study comparing Lantus, PZI & Lente insulins in cats

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julie & punkin (ga)

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Just not sure if everyone who gives advice has seen this article - it was new to me so i thought i would share it. seems like i see the question raised fairly regularly "which insulin should my cat use/should i ask my vet for?"

This 2009 study compared the use of different kinds of insulin in newly diagnosed diabetic cats. Levemir isn't included in the study, but it's action is very similar to Lantus (Glargine). The 7th page includes a graph showing remission among the cats in the first 100 days using each kind of insulin.
 

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Thank you Julie for sharing this with us. I hadn't seen it either, that I can remember, and I read it all (suggest everyone do the same), and then a couple more times just so I was sure I understood everything.

Just one correction to what Julie said. Although it was published in 2009, the actual study was conducted from 2002-2004. Why that matters is because the PZI mentioned in the study is the discontinued "PZI Vet" that was available up until 2008 or 2009. Not exactly the same as "today's" PZI, which is a compounded form of the old PZI. The "Lente" insulin mentioned in the subject line, in this case was Caninsulin (also called Vetsulin), which is an intermediate length duration insulin more suited to dogs than cats.
http://petdiabetes.wikia.com/wiki/Caninsulin
Caninsulin contains porcine insulin. Porcine insulin is identical to canine insulin[30], but differs from human insulin in respect of one key amino acid. Porcine insulin differs from feline insulin in 3 amino acid positions shown in the table below[31]. Human insulins (i.e. Lantus) differ from from feline insulin by all four key amino acids.

After reading this study, and understanding how it was conducted, (although this might surprise some folks who have seen me in opposition to Lantus in the past), I would probably pick Lantus if the day ever comes when I have another kitty with diabetes.
First off, the study consisted of 24 cats, 8 on each of the 3 insulin types. Originally there were 29, but one of the conditions was that the cat eat the diet specified in the study, and 5 cats wouldn't eat it. I was surprised by the diet actually, which was Purina DM, which is only 7% carbs, but I've read lots of cats just won't eat it after a couple of days.

There are a couple of things that I find troubling however.

What disturbed me....
The initial starting doses for all 3 insulins. Initial dose was determined based on initial BG readings. Kitties with BG above 360 were prescribed one dose, while those under 360 were given half the amount. I guess what troubled me was that the dose was pretty high (not a "start low, go slow" approach which is the suggested starting dose on FDMB). It was based on the cats' weight. For BG over 360, it was .5u/kg of ideal body weight. Under 360 it was .25u/kg ideal body weight. I have no idea really what the average "ideal body weight" of a cat is. Bob weighed 13 pounds (down from 18) at dx. But I'm just going to say he was fat, and guess that ideal would be in the 9-11 pound range to be fair to normal cats.

At a weight between 9-11 pounds, with a BG of 360 or higher, the initial starting dose would be 2u - 2.5u BID, which is a lot higher than what is usually suggested for any insulin - we usually go as high as 1u BID, and sometimes recommend .5u BID. I thought that was odd when I read the study.
And then the "go slow" part of the equation. We usually tell people to increase or decrease dose in .25 (or as high as .5) unit increments. In this study, adjustements were made in increments as high as 1u at a time.
So the study didn't follow the FDMB "standard" start-low, go-slow approach.

The other thing that bothered me was that of the 3 insulins, lantus is the only one we would recommend. PZI Vet is no longer available, and Vetsulin/Caninsulin is always recommended against when newmems show up saying they are using it. It would be awesome if Levemir and Prozinc (which is not the same as PZI, old or new) were used instead.

What I did like about the study was the absence of any Tight Regulation mention. The cats were dosed 12 hours apart, even amounts AM and PM. The only mention of BG results were at pre-shot and at nadir, outside of the first 3 days on insulin when all cats were tested every two hours. After the three day period, the cats were sent home with a set dose, and told to come back a week later for another test. If needed, based on preshot and nadir numbers after a 12 hour curve, the dose was adjusted and kitty went home with a new dose for another week. This continued every two weeks from that point on. A fructosamine test was run every four weeks. So it sounds like the only time BG was checked was during the weekly or bi-weekly vet visits when a 12 hour curve, testing every two hours, was done.

The info on food intake was sort of vague:
food intake was not restricted for any cat during
the first 2 weeks of insulin therapy. Dietary energy restriction was recommended after 2 weeks for cats with
body condition scores of 7 or above (on 1e9 scale).
It doesn't say at what time of day they ate, or how much, just that it was controlled after the first two weeks.

It also said that if the preshots on curve days were below 216, then if it stayed that low over the 12 hour period, the cat was sent home with no insulin and rechecked to see if it stayed that low. I think the term they used was "suspected of being in remission"
After a minimum of 2 weeks of insulin therapy, if the
pre-insulin blood glucose concentration was less than
12 mmol/l, insulin was withheld and serial blood glucose measurements were continued for 12 h to determine if the cat was no longer insulin dependent and
thus in remission. Cats suspected of being in remission were discharged from hospital without insulin
treatment and had their blood glucose concentration
measured weekly for 3 months, to confirm remission.
So their definition of "remission" and ours are a little bit different.

Cats also got a dose reduction if their preshots were below 250 or their nadir was below 126, and the reduction was .5u, which also sounded unfamiliar, both the numbers and the fact that reductions were given based on either preshots or nadirs.

End results -
100% of the lantus cats went into remission within 16 weeks.
25% of the caninsulin cats went into remission.
38% of the PZI cats went into remission.

There were zero lantus cats who went hypo (no clinical signs even though some of their numbers were considered hypoglycemic), but two of the Caninsulin cats, and one PZI cat did go hypo and required IV glucose treatment to bring them back up.

