1/17 Crystal - comments back from RVC London

I emailed Dr Neiseen at RVC London following my unsuccessful visist to my vet earlier this week.
I recieved a reply back from one of his students from the Feline Diabetic Remission team copied below. (I'm not sure whether the links will work for the papers he quotes though)

"I am one of Dr Stijn Niessen’s PhD students, and my thesis is studying feline acromegaly. There are several questions to answer I think:

1. do you think it worthwhile to have an IAA test done?

Depending on which paper you read, feline anti-insulin antibodies are either uncommon (Vet Immunol Immunopathol. 2000 Nov 23;77(1-2):93-102.Beta cell and insulin antibodies in treated and untreated diabetic cats. Hoenig M1, Reusch C, Peterson ME.) or very common (Res Vet Sci. 2013 Dec;95(3):886-90. doi: 10.1016/j.rvsc.2013.08.017. Epub 2013 Sep 4.Natural anti-insulin autoantibodies in cats: enzyme-linked immunosorbent assay for the determination of plasma anti-insulin IgG and its concentrations in domestic cats. Takashima S1, Nishii N, Hachisu T, Kojima M, Kigure-Hoshino M, Ogawa S, Suzuki T, Iwasawa A, Ohba Y, Kitagawa H). We know that dogs develop antibodies overtime when given insulin injections, but that this does not necessarily change their response to treatment (J Vet Intern Med. 2008 Nov-Dec;22(6):1317-25. doi: 10.1111/j.1939-1676.2008.0194.x. Epub 2008 Oct 3. Anti-insulin antibodies in diabetic dogs before and after treatment with different insulin preparations. Davison LJ1, Walding B, Herrtage ME, Catchpole B.). Another consideration is what can we do about the presence of antibodies, unless directec at that specific insulin, and my opinion is that we can do very little so it is unlikely to alter treatment. If directed at a specific insulin type, you could always change insulin type but this could always be trialled in the absence of an antibody titre.

2. I'm also pondering whether a switch to Levemir?

We do not know which is the best insulin type for cats, but longer-acting insulin types are probably best. Glargine is probably more suited to the cat that determir because one unit of glargine is not equivalent to one unit of detemir, glargine having a less impact per unit. So it is easier to make dose changes with glargine because of the differening potency.


3. this cat is drowning in insulin” and ”was on much too high a dose” all of which left me in complete turmoil as to whether I'm doing the right thing (this was what I was told by a French veterinery Professor via my vet)

If your cat truly has acromegaly, there will an increased an variable release of growth hormone from the pituitary tumour. Response to insulin will vary from day-to-day, but will typically be above the average dose of a non-acromegalic cat. I don’t believe there is a dose that is too high if the dose has only be gradually escalated and to effect. However, you are unlikely to ever get good control in the presence of acromegaly that has increased insulin requirements to 13.5 units twice daily. The spectrum of acromegalic cats and their need for insulin is wide, some only need one or two units twice daily, some need in excess of 40 units twice daily. The response to insulin by each acromegalic cat is different and so the dose required will be different. The concern about large insulin dosages is the risk of hypoglycaemic events or causing a Somogyi overswing, which occurs when blood glucose frops rapidly, the body then releases hormones like adrenaline, cortisol and growth hormone to increase blood glucose and you create insulin resistance than can last several days. Somogyi overswings are unlikely to occur if a patient’s insulin dose has been gradually increased over time with monitoring.


4. My advice would be to try to confirm the presence of a pituitary tumour. This can be done by an MRI or CT scan of the brain. If there is a tumour and the IGF-1 value is high, then acromegaly is extremely likely. If a diagnosis if confirmed, the best treatment would be continued insulin to effect in addition to treatment for the tumour. This can be readiotherapy or ideally removal of the tumour by hypophysectomy surgery. We offer surgery here as to Utrecht university. Each come with their advantages and disadvantages which should be discussed with whichever centre you visited and cost between £3000 to £4000. Following surgery, patients need hormone replacement therapy. If neither of these options are possible, your only option is to manage the diabetes as best possible knowing the limitations of treatment in the face of insulin resistance caused by the presence of too much growth hormone.


I would be happy to continue helping where possible by e-mail but could not take responsibility for her care which should be provided by your local veterinary practitioner. Please e-mail me back if you would like any further information."


I haven't replied yet, would be grateful of any comments you might have, but it looks like it's not particularly worthwhile having the IAA test done; it seems he would advise staying with Lantus rather than switching to Levemir and he confirms that there is never a dose that is too high for cats with acromegaly. Unfortunately his advice re the MRI or CT scan and surgery wouldn't be an option for me so I really just have to manage Crystal the best way I can.

