Carryover and Overlap....things to think about

As if there aren't enough variables to think about, I've been doing some reading lately on "carryover" and "overlap", so I thought I'd share...

We often think of Prozinc/PZI as "in and out" insulin. According to what I've read before, compounded PZI is advertised as
- having an onset around +2
- nadir/peak at +4 or +5
- duration of 8-10 hours

Prozinc, according to the manufacturer -
- onset by +3
- nadir/peak between +5 and +7
- duration of 10 to 14 hours

Before anything about carryover or overlap, first there are three other "concepts" I want to mention. These 3 things are critical to determine so that you can figure out what's going on with a cycle of insulin.
1- Onset
2- Nadir
3- Duration

You have to collect data to figure out when onset, and nadir are taking place. And you can get an idea from those as to what type of duration you're getting. A lot of times, I've read (and occasionally said) that a cycle of long duration can indicate a dose that might be "too high". I've reconsidered that. And I've also come to think that there's absolutely nothing wrong with a cycle that lasts "too long", as long as you know what to do with it when you see one. Actually, if you're getting long cycles, you can use that to your advantage, and smile when you see it happen.

Here's something I hadn't read before, from the petdiabetes wiki: PZI is considered to be a "long lasting insulin", although I've usually seen it described as an "intermediate" duration insulin. Yes, compared to a "depot" insulin like Lantus or Levemir, it is "shorter". But according to the wiki, BCP PZI has the following properties:

http://petdiabetes.wikia.com/wiki/BCP_PZI

No type of insulin is absorbed 100% all at the same time. A large portion of a dose might be, but part of the dose will be absorbed more gradually. And other stuff can affect the rate of absorption. Like how hydrated the cat is for instance. I've read on the TR forum that on any given cycle, the rate of absorption can vary by up to 50%. None of this is an exact science. Every cycle is different. So some days you might see a 10 hour cycle, and some days you'll see a 14 hour cycle. I think we go with "shoot every 12 hours" because it makes sense. Twice a day, same time every day, because then you can have a real schedule with this and with the rest of your life. But a cat can't tell time, and they sure don't follow any kind of schedule. They are pretty much on a schedule of "Eat, sleep, play, sleep, eat, groom, sleep, mess with the bean's head, sleep, nap, and sleep. Lather, rinse, repeat. And their "Shuffle" button can't be disabled.

Carryover - http://petdiabetes.wikia.com/wiki/Carryover

Overlap - http://petdiabetes.wikia.com/wiki/Overlap

If you have what seems to be a "long cycle" going on, then you're seeing duration that is longer than usual (assuming your prior data shows duration of 12 hours or less). But what's the problem with that? I don't see one. You can use that knowledge. You can see less of a rise after eating because the first shot isn't completely pooped out. You have a lower preshot, so you can reduce the dose if you want to. The dose will be working against a lower BG than "normal", and you can keep the numbers lower overall. Kitty can spend more time in good numbers, preferably below the renal threshold for as many hours per day as possible. That's got to help, right?

This isn't something you do without careful consideration. Can you test later in the cycle? Do you know what to do with low numbers when they happen? Have you collected enough data to feel good about when onset and nadir usually take place, and do you have a good idea what sort of duration you usually get?

When in doubt, err on the side of caution. Always. But in my opinion, if the choice comes down to "skip" or "shoot", if I were holding the needle, I'd shoot. I'd rather shoot a lower number with a lower dose than skip and pretty much count on a high preshot 12 hours later. To me, that's a missed opportunity, and a loss of momentum. Right when it looks like "progress is being made", you end up right back where you started.

All of this is "my opinion". I'm not a vet, my cat was only on insulin for 10 weeks three years ago, and I didn't test nearly as much or as often as most of you do. What I did do was use a sliding scale for 10 weeks, shot numbers well under 200 regularly, aimed for greens, ignored bounces, and loved Bob like today was our last day together every day. And my reward was two and half years of a life with him that I wouldn't have otherwise had, and that I wouldn't trade for anything.

Carl

 

Wow. Amazing information. Thank you so very much for putting this all together!

