Info Insulin Resistance - LONG - Really.

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Carl & Polly & Bob (GA)

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OK, so I've been doing a lot of reading lately, just trying to really understand this disease, so that I might be better equipped to "deal with" trying to help you all make sense out of your day to day struggles. Lot of that going on lately....

So, partly due to my level of frustration at not being able to put a precise timeline on digestion, blood glucose levels, and insulin cycles, I took another route.
I googled "how does insulin work in cats". What a wealth of info I found. (I have 7 tabs open right now in my browser).

My motivation is some questions I've seen posted lately that I haven't had a clue how to answer, mostly having to do with "why doesn't a dose work anymore", "why did I get a few good cycles and a bunch of flat ones", things like that. And the often bumped "Glucose Toxicity" thread caught my eye again.

One thing that made a light bulb go off in my head is how we routinely think that Insulin and BG are opposing sides in a fight, but in reality, they aren't. Actually, they are best friends. Without insulin, blood glucose is 100% useless to a living being. We seem to look at it like this: BG is poison, and insulin is the antidote for the poison. Not true at all.

Insulin's purpose is to allow glucose to leave the bloodstream, and enter every cell of a cat's body. The reason that diabetic cats are diabetic (hyperglycemic) is because their cells can't absorb the glucose out of the blood. The reason that they can't absorb the glucose is because there isn't enough insulin in the body, because the pancreas can't produce enough of it (or any of it), so we have to add it.

In a non-diabetic, all this stuff happens automatically, and apparently very quickly. When a cat eats, and turns the food into glucose, the pancreas puts out just the right amount of insulin in order to trigger the cells to absorb the glucose. The glucose is then used by the cells as "energy" or fuel to keep the cell functioning normally.
In a diabetic, the pancreas tries and fails to produce that insulin, and the glucose has no place to go, so it stays in the bloodstream until it eventually is detected by your handy-dandy meter as "BG" in excess of normal levels. So we add insulin twice a day to try to control that excess glucose, to enable the cells to absorb it and use it like nature intended. Unfortunately, we're always playing "catch up". We can't put it into the cat with anything close to the degree of "natural" pancreatic insulin production with regard to amount or timing. Our goal is to at least get the amount right, but that's really all we have any control over. We'll never be able to act like "an artificial pancreas" with the degree of success, say, an artificial heart might have. When we are successful, it's sort of like "in the ballpark" and it still manages to work in some cases. In one of Dr. Peirson's posts here, she said it something like "we need a monitoring system that checks BG continuously 24 hours a day, coupled with an insulin drip that responds to the changes 24 hours a day". Maybe our grandkids might get that, but it ain't happening for us.

This brings me to the subject line of the thread - insulin resistance. I've seen it mentioned here and elsewhere, and it's usually mentioned in extreme cases, where a cat is on a really high dose and still not responding. But after reading about it, that isn't right. Diabetes is insulin resistance.
http://www.2ndchance.info/diabetescat-i ... stance.pdf
In insulin-dependent diabetic cats, insulin resistance is manifested clinically as an inadequate response to an appropriate pharmacologic dose of insulin. There is no specific insulin dose that is diagnostic for insulin resistance.

Type 2 DM (noninsulin-dependent DM) is characterized by abnormal insulin secretion in conjunction
with peripheral insulin resistance
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This is from Dr. P's site, specific to type 2 diabetes, which we believe is what the overwhelming majority of our cats have:
Type 2 is characterized by two problems. The first, as in Type 1, is a diminished ability of the pancreas to secrete insulin. The second issue is one of insulin resistance. In other words, the receptors on the cell wall that would normally open the door to the cell to let the glucose in when insulin 'knocks', stop 'listening' to the insulin. The cells 'resist' the signal that the circulating insulin is sending and the glucose is not transferred to the inside of the cell, resulting in an elevated blood glucose (hyperglycemia) and cellular 'starvation'. The elevated blood glucose, in turn, sends a signal to the pancreas telling it to secrete more insulin. The elevated insulin may somewhat override the insulin resistance resulting in more glucose entering the cells, but eventually the pancreas can become exhausted or 'burned out'.
Glucose toxicity results from chronic hyperglycemia. Glucose toxicity wreaks havoc on the entire body - especially the pancreas and its insulin-producing cells. A vicious cycle then ensues as the insulin-producing cells are damaged resulting in less insulin being produced.
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Carbohydrates, Obesity and Diabetes

