#Afrezza and Easter Eggs – a different way to spend Easter weekend…

#Afrezza and Easter Eggs – a different way to spend Easter weekend…
#Afrezza and Easter Eggs – a different way to spend Easter weekend…

For a while I’ve wanted to try Afrezza. Well, let’s be honest. Since I heard about it. It sounded rather different from anything we’ve seen on the Type 1 treatment front (well, if you discount Exubera) and looked like it would do some interesting things. The talk from the many US users always expressed how good it was and the blog of Matt from Melbourne, at Afrezza Down Under made for some very interesting reading.

After conversing with him and his partner on the goings on regarding Afrezza in the US and whether it was treated fairly, plus some discussions around glucagon suppression, they sent me a few capsules of Afrezza to try out. This was very generous of them as it isn’t cheap.

Sadly, I managed to get Bronchitis just as it all arrived, so rather than test it there and then, I thought it wise to leave it on the back burner whilst I built the monitoring tools, and wait until I was fully fit to try it out.

Now firstly, let me be clear. This was undertaken with no medical oversight. I have read the clinical trials and submissions to the FDA for US clearance and satisfied myself that the risk from Afrezza is no higher than that from taking a Ventolin inhaler.

In discussion with healthcare professionals in the UK, the over-riding feedback I received was that they would never inhale insulin in any form as the addition of any growth factor to the lungs was an unknown quantity, and in the past, they had only recommended Exubera where they felt risk to the lungs was outweighed by quality of life to the user.

Therein lies the conundrum with Afrezza. Does inhaling a growth factor into the lungs run the risk of much greater issues? Lung cancer, specifically? The trials showed that the incidence of lung cancer in the trials was reasonably low. All of the data presented to the FDA is available in this previous blog post and there is a host more data relating to Lung safety trials listed here.

Suffice to say that I made up my mind that I was happy to try this out with a few cartridges and see how it went.

Trial One: The Fast Carb Trial

With that background considered, I elected Easter Sunday as my testing day and for full disclosure purposes, due to food onboard and a high glucose level of 10.5mmol/l I’d taken a correction bolus of 3.5u at 16.55. This was my test subject:

Why this bright pink Chocolate Pig from M&S? Well he was Easter chocolate and his carb content seemed perfectly matched to my I:C ratio given that the Afrezza I have is rated at 8u per capsule. So off I went and inhaled from the little device at 17.35:

 This was immediately before eating. I then stuffed my face with the rather fabulous pink pig (raspberry flavoured) pig for the next 10 or so minutes.

And then I watched. Now as I mentioned, there was a correction dose of Novorapid onboard, but I wasn’t quite prepared for what happened next. Normally, this pink pig would have shot my glucose levels up like a firework. Even with three units of Novorapid onboard. But this is not what happened. From this point, my levels never went up. They did the exact opposite.

As you can see from the picture below, they just went down, half an hour after eating.

Fast!

And they continued to go down fast,

In fact, they were going down so fast that an hour after eating (when nominally, from previous experience, the chocolate should have stopped being absorbed) they were here:

And I had taken 40g of carbs to ward off the drop.

Now it was my own fault. I didn’t need the earlier correction dose, but the rather more important point is the complete lack of any rise as a result of eating the pink pig. Nothing. Even with 3.5u of Novorapid on board and 94g of carbs being eaten I’d expect to see something. It just didn’t happen. Quite an astonishing result and also an indicator for the next time. Take it after eating!

Even after the munching on additional carbs, my bg level recovered to the 5s and stayed there. A truly remarkable result that demonstrated to me just how effective this delivery mechanism is. The initial drop was so profound that it was a little scary and I was very pleased of the realtime monitoring I had in place to understand what was going on. This would have been unpleasant without it.