I'm still absorbing, but this stood out initially:

If there is even a small amount of carryover for PZI/ProZinc, this might be why it does seem to take some cats a few cycles to settle into a dose? Almost like a mini-depot that boosts the power of the dose after a couple cycles?

 

Perhaps I should revise this then: Insulin dosing options

 

WONDERFUL thoughts and explanations Carl!

btw, LOVE your new avatar! We haven't seen Polly pics lately...

 

Lyresa,
Here are a few...

 

good info, carl!!!
this is the kind of information pzi users used many years ago when i joined the FDMB... often by those whose goal was to tightly regulate their kitties.

onset, nadir/peak, duration. if you know kitty's onset isn't until (let's say) +3, the number you're shooting at shot time really isn't the number you're looking at... you're really shooting the number/where kitty will be at in 3 hours (when onset occurs). use your data to help you pick out these patterns. this knowledge will help with your dosing decisions.

we call this "using overlap & carryover to your advantage".

bravo! nice post. stick a star on it and bump it up often for others to read.



edited to add:
LOVE your polly pics! she's adorable!

 

Thank you Carl! :YMHUG:

 

Thanks Carl. Awesome Info.

 

Thanks, Carl. Great explanations, as always. And, love the new Polly pix. She's gorgeous!

Hugs -

Libby (& Hershey, too!)

 

Any way to keep this at the top? It's quite useful. :smile:

 

Fabulous information and it makes a lot of sense for me. I know the way Simon uses his dose most of the time, but sometimes I am baffled and this is probably why...the "buildup" is what I did not factor in I guess. I do shoot at lower numbers cause I have a lot of data and know my cat pretty well, but as you said, "careful consideration" is very important. We are trying to get him back to OTJ status right now and don't want to lose momentum so am shooting if it is over 135 or so. GREAT POST and love the Polly pics too! :smile:

 

Bump

 

We've missed you bud! I'm sure you've been busy.

Much love!

 

Bump

 

bump - lots of good info here!

 

Bump

 

bump

 

Hi Carl, I have spent some time this morning scouring over all the good information that you have reposted. The skip or shoot is a real puzzle to me as well. There have been times when a dose gave Bubba a 95 PMPS and knowing that I could stall till the cows came home, I skipped and of course the AMPS was high. So, could you guide me as to what you would shoot with that number ? Also,did you have a sliding scale with Bob that you could share. I need guidelines, for instance if the preshot is in this range, shoot this. I understand you not wanting to give dosing advice. Let's just call it exchanging information. Thanks in advance.

 

Please, Bobbie, think carefully before considering shooting a 95 preshot. Even shooting a tiny amount could give you a very low nadir as he has only 50 points to drop. Then not only would you need to try to feed him back to a safe level but you'd create a likely bounce and get a higher pre shot the next time anyway. Other alternatives are to wait until he is at least 130-150 and shoot a token amount, or to lower the dose that gave you a 95 preshot.

If you want, start shooting numbers in the 120-150 range with tiny amounts on cycles you can carefully monitor to see what he might do. But Bubba's history is full of unexpected results, so using previous history for future doses is especially hard for him.

@Carl & Polly & Bob (GA) and I agree on lots of things. But there are things that we disagree on: I feel strongly that ECID. One of the reasons for that - although ProZinc is supposed to be an in and out insulin, over the past 6 years, I have seen many cats whose patterns don't reflect that. Lots of cats do seem to take a while to "settle in" to a dose. And I have seen many, many cats - several on the forum right now- who have a marked response to tiny amounts of difference in dose changes. Both of those are anecdotal, but since I am not a vet, it's all I have to go on.

And Carl, I can't believe that you think it is responsible to post what methods you used with Bob while urging others not to do the same, and then not post regularly to help those people because "you don't give dosing advice". Please, start posting here regularly and help people, but stop with the "drive by" advice, which you gave on your other thread. Your more "aggressive" voice is needed here to balance out my my less aggressive one, but it takes daily advice giving.

