I have "type 1" diabetes for 27 years. I hear similar stories like this (revolutionary cure working on animal models) every year or two. Until now non of them worked. I hope this one will be beeter but my expectations are quite low.
This is really compelling, and the principle seem like it should work in humans. Can anyone with more knowledge of biochemistry think of any reasons why this gluconic acid polymer approach might not work in humans?
Like most cool biotechnology tools like this, the hangups will probably come from ironing out safety, dosing, and delivery issues in the clinic, rather than some mismatch in the biochemistry. They mention one of them in the paper:
In the long term, a balance is assumed to be established between the amount of injected PLL-FPBA and cleared PLL-FPBA. Thus, the long-term toxicity of the complex formulation needs to be thoroughly evaluated for clinical translation.
Proving that PLL-FPBA only responds to glucose fluctuation (and no other physiological changes, with a large enough sample size to cover the range of possible physiological changes that could be experienced by patients), proving that it is biocompatible with all patients, proving that the dose-response is uniform and can be correctly tailored in all patients, and then proving that all of these results hold over very long periods of time with material that can be cost-effectively manufactured at scale will probably be the tricky part. There probably aren't any fundamental reasons that the chemistry of the gluconic acid polymer wouldn't work in humans.
Citations 13-40 provide a pretty good overview of the history of glucose-responsive insulins. These ideas are awesome and I hope they can be successful some day, but I also get the impression that engineering improvements (and cost reductions) in insulin pump technology will provide more immediate quality-of-life improvements for the broader Type-1 Diabetic population.
There is also what Sigilon (now Eli Lilly) is doing, which is to encapsulate living cells in a matrix they cannot escape. The cells sense glucose levels and secrete appropriate levels of insulin locally. In the current iteration I think the millimeter sized beads are injected in the peritoneum, and are removable.
There are different types of insulin (short acting, long acting) and the cheapest version isn't always best for a specific person depending on their individual situation. If you want more information on the structural factors of the unaffordability of insulin this article could help: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597930/
A box of Fiasp or Levemir insulin costs $477-$560.
The better insulins cost more.
If I give myself the $24.88 WalMart insulin, I can not eat lunch at my regular time and then have to eat in the middle if class. (Assuming I had a high blood sugar reading going into lunch and gave myself R an hour before lunch.)
If I can afford the Fiasp, I can go ahead and eat at my regular time. It's just expensive.
My concern is that I need to live a fairly normal life, and I need to work. If I can not eat lunch at a normal time at work, and if I have to get up every 2 or 3 hours all night long to deal with my diabetes, then I can not work a normal job.
This is not a weird objection. The companies distributing the "expensive insulin" also distribute the affordable insulin, and created the cost disparity. Something strikingly apparent to anyone interacting with insurance companies for any chronic condition.
To be clear, your parent is telling the truth in a very literal sense. However, as always, the devil is in the details.
First of all, this is a pretty recent development. The insulins available for cheap at WalMart used to be significantly worse.
The second bit is that wait, how can it be worse? Well, "insulin" isn't always one thing: there are a variety of brands and ways of synthesizing it. They also have different properties. So there are certain things about this specific insulin that may not be great for a variety of reasons. Type 1 folks (I have less experience with type 2, so I just don't speak on it) that have more money or better insurance tend to use two insulins: a long term one, and a short term one. You take the longer term once per day, and then the shorter acting one on a more "as needed" basis. Of course, everyone's health works differently, and so the exact specifics here are between you and your doctor. Anyway, the point is, that this insulin is short-acting, and so to use it correctly, you have less leeway with time and dosage, and that can be rough. And mistakes can be deadly. Josh Wilkerson is a famous example of this in 2019: the insulin his doctor desired for him was gonna be $1200. He opted for taking this WalMart insulin instead, and made a mistake while taking it, due to the differences between it and his previous insulin. For that, he paid for his life.