But a little on the side effects of inhaling insulin. What did I notice? After inhalation, I noted down three specific items:
  • A slight cough that took about 15 minutes to abate
  • A slightly tight feeling in my lungs that took about 5 minutes to clear 
  • A massive head rush!
I also noticed that the hypo symptoms using Afrezza were not particularly noticeable, with what I’d describe as a general light headedness rather than anything that I normally feel.
The upshot was that the fast carbs were massively defeated by the Afrezza – like I’ve never experienced with Insulin. A really astonishing feat and if you really want to eat sweets, chocolate and cake, then this stuff is marvellous. But eating sweets, chocolate and cake really shouldn’t be high on the list for anyone… 
All in all, for a first trial, it was a bit of a ride. But an exciting one and very, very interesting. Interesting enough for me to want to try something else.

Trial Two: The Chicken Katsu Curry Trial

Why Katsu Curry? Well it’s one of those classic dishes that creates a suden massive spike and then a prolonged release as a pleasant side effect of being a curry sauce, fried chicken and rice. I like to think of it as a killer meal, and when eating it with Novorapid, it requires an upfront, just before eating dose of 11u and then an extended bolus of 6u starting after the meal and lasting for five hours. 
It’s that bad. So how would the Afrezza cope with this one?
Based on the previous experience, I decided to eat the Curry, Tuna Sashimi and Duck Gyoza (Decadent? Moi?) and then inhale once the curve had started to head up. A bit of a sugar surfing technique. The dinner presented itself:
  And this was the glucose monitoring at eating:
There does seem to be a bit of an inflection point already, looking back at that graph, but I enjoyed my dinner and then waited. Or rather forgot.
A little later (half an hour or so) and I scanned my Libre. What would life be like without a plethora of tech to manage the condition, or at least help? This was the result:
 Oops. A little late in getting started. So I inhaled my 8u. Now the guidance is that Afrezza lasts for about 2 hours and the experience on the previous day seemed to confirm that. The Nightscout chart for this period is shown below and would seem to concur with this assessment:
Over about two hours post eating, the Afrezza kept me relatively flat and at about 9pm I decided to have a Guinness XX which is about 20g of carbs. It still managed to handle that remarkably well but I had clearly eaten more carbs than the Afrezza could really manage and added in a correction dose of 1.5u at 21.46 followed by 5u of extended dose, which seemed to stop the rise from getting too much.
There’s a clear aspect where the Afrezza doesn’t hang around in your system for anything like the length of time Novorapid does, so managing a meal like this would require a second dose later on if I had any 4u cartridges. 
Still, it demonstrated, to me at least, that this stuff really is a very interesting product. The rapid entry into the blood means it acts faster than anything I’ve ever encountered and the effect is really quite remarkable.

It also clearly demonstrates (even off just two uses) that Afrezza is perfectly designed for Sugar Surfing. You use it at precisely the points registered when you surf and the instant action just makes this work. Matt wrote a reasonably detailed view on this in the Afrezza Down Under blog and I can’t say I disagree with anything he’s written there. It really does provide flexibility in a way that other Insulins don’t simply by virtue of the speed of action and clearance.

The big question is the effect on your lungs and whether the insulin affects IGF receptors and in what way?
Based on what I’ve found here though, I can see why the users in the US go on about not having to change what they eat. It truly is remarkable stuff. The question, as always with these things, is the effect over the long term. We won’t truly know that until we can biopsy a few users!
In the meantime, I think it presents a great opportunity to modify the factors available to T1s (and T2s) to treat. For example, if you are going out for a meal and you’ve no idea what you will be eating, the rapid action of such a a product would be a godsend for stopping post-prandial spikes. It also offers a little bit of flexibility if you really do need to cheat. Well, maybe more than a little bit. Really rather a lot.
So I’m impressed. In fact, I’m very impressed. I really would like to know what the long term affect on lungs is, but as is often said, you have to weigh up your risks. 
As a T1, I know that the risk of complications lies in one way while the risk of long term effects on my lungs from this lies in another. Based on the 5 year data Mannkind published, those risks don’t seem that high. In the meantime, the risk of being killed by a random car is also there and reasonably high.
If we want to use available treatments, we have to weigh up those risks and what they mean to us. In no way is that a straightforward task.

From my limited testing, I get the feeling that for many, the benefits of this one may well outweigh those risks.

