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Post by uvula on Mar 22, 2016 16:37:28 GMT -5
I do not think it is "hyping" to say that Afrezza can prevent these complications. There is an entire "industry" based on something that is preventable.
www.dlsconference.com/
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Post by stevil on Mar 22, 2016 16:45:15 GMT -5
We need to show (and prove through clinical studies) that Afrezza lowers A1c levels (cause of neuropathies) better than anyone else before we can have any sort of differing voice at these kinds of conferences.
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Post by dpca10 on Mar 22, 2016 16:59:59 GMT -5
I respectfully disagree. HgbA1c shows chronic blood sugar elevation while there growing basic science evidence showing glycosilation from extreme sugar levels leads to the inflammation and vascular damage. Afrezza is the only insulin to address the posprandial spike. My investing mistake was to assume that Mannkind and Sanofi would take immediate action post FDA approval to show superiority in the arena of posprandial blood sugar control and bring awareness to diabetics and physicians in conferences exactly like the above link.
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Post by stevil on Mar 22, 2016 18:08:34 GMT -5
I respectfully disagree. HgbA1c shows chronic blood sugar elevation while there growing basic science evidence showing glycosilation from extreme sugar levels leads to the inflammation and vascular damage. Afrezza is the only insulin to address the posprandial spike. My investing mistake was to assume that Mannkind and Sanofi would take immediate action post FDA approval to show superiority in the arena of posprandial blood sugar control and bring awareness to diabetics and physicians in conferences exactly like the above link. Ha I know the science. Glycation is measured by A1c. A1c is an average measurement of the glycation of hemoglobin (red blood cells) in the body. This should be reflective of the average concentration of glucose in the blood over a period of time. People think that Afrezza is the only insulin that lowers A1c. They all do. That's the point of taking insulin- to lower blood glucose levels. The other thing that people don't appear to understand is that insulin has improved leaps and bounds over just the past 15 years. Neuropathies sometimes take decades to manifest. This means that the current line up of insulin will likely show lesser incidence of limb damage over the coming years. Progress has already been made in lowering A1c so it can be expected that we should see fewer opathies related to diabetes. I don't think that people understand the rationale of the scientific community. Things sometimes move slowly because they don't want to make the mistake of thinking correlation equals causation. Meaning, just because something appears in all diabetics (high blood sugar) doesn't always mean that it's what's causing disease. Obviously in this case we have reason to believe that correlation is, in fact, causation. But only because further study lends credence to those results. Once you find a link, you test it further to see if it's the actual cause. Why do I say all of this? Because the current metric physicians use for severity of diabetes is the A1c test. Does it make sense that decreasing spikes in blood sugar during its peak time should lower A1c? Does to me... However, nothing is taken for granted. The truth of the matter is we've never been able to test diabetics consistently (as far as I'm aware anyway) with an insulin that mimics the kinetics of a pancreas. The way to make waves is to be able to have data that backs up that theory. Data is collected during studies. Once data is collected, judgements can be made. I know that many on here will tell me that Afrezza has already shown that it lowers A1c better than any other insulin. I'm not the unbeliever here. I don't need much convincing, and I don't suspect many doctors would either. However, you can't use social media bloggers as proof. First, you don't know that they're being honest in their results. Second, you don't know if they have been more compliant with their therapy, if they changed their diet, if they exercise more than other diabetics, etc. There has to be a credible, conclusive study done that isolates Afrezza as the sole cause for lowered A1c. If a study is done and it is shown that Afrezza is no more successful at lowering A1c levels than other insulins, it's going to be difficult to place importance on its speed, other than decreased hypoglycemic events compared to other insulins (which also hasn't been tested yet). Again, it will be a surprise to no one if those results are proven after a study, but you can't claim it until you do that study. All this to say, we still need more tests to be completed before our voice can be separated from the herd. Unfortunately ours still blends in to some extent. Saying that your insulin works really quickly isn't as effective as saying it lowers A1c and reduces hypoglycemic events better than any other insulin on the market. Again, we can't claim either until we have data that backs it up FDA grants us permission to do so. |
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Post by LosingMyBullishness on Mar 22, 2016 18:55:10 GMT -5
stevil,
You said: People think that Afrezza is the only insulin that lowers A1c. They all do. That's the point of taking insulin- to lower blood glucose levels. ..Neuropathies sometimes take decades to manifest.
