damn this reddit thread is 3 months old? t1 here as well, and i struggle pretty bad. having been t1 for 20 years or more, i just can't click every article my friends and family send me promising progress for diabetics or potential cures. its just not worth getting my hopes up even when its a reputable outlet making some extraordinary claims. this sounds really promising but yea. its also depressing. its kinda too late to save me even if this comes very soon. which i doubt it will. However, this so called 'smart insulin' sounds to me much more like the shit produced by non-diabetics pancreases. like theres just no way the non-diabetic body is making a hormone that doesnt fully kick in for 90 minutes. that just wouldnt be as resilient and effective as what i witness in the people around me. its insane how they can, for example, eat a tub of ice cream on a whim and not be blasted into the 400s. or just go wild exercising at length on an empty stomach and not have an emergency low sugar.
There's already software that can definitely mitigate these problems you've outlined. I've been using AndroidAPS together with Lyumjev insulin, an insulin pump and a Dexcom system for several years now. Yes, I can go running with an empty stomach and yes, I can have a nice dinner without being in the high 400's... My glucose hasn't really been above 200 for months, and the last time was a leaking tube in the pump. My A1c has been between 5.5 and 5.9% for many years now. There's no need for ambulance to come and rescue me due to hypoglycemia.
If you're in any way technical, you should take a look into the solutions for artificial pancreas.
I've run it against my nightscout data a few times to get insights to my profile. So yes, you should install it somewhere and run a CGM app such as xdrip which can transfer your libre2 data to your nightscout database.
So yes, if you are interested on autotune, a nightscout is required for now.
I participated in studies where they administered insulin and glucose intravenously. It is wild how they can reliably drop my blood sugar from high to low within a few minutes. Subcutaneously this takes me hours to do in a stable way.
Not only veins, inhalable insulin like Afreeza is also really quick. Unfortunately it only appears to be available in the US (and maybe Canada?), not Europe/Asia from what I last remember.
Inhalable insulin (which is also very fast acting) iirc only allows a dose of 2 units. If your sugars are 400mg/dl (22ish mmol/l) one or two doses wouldn't put you into a coma if you knew your sensitivity. I'm pretty sure I've read up T1s talking about using it as such.
This is currently in a category of cures that are always a decade away. I am happy that the researchers are putting it out there to attract interest and investment, but the GRI-type insulins remained in lab settings for about 30 years now and it is somewhat troubling to not see progression into and through the stages of pharma clinical trials on T1D patients.
Clearly, there is tremendous potential to make money here – diabetes is a very serious epidemic worldwide. So why hasn't this progressed out of the lab?
I was curious about this myself so I looked up a bit more about this. Here's what I found;
>Even though there have been many publications and patents on the subject, no mechanism has yet been shown to be compelling enough to treat diabetes.[1]
>An apparent more effective strategy is to give insulin glucose-responsive properties that let it respond to glucose reversibly. Merck created a system ... because of its incredibly low efficacy, this system did not merit advancement past phase I clinical trials.[1]
It sounds like they're saying basically that they exist, but aren't yet effective enough to replace the old standard. This particular design is newer.
From the study linked in the article as citation 1:
>Here we report the design and properties of NNC2215, an insulin conjugate with bioactivity that is reversibly responsive to a glucose range relevant for diabetes, as demonstrated in vitro and in vivo. NNC2215 was engineered by conjugating a glucose-binding macrocycle and a glucoside to insulin, thereby introducing a switch that can open and close in response to glucose and thereby equilibrate insulin between active and less-active conformations.
Essentially it's a new attempt at making a GRI that's more promising. It's insulin attached to a molecule that binds to insulin to block it from working unless glucose is present, in which case it binds to glucose instead and allows the insulin to be active. Of course that also means it will need to go through full FDA approval process which would keep it about ten years away if it does really end up being effective enough.
But this time could be different! It's very cool conceptually too. The fact that it's possible to make a drug that works like that. It's amazing to see these novel drug delivery concepts develop in real time.
It's always a decade away because the progress promised shows up, and it improves quality of life a bit, but isn't enough and is very expensive.
We've gotten a variety of synthetic insulins with different rates that help control the disease. We've gotten pumps and meters and very cautious closed-loop feedback.
Now, an insulin itself that adjusts its potency based on blood sugar. We'll get that in the next decade or a bit more. But it'll be very expensive and it will be a relatively ineffective control mechanism-- making control a little bit easier for diabetics and blunting worst case episodes a bit.
I agree that many types of treatments have been advancing. Closed loop is a good example, and stem cell-based islet transplants are in real clinical trials now. We have gotten synthetic insulins that act much faster like Fiasp and stuff like Tresiba that's a multi-day action time prolonged insulin. GLP1 inhibitors are more commonly available for T1Ds, especially now that they are in weight loss drugs that doctors are starting to more easily prescribe off-label to T1s. Metformin has basically become on-label for T1Ds due to its benefits to insulin sensitivity. But the smart insulin hasn't made much progress for the last several decades.
I'm not saying it's all doom and gloom. I'm bringing attention to different rates these things evolve at and questioning why GRIs haven't left the lab since the 90s. :)
The molecular GRI work in the 90s was really proof of concept work that showed you could maybe build something like this, not something that looked a decade from approval. From what I remember, the early work spun off free radicals, had the middle of its set-point in the wrong place, and its "gain" was minimal.
IMHO: This is the closest thing to a "cure" coming out in the next decade. Like a couple injections a day, wearing a CGM to make sure it is working, no calculations, no worry about carb intake.
A lot of the other "cures" involve immunosuppressants which have a ton of bad side effects that can be worse than diabetes.
A lot of the other "cures" involve immunosuppressants
I'm optimistic about the VX-264 approach of islet cell encapsulation. Even if the encapsulation eventually breaks down, using stem cell derived cells (rather than cadaver pancreata) means you could simply replace the implant after a few years.
"cure" is quite a strong term for something that has to be taken ever day. Even a once a day pill requires a nontrivial patient effort to consistently self administer. Far better than today's manual monitoring of blood sugar to be fair, but we still have to worry about people missing doses and continuing to refill and keep taking such a prescription.
Maybe one day it could be made into a infrequent injection? Like if you just had to get a shot from your doctor every few months, perhaps that would be easier patient compliance. There was some new hiv preventative that recently demonstrated something like that, I wonder if the technique could be repurposed or not.
Here's a more accessible source:
https://www.theguardian.com/society/article/2024/aug/11/scie...
Reddit thread:
https://www.reddit.com/r/diabetes_t1/comments/1eppvf5/scient...