Bobbi and others, our first rule for advising anyone is "to do no harm". I take that very seriously. If someone wants to do something I consider harmful, I tell them and then urge them to monitor very carefully and be prepared to deal with low numbers. I always say "it's your cat and you hold the syringe" but think it would be irresponsible not to give my opinion on something I consider possibly harmful. That's why, after much thought, I replied to this thread.

 

I had a feeling you would weigh in Sue and I am so glad you did! . What would a token amount be? The reduction thing is very difficult for me to figure out because like you said "Bubba's history is full of unexpected results, so using previous history for future doses is especially hard for him". And if I were to wait till he came up to 130-150, what would the dose be?

He is not making this easy for me. I think he is one of those cats that takes a bit to settle into a dose also. Then he flattens out and stays stuck like he is doing now. He doesn't want to get out of the yellows.

I appreciate that Sue, and I also appreciate that you are present daily to help guide all of us. I guess I am looking for a magic bullet and they aren't any........

 

Why don't you start a new thread and have everyone look at his recent numbers after the surgery? I hope Carl will weigh in.

 

Will do.

 

Wow, before I could even give any input to Bobbie's question, I'm told I shouldn't?

Well, I will answer Bobbie's questions regardless.

First off, yes, I did have a couple of sliding scales for Bob. I was sent home with Bob after his DKA episode with these instructions from his vet:

If BG is less than 300, shoot 1u.
If BG is over 300, shoot 2u.

That was it, plain and simple. As the days and weeks went by, and Bob's numbers weren't really getting any better, my vet gave me this scale:

If BG is over 400, shoot 4u
If over 300, shoot 3u
If over 200, shoot 2u
If over 100, shoot 1u.
If below 100, call me on my cell phone and we'll talk about it.

The phone call never happened as Bob didn't give me an AMPS or PMPS below 100.
But I adhered to that scale for 3-4 weeks.

Then Bob's numbers started getting a lot better, and his mid-cycle numbers were blue and green. A couple of times, he dropped into the 40s.
At that time, without consulting my vet, I cut all of Bob's doses in half. And his numbers stayed about the same, and then improved.

I did shoot at a BG test number below 100. Twice. Once was a couple of weeks before Bob went OTJ, when I gave him 1u on a number in the upper 90s.
Once was on the last day or two that he got insulin. I shot .25u. In neither case did Bob's BG drop below the "hypo" line.

In 10 weeks, I saw two numbers below 50. Bob may have gone below 50 at other times, but I didn't test every nadir so I really have no idea. He never experienced a hypoglycemic episode, and I never once had to resort to Karo syrup, high carb food, or gravy. I fed him half a can of Fancy Feast Classic and went back to work on one occasion, and back to bed on the other occasion.

Am I saying that anyone else should do things the way I did? Absolutely not. Most of Bob's journey on insulin took place before I joined FDMB. I never asked anyone here for dose advice. I followed my vet's advice solely until I got gun-shy and cut his doses in half.

Am I proud of how I treated Bob's diabetes? Damn straight I am. In 4 1/2 years, I have not seen one cat here who was treated the same way I did things. Nor have I ever suggested or advised anyone to do things the way I did things. And I never will either.

Bob is the only cat that I am aware of that got every single shot of insulin he ever got by way of "IM". He did not get sub-q shots. Ever. He got shot in the back leg twice a day, straight into muscle. Because that was what my vet told me I needed to do, given the exact conditions of Bob's diabetes. She had never before, or since, had a caregiver give IM shots. I trusted her with Bob's life, and she saved his life in the early days. After that, I had no reason to not follow her advice. But I went "rogue" because I started getting concerned that his doses were too high. It turned out to be the right decision, as his numbers didn't go to crap on the lower doses, and a few weeks later he went into remission.

I firmly believe, and nobody will ever convince me otherwise that the reason that Bob went into remission was because he was treated aggressively with insulin, and it was caught fairly early on. Had I not been as aggressive as my vet advised, I believe it is highly probable that Bob would never had gone off insulin. And that's the primary reason that I feel aggressive is better than "patient".