Most people are aware that diabetes is more common in overweight humans than it is in people closer to an optimal weight. The same is true for cats. Fat (adipose) cells produce a substance that causes the cells of the body to become resistant to insulin. This increase in insulin resistance is the hallmark of Type 2 diabetes. As mentioned above, this is the most common form in the cat.
Cats are designed to utilize proteins and fats for their energy - not carbohydrates. They are lacking the necessary enzymes to efficiently utilize carbohydrates to meet their energy needs. When the carbohydrate level of an obligate carnivore's diet is higher than it should be - remember that a bird or a mouse is only 3-5 percent carbs and that most dry foods contain between 35-50 percent carbs - the excess carbohydrates are stored as fat. The increased fat cells, in turn, promote Type 2 diabetes via an increase in insulin resistance.
That said, if calories in exceed calories out - no matter whether the calories come from protein, fat, or carbohydrates - the cat will gain weight. This is why portion control is important no matter what diet you are feeding.
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This is from that first link again:
CAUSES OF INSULIN RESISTANCE IN CATS
There are currently no published prospective or retrospective studies specifically evaluating the causes of insulin resistance in cats. Common concurrent diseases identified in cats with DM or diabetic ketoacidosis include pancreatitis, hepatic lipidosis, cholangiohepatitis, urinary tract infection, renal failure, hyperthyroidism, inflammatory bowel disease, acromegaly, and heart disease. Treatment with exogenous glucocorticoids or progestagens is also a common historical finding. Clinical experience suggests that these concurrent problems also cause insulin resistance in cats.
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I "bolded" those two things for a reason, because they are seen fairly often here.
Pancreatitis
Pancreatitis is a common and frustrating problem in cats and may contribute to the pathogenesis of feline DM. Pancreatitis is also a common concurrent disease in diabetic cats and an important cause of insulin resistance. In a report of 37 diabetic cats that underwent necropsy, acute or subacute pancreatitis was identified in 2 cats; chronic pancreatitis was identified in 17 cats, and pancreatic neoplasia was identified in 8 cats. Chronic inflammation due to pancreatitis causes insulin resistance that may impair glycemic regulation (see Table 1). In a study of 104 cats with DM, there was a trend for poorer glycemic control in cats with pancreatitis compared with those without. Compounding the problem of insulin resistance in cats with pancreatitis is the cyclic nature of the disease. Because both insulin demands and appetite fluctuate with the severity of inflammation, clinical signs of poor glycemic control often coexist with an increased risk of clinical hypoglycemia.
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Bacterial Infection
Bacterial infection is an important cause of insulin resistance in diabetic patients (see Table 1). Hyperglucagonemia has been implicated as the cause of insulin resistance in people with bacterial infection, but this has yet to be documented in the cat. Cats with DM are at increased risk of bacterial infection, especially of the urinary tract. Decreased urine concentration and glucosuria increase the likelihood of bacterial proliferation within the urinary tract. In a study of 141 diabetic cats that underwent urine collection by cystocentesis, urinary tract infection was identified in 13% of cats.
Only 40% of the cats with urinary tract infections exhibited clinical signs. Other studies also have documented that bacterial infections are common concurrent
diseases in diabetic cats. Other common sites of bacterial infection include the oral cavity, the skin, and the biliary tract. Other factors that have been hypothesized to increase the risk of infection in patients with DM include impaired humoral and cell-mediated immunity, abnormal neutrophil chemotaxis, and defects in phagocytosis and intracellular killing of bacteria.
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Here's a site that puts things in really simple terms:
http://www.petremedy.com/cat/db/Causes.htm


The Simple Explanation.

