Saturday, February 12, 2011

Earning a crust

We seem to have had a fair number of diabetic dogs come through work recently. Most of them have presented in ketoacidosis. This is a direct consequence of catastrophic insulin deficiency. Hypoinsulinaemia leads to unrestrained lipolysis with production of ketone bodies to the point of profound metabolic acidosis, vomiting, dehydration and risk of rapid death. Oh, and weight loss.

I keep reading snippets about the unimportance of insulin in the control of weight loss from various sources in the blogosphere, so it's sort of tempting to inhibit lipolysis with a couple of big, high calorie blocks of butter or maybe by an Intralipid infusion (yeugh, soyabean oil intravenously, disgusting). But, what the hell, I'm still a bit of a traditionalist on occasion, so I still shut down lipolysis with insulin.

It doesn't seem to matter how much insulin you inject. Once upon a time I would have reached for soluble neutral insulin and bunged it in by intramuscular injection. I had been considering changing to using a GIK (glucose/insulin/potassium) infusion for ketoacidosis but the loss of any soluble insulin preparation from the veterinary market in the UK has stopped my thoughts along those lines.

So now it's lente insulin (the only formulation we have left) by subcutaneous injection and aggressive fluid therapy to allow its absorption. Ultimately it doesn't matter. Any old insulin at almost any old dose rate will inhibit lipolysis well enough to get ketone production under control. You then start seriously supplementing with potassium while catching the hypoglycaemia with an iv glucose infusion as soon as the insulin level in the blood gets high enough to start doing things other than inhibit lipolysis..........

Replacing the missing insulin inhibits lipolysis first. As the blood insulin level increases it then shifts potassium from plasma in to cells. Still higher levels get GLUT4s on to cell surface membranes and facilitate glucose transport.

This is utterly basic A&E work.

Of course the lipolysis of weight loss might just be different from the lipolysis of ketoacidosis. I dunno. Stranger things have happened.





The other thing which has happened is that I have accumulated a couple of these patients who have turned out to be unstable diabetics. They are fascinating cases. You have to understand that as a heretic I try keep my nose out of other clinician's cases, especially diabetic dogs. The basic standard veterinary approach to diabetes is to feed your patient a meal of utter crap, mostly made of sustained release carbohydrate, and cover it with an industrial dose of 12 hour acting lente insulin. Repeat every 12 hours. You can book the cataract surgery for a year's time on the day you make the diagnosis.

The first patient, I'll call her Grace, is a spaniel with a two year history of dry eye, failure to produce tears. A sort of type one diabetes of the eye... What does dry eye have to do with diabetes? Dr Penny Watson of Cambridge Vet School gave a very perceptive presentation about chronic pancreatitis leading to diabetes at the 2010 BSAVA congress. In dogs pancreatitis is often a chronic inflammatory disease which can end up as a "type one like" diabetes syndrome or, alternatively, as an exocrine secretion deficiency giving a failure to digest food. Occasionally both. Which happens to occur in a given individual is probably a genetic lottery.

This dog had had dry eye well before her pancreatic beta cell failure. Dr Watson pointed out that dry eye is an autoimmune attack on the tear producing glands and the attack is aimed at ductal tissue. Stem cells for pancreatic beta cells are derived from pancreatic ductal tissue, which is similar enough to tear gland ductal tissue to produce an association, both diseases in the same patient. Cocker spaniels are far more commonly affected than other breeds. She had some absolutely amazing immunohistochemistry slides.

A sort of Sjögren’s Syndrome of the pancreas, probably another gift of gluten.


The other patient is a middle aged terrier, let's call him William. He has a two year history of chronic hepatopathy before presenting as a type-one-like diabetic. I'd guess he has a combination of non alcoholic fatty liver disease combined with non alcoholic fatty pancreatic disease. He was on a diet of commercial ultra crap, rice mixed with a mess of enzymically degraded protein to limit pre existing skin allergies. Imagine trying to catch the glucose spike from a bowl of white rice with a slow onset sustained release insulin. That initial spike of blood glucose was being caught, too late, with an enormous dose of lente insulin. Two hours later he would have a blood glucose of around 10mmol/l, but dropping like a stone. Suddenly the next reading would be back above 30mmol/l. Dr Bernstein doesn't have a lot of time for the Somogyi overswing. I do, certainly for this dog. The liver is loaded with glycogen, it panics and dumps a fair dose of glucose to (over) correct the incipient hypoglycaemia.