All that said, NOBODY SHOULD EVER treat feline diabetes the way I did without the full support of your vet. It doesn't matter what "we" think. Of course everyone here is going to be more conservative with YOUR cat than they would be with their OWN cat. Otherwise we couldn't sleep at night, couldn't live with ourselves, if something we suggested caused you or your cat harm.

THAT'S WHY I DON"T GIVE DOSE ADVICE. Because in order to give you real honest advice, I would have to tell you to be more aggressive. Because I really believe that most cats are not being treated aggressively enough, and the longer they are diabetic, the greater the chances they will stay that way. Maybe remission isn't the end-all, be-all goal. Maybe just having a cat on insulin shots twice a day, well-regulated for many years is enough. That's perfectly fine. Humans live otherwise normal lives for years with diabetes. So do dogs and cats. The key is that if you have a well-regulated cat, you're giving it a longer healthy life. Remission isn't always "forever" anyway, as I found out two years ago (3 days from now). I'm just happy that Bob got to go 2 1/2 years without getting poked with sharp objects anymore.

Lastly -

Bobbie,
If you had asked me, when you saw that 95 the other day, "what dose should I give"? I would have told you to skip the shot. And expect a higher AMPS in the morning. Because it's just a higher AMPS.
It isn't that big a deal, and it isn't going to throw everything out of whack for days on end. And if you are interested in using a sliding scale, discuss it with your vet. They need to support it, and they need to have experience with it so that it makes sense for your cat.

 

Sue, you and I will need to agree to disagree then. I don't believe small dose adjustments make much of a difference. And while on occasion you might see overlap between cycles, it is the exception rather than the rule. I don't believe that you make dose decision based on the exceptions. And I don't, and never will buy into the "settle in" theory. The maker of Prozinc states that Prozinc is a 10-14 hour insulin. I buy that, hence the overlap on occasion. They also state that the longer the cat is on the insulin, the later the nadir might take place, and the longer the duration might last. But they never claim it will go beyond 14 hours. It is an "in and out" insulin. I believe, based on Dr. Lisa's posts, that the "marked responses to tiny amounts" that you see are not due to the tiny amounts, but due to more than a dozen other factors that she detailed so well. I think that the conclusions reached on the board, by many others besides you, are based on pre-conceived notions that are made to "fit" the conclusions in many cases. I believe that the "best answer" many times is "I don't know why. Just 'cuz."

I can't believe you think it's irresponsible, frankly. What am I supposed to do, just base my words on everyone else's experience except my own? I did what I did, I'm proud of it, and if someone asks me what I did, I'll damned sure tell them. I won't tell them how to do it themselves.
The reason that my "aggressive voice" is not heard is because when it is heard, the conservative voices eventually stop talking. And I simply do not, nor will I have in the future, have enough hours in the day to post in 20 threads each and every day, and be the only one talking.
The reason for my latest "drive-by" is because I looked at the PZI forum and saw a lot of people looking for answers that maybe weren't hearing some of the stuff I posted. It bothers me that so many cats are in such high ranges of numbers for as long as they are. And I'm not talking red and black numbers. I'm talking about yellows forever, an occasional blue, and a rare green. The longer a cat is in a condition of "hyperglycemia", the more damage is going on internally, and the healing ain't happening. The more hours a cat spends in the "normal range" per day, the better chances that it will heal, and maybe even get to the point of remission. Hyperglycemia causes organ damage. And hyperglycemia doesn't mean "above the renal threshold", whatever range of numbers you want to say that is. Ask 20 people and you'll get 20 different answers.
In order for healing to take place, according to the wiki information anyway, this must happen:

https://en.wikipedia.org/wiki/Diabetes_in_cats#Remission

If blood sugar is well controlled over a period of 2–3 months, glucose toxicity and amyloidosis cease to attack newly generated tissue, and many cats are able to regenerate some of the damaged pancreatic beta cells and slowly resume insulin production.

Not one word about the "renal threshold".

It also says this:
Remission is a realistic goal for treatment of type-2 diabetic cats (that is, 80–95% of all diabetic cats) who are properly regulated quickly.[36] Chances of success are highest in the first few months after initial diagnosis, due to ongoing damage from glucose toxicity caused by hyperglycemia. This limited time window is a good reason to start with low carbohydrate diet and very slow-acting insulins, the most successful known combination, right away.

