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Post by agedhippie on Sept 23, 2017 19:23:01 GMT -5
Claims that Afrezza cannot cause hypoglycemia are false. As a type 1, if I inhale an 8-unit cartridge before a meal , with a starting blood sugar level of 120, I will definitely be hypoglycemic if I don't eat anything. That's assuming my BS has been flat for the past two hours, not trending up. My guesstimate is I'd be hypoglycemic within 15-30 minutes and feeling the full effects of it. I don't think you would develop a severe hypo because of the way Afrezza works. It is working the same way a nondiabetic's insulin does. By introducing the first phase insulin response into the body, it signals to the liver the same way and the liver will attempt to compensate for low levels by producing more glucose. A lot of ill-informed comments get made here but usually it's not big deal. In this case it's actively dangerous. If anyone wants to try, well it's your funeral - probably literally. As a regular Type 1 you will have a severe hypo because 8u is going to drop you at least 250 points, so from 120 that's way below 30 (way below 0!). Your liver dump is not going to happen fast enough to save you because of the combination of the quantity of insulin and speed of action. Your body works incrementally to avoid overshoot and what you are describing is a huge overshoot which your liver is not designed to respond to. Untreated you absolutely will go into insulin shock and probably not survive.
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Post by mango on Sept 23, 2017 23:18:48 GMT -5
I don't think you would develop a severe hypo because of the way Afrezza works. It is working the same way a nondiabetic's insulin does. By introducing the first phase insulin response into the body, it signals to the liver the same way and the liver will attempt to compensate for low levels by producing more glucose. A lot of ill-informed comments get made here but usually it's not big deal. In this case it's actively dangerous. If anyone wants to try, well it's your funeral - probably literally. As a regular Type 1 you will have a severe hypo because 8u is going to drop you at least 250 points, so from 120 that's way below 30 (way below 0!). Your liver dump is not going to happen fast enough to save you because of the combination of the quantity of insulin and speed of action. Your body works incrementally to avoid overshoot and what you are describing is a huge overshoot which your liver is not designed to respond to. Untreated you absolutely will go into insulin shock and probably not survive. You might be right, but was just basing it on the fact that Sam Finta, who is a type 1, took a 4u with no meal at a starting level of 102 and it never got below 50. It took over an hour to get that to the 50. So I don't know. Point being, I never was the one that suggested doing it in the first place. If you eat something when you take Afrezza, which is the intended purpose of it in the first place, you are not going to get a hypo.
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Post by agedhippie on Sept 24, 2017 10:21:41 GMT -5
A lot of ill-informed comments get made here but usually it's not big deal. In this case it's actively dangerous. If anyone wants to try, well it's your funeral - probably literally. As a regular Type 1 you will have a severe hypo because 8u is going to drop you at least 250 points, so from 120 that's way below 30 (way below 0!). Your liver dump is not going to happen fast enough to save you because of the combination of the quantity of insulin and speed of action. Your body works incrementally to avoid overshoot and what you are describing is a huge overshoot which your liver is not designed to respond to. Untreated you absolutely will go into insulin shock and probably not survive. You might be right, but was just basing it on the fact that Sam Finta, who is a type 1, took a 4u with no meal at a starting level of 102 and it never got below 50. It took over an hour to get that to the 50. So I don't know. Point being, I never was the one that suggested doing it in the first place. If you eat something when you take Afrezza, which is the intended purpose of it in the first place, you are not going to get a hypo. The only time this was done properly was the Mannkind study back in 2014 conducted by Sansum. They worked out how much Afrezza each person needed to cover a meal and then gave that amount of Afrezza with 0%, 50%, 100%, 150% and 200% of the meal. They tried this for both Type 1 and Type 2. All the Type 1 participants went hypo when given 50% of the meal. The 0% test for Type 1s was abandoned on safety grounds although it was redundant anyway as the trial had already failed at 50%. Mannkind's own study emphatically says that you will go hypo from Afrezza if you don't eat enough carbs. My gut feeling is that Afrezza only needs to be dosed to within +/-2u though for normal insulin resistance which is a lot better than injected insulin which doesn't have that margin.
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Post by mango on Sept 24, 2017 17:20:37 GMT -5
You might be right, but was just basing it on the fact that Sam Finta, who is a type 1, took a 4u with no meal at a starting level of 102 and it never got below 50. It took over an hour to get that to the 50. So I don't know. Point being, I never was the one that suggested doing it in the first place. If you eat something when you take Afrezza, which is the intended purpose of it in the first place, you are not going to get a hypo. The only time this was done properly was the Mannkind study back in 2014 conducted by Sansum. They worked out how much Afrezza each person needed to cover a meal and then gave that amount of Afrezza with 0%, 50%, 100%, 150% and 200% of the meal. They tried this for both Type 1 and Type 2. All the Type 1 participants went hypo when given 50% of the meal. The 0% test for Type 1s was abandoned on safety grounds although it was redundant anyway as the trial had already failed at 50%. Mannkind's own study emphatically says that you will go hypo from Afrezza if you don't eat enough carbs. My gut feeling is that Afrezza only needs to be dosed to within +/-2u though for normal insulin resistance which is a lot better than injected insulin which doesn't have that margin. The participants were given Afrezza before the meal. It should be given at the beginning of a meal. Since it mimics the physiology of endogenous prandial insulin in a normal healthy pancreas, the first phase insulin release works in synchrony with the rising blood glucose levels in response to a meal. It must be given at the beginning of a meal to be most effective, in some cases a follow up dose needs to be given since it is has those kinetics its action will be done before the digestion of the meal is. No serious hypoglycemia was observed in the clinical trial you linked, so I doubt it is true what you said about glucose levels going well below 0. Sam Finta shows that you won't get a severe hypo when taking Afrezza at a starting blood glucose of 102 with no meal. It took 1 hour for the glucose level to drop to 50 and ~1 hour is when Afrezza has done all it's glucose lowering and in this case the low glucose level was naturally corrected. Afrezza behaves the same as normal pancreatic insulin.