With the standard management approach both dogs had immediately come out of ketoacidosis and had gained weight over several weeks. Did I mention that insulin inhibits lipolysis? Ok, I'll drop it in to casual conversation again. Insulin inhibits lipolysis. Weight gain? Now there's a surprise. Of course there is no ketosis but also no suggestion of normoglycaemia at any stage of a 12 hour glucose curve either.

For some reason Grace had been dropped in to the middle of an afternoon consulting session for a random, post absorptive blood glucose check with me, presumably to adjust her insulin dosage. I wasn't her clinician. I think this reading was somewhere around 25mmol/l. She was ravenous, depressed and polydipsic. Next morning I had her admitted, halved her insulin and fed her a can of cat food with a carbohydrate content of approximately zero, except whatever cooked liver was in the can. The curve came down from somewhere over 35mmol/l to about 14mmol/l and stayed there. We've incremented her insulin up and are aiming for peak blood glucose below 10mmol/l and post absorptive levels below 7mmol/l. Probably the best we can do with lente insulin.

William came to me because lente plus ultracrap was giving completely random blood glucose levels. His owner had been offered referral to an endocrinologist or to see the weird in-house vet who didn't feed sugar to diabetics. That's me. They chose to see me for some reason.

He behaved similarly to Grace when fed all meat cat food and half dose insulin, which is good but we probably need better glycaemic control if we are going to get his hepatopathy to halt. We're getting post absorptive glucose levels between 5mmol/l and 7mmol/l but there is a post feeding spike to over 14mmol/l, which suggests there is a lot of liver in the cat food to provide significant glycogen in the diet. But so far he's a lot more stable now than he ever was on ultracrap.


So why low carbohydrate? Why not simply adjust insulin to cover normal diabetic crap-in-a-bag?

This comes down to the difference between exogenous insulin and pancreas secreted insulin.

Let's recap the two main functions of insulin. First is the inhibition of lipolysis, I may have mentioned this before. This bit is easy.

The next is the suppression of glucose release from the liver. This is utterly core to normoglycaemia. This is not quite so easy.

This is because insulin is normally produced by the pancreas and it travels directly to the liver. There is first pass metabolism by the liver, lots of it. The liver extracts between 50% and 80% of all of the insulin produced by the pancreas. Relatively little ever gets to the systemic circulation. This residue is what should be controlling adipocyte function.

If we turn this on its head we can say that we need to provide relatively high levels of insulin by subcutaneous injection to achieve those levels at the liver which would normally be delivered from the pancreas. But we end up not just bathing the liver with this specific high concentration of insulin. To reach "pancreatic" concentrations at the liver, from a subcutaneous injection site, we will have to hit the adipocytes far harder than we want to. We might well achieve adequate control of hepatic glucose output but at the cost of suppressed lipolysis. Weight gain. And hunger of course.

You could add in a third role for insulin as the management of dietary carbohydrate, ie portal vein glucose sequestration in to the liver and its metabolism by muscles when it spills over in to the systemic circulation. Generally I regard this as what Douglas Adams described in the Hitchiker's Guide to the Galaxy as an SEP. This is a "Somebody Else's Problem".

You want to do that? Fine, you sort out the mess.

I really have to discuss this in some detail because it is perfectly clear that non diabetic humans, so long as they have a functional physiology, can generally deal with massive amounts of carbohydrate rather well. So well that they can lose weight, rather a lot of it, by eating a diet of potatoes alone. This perfectly compatible with why LC is the logical and necessary approach to diabetes. That needs a separate post with a few links to pubmed rather than me rambling on about how I earn my living.