12 Comments

  1. Thank you for the very impressive and honest review. How was the cough/headrush/tightening feel on the second time to dosed Afrezza.

    Lung cancer is scary, as are the long-term problems w/diabetes. FWIW I think the insulin is largely absorbed in the lungs & leaves little residue, unlike Exubera.

    Guess the big question is:
    1 – would you use Afrezza?
    2 – if so, do you think it could replace your Novorapid?

  2. No problem. The second time I used it, I noticed the same effects, although I was prepared so it was less of an issue. Having read through all the data that I could find, as I mentioned, I didn't think it comes across as any worse than using a Ventolin inhaler. Reading the five year trials of Exubera, the serious adverse effects stats showed that statistically, the results were insigificant

    https://clinicaltrials.gov/ct2/show/results/NCT00359801?sect=X4cb8970156#othr

    I don't believe that Afrezza is any worse, indeed the Technosphere delivery system seems to be much more efficient that that used by Exubera. The data pertaining to amount of insulin remaining in the lungs post inhalation for Afrezza is also dramatically lower than that in Exubera, and given the Exubera stats above, I find it hard to believe there would be any worse outcomes.

    Would I use Afrezza? I think it has a very useful place in the armoury of diabetes therapies. It makes the eating out scenario totally different and would allow the elimination of post prandial spikes if used for such eventualities. I'm not sure I'd want to use it particularly when I had a heavy cold though. It's often hard enough breathing anyway in that scenario. Would it replace my Novorapid? That's an interesting question.

    I think, when used with a pump, you have the ideal world. You can use Afrezza as the fast acting, sugar surfing, spike reliever. You can then use extended bolusing for those food types where you need to do something over a longer period, as per the Katsu Curry example in the post. Personally I think that one size is unlikely to fit every scenario and with the options available, a toolkit with a selection of useful tools is the best bet at the moment.

    I'm certainly considering buying some Afrezza as one of those tools though.

  3. I'm afraid your tests are fundamentally flawed. First, chocolate is about 40% fat and the carbs are derived from either sucrose and/or fructose. Fat causes delayed emptying of the stomach. Under normal circumstances, the stomach empties every 2-3 hours. With a high fat load that could easily be slowed down to 3-4 hours. In other words, likely NOTHING from the chocolate ever reached your system during the time you did the test. Furthermore, both sucrose and fructose have to be CONVERTED to glucose. In the case of sucrose, that is done by enzymes in the wall of the intestine and, for fructose, by enzymes in the liver. So even if you HAD managed to get the chocolate into the intestine during your test's time frame, it STILL would have caused only a gradual rise as the sugars were converted. And that is the reason why your glucose "crashed" — you were't getting ANY carbs from the chocolate. You "effectively" took the afrezza on an empty stomach.

    By the same token, "over about two hours post eating, the Afrezza kept me relatively flat" — no, it did NOT. Because afrezza is just humulin R, it follows a similar metabolic course and by 90 minutes it should no longer be having any effect on glucose.

    Also, you assert that "before eating dose of 11u and then an extended bolus of 6u," yet you are replacing that with an 8U dose of afrezza. Again, because of the biochemical properties of humulin R, 8U of afrezza translates into only about 2-3U of humulin. That is because in the bloodstream humulin converts to the inactive forms — dimers, multimers, and hexamers. These and the active monomer are all broken down by insulin degrading enzyme. The net effect is you actually get only about 1/3 to 1/4 of the active form of insulin for each unit of afrezza inhaled. Obviously enough, 2-3U could not replace 17U of novorapid. Since you neglected to provide a breakdown of the protein/car/fat content of the meal, there's really no way to tell when, to what extent, or even if afrezza contributed anything to the glucose control.

  4. Small correction — "8U of afrezza translates into only about 2-3U of humulin" should read "8U of afrezza translates into only about 2-3U of novorapid."

  5. Thanks for reading the blog post and your very thorough breakdown of the fundamental properties of Afrezza, chocolate and how the digestive system works. Lets be very clear here. This was not a scientific test to prove or disprove the efficacy of the Afrezza. It was, if you like, a User Test to understand how it worked for me.

