FUDiabetes

U200 Insulin in Pumps

So in another thread @Eric said

This got me thinking. Gary Scheiner did a trial a couple of years back - and said that it was good - but no real comment about the benefits.

My question is…
Apart from Humalog are there other U200 rapid acting analogs available?

Does U200 have better absorbtion characteristics than U100?

Is this a solution for folks like @Beacher who cannot take large boluses from an omnipod due to leakage around the cannula?

I know that the next generation of Omnipod PDM (the Horizon) has been designed and testing for U200 and U500 insulin from Lilly (basically I expect that the PDM is just calibrated for U200/U500 to get the units right.

Anyhow - interesting topic.

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I think the general idea is that a smaller volume would absorb faster. It isn’t that the insulin is faster, just the comparative surface area is greater for smaller bolus amounts.

We can’t come up with real math because the shape of the bolus is not a perfect sphere.

But if you use a sphere as a model (probably not the best shape to use as a model in actuality), you know that as a bolus amount gets larger, there is less surface area compared to the volume of the shot.

Using spheres as a model for the shape of a bolus, the surface area to volume ratio is equal to 3/r, where r is the radius of the sphere.

I saw a calculation once that doing 4 boluses of 1 unit each would have almost 50% more surface area than just one single bolus of 4 units.

So that is why the U200 is believed to be faster.

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I like that way of thinking. It also lines up with the anecdotal evidence about getting faster absorption out of small shot volumes versus large volumes.

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It turns out that you are on to something here. I saw a study once where the objective was to determine how close to a sphere it was, and the result was not very close. What actually happens is that the insulin spreads out in a thin layer, and when it reaches a certain extent it then jumps to start forming another parallel layer. So you end up with a 3-d structure of stacked 2-d layers. The 2-d layers are not discs, they are irregular. This was examined in samples of fresh porcine tissue.


“In summary, a wide variation in the size and geometry of insulin depots was observed, but never the previously suggested spherical insulin depot form. Formation of flow channels appears to follow a subcutaneous tissue layer until the fluidic resistance for further lateral spreading becomes greater than the fluidic resistance associated with moving to a new layer. Driving pressures for the insulin distribution are associated with hydraulic flow rather than cavity expansion or diffusion, at least in the short time window observed.”

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So what is your guess on surface area as a function of volume? Any way to calculate it?

When I was writing my previous post, I was actually thinking that a pancake was probably more realistic than a sphere. But I got lazy with the math and didn’t want to redo anything.

That question is more subtle than it first appears. In the results section of that paper, Figure 3 is a pair of microphotographs that show the dyed insulin flowing through the spaces between the adipose cells, so the total surface area would be relatively huge, like the total surface area of a sponge (the sum of the surface areas of all the bubbles included in the sponge.) The utility of that number is not clear to me, especially with respect to your discussion about the absorption rate of u200 vs u100. I don’t think the actual complex geometry of the insulin depot supports a sound conclusion about the relative rates of insulin diffusion into the capillary blood. Perhaps I could make up plausible-sounding explanations that come out to any answer I want, but I can’t deduce a factual answer. Best to just run the experiment and find out whether and to what extent u200 absorbs faster, instead of making plausible models and hoping they actually predict reality.

At least do you think we are pretty clear on the idea that more surface area would equate to faster absorption? Or is even that idea still up for debate?

Insulin can only absorb when exposed to the tissue. Insulin molecules that are completely surrounded by other insulin molecules can’t absorb. i.e. insulin can only absorb into the tissue, it can’t absorb into other insulin.

I plan to try it. But as you know, with diabetes, doing any kind of analysis from personal experience takes a lot of trial periods and then sometimes the best we could get is something like “I don’t know for sure, but I think it works a ‘little bit’ faster…”

Unfortunately, without a legitimate clamp study, I don’t think any kind of analysis we can do ourselves gives us much data.

I don’t know what to believe. Given the strange multi-layer planar spread of the insulin in the infusion depot, it may be that the surface area grows linearly with the volume, rather than as the square root of the volume. So on one hand, of course it makes sense that more surface area would equate to faster absorption. On the other hand, what’s the effect of double the surface area at half the density? In experimental computer science I encountered numerous “obvious” and “it stands to reason” conclusions that turned out to be false. And I gather this is also common in medical science given the recent pushback in the form of “evidence-based medicine.”

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If there is a benefit, I do think my benefit would be less so than someone who takes larger boluses.

As it is, I rarely take a bolus of more than 8 units. Cutting that into 4 units may offer a small benefit. But for someone who does a 30 unit bolus, cutting that into 15 would seem to offer a greater benefit (if there is indeed a benefit).

Does that sound like a reasonable presumption?

I’ll go as far as “plausible hypothesis,” but nowhere near “well-grounded belief.” In the literature in my field, it would be conveyed as “we suspect that” which means “we think this is so, but don’t have facts and maybe it’s completely wrong.” Experimental science is humbling.

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Is anybody contemplating of doing the Humalog U200 pump test? I am seriously considering this. I have to ask my DR. to write me a script for Humalog U200. I am now on Apidra. I need to justify this with a study and all I have is Gary Scheiner’s report. Perhaps that info is enough. I also have to make do with the pen as a source to load my pump cartridge. Maybe, I should wait for the vials to become available. Maybe, Apidra and Novolog will follow the leader. I’m curious if the lower volume will allow me to extend the infusion site to last longer than the 3 days I do now. My site gets sore after 30 days, a total volume of 180 units. If the soreness issue is volume related, theoretically the U200 should last twice as long, 6 days perhaps.

I will try it at some point. Not anytime real soon.

If your doctor is cool, say you want to try it in a pump. If they are not cool, leave the pump part out. I don’t know of any pumps that have been approved for U200 yet, so your doctor may freak about it.

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Thanks for the heads up Eric. Good advice. My Dr. is not diabetic. So, there’s the challenge.

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I use U200 in my Omnipod without any problem. We have a pump trainer here who is familiar and my endo has used it a number of his patients.

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Hi Skymom, welcome to FUD!

Have you had any problems remembering to cut your bolus and basal numbers in half? That’s the only thing that makes me not do it. I might accidentally double-dose.

Hi Eric,

My pump trainer helped me set it all up in the correct proportions and if I had to change my rates then I would talk to him if I was concerned. I haven’t had any problems and I’ve been using U200 for about 2 years.

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Did you previously use U100? If so, do you notice a difference in speed with U200?

One of the nice things about it would be less volume, which makes me think it could possibly absorb faster.

The downside would be that the smallest pump increment of 0.05 units of U200 would be like 0.10 units of U100. Sometimes that extra 0.05 can be pretty big for me.

Hi Eric,

I did previously use U100. But I am probably in a slightly different situation than you. I am a LADA with insulin resistance so I use a higher amount of insulin than most Type 1’s. using U200 means I can get enough insulin in my omnipod to last 3 days. Otherwise I would have to use a tubed pump with a bigger volume availability.

Sue

So how do you get the U200 from a syringe into the Omnipod then? Do you just bypass the mini syringe they give you? Don’t put a needle tip on and pull it int their syringe or what?