have that luxury of choice.