I've just increased to 14u this morning but she's still in the high pink numbers, any thoughts please?
Suki & Crystal

 

Comments regarding IAA: Getting the test done may be less of an issue as having gotten the test for acromegaly run. We have seen cats break through the insulin resistance (IAA) on a regular basis and if you look at Sandy/BG's spreadsheet, that is a good example. Doing what you're doing -- raising the dose of insulin in a systematic way -- is the treatment approach no matter what the underlying cause of the diabetes is. So the doctoral student is correct -- the presence of IAA should not alter your dosing strategy.

Switching to Lev: There is definitely more research on the use of Lantus vs. Lev. However, the dosing strategies are the same despite the two types of insulin being pharmacologically different. Many people with high dose cats prefer Lev given that it is less acidic than Lantus. It seems that for some cats, when you get to a higher dose, the acidity of Lantus makes giving a large dose uncomfortable for the cat. In addition, for some cats, Lev helps to flatten out some of the swings in numbers. I think this is your decision based on what you are seeing with Crystal. I suspect we see more cats on Lev than this student has seen.

"Drowning in insulin": I think the doctoral student is telling you exactly what folks here have said. Crystal needs as much insulin as she needs to get her numbers into a better range. For cats with acro, the student made reference to some cats needing over 40u. In very nice terms, she is saying that your vet's professor doesn't have the experience to know what he's talking about. Likewise, for a cat who's dose has been raised in a systematic fashion, chronic, Somogyi rebound is highly unlikely.

Additional tests: From what I've seen here over the past 5+ years, most people to not go to the expense of a CT or MRI to confirm a diagnosis of acromegaly. Most are satisfied with the results of the IGF-1 test. If they are planning or SRT (radiotherapy) to treat the tumor, then the vet program that is doing the surgery gets a CT and I'm assuming this is part of the cost of the procedure. I don't know of any cats here who have undergone hypophysectomy surgery. My last read on this was that it was new and fairly experimental. The out of pocket cost for a CT or MRI are very high and probably not really necessary given the blood test and seeing what Crystal's insulin needs are.

As for your current dose, I would increase every 2 days/4 cycles until numbers are coming down.

How are you feeling about the feedback?

 

You've gotten a great interpretation from Sienne. Hang in there and go with what has been found to work!

 

Hi Sienne, thanks so much for taking time to interpret the report. I guess really I just have to carry on doing what I'm doing and hope we get a breakthrough, although it's a bit of a downer to read "you are unlikely to ever get good control ..... ." I don't know exactly what I was expecting to hear. I had hoped to get a reply direct from Dr Niessen but, having said that, it sounds as if his student knows a hell of a lot more than my local vet. At least I have the vindication of the current level of insulin and increases (which is what you guys have told me all along anyway) and will just have to ignore the comments made by the French professor. As to support from my vet, I think this will be on a very limited basis in future, just for routine checkups, as I know she is not comfortable with the current high dose and frequent increases. However, I will give her a copy of the RVC report as and when we next meet up.

Thanks BJ for your words of encouragement, I do fully intend to "hang in there" - with a little help of course from FDBM!

 

Don't become frustrated. People have had acro kitties go into remission -- it's rare, but it's happened. The bottom line for all of our kitties is that they don't know that they have a high dose or a low dose condition. They know if they feel good or if they don't. They are the same cats as they were the day before they were diagnosed and regardless, we love them dearly and that doesn't change.

 

I'm headed out to a meeting shortly, but wanted to get some comments in while you are still up. Firstly, Sienne has given you a great response. It's good to hear that people are studying and getting PhDs in acromegaly. I'm really happy to see a reply with some articles on IAA in cats - we have seen hardly any of those to date. And for the record, of the high dose kitties here now that have done tests done, the majority have IAA in the picture. You just have to be aware that if Crystal does have IAA, there can be sudden needs for less insulin if the IAA is broken. I know of other people with acro kitties that chose not to get the IAA test done.

I'd say with the dose, the IGF-1 test, and the other symptoms Crystal has (weight gain, pot belly), a CT scan will just tell you what you know already. Once you hit a good dose, Crystal will become a lot more regulated. It can take time. Even with SRT Neko still likes to bounce around and occasionally see pink. We have seen non treated cats (Tommy, Cobb) become quite well regulated.

As for Levemir, there are possibilities you will see differences with a switch. Many have. But also a chance you won't. I was lucky and Neko is flatter on Lev. Can't remember the reference now, but I remember reading that there isn't a difference in potency between the two in cats, unlike in dogs.

One cat here had hypophysectomy (years ago). As of mid summer last year, RVI had done 15 such surgeries. It's still very new with some risks.

