[HN Gopher] Newly designed 'smart' insulin could improve type 1 ...
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Newly designed 'smart' insulin could improve type 1 diabetes
treatment
Author : lnyan
Score : 86 points
Date : 2021-08-09 12:09 UTC (1 days ago)
(HTM) web link (www.sciencealert.com)
(TXT) w3m dump (www.sciencealert.com)
| ruined wrote:
| is the old insulin free yet
| boublepop wrote:
| 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 wrote:
| Wal-Mart insulin will do in a pinch, but it's pretty garbage
| compared to the better formulations
| TheBlight wrote:
| Will they give it away for free in parking lots to anyone who
| shows up?
| AnthonBerg wrote:
| This is the paper in question:
| https://www.pnas.org/content/118/30/e2103518118
|
| Direct PDF link:
| 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.
| code_duck wrote:
| 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 wrote:
| _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 wrote:
| I wanted to add that one also must know how insulin is dosed
| to understand this.
|
| Type 1 diabetics typically take two different insulins. One
| is a 'long acting' that slowly absorbs over 16-24 hours, like
| what would be called time-release for oral medication. This
| insulin provides for metabolic function and counteracts the
| glucose your liver unpredictably and uncontrollably releases
| at certain times. People with pumps drip regular insulin at a
| slow rate for the same effect. I assume nothing would change
| there.
|
| The other type is called 'fast acting' or bolus insulin. This
| is taken usually in one large dose prior to meals to handle
| the large rise in blood glucose that follows carbohydrate
| consumption. The insulin we are discussing here is a
| replacement for fast acting insulin.
|
| The -ideal- situation for fast acting is for it all to be
| consumed at the end of digestion. You want fast acting to
| match 1:1 with the carbohydrates you ingest, every time, with
| none left to cause hypoglycemia (overdose). other metabolic
| needs are already handle by the pump drip/long-acting. This
| innovation would remove the danger of overshooting the
| insulin dosage and causing hypoglycemia, which is huge.
| code_duck wrote:
| 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 wrote:
| _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._
|
| Get another two decades of experience and then we can talk.
|
| It's entirely possible to have blood glucose below 70 mg/dL
| without having "too much insulin"; healthy adults routinely
| fall below this level during periods of metabolic
| starvation. At such times, the body is in a state of
| ketosis -- this is normal and healthy! -- but as long as
| there's enough insulin (which there is, in healthy adults)
| this does not result in acidosis. When A.B. fasted for 382
| days, his blood glucose levels stabilized around _30_ mg
| /dL while he remained ambulant.
|
| Ketoacidosis is not so much caused by hyperglycaemia as it
| is co-occuring as a result of hypoinsulinaemia.
| code_duck wrote:
| Okay. See you in 20 years then! Just don't raise the bar
| and tell me it's 40. Currently I have 18 months
| experience thinking about this.
|
| In the meantime, I am not an expert and am quite willing
| to be informed. I generally assume that other people in a
| general discussion audience are not familiar with
| diabetes treatment or biology at all. If you are, that's
| great.
|
| I have not heard of healthy states of hypoglycemia
| before, other than that many people naturally experience
| it during sleep. I have a friend whose mother suffers
| from hypoglycemia and she suffers the same ill effects as
| it how 1 diabetics commonly experience. I am aware that
| other metabolic causes exist for blood glucose levels to
| be reduced besides insulin.
|
| Do you mean metabolic ketosis, the type that people try
| to achieve intentionally through diet? I am aware that
| states of ketosis exist without acidosis, such as that
| one. I'm not intimately familiar with the biological
| details.
|
| Yes, I am aware that ketoacidosis is caused by a complete
| lack of insulin, and the complete lack of insulin leads
| to hyperglycemia, not some other causative relationship.
| cperciva wrote:
| _I have a friend whose mother suffers from hypoglycemia
| and she suffers the same ill effects as it how 1
| diabetics commonly experience._
|
| I'm guessing reactive hypoglycaemia? That's caused by the
| body overproducing insulin in response to meals; it's
| also believed to be a common prologue to T2D since it
| "trains" the body to be less sensitive to the
| (over)produced insulin.