Peter

33 comments:

Nostril Damus said...

Great to see you again Peter ! I have a reason to turn my PC on again now.

Cheerz
J

Nigel Kinbrum said...

Hmmm. Pets with leaky guts? Is Keep 'em tight. of any relevance?

Mike said...

Good to see the weird vet that doesn't give sugar to diabetics posting again.

Aravindan said...

Great article. This dovetails nicely with the post from Kurt Harris on carbohydrates. Looking forward to the follow-up post so I can go on my potato-only diet :-)

Lucas Tafur said...

"I really have to discuss this in some detail because it is perfectly clear that non diabetic humans, so long as they have a functional physiology, can generally deal with massive amounts of carbohydrate rather well."

Exactly. But the key is, you can live despite a high carbohydrate intake, not because of it. That "you can" does not translates to "you must". Your body is not made to eat large amounts of carbohydrates.

Great to see you blogging again, Peter.

LeonRover said...

Hey Peter - Glad to see you back.

Many years ago a vet in Leeds mentioned that during the War vets could treat humans in emergencies, such was the lack of MDs. This concession was later withdrawn. Maybe it should be restored!

Lucas

"Your body is not MADE to eat large amounts of carbohydrates."

Well, MY body clearly ha not, 'cos I vary between eating lots of spuds, in Kitavan proportions, to all meat eating; but hey, we Irish have always LOVED our spuds. Little nugget of information for you: at one time many men with the name Murphy were nicknamed Spud, and potatoes were known as murphies.

Human digestion has the capacity - unless damaged - of eating and thriving on an omnivorous diet. Thus humans live on a variety of food sources, and a foraging strategy based on the particular local availability.

Tony said...

The first patient, I'll call her Grace, is a spaniel with a two year history of dry eye, failure to produce tears. A sort of type one diabetes of the eye... What does dry eye have to do with diabetes?

Isn't Sjorgen's an autoimmune disease? As is IDDM/T1DM? Cereal-grains in dog foods that's what both have in common, I would guess. Gluten and WGA, the autoimmune-team. Yeah!

Kurt G. Harris MD said...

@Tony

Yes for both type1and sjogren

@Peter

you said

"In dogs pancreatitis is often a chronic inflammatory disease which can end up as a "type one like" diabetes syndrome or, alternatively, as an exocrine secretion deficiency giving a failure to digest food. Occasionally both."

Not just dogs. I should try to find the images in my archive. In the past few years I have encountered two patients who were THIN that were being treated for abdominal pain and unexplained weight loss. Abdominal CT scans were requested. Both patients had severe pancreatic atrophy on CT. When I spoke with them they were both being treated as type II DM with metformin, which was rather ineffectual as they were likely not making much insulin, lacking about 95% of the normal pancreatic volume. So I called the referring docs and suggested fasting insulin and C-peptide levels to confirm their combined endocrine and exocrine pancreatic insufficiency.

I've heard some bang on about how tight glycemic control with ADA diets do not improve outcomes, so maybe the NEFA are more poisonous than the glucose. But I think the fact that we must flood the periphery with insulin to speak at a volume the liver can hear might have something to do with that - that and the toxicity of the drugs!

Glad to have you back!

Dr. B G said...

To quote a genius 'we've got our work cut out for us'...

DKA T1DM and T2DM animals (like humans) keep me employed, like you.

Dr. B G said...

(actually ALL autoimmune animals...SLE fibromyalgia migraine Sjogrens gallbladder NASH PCOS Hashi Grave's brain/ autism/ aspie/ spectrum Crohns...etc)

admin said...

would be interesting to read more about your take on the interactions between pancreas, liver and insulin. you have a way of explaining things that even neophytes like myself get.
am trying to assess the LC impact on someone who had a Whipple procedure done to remove the bile duct, bladder and duodenum.

david said...

that admin post was mine. not sure how I did that...

blogblog said...

I'm babysitting my sisters twin Cocker spaniels at the moment. They are both grossly obese - about 25kg. They are normally fed bones and canned food but my sister also feeds them a big serve of grain-based dry food.