    Let me also comment on your speculation regarding the use of chocolate and your assertion that I got no carbs from the chocolate. Whilst there are some great metrics out there, I can assure you that, as a Type 1 Diabetic, your postulation "likely NOTHING from the chocolate ever reached your system during the time you did the test. Furthermore, both sucrose and fructose have to be CONVERTED to glucose. In the case of sucrose, that is done by enzymes in the wall of the intestine and, for fructose, by enzymes in the liver. So even if you HAD managed to get the chocolate into the intestine during your test's time frame, it STILL would have caused only a gradual rise as the sugars were converted." is an interesting one to me. It suggests to me that you are not a type 1 diabetic.

    If it were true, whenever I ate chocolate, I would not see a blood glucose rise for hours afterwards and it would be really slow. Sadly, I, and many other Type 1s do not experience chocolate like this. The carb absorption of chocolate for many T1s is much, much faster than this, so in my experience it is wholly valid as a test for Afrezza.

    With regard to Humulin R and the pharmacodynamics of the insulin, whether it lasts 90 mins or 120 minutes is neither here nor there. Again, what I am comparing is the user experience of using these insulins. On the Katsu curry test, the actual meal breakdown is irrelevant when comparing it to my experience of eating the same food using injected Novorapid.

    With injected Novorapid, the insulin needs to be injected 20 mins before the meal to have any hope of maintaining a flat line thanks to the carbs in the rice. Even with the fats from the deep fried chicken and sauce, there is not a slow increase in glucose levels, and I see an extended upwards pressure thanks to the protein and fat effect.

    You clearly didn't read the post fully as you'd have realised that I used an extended bolus following the period I expected the Afrezza to expire in. We weren't replacing 17u of Novorapid with 8u of Afrezza, but rather 11u of Novorapid with 8u of Afrezza which was in line with the amount required to handle the 8u of Afrezza in your already mentioned cat incident. In addition, if the food and Afrezza were not working against each other, following the Katsu curry, I would have ended up massively low. This didn't happen either.

    As a result, your assertion that actually, throughout these tests, on me, for me to find out how Afrezza works, I was never testing Afrezza because the physiology doesn't stack up is slightly offensive. If the Afrezza really was not doing anything and "there was something else at play", in effect, describing the Afrezza as "Snake Oil", then I have miraculously become a cured Type 1 diabetic that has then reverted. A situation that I'm sure you'll agree is even less likely than Afrezza operating like it says on the tin!

    I have been left with the impression that for some reason you are an "Afrezza Basher" and you have some interesting issues with it. What these are I can't tell. I'll just bring you back to the original point.

    This was a test of user experience based on user experience, as I have mentioned throughout this response. It was not a scientific study to determine any outcomes and convince others to buy Afrezza (or not!) and the huge lack of significant highs as a result of the foods eaten, based on my experience, demonstrates to me that Afrezza was doing something. In all fairness, that's all I was looking to do!

  6. Treets. Glad u liked Afrezza. Many people are against it and Mannkind Corp. Due to its EXTREMELY disruptive tech. Personally, I am an investor. If Afrezza finds a place in your daily life, that is great. If not, so be it. But NO ONE has the right to bash u for your blog or lifestyle. Best. And secretly hoping for worldwide adoption soon. Haha.

  7. Your use of the word "Afrezza Basher" is quite interesting, andI never described afrezza as "snake oil. All I did was relay well PROVEN and well accepted information about human digestive physiology and insulin metabolism. I further pointed out that your "test," as described by you, could not be considered valid based upon that information. I don't see how that can be construed as "bashing."

    You, on the other hand, apparently want to claim that your physiology is practically UNIQUE and unlike the physiology of 99.99% of the rest of the planet. You nevertheless seem to try and argue for the validity of your "test" for diabetics in general by presenting a positive experience based upon a chocolate bunny and a "katsu" meal. If you wanted to do a REAL test, then you would get a few bottles of glucose tabs, and then, starting on an empty stomach, take a fixed number, and then dosing afrezza at various times before and after and recording the data. Then repeat using your standard insulin regimen and compare the two. THAT would be a test that could offer some insight for diabetics in general as to how the drug performs.