Summary - stay the course. You are doing great!

 

I'm glad you heard back from the student. I also agree that Sienne's given you great information. The general strategies with iaa and acro are the same - the major difference is that for iaa there is a self-limiting component. It only lasts somewhere up to a year. You respond in dosing based upon what you get with BG tests, so if there comes a point where you're suddenly seeing all greens/blues, you may need to immediately drop the dose. When iaa "breaks" the insulin that has been bound up to antibodies is released, meaning that the cat suddenly has more insulin available in its body than what you just injected.

With acro, the output from the tumor can also wax and wane, which also means that you increase or decrease in response to the BG tests. If the tumor output wanes, then you also may be quickly going down the dosing scale. I think of this as similar to what happens after the cats who have radiation therapy (SRT) need reductions in dose. Yes, the numbers will tell you that the dose that was right before is now too high.

There are some cats on the facebook group that have had the hypophsectomy as well. It removes the acro tumor entirely and cats will go off of insulin with it, but it is riskier than any of the other options. Well . . . all of these options have risk. These kitties have a major health problem and you are always weighing out the pros and cons of each path to take. Just giving insulin is a reasonable path. The con is that it doesn't address the damage of the growth hormone in the body. But depending upon how old the cat is and how much longer s/he might be expected to live anyway, that might be a reasonable response. Tommy was 16 when he was diagnosed with acro - his tumor output was fairly high, and Lauren opted to just give more insulin in response. She kept him tightly regulated and he lived to 20 with it. That was pretty amazing and is a great role model. I'll get you the link to his ss. Looking at what others with high dose kitties have done (Wendy's Neko, Peg's Toby, Marilyn's Polly - there are more but those are the ones immediately to mind - will help you see how this works in practice.

We did not have a follow-up CT scan for punkin until we were at Colorado State Univ for his SRT. It was included as part of a study, so no fee for us. Personally, I probably wouldn't spend the $$ on it unless it was needed for some other reason.

On the German Katzen Forum - connected to Kristin Roomp and her diabetic cat, Tilly, they don't encourage people to test for high dose conditions. They are dogged about the dose and keeping control of BGs, and she says most of their cats don't get over about 10u per shot. Tilly's page is here. Her dosing guidelines are based upon the same Rand/Roomp (Kristin) protocol that we use but there are some slight differences, for example the suggestion that for a cat constantly over 300 you can increase every 2 days, that can be helpful for high dose kitties.

Oh, and we've had cats get to more than 100u per shot, although many acro cats seem to settle in around 20u or so as long as they aren't allowed to stay in high numbers constantly, encouraging a never-ending cycle of glucose toxicity that bumps up the dose incessantly.

In Crystal's case, I don't think there is any chance she is overdosed. She has a diagnosis of acromegaly. You've been methodical and reasonable in your dose increases. I just think her tumor is putting out enough hormones that she needs more insulin. Getting on top of her BGs will help control the dose increases because of Glucose Toxicity.

I think we've seen enough kitties do substantially better on Lev that it's worth a try. Not every cat does, and I wouldn't switch while I still had Lantus left, but when you're ready for a new prescription I would try it. I think that student isn't correct in that one item.

 

All I can do is echo everything others have said.

You are in the right place with people who understand and can help. I know that. My Polly and I lean on this place full weight and everyone here holds us up.

You are doing a great job ... a fantastic job. As Wendy just said,

Marilyn and Polly

 

Ah, here's one of Tommy's condos from 5/2011 talking about how to proceed with his BGs. And here is his ss. Lauren and I joined about the same time and our guys got the acro diagnosis a few days apart. It was really, really nice to have someone else going through it together. I would encourage you to check in on the threads of other high dose kitties and learn from what's being told to them. Feel free to ask questions, too. The significant difference was that when we got the diagnoses, people from the high dose group immediately started saying that acro cats couldn't go into green numbers - to keep them above 100. While it didn't make sense to me, I did listen and mostly followed that guideline. Lauren ignored them, dropped off of FDMB for the most part (because she was feeling badgered, primarily by one person from facebook), and she stayed the course keeping Tommy in green as much as she could.

We had Punkin treated with SRT, and I made dose decisions out of fear that what had been told to me was accurate and that it was risky for him to go below 100. Now logic would say that the cat who could go into greens safely before he got a test done is the same cat that could go into greens safely AFTER the diagnosis came in. But fear is a funny thing and logic doesn't necessarily play a part in it. So I'm sharing that all just to be honest.