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Post by agedhippie on Sept 24, 2017 18:58:00 GMT -5
The only time this was done properly was the Mannkind study back in 2014 conducted by Sansum. They worked out how much Afrezza each person needed to cover a meal and then gave that amount of Afrezza with 0%, 50%, 100%, 150% and 200% of the meal. They tried this for both Type 1 and Type 2. All the Type 1 participants went hypo when given 50% of the meal. The 0% test for Type 1s was abandoned on safety grounds although it was redundant anyway as the trial had already failed at 50%. Mannkind's own study emphatically says that you will go hypo from Afrezza if you don't eat enough carbs. My gut feeling is that Afrezza only needs to be dosed to within +/-2u though for normal insulin resistance which is a lot better than injected insulin which doesn't have that margin. The participants were given Afrezza before the meal. It should be given at the beginning of a meal. Since it mimics the physiology of endogenous prandial insulin in a normal healthy pancreas, the first phase insulin release works in synchrony with the rising blood glucose levels in response to a meal. It must be given at the beginning of a meal to be most effective, in some cases a follow up dose needs to be given since it is has those kinetics its action will be done before the digestion of the meal is. No serious hypoglycemia was observed in the clinical trial you linked, so I doubt it is true what you said about glucose levels going well below 0. Sam Finta shows that you won't get a severe hypo when taking Afrezza at a starting blood glucose of 102 with no meal. It took 1 hour for the glucose level to drop to 50 and ~1 hour is when Afrezza has done all it's glucose lowering and in this case the low glucose level was naturally corrected. Afrezza behaves the same as normal pancreatic insulin. I think this comes to a matter of semantics. The protocol says, " immediately before starting meal", I would say that means "given at the beginning of the meal. The trial data is clear, at 50% of meal all the Type 1s went hypoglycemic. Sansum and Mannkind saw the writing on the wall and abandoned the no meal test (atcually they terminated the whole trial). That's good enough for me, remember this is the Sansum that did the Afrezza with APS work that gets mentioned whenever anyone talks about an AP. There was one severe hypo, it was a Type 2. So much for Type 2s not getting hypos from Afrezza. I really don't care if anyone wants to take 8u when they are at 102, they know what will happen now and it will be their funeral. If they are stupid enough to do that they deserve their entry in the Darwin awards.
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Post by mango on Sept 24, 2017 19:06:10 GMT -5
The participants were given Afrezza before the meal. It should be given at the beginning of a meal. Since it mimics the physiology of endogenous prandial insulin in a normal healthy pancreas, the first phase insulin release works in synchrony with the rising blood glucose levels in response to a meal. It must be given at the beginning of a meal to be most effective, in some cases a follow up dose needs to be given since it is has those kinetics its action will be done before the digestion of the meal is. No serious hypoglycemia was observed in the clinical trial you linked, so I doubt it is true what you said about glucose levels going well below 0. Sam Finta shows that you won't get a severe hypo when taking Afrezza at a starting blood glucose of 102 with no meal. It took 1 hour for the glucose level to drop to 50 and ~1 hour is when Afrezza has done all it's glucose lowering and in this case the low glucose level was naturally corrected. Afrezza behaves the same as normal pancreatic insulin. I think this comes to a matter of semantics. The protocol says, " immediately before starting meal", I would say that means "given at the beginning of the meal. The trial data is clear, at 50% of meal all the Type 1s went hypoglycemic. Sansum and Mannkind saw the writing on the wall and abandoned the no meal test (atcually they terminated the whole trial). That's good enough for me, remember this is the Sansum that did the Afrezza with APS work that gets mentioned whenever anyone talks about an AP. There was one severe hypo, it was a Type 2. So much for Type 2s not getting hypos from Afrezza. I really don't care if anyone wants to take 8u when they are at 102, they know what will happen now and it will be their funeral. If they are stupid enough to do that they deserve their entry in the Darwin awards. It's not semantics. It is well established that the protocol impaired outcomes. Afrezza should be given at the beginning of a meal (current consensus is ~10 minutes), not before. Before and beginning do not have the same meanings. Timing is important and knowing the difference between before and beginning can be the difference between postprandial hyperglycemia and postprandial glucose homeostasis. I think you're pulling at air at this point.
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