The third is, this is still inacessible for various reasons, including money. WalMart is not located everywhere. It still costs money to get to WalMart and back. Also, it's $25 per vial, but that says nothing about other costs too. How many vials do you need for a time period? Depends on the person. And a lot of factors. But let's just spitball one: this bottle has 100 units in it. A starting daily dosage, in my understanding, is like, 0.4-1 units per kilogram of body weight. I weigh about 200 lbs. If we take the low end of that range, that would mean I would need roughly 32 units per day. This means I'm using two and a half vials of this per week, at $80/vial that's $200/week or $10,400/year. It really adds up.
This also doesn't take into account other costs: you're gonna be needing to buy test strips as well, so that you can have some idea of how much you need to take. You're also gonna need to buy needles. These are single use. Oh and don't forget that, while you can buy these needles over the counter with no prescription, pharmacists are able to refuse to sell it to you for any reason, say maybe if they think you're going to be using those needles for other kinds of drugs, so you'd better not be in a bad way when you go into the pharmacy, or risk literally having the medicine that allows you to live with no way to put it into your body.
So yeah, like, don't get me wrong, it's a good thing that they sell it. But people like to act all "mission accomplished" about it, when it's just not that simple.
From the article, this is a small animal study involving less than 10 animals, no one knows if this even works in humans or if the benefits seen here will translate into a larger study.
This is so far from being a commercial product that asking about costs means nothing.
That's misleading. It might be a technical violation, but it is decriminalized. Bringing back a 90-day supply of personal-use non-controlled medications is completely fine. To be safe, carry a prescription and declare the medications at the border.
This is to help Type 1 Diabetics- it has nothing to do with lifestyle nor diet. It is where the pancreas stops producing insulin.
It normally starts in children, hence it is also known as juvenile diabetes.
Unfortunately, it cannot be controlled by limiting food consumption, but requires significant work around monitoring food intake, blood glucose levels and various insulin injections (or a pump).
My wife has been diagnosed for 30 years now - it is an all consuming disease- never a day off once diagnosed. Think of a time where you have been so ill, you can barely move. Well, she’s felt that AND had to ensure her blood sugar levels are maintained. If she doesn’t, then she will feel even worse, and potentially die from a coma (too low sugars) or have a significantly reduced lifespan along with many complications around eyes, heart, circulation amongst other things.
Oh, and as she is going through perimenopause, all the work and knowledge she has gained goes out of the window as her sugar levels increase or decrease without any reason due to hormones.
Any improvements to Type 1 Diabetes management can really improve quality of life, as well as decrease the cost of care (and means she can contribute more to society too).
I want to point out that this is an idiotic take even outside of the fact that type 1 diabetes has nothing to do with diet.
1. A lot of children get type 2 diabetes. Children are marketed to in very manipulative ways, aren't yet fully educated, have weak impulse control, and are handed insanely sugary drinks and foods.
2. Sugar is being put into everything. Unless you're cooking for yourself (hard to do when you're working a ton) for every meal it's hard to ensure you aren't getting tons of sugar.
3. The food pyramid and other systems have been encouraging a high carb / high sugar diet for decades, there's tons of misinformation about it.
That sounds like Type 1 diabetes. Your pancreas doesn't generate insulin in Type 1, and in type 2 your body has insulin resistance, which makes the insulin that your body makes ineffective at regulating your blood sugar.
Type 2 diabetes is not a single disease, but rather a combination of failed signaling pathways in a variety of tissue.
For some people, they will have insulin resistance in fat cells, so lipolysis continues even during high insulin levels.
Some people will have hepatic insulin resistance so their liver does not uptake glucose as glycogen as readily or inhibit gluconeogenesis.
Some people will have insulin resistance in the pancreatic alpha cells, so glucagon production continues in the presence of insulin.
Some people will have skeletal muscle tissue insulin resistance, where excess glucose is not as readily taken up by skeletal muscle tissue (our most metabolic active tissue).
Some people can also have insulin resistance along side decreased insulin production in the pancreatic beta cells. This is mixed type 1 and type 2.