Based on the end results, and knowing that all the lantus cats went into remission without using TR, I'd have no problem using or recommending Lantus in the future. I do wish, however, they would do another study that included Prozinc and Levemir so we'd have good data on the three most common insulin types used now.

Carl
 
This study give a lot of hope to those of us unable to do the Tight Regulation Protocol on Lantus. It seems like given the proper diet, achieving normal BG level control , and maintaining a pretty normal weight gives the best chance of remission, even if you are not able to test BG more than 2 or 3 times a day. It's also encouraging to see that all cats attained remission, even though some took longer than others. My vet said he would probably give up on remission after 3 months, but I feel like some cats just take longer than others. Very encouraging. Thanks a bunch!
 
I was surprised by the diet actually, which was Purina DM, which is only 7% carbs, but I've read lots of cats just won't eat it after a couple of days.

Note it's Purina DM canned they used. The Purina DM dry is less awesome and it has "max 18% carbs" according to its packaging (amazing they actually put the carb count on the bag, so good job Purina in that respect). The Purina DM canned seems to be a pretty standard choice for a low carb, high protein food for these kind of studies. I've also seen lots of people say their cat wouldn't eat it for long, my guy has been eating it as well as the other wet foods we've tried for over a month now, depends on the cat of course.

What disturbed me....
The initial starting doses for all 3 insulins. Initial dose was determined based on initial BG readings. Kitties with BG above 360 were prescribed one dose, while those under 360 were given half the amount. I guess what troubled me was that the dose was pretty high (not a "start low, go slow" approach which is the suggested starting dose on FDMB). It was based on the cats' weight. For BG over 360, it was .5u/kg of ideal body weight. Under 360 it was .25u/kg ideal body weight. I have no idea really what the average "ideal body weight" of a cat is. Bob weighed 13 pounds (down from 18) at dx. But I'm just going to say he was fat, and guess that ideal would be in the 9-11 pound range to be fair to normal cats.

I wonder if this has to do with the animal being at the vet for the first few days, and (presumably) being better ready to respond to a severe hypoglycemic incident. Here's the protocol from Marshall and Rand, from March 2009, for infrequent monitoring of BG like they used in this study (curve done at the vets every 1-2 weeks), still recommending the same starting dose based on initial BG values as in the above paper:

http://www.uq.edu.au/ccah/docs/diabetesinfo/link3.pdf

They do go with 1u/cat bid if there is to be no monitoring the first week(love the "per cat" unit). This is different from their tight regulation protocol which suggests a starting dose of 0.25u/kg with all BG tests performed at home.


I don't see it explicitly mentioned (I may have missed it), but since they mention the range 4-7 mmol/l as the normoglycaemia target range I would suspect they are using lab tests to determine blood glucose levels in the PZI vs Glargine paper and not a human portable blood glucose monitor.

Also interesting is that when a dose reduction was called for and you were at 1u bid, they drop to 1u sid. I wonder if they were avoiding .25u adjustments and trying to do a 0.5u dose due to lack of confidence that the caregivers would be able to accurately dose these amounts.
 
Brian,
I wonder if they were avoiding .25u adjustments and trying to do a 0.5u dose due to lack of confidence that the caregivers would be able to accurately dose these amounts.

About a month or so ago, Dr. Pierson posted this in PZI when discussing incremental dose increases or decreases:

I am going to digress again here: Regarding the word "slowly" - Unfortunately, my colleagues rarely raise or lower a dosage by any amount less than a full unit. I am trying VERY hard on VIN to change this mindset and to remind them that there really are smaller doses. I am having luck with getting them to embrace 0.5 unit increments but forget anything lower. I get laughed at when I mention anything lower than 0.5 units….mainly because they feel that it is impossible to accurately measure. I also got laughed at when using "fat" and "skinny". On a good note, at least they are now discussing syringes with half unit marks.

So yes, the vets might feel accuracy in measuring is in question, but maybe not only for the caregivers, but for anyone?
 
I wonder if they were avoiding .25u adjustments and trying to do a 0.5u dose due to lack of confidence that the caregivers would be able to accurately dose these amounts.

Perhaps it was due to the fact that, in Australia, there are no syringes with half unit markings available.
 
Even for vets? That's unfortunate. How does one do micro dosing? Can you buy them by mail?
 
Well, we had to order a box from the US. Our vet tried to find some for us, but had no success. I guess most people just have to eyeball the smaller doses.
 
Wow, I'm feeling better about my vet after reading this. I had my doubts at first, but she did come around on the diet. And at our last visit she increased Brody's dose from 1 unit to 1.5 units. She told me that the syringes weren't marked for half units, but she was confident I couldt fill it between the 1 and the 2 :smile: Since we were cutting out his dry food she didn't want to increase it too much.

Thanks again for everyone's feedback and comments. I learn a lot just reading the reply to other member's questions.
 
i would point out that the purpose of this study was to compare those specific 3 insulins. the purpose of the Rand/Roomp protocol that people call Tight Regulation is specifically to target cats toward remission.

i think it is inaccurate to assume that cats will not go off of insulin after months. Mr Tinkles (Laurie & Mr Tinkles) was on for 21 months before he went off recently - and he was one of the very bouncy cats. those seem to be harder to regulate and it's a testimony to Laurie's dedication that she was able to work him off of it.

cats that are newly diagnosed are definitely easier to get off of insulin. no doubt about it (assuming they have no concurrent condition that changes the game) but i would not ever assume that it wasn't possible just because the cat had been diabetic longer than a month or two.
 
Julie
can you share that with "kalyv" who just posted a question on the same topic? It's here in Health...
carl
 
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