Partly one in all this microseries, I checked out lifespan, dose sizes and expiry of the GlucaGen units that we get within the UK, and price round £20 per set to the NHS.
While that is all necessary data, it was included as half of a bigger experiment to see what microdosing glucagon appeared like, and whether or not there was an applicable mannequin that could possibly be used with open supply APS methods in a twin hormone arrange utilizing two pumps.
This text units out what I’ve realized from very restricted use of two GlucaGen kits, and what it would imply in adapting an open supply codebase.
The Speculation
Based mostly on what we find out about pancreatic exercise, the effectiveness of exogenous glucagon might be in proportion to insulin on board, with each hormones performing as switches to the liver.
Insulin, nevertheless, works with skeletal muscle, so when supplied exogenously, has restricted impact on the liver.
The identical skeletal muscle has no glucagon receptors, so glucagon solely actually impacts the liver and the mind. When delivered subcutaneously to numerous physique elements, it principally impacts the liver.
The important thing information being captured was:
Time to impact – how lengthy earlier than the glucagon dose countered a drop
Dimension of impact given insulin on board – what constructive impact was noticed and did it range with IOB
Surprising uncomfortable side effects
Results with and with out alcohol
Along with these factors, another observations had been captured in an try to know the results.
The method
The intention right here was to determine how glucagon is likely to be dosed to minimise hypos within the context of the oref1 mannequin.
Inside that there’s a “Carb required” perform that provides up recommendations for carbs to counter future hypos. The thought was to make use of that as a set off and see whether or not it was a legitimate indicator for dosing glucagon.
Information was captured in Nightscout, utilizing the notes perform to determine the glucagon doses.
Observations
Time to impact
Firstly, time to impact. Given numerous literature about intramuscular administration of glucagon, the expectation was that it might take someplace between 10 and 15 minutes for subcutaneous utility of glucagon to take impact. This proved to be an inexpensive estimate, and certainly, it was doable to watch adjustments in glucose attributable to glucagon administration in that time-frame.
As the instance within the picture under reveals, the impact could possibly be very fast.
If we zoom in on the famous glucagon dose, we are able to see the short response to it. The crimson line reveals the purpose of the 5iu dose.
This, nevertheless, is an instance within the first interval of testing, the place alcohol was not included. Throughout this part, the appliance of glucagon proved to be very efficient, nevertheless, throughout the second part, the place there was alcohol concerned, there was zero impact from the glucagon after consuming (which is anticipated given the one course of focus of the liver).
Dimension of impact and IOB
After capturing just a few information factors (taking into consideration that this can be a very small information set), my speculation was that the next curve could possibly be utilized to find out the anticipated rise given the IOB ranges, after 5iu of glucagon given to me.
Under basal fee and between 100% and 150% of basal fee, the curve labored, nevertheless, as soon as the share of IOB elevated above 150% relative to basal fee, the connection between the distinction turned extra between anticipated drop and the extent above that that the glucagon maintained.
Primarily, the place IOB was higher than 150% of basal fee, a number of doses of 5iu of glucagon can be required to cease a tough drop, and there’s a good bit extra work to do to determine the connection.
Surprising uncomfortable side effects
Maybe much less shocking than it ought to have been, utilizing glucagon to deal with low ranges or the chance of low ranges, leads to a “hungry liver”. As folks with sort 1 diabetes, we get used to the liver not attempting to transform glucose to glycogen as a result of it doesn’t get any signalling, nevertheless, I observed that my postprandial highs had been decrease, for a great 12-18 hours after a glucagon dose, because the liver appeared to replenish its lacking glycogen. General, within the alcohol free interval, the general time in vary was good, with very low time under vary. Is it doable that utilizing glucagon as a further hormone reduces the sleeping liver impact?
In the course of the three days of testing with out alcohol, the outcomes had been good, given the meals eaten (this consists of snacks within the workplace, and comparatively excessive carb consuming). I used to be in a position to enable the AID algorithm to overdose for mealtimes after which catch as crucial with glucagon. Noticeably, there wasn’t any discount in common complete every day dose.
Results of alcohol…
With alcohol although, the results had been somewhat completely different. On condition that the Enhance algorithm hadn’t been modified to keep in mind the glucagon dosing, except for glucagon having no impact when there was alcohol on board (AOB), there was a secondary aspect impact that it brought about lows in a single day that I wouldn’t usually see. This appeared when the Enhance performance is disabled and was because of customary oref1 perform. I primarily turned extra delicate in a single day than regular.
This got here as a little bit of a shock. Whereas I anticipated that there can be no results from dosing glucagon with alcohol, I wasn’t anticipating some sort of delayed impact. This occurred on a number of events so I’m fairly positive that it was linked to the glucagon administration.
What can you are taking away from this?
I feel that it’s honest to say that utilizing glucagon to stave off low glucose occasions is an inexpensive method to utilizing an AID. It does include some caveats although, specifically, it doesn’t work with alcohol, and the place IOB is considerably higher than basal fee, it could not have a lot of an impact, because the liver is shutdown by no matter of the IOB is attending to it, despite that being very small ranges.
While we’ve established that reconstituted glucagon does appear to outlive for 3 days as soon as made up, and in concept may present a low value choice when utilizing a system, it’s not the reply to all the pieces.
The problems noticed with alcohol and IOB characterize issues that must be taken into consideration when incorporating glucagon right into a system and as part of a multi-hormone system, and self monitoring for these results can be a key a part of introducing its use into any type of open supply AID system.
This, nevertheless, is an n=1 commentary utilizing very small quantities of glucagon and offering very small quantities of information. I’d like to see what the likes of Betabionics have discovered of their twin hormone method.
At this stage, I’d counsel that whereas it presents promising choices, and I can see the way it staves off low glucose ranges successfully in lots of circumstances, I’m undecided it’s the reply to everybody’s hopes on this planet of sort 1 tech. As an grownup, there are numerous instances that might deem it ineffective. I feel the key concern is the whole unreliability after alcohol, which is once you’d be most probably to wish that security internet.
I’d be intrigued to study extra concerning the Inreda system, and the way it manages within the context of alcohol. I assume that throughout the algorithm, there’s a “no response” perform that accepts that if there’s no response to glucagon, it ought to cease attempting and do one thing else. I feel there can be the necessity for that inside an open supply model of a system that integrated glucagon. There’s additionally a necessity to change the system’s view of sensitivity publish glucagon dosing, which might additionally want measurement and incorporation.
All of these items current choices and I feel it’s nonetheless doable to enhance administration of sort 1 with the addition of glucagon in an AID.
It’s merely that diabetes is way extra advanced than two hormones and an algorithm, so whereas we would make it higher, it received’t be excellent.