8 ms·

Newly designed 'smart' insulin could improve type 1 diabetes treatment

113 points by lnyan 5y ago

AnthonBerg 5y ago
This is the paper in question: https://www.pnas.org/content/118/30/e2103518118 https://www.pnas.org/content/118/30/e2103518118 Direct PDF link: https://www.pnas.org/content/pnas/118/30/e2103518118.full.pdf https://www.pnas.org/content/pnas/118/30/e2103518118.full.pd... The sciencealert page is a digest of the author’s university’s digest. The papers themselves are usually much better material. Quite understandable in my experience. That said, as someone in a relationship with autoimmune diabetes, I hope this work comes to fruition. It’s obviously a good idea to try to research and develop this further.
cletus 5y ago
Cynical title: Change with questionable benefit extends patent life and thus prices of insulin even further. To be clear: I don't know a lot about insulin. I'm fortunate enough not to be diabetic. So there may have been useful advancements in insulin. The price of insulin in the US does seem to be awfully high however. It is a common practice for pharmaceutical companies to alter the active molecule in some way, claim the new version has benefits, reset the patent timeline and stop producing the old version. EDIT: in case it wasn't clear, if this is actually good for diabetics, that's fantastic. Insulin in the US shouldn't be as expensive as it is. I'm just seen too much profiteering (eg Epipen) by that industry.
- _Microft 5y ago
  I am not a biologist but the proposed behavior of the molecule seems highly beneficial for the patient. It is supposed to only activate in presence of enough glucose instead of always. This is meant to prevent dangerously low blood sugar. They only conducted experiments with fructose so far.
- Trasmatta 5y ago
  I am T1 diabetic, and this change, if it works, could absolutely be a game changer. > So there may have been useful advancements in insulin There have been massive advancements in insulin over the past couple of decades. Today's long acting and short acting insulins are a massive improvement over the older kinds. The price of insulin in the US is a disaster (when not covered by insurance), but otherwise the quality of insulin treatment is better than it's ever been.
  - randcraw 5y ago
    I'm a T2 diabetic, and though I don't (yet) take insulin, I'm pretty sure this could be a very big win for other T2s who do. Dosing insulin is clumsy with an insulin pump, and always hit-or-miss without one (insulin arrives too early or too late or in the wrong amount). The adaptive release of insulin only when glucose levels rise could provide a near-ideal therapy for millions. If it's affordable...
- jcims 5y ago
  I'm not an expert, but have a lot of exposure to this through my kiddo who is a type-1 (insulin deficient) diabetic. This could represent a step function change in her therapy. Only for folks using the latest and greatest in closed-loop pump therapy is there even an approximation of the pancreas function to elevate insulin levels in response to elevated blood glucose levels, and even then its too slow to be effective. Diabetics that want to closely manage their blood glucose levels have to carefully plan how they eat and how active they are, modulo sickness, periods/etc. If it was possible to have a latent insulin bolus floating around the bloodstream that could react to gluecose directly, it could provide an important buffer and possibly even a wonderfully passive approach to therapy vs. the ridiculous dance that patients undergo today.
- Someone 5y ago
  If patents were a significant factor in the high prices for insulin in the USA, you would expect prices to be similarly high in all countries that recognize those patents. They aren’t. https://www.rand.org/pubs/research_reports/RRA788-1.html https://www.rand.org/pubs/research_reports/RRA788-1.html: “Although the ratio of U.S. to other-country prices varied depending on the comparison country and insulin category, U.S. prices were always higher (often five to ten times higher) than those in other countries.“ “Other countries” includes Canada and Germany, so they didn’t look at particularly poor countries. The linked PDF says “The average U.S. manufacturer price per standard unit across all insulins was $98.70, compared with $6.94 in Australia, $12.00 in Canada, $7.52 in the United Kingdom, and $8.81 across all non-U.S. OECD countries combined”