My take is that it is not about lowering A1c to a certain average value that is important regarding neuropathies. It is the avoidance or shortening of intervalls of high A1c values. My guess (and yes, I am not aware of a study that substantiates this) is that every time period of high A1c has a negative impact on the nerves. Over time this accumulates to a major defect which is then interpreted as neuropathy.
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Post by agedhippie on Mar 22, 2016 19:25:07 GMT -5
stevil, You said: People think that Afrezza is the only insulin that lowers A1c. They all do. That's the point of taking insulin- to lower blood glucose levels. . .Neuropathies sometimes take decades to manifest.My take is that it is not about lowering A1c to a certain average value that is important regarding neuropathies. It is the avoidance or shortening of intervalls of high A1c values. My guess (and yes, I am not aware of a study that substantiates this) is that every time period of high A1c has a negative impact on the nerves. Over time this accumulates to a major defect which is then interpreted as neuropathy. The A1c is important because it is elevated levels that do the damage rather than spikes. Since an A1c is the result of the average level over a three month period it tells you what that level is running at. A low A1c means a low average and a lower risk of neuropathy. Shortening elevated levels is not really helpful for neuropathy if the average level is still high. |
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Post by LosingMyBullishness on Mar 22, 2016 19:40:31 GMT -5
stevil, You said: People think that Afrezza is the only insulin that lowers A1c. They all do. That's the point of taking insulin- to lower blood glucose levels. . .Neuropathies sometimes take decades to manifest.My take is that it is not about lowering A1c to a certain average value that is important regarding neuropathies. It is the avoidance or shortening of intervalls of high A1c values. My guess (and yes, I am not aware of a study that substantiates this) is that every time period of high A1c has a negative impact on the nerves. Over time this accumulates to a major defect which is then interpreted as neuropathy. The A1c is important because it is elevated levels that do the damage rather than spikes. Since an A1c is the result of the average level over a three month period it tells you what that level is running at. A low A1c means a low average and a lower risk of neuropathy. Shortening elevated levels is not really helpful for neuropathy if the average level is still high. Sorry, if my argument was misleading. I do not doubt that the levels have to be low on average. Yes, they have to. I mean that it is not sufficient to be low on average. What has to be avoided are short periods of abnormal levels before external insulin kicks in. If there is a delay, there will be damage. Small ones, but they accumulate over time. |
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Post by stevil on Mar 22, 2016 19:59:42 GMT -5
stevil, You said: People think that Afrezza is the only insulin that lowers A1c. They all do. That's the point of taking insulin- to lower blood glucose levels. . .Neuropathies sometimes take decades to manifest.My take is that it is not about lowering A1c to a certain average value that is important regarding neuropathies. It is the avoidance or shortening of intervalls of high A1c values. My guess (and yes, I am not aware of a study that substantiates this) is that every time period of high A1c has a negative impact on the nerves. Over time this accumulates to a major defect which is then interpreted as neuropathy. The A1c is important because it is elevated levels that do the damage rather than spikes. Since an A1c is the result of the average level over a three month period it tells you what that level is running at. A low A1c means a low average and a lower risk of neuropathy. Shortening elevated levels is not really helpful for neuropathy if the average level is still high. , yes, you are correct. High glucose at any moment is harmful and can cause damage, although I'm unaware if they've pegged "high" to a specific number as there are several different causes for why glucose spikes are thought to cause opathies. There are so many pathways, both hormonal and metabolic that rely on glucose for their signaling and it's still an advancing field. Not everything is well known at the cellular level yet. This might mean that the current prandials may be doing an adequate job in this department. Basals have also come a really long way and may be just as important in lowering A1c as a good prandial, but I'm not sure. Like I said, opathies take a long time to manifest, so it won't be known for some time how well or if our current line up is curtailing this problem. Unless they have pegged it to a certain number through microscopic analysis, it's quite likely that the current regimens are "doing the job" as far as the opathies go. Only time will tell pending better testing methods. However, like agedhippie said, the more important number is A1c, since it's a number that shows the average concentration. Again, that's what is taught right now because that's what's been studied. Who knows if it'll be proven that the first phase is actually when most of the damage is done... but to my knowledge, this hasn't been tested yet, although I suppose they could have compared results over time with other prandials as they've gotten quicker... So it's possible.... |
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Post by uvula on Mar 22, 2016 20:08:19 GMT -5
Interesting conversation. I don't think anyone knows exactly how much of the damage is from high A1C and how much is from spikes because until Afrezza there was no real way to study this (unless you wanted to force glucose into non-diabetic patients for 20 years.) Common sense says that low A1C without spikes has got to be a good thing. Do we really need a double blind study to prove this? Think of the old parachute analogy.
