My month with the newest kid on the block & a hypothesis on the #Fiasp effects.

To some level I can’t quite believe that I’ve been enjoying the company of Fiasp for a whole month (well, in February, four weeks constitutes a month…). At first it was a joy, with massively reduced bolusing time and huge efficiencies, however as the month has progressed, our friendship has soured somewhat. I’ve been needing more and more of it and it’s not been much fun trying to work out what’s been going on.

But let’s take a step back and look at the stats from the flip over. First up, we need a comparison, so here is the data from mid-February to mid-March. We have a months worth running from 17th Feb to 21st March, giving 31 days, with a limits set at 4 being low and 10 being high, in accordance with similar studies.

In the grand scheme of things, these aren’t too bad looking sets of numbers, so comparing this to Fiasp is quite interesting. For the month of 24th March to 21st April, the data is shown below (and let’s remember this includes Easter and a little too much chocolate):

Statistically, from an Hba1C perspective, there doesn’t seem to be a huge amount of difference (the benefits of a Hybrid Closed Loop, I guess), but the AGP graph appears to show that afternoon and late evening highs as a result of eating have been reduced, overall resulting in a slightly greater time in range.

Now this can be split into two different periods. The start of the month using Fiasp and the end of it. The start is the top, the end the bottom.

What you can see in the second is that the 25th-75th percentile range seems wider and that post prandially, I appear to be marginally higher.

We see that, if anything, the second two weeks saw a greater amount of time low (almost twice as much) as the first two week period.

Putting the two together sets of data together, this is the start of where we start to see some of the unexpected behaviour kicking in.

Over the first two weeks, the average TDD was 46.9u, and in the second, 52.7u. This is a 12.3% increase in TDD, that could be explained by Easter, but that seems unlikely to be the only cause. I’ve discussed in other posts how I’ve seen what I felt was random behaviour and unexpected requirements for large amounts of insulin, and as a result, I’ve probably rage bolused a little too much, resulting in the increase in lows.

Since I’ve mentioned this, I’ve heard from others that they’ve seen similar behaviour, with one person saying they’d “bolused with it and it was like using water” and another mentioning that they’d found themselves using 1.5x as much insulin and coming out in welts, so were going back to Novorapid.

As is my wont, I decided to go and dig into Fiasp to try and understand what might be going on. This stuff is just insulin, right?

Well, yes and no. Firstly, my research took me into the realms of the Novo patents for Fiasp, and this particular item: Preparation comprising insulin, nicotinamide and arginine – WO2013186138A1

So what is this? it’s the 2013 filing of a patent application for the use of Nicotinamide (the water soluble version of vitamin B3) and Arginine in insulin.

Why is this interesting? It’s use of the word “Surprisingly” in the description that Nicotinamide speeds up the absorption of Aspart. And also the suggestion that the discovery that the use of Nicotinamide causes the insulin to become less stable, creating more “High Molecular Weight Proteins” (HMWP) or insulin dimers instead of monomers. The Arginine is used to reduce this affect. The issues with HMWP in insulin are detailed here.

Why would this be interesting? What’s the deal with Nicotinamide and Insulin? Why use the term “Surprisingly”? Well, further digging presents some research, and a not insignificant amount, that has shown that Vitamin B3 is linked to insulin resistance and a drop in insulin sensitivity, as detailed in the lists of research studies from Examine.com. Indeed, this article from Diabetes Care in 1999 looked at using Nicotinamide as a method of reducing the affects of Type 1 Diabetes and was viewed at the time by some as a cure, and happens to mention insulin sensitivity effects.

The key here is the use of vitamin B3 supplements in fairly large doses affecting insulin sensitivity. The sample sizes are fairly small, but the results don’t seem insignificant. With Fiasp, we seem to be using something that appears to be known to affect insulin sensitivity to speed it’s absorption. And although the sizes of the dose of B3 are miniscule, it still seems to be having an effect, and one that builds up.

There is a certain irony that Novo are using something that has been shown to decrease insulin sensitivity to speed up the absorption of insulin.

At the end of my first month with Fiasp, I’ve redone my insulin sensitivity testing, and the results are really quite stark. My ISF has got worse by 37.5% (1u now drops me 1.6mmol/l vs 2.8mmol/l at the start) and my IC ratios have increased accordingly. But at these levels, Fiasp is back to working as it should be. To the extent that the fiasp/katsu experiment that was previously done has been repeated, with very similar results and a flat glucose line, a couple of hours after eating, but that is a lot of insulin….

My hypothesis then is that by adding a form of B3 to the insulin in order to make it absorb more quickly, the slow build up has caused insulin sensitivity to drop over the month, and the results were the variable figures I had been seeing. In addition, where I had cannulas going in to me where there is less of me, I saw increased resistance as the B3 was unable to dissipate as effectively.

I need to spend time at this new level to see if it is maintained or gets worse again, but it seems to make sense. I also wonder if the insulin sensitivity issues that B3 can cause that seem to be one-offs are linked to this same mechanism or whether it’s simply a part of the process of insulin desensitization and giving an inappropriate dose for the food that’s been eaten?

The other thing I noted from the studies that Examine.com links to is that in some cases, blood lipids were also affected, which suggests that this is something that may need to be observed carefully in all Fiasp users.

Given this, what recommendations should we take away from it?

I think I’d start by suggesting that at least once a week while getting started on Fiasp, you need to check your ISF and IC ratio. For those of us that have reported it, it has changed as we’ve used Fiasp for longer. And by changed, I mean has gotten substantially worse.

The second thing I’d question is whether people want to use Fiasp, given this potential effect on insulin sensitivity. I know that there are people that value this being low, and I suspect that using Fiasp this won’t be maintained.

Finally, it probably makes sense to have your blood lipids checked before and after using this insulin to see if there are any detrimental effects. The research on this point was somewhat inconclusive.

Whilst so far it’s only an N=3 population of people reporting changes in insulin sensitivity, it looks as though the excipient that makes Fiasp faster also, over time, makes it less effective per unit used.

I’m not sure how clever or sustainable that is in the long run.