Other than the genes your cat inherited, there are two primary causes of diabetes:
1) a long-term diet that has been high in carbohydrates and
2) nutritional deficiencies.
Your cat's body breaks down carbohydrates into sugar (glucose) which then enters their blood stream. The more carbohydrates consumed, the higher their blood sugar goes. In response, their body produces insulin. Insulin's job is to push the blood sugar into the cells.
On the surface of the cells in their body are insulin receptors, which act like little doors that open and close to regulate the inflow of blood sugar.
After many years of consuming a high-carbohydrate diet, their cells have been bombarded with so much insulin that these doors begin to malfunction and shut down.
With less doors open, their body needs to produce even more insulin to push the glucose into the cells. More insulin causes even more doors to close and as this vicious cycle continues, a condition called "insulin resistance" sets in.
When their body can no longer produce enough insulin to push the blood sugar into the cells, diabetes results. It is simply an extreme case of insulin resistance.
The key point for you to understand is that your cat's energy, wellness and longevity are primarily dependent on improving the sensitivity of their cells to insulin - how well their cells open and close the doors and allow the sugar to be cleared from the blood.
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What's the Bottom line?

Since feline diabetes is really a severe case of insulin resistance, the solution to their condition is to find a way to increase the sensitivity of their cells to insulin and help their body get the sugar out of the blood and into the cells so it can be metabolized and turned into energy. (This inability to metabolize sugar is one of the reasons why most diabetic cats are often sluggish and appear tired.)
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Note, that site is trying to market some supplements that are supposed to help manage nutrition, but the info is there and easy to understand.

Another thing that I have repeatedly read here is about "liver panic" and how when the BG goes to low, the liver will dump "glucagon" into the blood to raise the BG. Well,the liver does dump stuff, but not Glucagon. It turns out that glucagon is actually produced naturally by a part of the pancreas called " the islets of Langerhans" (which to me sounds like a wonderful destination for a cruise or vacation, doesn't it?).

Here's a good explanation of what takes place in the blood, pancreas, and afterwards the liver when BG rises or falls:
http://bloodsugardiabetic.com/diabetestreatment/insulin/how-the-body-regulates-blood-sugar/
Blood Sugar Levels Rise

If blood sugar levels increase (e.g. after a meal), the beta cells of the islets of Langerhans in the pancreas produce insulin. The insulin has an effect on various organs of the body, increasing cell permeability to glucose and increasing enzyme activity in the cells allowing the glucose to be taken up and stored.
The liver and muscle tissue converts glucose to glycogen and stores it. This helps reduce the levels of sugar in the blood. In addition, the breakdown of fats in fat cells is inhibited, so that glucose will be used preferentially for energy.

Blood Sugar Levels Fall

The alpha cells in the islets of Langerhans of the pancreas product glucagon. Glucagon is “antagonistic” to insulin, basically having the opposite effect on the organs of the body. Glucagon increases the conversion of stored glycogen into glucose in the liver and muscles thereby increasing blood sugar levels.
Glucagon also increases the uptake of amino acids and glycerol into the liver so that more glucose can be synthesized.