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Post by stevil on Mar 22, 2016 20:11:37 GMT -5
It appears the FDA would require that, yes. They have been less than lenient so far, so that would be my best guess... That is, if we wanted to make claims about reduced chance for opathies... but I suppose I can't make that claim for them. Maybe they will be satisfied simply with the lowering of A1c. I hope so  |
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Post by agedhippie on Mar 23, 2016 7:43:25 GMT -5
This might mean that the current prandials may be doing an adequate job in this department. Basals have also come a really long way and may be just as important in lowering A1c as a good prandial, but I'm not sure. Like I said, opathies take a long time to manifest, so it won't be known for some time how well or if our current line up is curtailing this problem. Unless they have pegged it to a certain number through microscopic analysis, it's quite likely that the current regimens are "doing the job" as far as the opathies go. Only time will tell pending better testing methods. However, like agedhippie said, the more important number is A1c, since it's a number that shows the average concentration. Again, that's what is taught right now because that's what's been studied. Who knows if it'll be proven that the first phase is actually when most of the damage is done... but to my knowledge, this hasn't been tested yet, although I suppose they could have compared results over time with other prandials as they've gotten quicker... So it's possible.... Basals are at least as important as prandial. If I get a problem with my basal I can easily end up in hospital within 24 hours. Because the body continually outputs glucose to ensure that the body functions properly it will steadily build up in your blood as a diabetic even without eating. Eating just raises the level quicker. This is one reason you have sick day protocols for diabetes. People tend to judge diabetes and complications purely by glucose levels but that is over simplistic. The truth is that glucose is the easiest thing to measure and has strong linkage. The problem is that diabetes is a broken glucose metabolism and is far more complicated. As a couple of examples, in Type 1 along with making insulin the body also stops making amylin (synthetic amylin, Symlin, is available). Also when insulin is produced there are by-products which have historically been thought to be waste products but now they are beginning to think those have a role in heart health. This is all before you start getting into lipids, B12 and D deficiencies, and various other issues. There are a few pivotal studies The UKPDS study which has tracked a large group of Type 2 diabetics, DCCT and it's follow on EDIC run over 30 years looking at progression, treatment, complications, and similar. There are others as well but those are the landmark studies. The treatment to day and why complications arise are in large part derived from these studies since they run over such a long time line. The UKPDS study has 84 papers not counting all the papers published based on it's data! Because these studies have such longevity and large populations it is possible to compare treatments and outcomes. The biggest issue for UKPDS is their sample group is now dying of old age. Reflected in these change in drugs used and insulins that are now giving greater life expectancy. Cochane Reviews is the other process that is worth talking about. Coupled with massive data sets like the UK NHS dataset it is possible to see outcomes for for all sorts of permutations that would not be possible in regular trials. That's a braindump but this is a topic I spend a lot of time researching to help me understand and manage things. |
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Post by mindovermatter on Mar 23, 2016 8:14:09 GMT -5
I am more interested right now in the "Afrezza Salvage Project" about to get underway.
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Post by 4allthemarbles on Mar 23, 2016 10:49:41 GMT -5
Clever
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Post by matt on Mar 23, 2016 16:42:40 GMT -5
We need to show (and prove through clinical studies) that Afrezza lowers A1c levels (cause of neuropathies) better than anyone else before we can have any sort of differing voice at these kinds of conferences. MNKD will never have a voice at these sorts of conferences, which are populated almost exclusively by vascular surgeons. Once a patient has advanced to PAD and/or critical limb ischemia, no amount of insulin is going to reverse that condition. The time to prevent PAD is when the patient is still in the care of the endocrinologist / internal medicine types, the vascular surgeons "cure" patients with a knife. |
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