  - jellicle 5y ago
    All of those countries set how much they'll pay for insulin. They have price controls. The USA does the opposite; requires governmental medical insurance providers NOT to bargain with pharma companies and instead explicitly requires them to pay whatever price the pharma company sets. Low prices could come from either a) a robust, competitive market in producing and selling insulin or b) governmental price controls. The USA explicitly chooses not to have either. Other countries typically choose b) backed up by a threat of a) (if you're a pain in the ass over our negotiated price controls, we'll go source a large supply of insulin from somewhere else).
    - boublepop 5y ago
      > The USA does the opposite; requires governmental medical insurance providers NOT to bargain with pharma companies and instead explicitly requires them to pay whatever price the pharma company sets. That’s either a gross misunderstanding or deliberate misinformation. There is both price negotiations and significant rebates negotiated by pharmacy benefits managers who will often make 75% of the profit on the sale of the drugs back as rebates. They then distribute that back to insurers and other parties. Sadly those enormous rebates don’t seem to reach or benefit the patients.
      - 5y ago
- hooande 5y ago
  This comment is just wrong. This isn't a 'questionable benefit', it's a major change to the fundamental technology. This has nothing to do with price or profits at all. Comparing this theoretical advance to existing insulin is like comparing electric vehicles to gas powered cars. It's a difference in kind, not degree. To explain, currently your pancreas is measuring your blood sugar and producing more or less insulin to keep it at a safe level (let's call that level "100"). A type 1 diabetic has to do that process manually, measuring their blood sugar with a device and taking enough insulin via needle to keep it at 100. It's possible to overshoot and have blood sugar go far below 100, which can do real damage to cells that need sugar as an energy source. Obviously if you have to measure and adjust several times a day, every day, even a 1% human error rate is going to come up often. This theoretical insulin would stop working if there wasn't sufficient sugar already in the blood. As another comment said, it would basically stop working if your blood sugar was below 75 or 80. Right now diabetics are at risk from blood sugar being too high OR too low. This would cut out half of that risk, and be life changing for millions of people. Has nothing to do with price, and as always I must mention that generic insulin is abundant and readily available at low prices to anyone. I don't expect everyone to follow the details of insulin and having diabetes. But it would be nice if medical advancements could be discussed without people conflating the topics with their pet political issues.
ruined 5y ago
is the old insulin free yet
- boublepop 5y ago
  It costs 25$ in wallmart, or if you are uninsured and low income there are patient care programs that will provide it to you for free.
  - Trasmatta 5y ago
    Wal-Mart insulin will do in a pinch, but it's pretty garbage compared to the better formulations
code_duck 5y ago
We have been hearing of this in the type 1 diabetes community for some time and it sounds very promising. As the article explains, the main risk of insulin use is hypoglycemia, which is essentially the result of an insulin overdose. When you dose insulin, you have to carefully match it to the carbohydrates you subsequently consume and the glucose your liver secretes. Too little insulin and you will have high blood glucose, too much and you will suffer low glucose. Highs are uncomfortable and risky long term, but lows are very uncomfortable and immediately dangerous. For insulin to stop working once your glucose got to 75-80 would be perfect. If the insulin also stayed there and activated as soon as your glucose went up, that might be even better than having a fully functional pancreas.