The importance of glycogen as stored energy

Since all of the cells in your body require a continuous supply of energy, it is important that your body stores excess “energy” eaten during meals so that it can be used when food is less plentiful. Excess glucose is converted to glycogen by the mechanisms we saw above.
Glycogen is stored in the liver and the muscles. When your body is active, energy requirements increase and stored glycogen can be converted to glucose to be used as energy. If stored glycogen levels get too low however, cortisol is secreted from the adrenal cortex, and this stimulates the conversion of proteins and fats into glucose so energy levels can be maintained.
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So what does the glucagon do?
Glucagon and Insulin
Glucagon increases the amount of glucose in the blood by accelerating the rate at which the liver converts stored glycogen into glucose and releases it into the blood. Insulin decreases the amount of glucose in the blood by transporting glucose from the blood and into the muscle cells. It also stimulates the conversion of glucose back into glycogen so that it can be stored.
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It makes the liver dump glycogen, coverted into glucose, into the blood so that it can show up in your next PS reading!
And what happens when there is too much insulin? It does exactly what we don't want it to do:
Other Effects
Insulin also has a few other important roles in the body. Insulin facilitates the storing of excess glucose in the form of glycogen in the liver. Elevated levels of insulin also cause the liver to make more fatty acids. Insulin inhibits the breakdown of fat in adipose tissue for energy. Insulin also allows cells in the body to take up more amino acids, so that they can make more proteins
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.
In balance, that's a good thing, and in a non-diabetic, it would do so in amounts that made sense in the body. But if insulin is excessive, and it cause the liver to store more glycogen, then when the BG goes too low, and the pancreas puts out glucagon, and it makes the liver dump the glucose from the glycogen, then the pancreas (and the insulin) is sort of working against itself, isn't it?

So, what does this all mean? It means Carl is trying to learn junk. Look, y'all, I don't have a sugarkitty on insulin at the moment. I'm here because I want you all to be able to say that too. Diabetes is just a freaking disease, and it doesn't need to kick our collective butts. No, some kitties will never "get there". But that doesn't mean they don't have a chance at it. What the hell is so special about Bob, or Kitten, or Scout, Cello, Harry, Curt, Stinkyboy, Sev's Kitty, or any other furry that has gone OTJ? Nothing. It just happened. Not by itself of course, don't get me wrong. The beans had something to do with it, this Forum had a tremendous bit to do with it, but it can happen to any of us or any of our kitties.
I just want to learn all I can about it, which is why I'm doing all this "research". It's why I'm still around.
Well, that, and to show off my pics when I get a good one!

Too tired to continue tonight.

Carl

P.S. I haven't read the whole thread, but a discussion on this topic took place on the old board too. It was on page two I think, of my google search. But so cool that FDMB discussions get hits on Google!
http://www.felinediabetes.com/phorum5/r ... 616,675616
 
This was part of another response I just wrote, but then I thought it makes more sense over here:

Carl's new research: the pancreas actually produces the hormone that signals the liver to dump glucose. So bounces are part of the pancreas figuring out again how to self regulate....if you're getting a very low nadir and a bounce because of too much injected insulin not good, but if you've injected an amount that normally does not send the cat too low and this cycle BAM, cat goes to 50, I call that the P taking over. It might make too much insulin and try to correct BG and you get a bounce, but it's learning how to function again. I think some of OUR crisis situations are less of a worry to the cat, I have seen some charts where kitty goes low on a dose that shouldn't do that and throughout the 15 min testing the cat is eating a TON of food, and BG still stays down. This could only be because you are fighting a overdose of injected insulin or kitty is making it themselves, and when you know you shot a safe dose what else can it be but Mr. P trying to keep BG in absolutely normal non-diabetic numbers that scare the crap out of us because we've been told over and over that they are not safe?
 
Wow! Awesome Carl. Felt like i was sitting in my anatomy and physiology class again in college. Wish you could educate some of the vets with this knowledge and info!

Thank you for hanging around with us sugar kitties. I love the science behind everything and FD drives me crazy trying to figure it out scientifically. This helps in understanding it a little better. THANKS!!! Keep reading!

lori
 
Great stuff, Carl. thanks for doing the work and compiling it - and posting it!

I do think that "liver panic" had it's origins in the right "science" but it just became easier to say the "liver" panicked and dumped stored glucose than try and explain the pancreas/glucagon initiation of the process. Then it gets repeated by well-meaning people who don't know the science and misunderstanding ensues. Maybe we can come up with a better short hand for the process - can't think of anything right now though.