|
| No surprise that hypoglycaemia resulting from an excess
| of insulin is similar to hypoglycaemia resulting from an
| excess of insulin!
| AnthonBerg wrote:
| _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._
|
| It would be cool!, but I'd go for the pancreas: As far as I
| know, the pancreas releases insulin in pulses. Each pulse 3-5
| minutes after the other? The pulses seem to matter. Supposedly
| the loading-unloading cycle on the insulin receptor seems to
| help prevent insulin resistance. (It does somehow make
| intuitive sense to "shake" cells' sensors a bit to help them
| stay on target.)
|
| Another thing is C-peptide. It's a "byproduct" of the insulin
| protein folding in the pancreatic cell. I believe C-peptide is
| now known to be a biologically active control molecule with
| antiinflammatory properties.
|
| Source: The Wikipedia page on insulin iirc. I an only a layman
| and may be severely mistaken about all of this.
| code_duck wrote:
| Of course you need insulin. Just not when your glucose is 75
| (below 70 is hypoglycemia).
|
| Sure, it's complex.
|
| People with type 1 don't have any insulin production at all,
| and typically get it in large doses (syringe) that absorb
| slowly or dripped out from a pump. With no endogenous
| production, we do not make c-peptide (it's a protein or
| something cleaved off of pro-insulin in the body's synthesis
| of insulin. Levels are measured in blood tests to determine
| your level of insulin production - after honeymoon period,
| type 1s produce no insulin and therefore no c-peptide).
| AnthonBerg wrote:
| I was referring specifically to the text as quoted,
| especially "even better than having a fully functional
| pancreas" :)
|
| I'm intimately familiar with Type 1 diabetes. I find the
| nuances of what the pancreas does to be quite fascinating,
| and the closer we get to understanding what matters and to
| replicating it, the better.
|
| I believe that one wants the pulsatile secretion as well as
| C-peptide.
|
| There are some recent results on C-peptide as far as I
| know. I believe there is still a noteworthy amount of
| C-peptide after the honeymoon, and I believe it is good to
| try to prolong the honeymoon as long as possible to retain
| as much C-peptide functionality as possible.
|
| C-peptide is an active signaling molecule. It makes sense:
| The body produces a complex and easily identifiable protein
| chain as a byproduct of the crucial insulin molecule.
| C-peptide is more stable than insulin itself and remains a
| bit longer in the body. It stands to reason that the
| ancient and highly-preserved evolutionary function of
| insulin metabolism has picked up a good use for C-peptide
| as a signal carrier on the way.
| code_duck wrote:
| Ha, yes, it wouldn't -really- be better than your body
| working as intended. My thoughts were that for regular
| people, your body has to react to raising glucose by
| releasing insulin, while with this new insulin, it would
| already be in your blood.
|
| That pulsing secretion could be achieved with a pump.
| Maybe they already do it?
|
| I have LADA, which is known for a very long, gradual
| honeymoon period. I've looked into the studies intended
| to prolong function but they involve immune suppressants,
| as far as I can tell, which doesn't seem like a great
| idea in the Covid age.
| [deleted]
| cletus wrote:
| 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.
| Trasmatta wrote:
| 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 wrote:
| 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 wrote:
| 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.
| hooande wrote:
| 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.
| _Microft wrote:
| 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.
| Someone wrote:
| 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:
|
| _"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 wrote:
| 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 wrote:
| > 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.
| jellicle wrote:
| > > requires governmental medical insurance providers
| RHSeeger wrote:
| Add to that that the insulins used by a lot of people are
| over 20 years old and off patent. However, they are biologics
| and, as such, can't be simply made as a generic. Any
| "generic" needs to go through testing and approval, which
| means the generics (like Basaglar is for Lantus) aren't that
| much cheaper (80% of the cost, I believe).
| ryneandal wrote:
| 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.
| gorb314 wrote:
| 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 wrote:
| 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 wrote:
| 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.