The dogs are on a two week diet while they are with me. The bones and canned food are still on the menu but the dry food is out.

I know the dogs will be back on the crap in a few days but at least their bodies have had a short respite.

blogblog said...

I had just every disease known to humanity when I ate a SAD:

- permanent severe depression
- polydipsia
- polyuria
- dry eyes
- a gastric ulcer
- acid reflux
- Crohn's
- gum disease

All of my problems quickly disappeared on a paleo diet.

bopes said...

Please continue to ramble on, and welcome back!

Peter said...

Hi All,

Nigel, G, Tony, Kurt, blogblog:

I think I would be out of a job without gluten and general CIAB. Gotta pay that mortgage, as well as the rent!

Kurt, glad you're back posting, some reading to do there!

Peter

annefromorry said...

Peter, glad to have you back! I've had guide dogs for 32 years now and my current dog, my 3rd, is coming up to ten years old. She's a lab x golden retriever and is slim and healthy. The director of the guide dog school in Paris tried to insist that I feed my dogs on dried crap but I flatly refused. He then started wondering aloud why guide dogs these days don't live as long as they used to—except for mine, of course, who've so far lived to 15+. I tell him it's the carbs, but he won't listen.

Galina L. said...

Since I don't keep pets(allergies), I newer thought about how to feed pets properly until I read your post. It is so strange to treat a carnivore as an omnivore and difficult to understand how vets came to such ideas. The only reasonable explanation - budget considerations. However, budget must fly out of the window when vets bills arrive. Today I unintentionally walked through a pet food isle in the store and the first time in my life look at the pictures on the packages with a dog food - 99% fat free staff, images of corn and vegetables.
People , whose pets died, mostly mention some form of cancer. Do dogs die of heart attack? Usually people on a wrong diet have problems with their hearts and blood pressure earlier in life then cancer. Do they suppose to have lower basal insulin level because their natural food consist of meats and animal fats? Probably you are inundated with comments and questions now and I asked you just out of curiosity. If you wouldn't comment, I will understand.

blogblog said...

Galina,

buying cereal based foods is totally false economy.

My last cat lived for 22 years. His only veterinary bills were for being desexed and vaccinated. He ate nothing but regular canned supermarket cat food and table scraps.

Fred (the cat) had no health issues at all until he developed a brain tumour at the end of his life. He was still catching mice as a 16yo and climbing trees until he was 18.

My local vet once told me that non-pedigree cats very rarely have health problems if they are vaccinated and fed properly. She only fed cats on supermarket canned food.

Megaera said...

Peter - several years ago I had an aging Lab (we assumed he was about 12 but had no way to know since we'd acquired him as an adult stray, the vet then guessing him to be 2 or so). Hugo seemed to be reasonably healthy, but slowly was becoming incontinent of urine: he would walk through the house and wet, seemingly unaware of what was going on. He also drank a LOT of water. I assumed this was not so much medical as old age, and just got very careful about putting him out every hour or so. He had vet checkups, and I described this, but they put it down to age after testing for diabetes and apparently getting negative results. I guess.

About this time I was studying to be a medic, and the endocrine system section fascinated me, especially since his symptoms seemed rather too much like diabetes to be coincidental. I all but stopped his kibble (just a bit for a little bulk -- Hugo was food-obsessed) and started giving him canned catfood, which I gathered was higher protein than dogfood, and whatever meat table scraps I considered safe for him. Within two weeks the incontinence went away, bit by bit, and after a couple months his coat, which had been a bit mangy and scruffy, had gone back to looking sleek and healthy, and he seemed much, much happier. Still had hip issues for the rest of his life (two more years), but I think they were good ones for him.

I've always tried to give my dogs the highest protein kibble I could get, and they've mostly lived long and healthy lives, but I'm spending much more on soft protein now and extra fat, based on my experience with Hugo. Any comments or suggestions?

Peter said...