The end result was that Tommy lived 4 years with the acro tumor to age 20. Punkin lived 2.5 years with acro, to about age 15-16. And honestly, Lauren did better with Tommy than I did with Punkin. Punkin may have been older than we thought, and he seemed to have a lot of other health problems - so it may be an issue of comparing apples and oranges. But I did think that Lauren's commitment to keeping Tommy tightly regulated kept his dose down and protected the rest of his body from the damages of high blood sugar.

It's a balancing act. I don't think anyone here would criticize the path that someone chooses - you just educated yourself and do what you need to do.

 

@Wendy&Neko @Sienne and Gabby @julie & punkin (ga) @pollydoodle

So many thanks to all of your for your wise counsel and encouragement, I suppose I've been going through a bit of a crisis of confidence since the vet visit. So much to learn and I feel as if I will never get the hang of it. I read lots of different posts and everyone seems to know exactly what they are doing/ talking about, I wonder if I will ever understand all the complexities. I have started regularly checking in on your posts anyway, as well as Suzanne & Cobb as these are obviously of the most interest to me. My hubby bought me a tablet for Christmas and now moans about the amount of time I'm on it doing research with my crazy cat ladies (his words, not mine) - thank heaven for all you crazy cat ladies, you are our lifeline.

Julie, I'm reading all the links you suggested especially Tommy's. Cobb was one of my case histories I put to my vet but whether she read it I'm not sure. I appreciate your candour in sharing your past experiences and fears, I know exactly what you mean.

On a good note, Crystal has just tested with a yellow at +5.5 the first for over 6 cycles when I missed a dose, so that has raised my spirirts. Little minx then dived into the Felix left out for the civvies when I wasn't looking so I won't bother testing her until a +10 this afternoon.

I think I will give the Levemir a chance, I have one more Lantus pen to use and then I'll make the change and see what happens but will check back with you all for guidance on the reduced dose I should be using. Meanwhile, I'll go with a 0.5 increase tomorrow to 14.5.

Hoping your kitties are allowing you to have a relaxing Sunday, hugs to all and heartfelt thanks again.

 

I think you may want to keep in mind that many of us have been dancing this dance for several years. I doubt there's anyone here who wasn't overwhelmed the first several months of this experience. Back when I started, there was another person on the Board who I got to know outside of FDMB. It turned out that she was an MD. She was just as overwhelmed as the rest of us when it came to managing her cat's diabetes despite having many diabetic human patients in her practice.

The good news is that you haven't become immobilized by the information overload. Rather, you've started reading. For me, that's the best way to get a handle on the information.

 

Hi Suki,

We were very fortunate that Jersey was not a high-dose kitty, so I can't offer any advice in that regard. However, I can completely relate to your loss of confidence and feeling like you're lost. I felt that way when we first started. Everyone else here seemed so "together," and I felt like I was just drowning in a sea of numbers that made no sense to me. My (two) vets were telling me two different things, and the people here were telling me something else. I just wanted to throw my hands up in the air and bawl like a baby. In fact, I did that on several occasions. The people here are definitely a lifeline, like you said, and they helped me pull it together each time I fell apart.

My husband thought I was crazy, too, for spending so much time on the boards in the beginning...and he wasn't very confident about taking advice from strangers on the internet. I, of course, ignored him. After a while, he started asking about them by name ("How's Trixie doing?") He'll never admit it, but I think he came to care about the people on this board just as much as I did - and he never made a single post here!

You're doing great. Just take one day - and one step - at a time!
Shelly

 

Hi Suki,

You've gotten some great responses already! You know we are all here to support you.

Here are a few of my thoughts...

I disagree that you shouldn't get the IAA test done. I know, and to some extent I agree, that the majority of people on here think I should have had Cobb tested for acro. We didn't. We had our reasons. Some financial. Some other reasons. But I know we are missing that piece of the puzzle in Cobb's medical history. I think the IAA test has value for one main reason. When the IAA breaks, you really can go flying down the dosing ladder. And if you have an IAA diagnosis, you have that in the back of your mind and are as prepared as you can be for it.

I also think (and I haven't had time to really organize my thoughts on this, but I'll offer them here in a rough draft form) that one way to overcome the antibodies is to flood them with insulin and confuse them (safely, of course). I think an IAA cat can benefit greatly by adding R insulin into the mix. I think by giving two types of insulin regularly the antibodies can get "confused." Which insulin are they supposed to attack? I don't know...I have no proof of my working theory.

As one who has switched from Lantus to Levemir, I also disagree with the doctoral student. I have found Cobb's responses to Levemir incredible. I think his IAA was, perhaps, insulin specific, and if your dose on Lantus just continues to climb, I don't see what it would hurt to at least try the switch and see how Crystal responds. I don't know how much Lantus is over there, but the savings of a lesser dose for us was worth the switch!

