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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

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
    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 5y ago
      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 5y ago
        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!
- code_duck 5y ago
  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.
AnthonBerg 5y ago
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 5y ago
  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 5y ago
    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.

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
  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 5y ago
    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 5y ago
      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!
code_duck 5y ago
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.

AnthonBerg 5y ago

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 5y ago
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 5y ago
  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.