| danudey wrote:
| The only inhaled insulin I can find is Afrezza, and WebMD
| says:
|
| > It's not for diabetes emergencies such as diabetic
| ketoacidosis (DKA).
|
| So probably not great for this. Seems more like something
| you take during a meal to keep from going hyperglycemic and
| not something you take when you're having problems.
|
| https://www.webmd.com/diabetes/inhaled-insulin
| [deleted]
| zippergz wrote:
| I know people who quite successfully use it in place of a
| pump, along with a single basal shot from a pen each day.
| It's just a small inhaler with disposable plastic dose
| dispensers in various numbers of units. It because it works
| so quickly it is not a problem to measure accurately. If
| you use too little, you'll quickly know and can take
| another. But you are correct that it could not replace
| basal insulin. I suppose you also could use it as a
| supplement to a pump and there are probably people who do
| it, but not in my circle.
| 1123581321 wrote:
| Fellow T1 here--when you're in that situation you shouldn't sit
| while your bolus barely keeps up with fast carbs, you should do
| something physically active to help get your numbers down more
| quickly.
|
| I share your wish in your last paragraph very much!
| disabled wrote:
| It's a nice thing to say and all, but not everyone with T1D
| is abled-bodied. There are other people with T1D who also
| have to work in an office right after their mealtime so it's
| also a form of classism. You are also pointing out something
| that is extremely obvious to people with T1D. You could try
| to be more thoughtful with your posts and actually post
| something substantive, useful, and original instead.
|
| Also, your post below about "first world problems" is
| offensive. First world problems do not exist and it is
| unbelievably offensive to people suffering in developing
| countries, like in many places in Africa. Trust me, I know,
| as I have immediate family who recently lived in Africa on
| assignment in one of the most corrupt countries in the world
| for a couple of years. You would not believe how insensitive
| "first world problems" actually is. I suggest you cut it out
| of your language, now. Same goes with first world/third
| world. You need to use "developed countries" and "developing
| countries".
|
| Please be mindful of your language.
| pixl97 wrote:
| If only physical activity paid as much as holding a chair
| down.
| 1123581321 wrote:
| Yes, it's tough (for the first world.) I've done walking
| meetings and during COVID some conference calls on the go,
| but if I ate a bunch of pasta for lunch and didn't take my
| insulin first, and have typing to do...
| zby wrote:
| What the article speculates is a way to load up insuline in the
| blood that would not act if the blood glucose is below let's
| say 120 - but when it is above - then the insuline opens and
| acts. This is the fastest possible way of it to act. Even if it
| degrades and you could not keep much of it constantly in the
| blood stream - then you could inject it much before the meal
| and it would just start acting when the blood sugar increases
| and also you could inject more than enough and not worry about
| injecting too much of it - because it would never lead to hypo.
|
| This would be the ideal - in a way it would be better than
| functioning pancreas - because pancreas needs a few minutes
| before releasing insuline and this would act instantly.
| RHSeeger wrote:
| It would be nice to have something like this with a several
| hour window. I currently suffer from the dawn phenomenon, and
| my blood sugar spikes by 100+ most mornings (starting
| anywhere between 5am and 7am). It's super frustrating to have
| to get up every day at 630-7am to check my blood sugar and,
| if necessary (most days), take some insulin.
| UnpossibleJim wrote:
| Waking up to the GCM an hour before the alarm every morning
| is horrible. While maybe not the worst thing about being a
| T1, I'm still loathe to do it =P
|
| I will say this, though. The CGM (continuous glucose
| monitor) was one of the best things to help me regulate my
| blood sugars - even though insurance hates to cover it from
| time to time (not always - it's weird). As a person who has
| a tendency to suffer from extreme lows, I'm excited for
| this new "hinged" insulin, should it make it to market.
| [deleted]
| FigurativeVoid wrote:
| That's a really great point. I am T1 as well. The improvements
| I would love is an insulin that is denser and more stable.
|
| If we had insulin that was say.. 1000 units/mL (10x stronger)
| and didn't degrade as fast, then we could have some really cool
| and slim devices. You could also have a longer lasting pump
| site.
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(page generated 2021-08-10 23:01 UTC)