Additionally, if you had the IAA dx, you may feel more comfortable using R insulin, although I know Julie used it on occasion with Punkin, and he didn't have IAA.

I disagree that you won't ever get good control. Lauren and Tommy were my inspirations. He had both acro and IAA and he was amazingly regulated. I think she held him at 2units for quite awhile. That control just depends on when the antibodies go away and the rate at which the growth hormone is secreting from the pituitary gland. If it's a drip, not a gush, you'll likely have better control.

A few things I do agree with...not knowing won't change your overall treatment. You'll still follow the protocol with increases, meaning you'll at least hold the dose for 4 cycles. Also, given the acro, you won't be overdosing on insulin. You give the amount of insulin required to offset the acro effects. I agree with Julie, no chance of overdosing here.

As for these "crazy cat ladies," my husband said the same thing. However, now anytime I have a question, he says..."why are you asking me? Go talk to your people!" I'm sure yours will come around.

Honestly, I can't say enough about our switch the Levemir. You've seen Cobb's spreadsheet. His numbers speak for themselves. I'm excited to go to the vet in April and show her Cobb's response. Our last visit he was at 20 units. We climbed to 31u, switched insulins and are now down to 6u.

I'm sure the doctoral student didn't mean to be a downer. You are doing a great job with Crystal! I always think it is important to remind people - while a vet may be overseeing our cats' care, we are the ones treating them.

~Suzanne

 

@Shelly & Jersey - thanks for dropping in and sharing your experience, it does make me feel better to hear other people's reactions have been the same as mine when they started this journey. It's funny how the hubbies are so sceptical at first, I hope mine comes round in time, although he's already said to go with my instinct and ignore what the French vets are saying.
@Suzanne & Cobb - I was hoping you would check in too and add your comments. With regards to the IAA test, I still don't know whether I could even get this done at RVC, I haven't replied yet but will ask them if it's a possibility, I'll keep you posted. I really hope you are right about getting good control, as you say, perhaps the change to Lev will be a deciding factor, (there's no difference in the price between the two here). Anyway, it wont take me long at this high dose to use up my current Lantus. I couldn't agree more with your last comment about the owners being in the front line of care, there is also all the emotion involved as well which the vets don't have to wrestle with.

 

I know how your feeling just took Toby up to 14 units this week. Although he is not regulated we are seeing a lot better numbers. Thanks to everyone on the board that have helped keep me sane. It's been a very trying time to give so much insulin and not to be able to regulate him. We haven't done any tests for high dose cats. My vet. felt that the out come
would be the same more insulin. So we are just plugging along with the help from the members of the board. Toby seems to feel alright and we will try and keep him as healthy
as possible. Take Care Peg and Toby

 

Thanks Peg, I appreciate your support, it's good to check on other kitties at a similar dose rather than be so self absorbed with just your own. Hope Toby makes good progress and you see some good figures soon, I'll watch out for your posts with interest.

 

You can really learn a lot from reading other people's posts. It's perfectly ok to ask questions about whatever is being talked about, too.

And yes, I used R fairly regularly. It's a good tool - if you want to learn how to use it, suki, just say so. Lantus & Lev don't have a quick response to dose increases - think of them as steering a barge. A little dose change and wait to see what it does. R is a quick in and out insulin - lasts around 4 hours in the cat's body. Think of it as a speedboat - a little correction to the steering wheel and the boat immediately turns. If a cat has iaa that can cause the time of action to last longer. Most people with high dose cats find a combination of the two insulins can be really helpful.

When a person wants to use R we like to start with a tiny dose, in case there is a strong response. We typically start with 0.1u and then you test hourly for the next 4 hours. The next time, we try 0.25u and repeat the hourly tests. If needed, we might try 0.5u in the same way. Once you've established how your kitty responds to R, then we develop an "R Scale" meaning that we can see if the cat's BG is in x range (say over 400), use this amount of R, if it's in another range (say 250-400), use B amount (a smaller amount) of R. Then you can do it on your own, as you see it's needed.

Let us know if you want to learn this - one of us who have used R will make a date with you and check in with you hourly for the following 4 hours.

 

Thanks Julie, it's an interesting possibility to bear in mind for the future. I think I'd like to give the levemir a go on it's own first just to see how Crystal responds but I'm certainly open to all suggestions. I did mention using R insulin to my vet at the last visit, but she didn't know anything about it, so it will be back to you if I do go that route!
Crystal's had another yellow test this evening and I hope to get another one in before bed but have to wait for her to return from a little hunting trip first, hope it's a quick one.