- cperciva 5y ago
  For insulin to stop working once your glucose got to 75-80 would be perfect. I'm not so sure about that. Insulin does more than just regulate blood glucose levels; it also affects fat metabolism, potassium levels, and many other things. If the insulin "turned off" completely we could see patients who went into ketoacidosis as a result of fasting and/or exercise.
  - code_duck 5y ago
    Yes, your body cannot have zero insulin. You do not need/want more insulin once your glucose is 70-75, though. I'm quite familiar with both hypoglycemia and ketoacidosis, having nearly died of undiagnosed type 1 last Spring. Ketoacidosis is typically associated with hyperglycemia. It happens when your body has no insulin. There is what's called euglycemic ketoacidosis but it's rare. In typical ketoacidosis, your blood is very high in glucose, but lacking insulin, your cells have no way to obtain it. Since your body cannot get energy out of your blood in the normal fashion it starts to digest ketones, which acidifies the blood and creates many harmful effects. In the situation we are discussing, when your glucose rises above 75 from food or liver secretion, the novel insulin would start working, preventing ketoacidosis.
    - cperciva 5y ago
gorb314 5y ago
I think this is an interesting research direction. From my perspective though, being a T1, what I want is an even faster acting insulin than we already have, with a shorter "on" time. To explain: the shortest acting insulins we have right now take effect about 30 minutes after injection. Then the dose stays active for about 4 hours. So for me to react to a high blood sugar, and until I can be certain that I did not inject too much (nor too little), can take up to 4 hours. That is almost unbearably long, especially when my blood sugar climbs through the roof, and I am not sure whether it is because my pump line was blocked. Overloading on insulin (called "stacking") to compensate for a crazy high blood sugar can be very dangerous - plus I can't think straight when my sugar is that high. Nothing sucks more than having to sit and wait for a high blood sugar to come down... Contrast that lagged response time to eating food, especially high GI sugars such as a soft drink, orange juice, or even bread. This can spike my insulin in a matter of minutes. All this makes matching sugar spikes with insulin response curves very hard; it is a one-side-overdamped-and-other-side-underdamped dynamic system. Any diabetic will tell you how crazy a "roller coaster ride" can be, which is what happens when you overcompensate on either end. To get back to the topic of the 'smart' insulin: if this research can lead to an insulin that can always be in my bloodstream, ready to act when my blood sugar rises, and stop when my blood sugar falls, and if it can do this quick enough, then that would be a game changer.
- zippergz 5y ago
  Have you tried the inhaled insulin? It takes effect MUCH faster than any injected insulin, does it’s job, and is out of your body quickly so also reduces the risk of stacking. In some ways it is not as convenient as a pump, but it works much better in terms of timing.
  - zby 5y ago
    How do you take it? I imagine it would be ideal to quickly beat hyperglycemia when you underestimate a meal bolus. But I don't see it replacing a pump (or pens), because it would be difficult to: measure it exactly and keep supplying it continuously.
ryneandal 5y ago
I'm a fan of anything to make management of T1/LADA simpler. Didn't realize how much of a chore management is until I was diagnosed with LADA in October of 2019. I feel for all of you that have been dealing with T1 for years/decades. It's exhausting.
TheBlight 5y ago
Will they give it away for free in parking lots to anyone who shows up?