Let us know when you come across cruises to the Islets of Langerhans - we can all go as a group! And bring our sugar kitties (but they have to stay in the staterooms or no one will get out alive).
 
Sheila & Beau & Jeddie said:
Let us know when you come across cruises to the Islets of Langerhans - we can all go as a group! And bring our sugar kitties.
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I'd like to reserve a place on that cruise! ;-) ... and just think of the kitty buffet on board!!! :lol:
 
This is very interesting Carl. Thanks for posting the information. I for one am really glad you are here offering help.

I'm trying to read this info and think about what it means for Sid's situation. I think Sid's intestinal disease plays a big part and then he keeps developing infections that throw everything off. I think his pancreas is firing off all kinds of miscues! I know his fspecl test for pancreatitis came back normal but on an ultrasound his pancreas was a black spot and very diffuse (I think). So something not so good is going on in addition to the lymphoma and IBD...

Anyway, thanks for all your work you do for us :-D
 
excellently compiled articles! All information is great, just helps us beans try and figure out what's going on. AND.. if i think I'm reading it correctly, the bounces (whilst hideously annoying!) actually suggest that there IS life left in that there old pancreas and it's trying very hard to reboot itself and get going. So.. whilst it's very depressing to see those bouncy numbers (and i seem to have the king of bouncers at the moment!).. i THINK it actually means that there is hope, and things are on the right track.. and that the pancreas isn't completely destroyed already. Correct me if I'm wrong?!

it might also explain why kitties (at least mine anyway!) seem to be looking/feeling totally icky when they are up in the red and black numbers when we first start this journey and then when they start the bouncing, and therefore the high numbers are SELF induced.. they don't seem to be nearly as sad feeling at all. I know that Rupert can have hideous numbers and look quite quite fine and dandy when he's bouncing.

all very interesting!
 
I think that it does indicate that the pancreas, at least in part, is working, yes.

Carl
 
hmm... So that means having a tigger isn't really a bad thing? Cool. Cass still has a chance.
 
Well, it's still something we hope will go away or at least not happen all the time, but from what I read, it sounds like bounces mean that part of the pancreas is doing what it supposed to do.

Of course Cass still has a chance!

Carl
 
I've had my hands full with numerous “crashing kitties” lately. Without having time to read the massive amount of info in this post...this is the one topic that caught my eye...I don't know if this is helpful, but since Marilyn has been such a difficult kitty, the following is a "note to self" that I added to the top of her Excel SS a couple months ago (along with a few others):

The pancreas releases glucagon when blood sugar (glucose) levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is then released into the bloodstream.

Once I discovered that little tidbit, I just assumed the term "liver bounce", used all over the boards, is a shortcut phrase for the entire process. The way I see it, the "liver bounce" is basically the end result of a process that's started by the pancreas. So if this is the case, the term "panicky liver" is FDMB speak, for panicky pancreas...triggering the liver to set things straight...to keep the body out of (what the pancreas perceives to be) harm's way.

What bugged me about this realization was....if Marilyn's pancreas is supposed to be "resting", in order to heal, so she can possibly go OTJ...then how in the world is all of this "bouncing", and newfound "flatness", resting the pancreas? It didn't seem "right" to me. So after 4-months of dives, bounces, and most recently, high flatness...I started to "panic", and decided it was time to take control of her situation. My theory was...if I could stop the rebound process...her pancreas might truly rest, and in turn, heal. It turns out that "stopping the rebound process" is not for the faint of heart...or those who have to leave the house...so it's not practical...but it is possible.

I might post about it, eventually, when I have more time. I've actually been holding back on posting, since I've been making some bold strategic moves, that may not have a place on these forums. All I know is...today was her best day yet...so we're working on it. She went 39-hours without R, 23-hours without ProZinc, and 14-hours without N, and handed me a BG reading of 82. Although it's a work in progress, I'm hoping for a happy end to this "dive, bounce, flat-fest", that I could no longer imagine was, in any way, "resting her pancreas".