An explanation can be pieced together from recent studies[37] in which diabetes in cats is perpetuated, if not always caused, by a combination of glucose toxicity[37] andamyloidosis, such that the insulin-producing islets of the pancreas become clogged with amyloid deposits. Cats may present with type-2 (insulin-resistant) diabetes, at least at first, but hyperglycemia and amyloidosis, left untreated, will damage the pancreas over time and progress to insulin-dependent diabetes


The whole key seems to be getting the cat regulated quickly, because as time passes, the damage keeps happening and the chances go down. "Drowning in glucose toxicity" is the way Dr. Lisa puts it.

No, Sue, I won't be stopping by daily and offering advice. And since my "drive by advice" isn't welcome, I won't be doing that either. I'll occasionally drop by and bump some info threads however, so that people can see them and draw their own conclusions.

 

Carl, thank you so much for taking the time to explain how you worked Bob's sliding scale. I really appreciate it. Your more aggressive approach is very interesting to hear about and needed to hear about and as Sue said " Your more "aggressive" voice is needed here to balance out my my less aggressive one, but it takes daily advice giving." I can't speak for Sue and won't try to but it seemed to me when I read the above, that your voice is most welcomed. Thanks again for taking the time to give me your reply and to explain it very thoroughly.

 

Perhaps my cat is an exception, but in our case "small dose adjustments" can make a HUGE difference.
And by 'small' dose adjustments I mean even adjusting by really, really small fractions of a unit, such as making a dose a smidge fatter or skinnier. This sensitivity to subtle changes in dosage has been an issue for us for some years now....

 

Elizabeth.....fats and skinnys...how many drops are we talking? One, at most two? Where's the real proof that the number differences were due to a drop or two of insulin? I know people want to believe that, but the fact is that there is no way to prove the conclusion. I don't care if one uses calipers to set the dose. Syringes are a cheap mass produced piece of plastic with an inscribed scale, all put on by machines that have margins of error built in. If a syringe were truly as accurate as they'd need to be in order to get an exactly duplicated dose in them, they'd cost more per syringe than a 5 pen set of Lantus does. If your syringe costs you 50 cents, it cost the manufacturer at most a dime to make. By the thousands.

I still maintain that people, in order to explain what they are looking at, make the numbers fit their pre-conceived notions.

Instead of accepting the biological reality that the amount of insulin given on any given shot has little influence over the cycle compared to all of the other things going on inside a cat's body over a 12 hour period.

If you gave your cat the exact same dose every single shot, down to the molecule, you will not see any duplication of numbers from one cycle to another. There's too much "fudge" involved. The carb content of the food is NEVER going to be the same from one can to the next. The meter is NEVER going to be accurate any closer than "ballpark". Heck, if you're using an insulin that needs to be "mixied" by rolling it or gently shaking it, the strength of juice from one shot to the next isn't going to be exactly the same.

In order to accept that a drop of insulin is going to change the numbers, every single other factor would need to be a "constant". When in fact, NONE of them ever are.

As I have said countless times... there are only 3 things you control.
1 - the type and amount of food given
2 - the timing of meals
3 - the amount and timing of shots

In order to stay sane, we have to believe that "we have control over" something, because we really don't have much control over any of this. I guess the easiest thing to believe you have control over is the size of the dose.

Sorry, nobody here will ever convince me that micro-dosing matters.

 

I'm not trying to convince you of anything, Carl.
I'm just writing about my experience with my cat.

 

Which is all any more of us have - our personal experiences and what we see has worked for others. And that ECID
Thing. Which is why it is important to have different voices and approaches and be around when someone takes our advice.

I appreciate that you are posting on PZI, Carl. Your voice is needed as is everyone's.