113 points by lnyan 5y ago

This is the paper in question: https://www.pnas.org/content/118/30/e2103518118 https://www.pnas.org/content/118/30/e2103518118 Direct PDF link: https://www.pnas.org/content/pnas/118/30/e2103518118.full.pdf https://www.pnas.org/content/pnas/118/30/e2103518118.full.pd... The sciencealert page is a digest of the author’s university’s digest. The papers themselves are usually much better material. Quite understandable in my experience. That said, as someone in a relationship with autoimmune diabetes, I hope this work comes to fruition. It’s obviously a good idea to try to research and develop this further.

cletus 5y ago

Cynical title: Change with questionable benefit extends patent life and thus prices of insulin even further. To be clear: I don't know a lot about insulin. I'm fortunate enough not to be diabetic. So there may have been useful advancements in insulin. The price of insulin in the US does seem to be awfully high however. It is a common practice for pharmaceutical companies to alter the active molecule in some way, claim the new version has benefits, reset the patent timeline and stop producing the old version. EDIT: in case it wasn't clear, if this is actually good for diabetics, that's fantastic. Insulin in the US shouldn't be as expensive as it is. I'm just seen too much profiteering (eg Epipen) by that industry.

_Microft 5y ago
I am not a biologist but the proposed behavior of the molecule seems highly beneficial for the patient. It is supposed to only activate in presence of enough glucose instead of always. This is meant to prevent dangerously low blood sugar. They only conducted experiments with fructose so far.
Trasmatta 5y ago
I am T1 diabetic, and this change, if it works, could absolutely be a game changer. > So there may have been useful advancements in insulin There have been massive advancements in insulin over the past couple of decades. Today's long acting and short acting insulins are a massive improvement over the older kinds. The price of insulin in the US is a disaster (when not covered by insurance), but otherwise the quality of insulin treatment is better than it's ever been.
- randcraw 5y ago
  I'm a T2 diabetic, and though I don't (yet) take insulin, I'm pretty sure this could be a very big win for other T2s who do. Dosing insulin is clumsy with an insulin pump, and always hit-or-miss without one (insulin arrives too early or too late or in the wrong amount). The adaptive release of insulin only when glucose levels rise could provide a near-ideal therapy for millions. If it's affordable...
jcims 5y ago
I'm not an expert, but have a lot of exposure to this through my kiddo who is a type-1 (insulin deficient) diabetic. This could represent a step function change in her therapy. Only for folks using the latest and greatest in closed-loop pump therapy is there even an approximation of the pancreas function to elevate insulin levels in response to elevated blood glucose levels, and even then its too slow to be effective. Diabetics that want to closely manage their blood glucose levels have to carefully plan how they eat and how active they are, modulo sickness, periods/etc. If it was possible to have a latent insulin bolus floating around the bloodstream that could react to gluecose directly, it could provide an important buffer and possibly even a wonderfully passive approach to therapy vs. the ridiculous dance that patients undergo today.
Someone 5y ago
If patents were a significant factor in the high prices for insulin in the USA, you would expect prices to be similarly high in all countries that recognize those patents. They aren’t. https://www.rand.org/pubs/research_reports/RRA788-1.html https://www.rand.org/pubs/research_reports/RRA788-1.html: “Although the ratio of U.S. to other-country prices varied depending on the comparison country and insulin category, U.S. prices were always higher (often five to ten times higher) than those in other countries.“ “Other countries” includes Canada and Germany, so they didn’t look at particularly poor countries. The linked PDF says “The average U.S. manufacturer price per standard unit across all insulins was $98.70, compared with $6.94 in Australia, $12.00 in Canada, $7.52 in the United Kingdom, and $8.81 across all non-U.S. OECD countries combined”
- jellicle 5y ago
  All of those countries set how much they'll pay for insulin. They have price controls. The USA does the opposite; requires governmental medical insurance providers NOT to bargain with pharma companies and instead explicitly requires them to pay whatever price the pharma company sets. Low prices could come from either a) a robust, competitive market in producing and selling insulin or b) governmental price controls. The USA explicitly chooses not to have either. Other countries typically choose b) backed up by a threat of a) (if you're a pain in the ass over our negotiated price controls, we'll go source a large supply of insulin from somewhere else).
  - boublepop 5y ago
    > The USA does the opposite; requires governmental medical insurance providers NOT to bargain with pharma companies and instead explicitly requires them to pay whatever price the pharma company sets. That’s either a gross misunderstanding or deliberate misinformation. There is both price negotiations and significant rebates negotiated by pharmacy benefits managers who will often make 75% of the profit on the sale of the drugs back as rebates. They then distribute that back to insurers and other parties. Sadly those enormous rebates don’t seem to reach or benefit the patients.
    - 5y ago
hooande 5y ago
This comment is just wrong. This isn't a 'questionable benefit', it's a major change to the fundamental technology. This has nothing to do with price or profits at all. Comparing this theoretical advance to existing insulin is like comparing electric vehicles to gas powered cars. It's a difference in kind, not degree. To explain, currently your pancreas is measuring your blood sugar and producing more or less insulin to keep it at a safe level (let's call that level "100"). A type 1 diabetic has to do that process manually, measuring their blood sugar with a device and taking enough insulin via needle to keep it at 100. It's possible to overshoot and have blood sugar go far below 100, which can do real damage to cells that need sugar as an energy source. Obviously if you have to measure and adjust several times a day, every day, even a 1% human error rate is going to come up often. This theoretical insulin would stop working if there wasn't sufficient sugar already in the blood. As another comment said, it would basically stop working if your blood sugar was below 75 or 80. Right now diabetics are at risk from blood sugar being too high OR too low. This would cut out half of that risk, and be life changing for millions of people. Has nothing to do with price, and as always I must mention that generic insulin is abundant and readily available at low prices to anyone. I don't expect everyone to follow the details of insulin and having diabetes. But it would be nice if medical advancements could be discussed without people conflating the topics with their pet political issues.