Good topic to bring up, Carl. I actually wanted to start a Think Tank topic a good while ago...but the Barn Cats, would never allow me the time needed to get my thoughts together. Nice job!
 
Deb,
Do not despair! The Islets are not an all or nothing thing.
Islets of Langerhans: Known as the insulin-producing tissue, the islets of Langerhans do more than that. They are groups of specialized cells in the pancreas that make and secrete hormones. Named after the German pathologist Paul Langerhans (1847-1888), who discovered them in 1869, these cells sit in groups that Langerhans likened to little islands in the pancreas. There are five types of cells in an islet: alpha cells that make glucagon, which raises the level of glucose (sugar) in the blood; beta cells that make insulin; delta cells that make somatostatin which inhibits the release of numerous other hormones in the body; and PP cells and D1 cells, about which little is known. Degeneration of the insulin-producing beta cells is the main cause of type I (insulin-dependent) diabetes mellitu
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s.

It is the alpha cells that produce glucagon and direct the liver to dump. The beta cells are the the ones that produce the insulin. And here's another new word for me to explore.....what the heck does somatostatin do?
Decrease rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine[5]
Suppresses the release of pancreatic hormones
Inhibits insulin release when somatostatin is released from delta cells of pancreas[7]
Inhibits the release of glucagon[7]
Suppresses the exocrine secretory action of pancreas.
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Not quite sure where that takes us, but it sounds like somatostatin is the key, since it seems to be what allows or doesn't allow the alpha and beta cells to do their thing?

I might post about it, eventually, when I have more time. I've actually been holding back on posting, since I've been making some bold strategic moves, that may not have a place on these forums. All I know is...today was her best day yet...so we're working on it.
Click to expand...

Please do post about it eventually.... have you considered that no matter what it is that you are trying, there might be another cat/bean or three that might benefit from it? Had I not "slipped" and told people that I shot Bob with IM shots the whole time, maybe Lydia and Sid would be worse off, because when someone saw it, they PM'd me and asked me to chime in... even though my "slip" was pretty much met with a less than positive response. This place is all about learning from each other, not about following the status quo like a bunch of lemmings. Some of the first lemmings off the cliff might not feel that way, of course... The very first person who said "hey, you can test BG with a human glucometer" was probably not well received...

Carl
 
I had reason to look for this today and thought I'd bump it. It's got some useful information in it.

Carl
 
Thank you for your research Carl.
This also gives me insight on how the Liver goes hand in hand with diabetes.
Thank you for caring so much!
 
WOW! Just WOW! :o @-) :shock:

How did I miss this post for so long? Maybe because we were in Lantus land at the time. who knows? Thank you for the research you did, it is greatly appreciated, not just by me, but by everyone, I'm sure.

Good to see ya Carl. :YMHUG:
 
@Carl & Polly & Bob (GA) Wonderful post. I would suggest the information part of this post be put as a sticky in the health links and should be one of the first reads for new members. It is a much more detailed description of the whole involvement of multiple processes within the body without being so "scientific" that it would be too hard to follow for people new to feline (or any) diabetes. Understanding the processes and the variables is such an important part of learning to deal with the sugar dance and its ups and downs.
 
So I have a question....
I haven't had money to do a blood panel in a long time,
but years ago when I adopted my kitty and he had F.L.U.Ts we ended up in the ER 6 days after adoption and his blood panel showed liver damage.
Everytime I give a food high in phosphorus his bg sky rockets and he lays in the litter box.
so im assuming he has kidney damage from prolonged diabetes.
Is it possible its actually still his Liver?
when I change doses on insulin he does great for a few days and than nothing.
3.0 seems to high and 2.5 insulin gives good numbers but still kinda high.
These articles have me thinking.
Thank you!
 
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