 

I'm already convinced. The point I've been trying to make is simple. People post that they see big differences due to tiny micro-adjustments, and there is absolutely no proof that one led to the other. It is only anecdotal evidence. Then people read this, and assume it's true. Adjust by a drop and see movement. In spite of no proof, and in spite of the words posted by a leading vet in the FD community.
Which, in my opinion, is a disservice to both the cats, and the caregivers. Without a direct correlation, which you will never be able to prove given dozens of known variables, it isn't a matter of convincing me. It a matter of misleading your larger audience.
Believe what you want. Some people believe in Santa.

 

Carl. I have always held you in high regard. But sometimes your comments seem extremely unkind. I don't expect you mean it to come across like that.

FWIW, I don't believe in Santa. Or in fairies at the bottom of my garden. Or in God. I'm not sure that I 'believe' in anything very much. I have, however, learned to have a little faith in my own direct experience.
I have a cat that has been on insulin for almost 9 years. And in recent years I've observed that tiny dose adjustments can make a big difference with him. I do not consider that to be a matter of 'belief'.

When considering how a cat responds to any given insulin shot I have made all the same comments to people that you made in one of your posts above (about the many variables involved; some of which are in our control, and many of which are not); and I've added other things to that list also.
However, it is still my experience that - despite that list - my cat is now affected by very small dose changes.

I do not think I am misleading anyone in stating my own experience. And I find your suggestion rather upsetting given that 'misleading' anyone is the very last thing I would ever want to do.

 

I debated whether to add a comment after Carl's snide and unnecessary comment, Elizabeth, but I knew you could stand up for yourself.

Carl, it has always been the norm here to peer review other's comments. And over the years, I have seen it done many times, with kindness, directness and even bluntness. But I don't think there is ever a need to be rude and condescending. I understand your experience is different from others, but I don't think that makes it any more valuable or true. Dr. Lisa's comments about dosing PZI were made, what, 5 years ago? I wonder whether she might have changed over time. Who knows? I certainly know my thinking has changed in the last 5 years, with every new cat I have seen adapt to ProZinc/PZI in different, unique ways.

I think direct anecdotal experience, especially over 9 years as Elizabeth's has been, is to be respected - not discounted. In the last few months, on a number of different threads, I have found some of your comments to be out of line and unproductive and disrespectful. And very different from the way you have posted in the past. And against the norms on this board I have always respected.

 

"Dr. Lisa's comments about dosing PZI were made, what, 5 years ago? I wonder whether she might have changed over time."

It was 2012, I think, but whatever.
And no, Sue. I don't think anything would change with what she said. And honestly if you think her points were specific to "dosing" then you continue to miss her point, and mine as well.

 

"In the last few months, on a number of different threads, I have found some of your comments to be out of line and unproductive and disrespectful. And very different from the way you have posted in the past. "

Ok, here's the thing. The "old Carl"? The one you and others came to know and love? He died. He no longer exists. In the past two years, the new Carl got slapped right upside his head by a big dose of reality. And what I have come to learn is that life is far too short for me to worry about what anyone thinks about what I think, do or say. So I no longer mince words, speak platitudes, or feel guilty for saying anything. I bump things I think need to be bumped, I say things I think need to be said, and if that offends you, then I can't help you.
I do not care anymore what you or anyone thinks about my "style".

 

Sometimes a person's pain is so great that it spills over and causes pain to others. I have long suspected that this may be the case with you.

I am sorry if life has dealt you a cruel blow, Carl.
I hope the situation can be resolved. But if it cannot be resolved then I sincerely hope that - for your own sake - you can make your peace with it (if that is what you want).

 

Thank you, Elizabeth.

Ok, I'm locking this thread. Its original intent was to be informational.
That is no longer the case.

If you scroll way back to post #20, it was hijacked. Instead of an appropriate response to a newer member, politely letting her know that questions might better be posted in a normal thread, Sue decided to tag me, and then proceeded to let me know my advice was not "responsible", and then said I needed to post daily and stop with the "drive by advice".

And then devolved to this.

Now I'm going to have to create a new " info" thread on the original subject, which hopefully can remain free of "commentary" in the future. I see no point in continuing this one and bumping it months from now just so new members can relive all of this drama.

Good luck to all of you.