ruined 5y ago

is the old insulin free yet

boublepop 5y ago
It costs 25$ in wallmart, or if you are uninsured and low income there are patient care programs that will provide it to you for free.
- Trasmatta 5y ago
  Wal-Mart insulin will do in a pinch, but it's pretty garbage compared to the better formulations

code_duck 5y ago

We have been hearing of this in the type 1 diabetes community for some time and it sounds very promising. As the article explains, the main risk of insulin use is hypoglycemia, which is essentially the result of an insulin overdose. When you dose insulin, you have to carefully match it to the carbohydrates you subsequently consume and the glucose your liver secretes. Too little insulin and you will have high blood glucose, too much and you will suffer low glucose. Highs are uncomfortable and risky long term, but lows are very uncomfortable and immediately dangerous. For insulin to stop working once your glucose got to 75-80 would be perfect. If the insulin also stayed there and activated as soon as your glucose went up, that might be even better than having a fully functional pancreas.

cperciva 5y ago
For insulin to stop working once your glucose got to 75-80 would be perfect. I'm not so sure about that. Insulin does more than just regulate blood glucose levels; it also affects fat metabolism, potassium levels, and many other things. If the insulin "turned off" completely we could see patients who went into ketoacidosis as a result of fasting and/or exercise.
- code_duck 5y ago
  Yes, your body cannot have zero insulin. You do not need/want more insulin once your glucose is 70-75, though. I'm quite familiar with both hypoglycemia and ketoacidosis, having nearly died of undiagnosed type 1 last Spring. Ketoacidosis is typically associated with hyperglycemia. It happens when your body has no insulin. There is what's called euglycemic ketoacidosis but it's rare. In typical ketoacidosis, your blood is very high in glucose, but lacking insulin, your cells have no way to obtain it. Since your body cannot get energy out of your blood in the normal fashion it starts to digest ketones, which acidifies the blood and creates many harmful effects. In the situation we are discussing, when your glucose rises above 75 from food or liver secretion, the novel insulin would start working, preventing ketoacidosis.
  - cperciva 5y ago

gorb314 5y ago

I think this is an interesting research direction. From my perspective though, being a T1, what I want is an even faster acting insulin than we already have, with a shorter "on" time. To explain: the shortest acting insulins we have right now take effect about 30 minutes after injection. Then the dose stays active for about 4 hours. So for me to react to a high blood sugar, and until I can be certain that I did not inject too much (nor too little), can take up to 4 hours. That is almost unbearably long, especially when my blood sugar climbs through the roof, and I am not sure whether it is because my pump line was blocked. Overloading on insulin (called "stacking") to compensate for a crazy high blood sugar can be very dangerous - plus I can't think straight when my sugar is that high. Nothing sucks more than having to sit and wait for a high blood sugar to come down... Contrast that lagged response time to eating food, especially high GI sugars such as a soft drink, orange juice, or even bread. This can spike my insulin in a matter of minutes. All this makes matching sugar spikes with insulin response curves very hard; it is a one-side-overdamped-and-other-side-underdamped dynamic system. Any diabetic will tell you how crazy a "roller coaster ride" can be, which is what happens when you overcompensate on either end. To get back to the topic of the 'smart' insulin: if this research can lead to an insulin that can always be in my bloodstream, ready to act when my blood sugar rises, and stop when my blood sugar falls, and if it can do this quick enough, then that would be a game changer.

zippergz 5y ago
Have you tried the inhaled insulin? It takes effect MUCH faster than any injected insulin, does it’s job, and is out of your body quickly so also reduces the risk of stacking. In some ways it is not as convenient as a pump, but it works much better in terms of timing.
- zby 5y ago
  How do you take it? I imagine it would be ideal to quickly beat hyperglycemia when you underestimate a meal bolus. But I don't see it replacing a pump (or pens), because it would be difficult to: measure it exactly and keep supplying it continuously.

ryneandal 5y ago

I'm a fan of anything to make management of T1/LADA simpler. Didn't realize how much of a chore management is until I was diagnosed with LADA in October of 2019. I feel for all of you that have been dealing with T1 for years/decades. It's exhausting.

TheBlight 5y ago

Will they give it away for free in parking lots to anyone who shows up?