Galina, blogblog and Mehaera,

I agree, protein based diets for cats and dogs. Megaera, Lutz felt that many endocrinopathies might be LC responsive, Cushings Syndrome comes to my mind. There does appear to be a chronic inflammatory lesion in the pituitary for a long time before the micro adenoma forms (my wife had a journal club paper on equine Cushings which suggested this). Of course various gluten issues may be involved in inexplicable neurological problems too....

Peter

BTW My generic advice to puppy owners is to choose the highest meat content food which is gluten free.

blogblog said...

I had a friend with a grossly obese labrador with atopic eczema. The dog was getting regular cortisone injections. On my advice the dog was switched to raw meat and bones. The eczema rapidly resolved.

The vet thought my friend was a lunatic when she mentioned the dog's raw meat diet.

Sue said...

Peter, what's your though on fat being bad for diabetics as per the vegan crowd. When someone is eating a fat diet don't they get a temporary insulin resistance and decreased tolerance to sugar? Isn't that a protective mechanism so any glucose that is around is saved for glucose-dependent cells?This study:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1394223/pdf/jphysiol01610-0047.pdf

Galina L. said...

I recently received a link to the article about insulinogenic properties of a protein http://care.diabetesjournals.org/content/7/5/465.short from another low-carber and found an article about insulinogenic effect of different foods from The American Journal of Clinical Nutrition http://www.ajcn.org/content/66/5/1264.full.pdf+html.
Probably, you don't have time to read all that, but what are your thoughts about why insulin response from a meat(according to articles it is much more then I thought) doesn't affect ketosis much? I am trying to be in ketosis because it helps me to manage migraines and some other things.

Megaera said...

Peter: is there anything for or against supplementing a dog's diet with olive oil? I've given a cat that was eating her own fur cod liver oil with calcium which she consumed ravenously for a while, and when she stopped eating herself naked she stopped eating the oil and would never touch it again... but my dogs would love the oil, if I would give it to them. So, good or bad?

Kim0 said...

Data from dogs

All those dogs must give quite a dataset,
likely suitable for mathematical modeling.
Perhaps I should try that.

http://kim.oyhus.no
Ms.Physics

scall0way said...

Great to see you back again! Amazing how often I hear of diabetic cats and dogs, also obese ones. I had a sheltie who was obese, and just got fatter and fatter on the low-fat, high-carb diet the vet wanted her on.

Finally I began researching online and threw in the trashcan the "diet" food from the vet. Although Willow was about 7 years old and very sedentary I switched her to a "high protein for active puppies" chow, and she began losing weight immediately! Then we moved on to Evo Innova high-protein, low-carb, grain-free kibble supplemented by "pet meat" - beef ground up with bones, blood and organs - that I got from an Amish farmer, and she lost even more weight and became much more peppy! And had a much better life until cancer caught up to her last year, a couple months before her 14th birthday.

So when I got my collie, Bran, he was on the Evo Innova supplemented with the Amish "pet meat" right from the start. Alas, it didn't stop him from succumbing to an aggressive nasal sarcoma at only age 6 - the youngest age I've ever lost a dog.

So there are always outliers. I fed my Maggie a fairly grain-based diet most of her life, not knowing any better until she was getting quite old. Yet she lived to be almost 16, was racing around like a puppy until the last month before her death, never got a single gray hair around her muzzle, and I even had another customer at the vet's office ask me if she was a puppy (because of the way she was tearing around the waiting room) when I brought her in for a required rabies shot at age 14. :-)

cbcb said...

Hi - have been following your blog for awhile - most interesting! Had a question about your views on benign lipomas in dogs (fatty tumors) and how you treat them. (Do you attribute many of them to the grain or carb content in even premium pet foods?)

Peter said...

Hi david, sorry I missed your comment. I know of people without a gall bladder who have gone LC but the Whipple op does sound quite extensive. My guess would be to go mixed paleo (which I can see no objection to by anyone) and see if it is possible to creep the carbs down...

Hi annefromorry, no surprise there...

Hi Galina, vet students don't want to learn about dog food. Cutting, stitching and chemotherapy get more attention.