    • @ Anonymous You clearly have no clue how digestion works in a T1D. T1Ds have impaired amylin production (responsible for slowing down digestion) and GLP-1 production in the intestines (which keeps glucagon action at bay = less hepatic gluconeogenesis in response to food). Having said that, a food like chocolate will digest, absorb, convert and increase blood glucose WAY WAY FASTER in a T1D than in the rest of the population with a working pancreas.

      @Treets, thanks for the review. I’m interested in trying Afrezza myself in the near future!

  8. Once again, I come back to the point that this was me trying out Afrezza and an article about me doing so. Given that I know how I react to the various foods, I wasn't publishing a set of comparable data. I'm not sure how that invalidates my findings. As mentioned, I was surprised at the results with using Afrezza versus other insulins that I have already had experience of, when eating both Katsu curry and Chocolate.

    Secondly on your point about proven aspects of digestion and chocolate. I'm not clear where you've got it from. You make it very clear that as far as you are concerned, chocolate takes a very long time to get into the blood stream and causes a very slow rise due to processing taking a long time, and that this is normal behaviour for 99.99% of the population. I'll give you that in a normal, insulin producing person with no insulin resistance and normal levels of insulin production, you're probably right.

    I, however, like most Type 1 Diabetics, am not one of those, and as a result, get a very different reaction. And you'd be right in thinking that we are less than 1% of the population. We make up about 0.6% of the population. Speaking with other T1s, they get a very similar reaction to chocolate that I do. It starts to have an effect within 15 minutes and generates a rapid rise in blood glucose. Even in type 2 patients, the effect of chocolate on their blood glucose shows significant rises at 60 and 90 mins (http://www.ncbi.nlm.nih.gov/pubmed/1782928 – it's a small study, but gives you some idea).

    Aside from this, I completely agree that if I was to take a purely objective, scientific approach to testing Afrezza, much as the manufacturers had to do to get it certified by the FDA, I would have undertaken a different test. What I was finding out is how this works for me, in my body, on reasonably normal foods. That's how I would use it, not by eating glucose tablets in varying amounts. And this article is an observation of the effects on me.

    So while your assertions are that it simply isn't possible for Afrezza to have done what I observed it did, eating real world foods that I know cause significant glucose level changes proved to me that there was an effect. Either that or somewhere along the line, I stopped being Type 1 for a couple of days…

  9. If you want to significantly reduce the cough, drink water before and after your dose. You should notice a big difference. Its a dry powder, dry powder on a dry throat, that will make you cough. Water will make a big difference.

  10. I am based in the uk. I have used afrezza. I am type 1. My name is brendan. Its an amazing product for all of the aforementioned reasons. Chocolate causes a massive increase in blood glucose levels in a type 1. Afrezza can deal with this and also more importantly it suppresses hepatic glucose production from the liver meaning post prandial levels are excellent. I completely agree with the comments regarding amylin and glp-1 This just shows how effective afrezza is. It deals with glucose loading from meals and helps stabilise and reduce tge liver dump aka glucogenesis.

  11. I love Afrezza. I only eat 30 carbs for breakfast but i spike no matter what so I exercise right after breakfast to keep my numbers low. It’s when I can’t exercise… Afrezza saves the day. It so great knowing I can keep my numbers in check. Also I swim 3 days a week but since I’m off the pump for 1-1.5 hours my BS rise rapidly once I’m out of the pool. Again Afrezza works and I can even eat a protein bar and will be good to eat lunch. Without it and taking a correction it may be 1pm before my BS are down so I can eat lunch.
    It is a marvel like the pump. I have the Dawn phenomena so no matter what injection pattern I tried I was high in am. The pump cured that…I take .2 from 10am until 3am and slowly increase to .6 to 6am. Works beautifully. I rarely wake up with a high now. A cure would be nice but options are the next best thing!!!

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