Diabetes

The only thing worse than to be placed on an extremely high TKI dosage is to be unnecessarily kept on that extremely high dosage for a prolonged period of time which increases the probability of serious side-effects.  I don't know the reasoning for you to be put on that high TKI dosage initially but it certainly seems that your TKI dosage should have been reduced a long time ago.  

What is your current PCR level?

Any PCR level below 0.01% is indistinguishable from "undetected". It is in the noise of the test. You are in a very good place.

You should discuss with your doctor lowering your dose or even stopping treatment and test response.

Regarding your diabetes (type 2). Diabetes is a metabolic disease with strong association with excess carbohydrate consumption. And there is evidence that nilotinib can be a partial cause (5.7% 2011 study).

Type 2 diabetes, however, can be managed and in some cases reversed naturally. Putting your body into ketosis (generate ketones for energy) helps improve insulin sensitivity and otherwise lower blood sugar levels. When few carbs are eaten (or none during fasting), the liver has to make sugar over time by metabolizing fat and protein. This process is conserved and helps lower excess blood sugar - and dramatically in some cases. As long as you are still able to produce insulin (not type 1 diabetes), regeneration and improved insulin response is possible.

Exercise, especially, high intensity large muscle group exercise helps clear the blood of excess sugar as well especially in the morning (which I don't do and should!).

See Genetic Risk of Prediabetes and Diabetes Development in Chronic Myeloid Leukemia Patients Treated With Nilotinib

Pete I am sorry to hear this!! I believe Nilotinib long term can cause diabetes. I too am on it for 5 years and I am waiting for the day they tell me this too! But I have to ask please tell me you’ve not been on 800mg for 8 years!!! I am approaching MMR 4 if I hold that for a year I am going to ask for 300mg as apposed to my 600mg.

If it helps hindsight doesn’t help you. You’ll never know for sure, is it age, genetics, the fact you had too many take outs? Who knows a bit like getting CML I’d say. Hopefully you’ll be able to manange well but my first instinct is Nilotinib high dose for too long!

Al

Oh Pete! If you’ve not suffered enough…. I like to be as honest as possible and although I cannot be certain as I am not doctor, but it do believe that the 800mg for so long hasn’t done you any favours other than keeping Leukaemia at bay, which in itself sounds hypocritical considering what that entails.

I remember when first being diagnosed and thinking to myself should I “beat” cml what price does it come with. And I believe as wonderful as TKIs are for the “majority” we are basically consuming a form of acid, and the fact that we cml’ers get so many symptoms, is testimony that the body doesn’t agree at all.

My opinion is such that once cml is under considerable control < MMR4 we can slowly reduce dose. The long term affects of TKI as you know are really unknown and in it’s infancy in the grand scheme.

But but but, although your news is unwelcome and it brings along its own problems, I believe you’ll carry on for many years and be with and love those who mean all to you. I too dread the day I get another diagnosis but I believe it’s u realistic taking a substance daily that would prob kill your dog in one sitting should they consume it.

Stay strong and always air your pain.
It’s the only way through!

Al

Type 2 diabetes is a metabolic condition. Drugs (including TKI's) can exacerbate the condition, but TKI's alone are unlikely to be the sole cause.

In simple terms, the liver and the pancreas get out of whack. The liver is often at the root of diabetes type 2. Fat in the liver prevents the liver from responding to insulin properly. This causes excess sugar to be produced and/or released by the liver into the blood. In addition, as we age, the ability of the pancreas to produce insulin can be an additional factor in that more insulin is needed to get the "liver's attention" to stop releasing sugar and the cells which produce insulin over time burn out. The liver takes extra sugar from the gut (eating sweets, processed carbs, etc.) and stores it in the liver. Once the sugar is stored to the max, extra sugar is turned into fat. This fat tends to store in the liver itself. Alcohol does the same thing - it is processed into fat and stored in the liver - first. As the body calls for more sugar, the liver releases the stored sugar before it releases fat. The solution to this problem is straight forward - stop eating sugar.

Steps can be taken to reverse the type 2 diabetic process. Clearing out the fat from the liver increases insulin sensitivity and improves sugar control. Fasting can certainly do that, but a diet low in carbohydrates will also cause the liver to make less fat in the first place. In addition, exercise - especially high intensity sweat producing exercise creates a sink for excess sugar to be burned and causes the liver to clear out its excess sugar and begin to metabolize fat. Working muscles love sugar and will burn it if available. But the key organ in all of this is mostly the liver. Once stored sugar is used up, the liver will start to metabolize the fat it has and make sugar (fat + protein = sugar). The body must have about 4 grams of sugar at all times. If you are not eating sugar, the liver will make it (gluconeogenesis). A sure way to know you are in this state is if ketones are present in your blood. Ketosis means you are burning fat for fuel. And this fat is coming from your liver first. This is a good thing. The liver put the fat there and the liver can get it out of there as well.

Having an ultrasound scan done of your liver will almost certainly show you if you have a 'fatty liver'. Getting fat out of the liver will go a long way to reversing type 2 diabetes for most people before it becomes irreversible.

It is very true that cutting calories (i.e. losing weight) helps the liver clear out its fat. Getting fat out of the liver helps it to pay attention to insulin and thereby regaining sugar control.

Hi Pete,

Yeah I am not so sure I agree with your doctors analogy. 1 litre of water and 1 litre of whiskey will do two very different things. TKi and especially Nilotinib is highly toxic. (My months supply of tabs turns up covered in yellow labelled highly toxic tape, and I’ll never forget being passed my first supply of medication the nurse put 2 pairs of gloves on just to pass me the box and this was 2018 pre Covid era) Want I do know is that 800mg Nilotinib is considered “high dose” and is offered when resistance has occurred which in your case it did as you “failed” Imatinib. So you were defo on the right starting dose but 8 years on 800mg hasn’t done you any favours. Std dose in the uk is 600mg which I am on.

Aside from all that hindsight doesn’t help anyone, I would suggest seeing as your cml is well under control you reduce to 400mg and see how you go. I am on 600mg and feel like shit at times but it’s manageable but I am defo not my pre CML self.

You’re in a safe place so I’d recommend reducing dose and seeing how you hold the line. My bet is no change in your circumstances and maybe your other organs won’t have to work so hard. Nilotinib is one of the “worst” TKIs if you examine its toxicity profile. But it is a wonderful drug for treating CML and inducing a decent TFR outcome.

As scuba suggests maybe it’s unlikely to just be TKI but my hunch is that it is, as it’s reared it’s head quite quickly, maybe if we’re some other long term lifestyle decisions it might have shown it’s head more gradually? What do I know I just try to be as logical as possible….

All the best mate and let us know how you get on. I hope to reduce to 400mg from 600mg “if” I achieve and can hold MR4 (I am very close at 0.016) for a year.

Al