IHD does happen in dogs but it's not as common as the big C.

Hi Sue, there will be more on that in future posts.

Galina, you only need 60g or less of protein a day. That will not blunt ketosis in the way that 150g or even 300g might...

Megaera, too little info to comment really. Olive oil is largely non essential but there may have been all sorts of effects from the A, D and omega threes in CLO...

Hi Scall0way, yes lots of outliers...

Hi cbcb, I have wondered about insulin an lipomata. I tend to leave them alone unless they are in a potentially inconvenient location. A fine needle aspirate is pretty reliable for confirming lipomas are lipomas. They are usually simple from the surgical point of view with no need for aggressive margins, just shell them out through the smallest skin wound you can use and think about a surgical drain if the cavity is toooo large.

Peter

Tony Mach said...

Regarding Sjörgen's:
Isolation of an Infectious Endogenous Retrovirus in a Proportion of Live Attenuated Vaccines for Pets

The genomes of all animal species are colonized by endogenous retroviruses (ERVs). Although most ERVs have accumulated defects that render them incapable of replication, fully infectious ERVs have been identified in various mammals. In this study, we isolated a feline infectious ERV (RD-114) in a proportion of live attenuated vaccines for pets. Isolation of RD-114 was made in two independent laboratories using different detection strategies and using vaccines for both cats and dogs commercially available in Japan or the United Kingdom. This study shows that the methods currently employed to screen veterinary vaccines for retroviruses should be reevaluated.


More here:
http://thedailybite.wordpress.com/2010/04/13/infectious-retroviral-contamination-of-cat-and-dog-vaccines-discovered/

And here:
http://treatingxmrv.blogspot.com/2011/05/aloha.html
http://treatingxmrv.blogspot.com/2011/05/further-comments-from-dr-snyderman.html
http://treatingxmrv.blogspot.com/2011/03/science-fiction-or-science-fact.html
But don't let it distract you (at least not too much) from your nutritional studies.

Best,
Tony Mach

Peter said...

Very interesting. I'd heard about SV40 so I guess I shouldn't be surprised at veterinary vaccine contaminants......

Peter

youtube.com said...

Two old references from the 1990ties (its retroviruses after all!) regarding Sjörgens:

Detection of serum antibodies to retroviral proteins in patients with primary Sjögren's syndrome (autoimmune exocrinopathy). (1990)
http://www.ncbi.nlm.nih.gov/pubmed/2363733/

Are endogenous retroviruses involved in human autoimmune disease? (1992)
http://www.ncbi.nlm.nih.gov/pubmed/1323968

From what I heard even thinking about exogenous retroviruses and hinting that not only animal diseases might be caused by them, is a career limiting move (CLM) over at the CDC and much parts of retrovirology in general – endogenous retroviruses seem safe. As a rule of thumb, exogenous retroviruses ONLY effect animals, HIV being the ONLY exception. An human disease that you can find in animals and might be caused by retroviruses? Uh, oh. An equal class of CLM is finding anything else than proof that human vaccines are anything other than perfectly safe.

What is telling from my point of view that whole fields of research into disease like cancer, autoimmune and MS seem to crawl along very very slow. Where are the advances in medicine and biology of the last thirty years? There is a perverse focus on molecular-biology, on presumed mitochondrial "malfunction", on genetic "defects", on one-pill-fixes, coupled with a perverse ignorance on all things environmental, be it nutrition, be it pathogens. Your genes are broken, your mitochondrias are malfunctional, your biochemestry is out of whack. Yeah right. What about "Nothing in biology makes sense except in the light of evolution"? What about the part were you can understand an organism only in the context of its environment? Where does it say that pathogens aren't evolving? We are being scared with swine/bird/dinosaur/squeaky duck/whatever flu, but about the chronic diseases people struggle with? Take it with some grains of salt (preferably sea salt), but this whole vaccine business is definitely un-paleoish.

Tony Mach

Susanna Heinze said...

I love this post! I was smiling the whole time.