I just started on Afrezza. Wish it came in 2-unit doses

Treatment Insulin
21

Basically, Matt explains that Afrezza works best at stopping blood sugar from rising in the first place. And for correction (when blood sugar level is already high), Afrezza will need relative larger dosage. And for Afrezza, timing is much more important than dosage itself. [And after many tests, Matt seems to agree with Sam and others here in this forum that dosing around 10 minutes after start eating generally works best.]

Quoting Matt:

"I have previously mentioned the importance of dosage timing when taking Afrezza, but have not gone into much detail. So I thought it would be worthwhile talking about what I have learned so far about timing.

As a general rule, I dose about 10 minutes after I start eating, which is before my glucose levels start to rise from the meal. As I mention in the video, the best time to dose seems to depend on the fat content of the meal. And for some high fat meals, a follow up dose of Afrezza is neccesary.

I have found the same rule also applies if a follow-up dose is required. It is important to have the follow-up dose before the levels begin to rise out of range. If I had a CGM with alerts, I would use this to notify me as soon as it levels began to increase. That way I wouldnā€™t miss the optimum time for the follow-up.

It is worth remembering that much, much more Afrezza is needed to correct high glucose levels than to cover meals. As the video details, if I wait too long to dose, the dose required may be four times higher!"

If the connection to his website is slow, you can view his videos in Youtube at:

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@v_prediabetic, hereā€™s an example of the what I call the 24-hour echo. At 1:40 this morning my blood glucose dropped below 65 mg/dl and went as low as 45 mg/dl. This low lasted 1 hour and 20 minutes. this despite my CGM waking me up and me taking 6-8 glucose tabs during that time. This low was probably caused by the two glasses of wine that I drank the evening before. My liver got busy metabolizing the alcohol and stopped putting out its usual stream of glucose. I failed to back off on my basal rate and my basal insulin drove my blood sugar low.

So, tonight I expect that right around 1:40 a.m. my blood glucose will drop low, even though I did not drink any wine tonight. I will probably try to compensate by starting a minus 20% temp basal rate starting at 11:30 p.m. Itā€™s as if the body has a metabolic memory. Iā€™ve witnessed this phenomena in me many times.

Iā€™ve had the same thing happen with going high. I may make an insulin dosing calculation error and go high as a result. Twenty-four hours later, absent that same triggering mistake, my body will still want to go high.

23

That is really interesting. Thank you for your ā€œ24 hour metabolic memoryā€ description which may explain a lot of what I experience as well. As CGM (and eventually Artificial Pancreas) data builds up, these kinds of phenomena may become commonly understood and addressed (?). I have a lot of bg excursions both low and high that I still donā€™t understand 10 years into this disease but it really does seem related to how the liver works. And maybe the quick action of Afrezza changes those liver dynamics by reducing the amount of bg stored (and later dumped) by the liver (?).

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i had a high carb lunch today. how could i use the metabolic echo to my advantage in planning my day tomorrow? after my high carb lunch i took 500 mg metformin (yes, i know it doesnā€™t act like fast acting insulin) and did half an hour easy on my exercise bike. i ran out of strips so i didnā€™t measure, but iā€™m sure my blood sugar was at least in the 150s at 2 pm. then after a half hour of biking, it probably went to 115 or so ( could be even lower). would an echo look like this- at 2pm tomorrow my blood sugar would be in the 150s no matter what i ate, and then it would go down to 115 an hour later? when i have strips, i may do a little experiment. iā€™m just wondering what your thoughts are.

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No, it doesnā€™t work that way. Sorry if my explanation misled you.

The 24-hour metabolic echo that I write about can best provide some caution for the following day when your blood sugar is more extreme today. Like if it goes to 250+ and stays there for a few hours. I think your blood glucose going to 150 after eating is a mild BG excursion and will have little effect tomorrow. If anything, given the same food, medicine and exercise inputs, your blood sugar will be pushed toward the same experience you had today.

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but if the metabolic echo is a real phenomenon, it should hold true even for slight variations, donā€™t you think? i mean, the echo serves some purpose for the body. maybe we can only discern it at large bg excursions, but it seems possible that the echo happens even for slight excursions. what do you speculate is the purpose of the metabolic echo?

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Itā€™s purpose or reason is only speculation on my part. Perhaps manā€™s evolution subject to the circadian rhythm of day and night as well as the annual change of seasons influenced our DNA.

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art de vany, one of the pioneers of the paleo movement, is the other person iā€™ve read whose written about this kind of metabolic memory. his hypothesis is that the body needs to predict (to prepare for?) future conditions (for insulin output?glucose output?). it uses present conditions to do so.

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Pretty much the rapidity. In the bloodstream, insulin exists in a state of equilibrium:

insulin receptor/monomer <=> monomer <=> dimer <=> multimer <=> hexamer

Beta cells store insulin as the hexamer, and they release it into the blood as the hexamer which then dissociates according to that equation. The monomer is the only active form, however. The insulin receptor binds the monomer very tightly. Once bound the receptor/monomer complex triggers a cascade of events leading to facilitated diffusion of glucose into the cell. The receptor/monomer is then internalized, the complex breaks apart, the insulin is degraded, and the recptor recycled to the surface. Afrezza insulin is just human insulin, and once absorbed follows the same rules.

Insulin degrading enzyme (IDE) is responsible for clearing insulin that is not used. It degrades all four forms of insulin and immediately begins degrading all four in the bloodstream. In effect ā€“ note that this is oversimplifying ā€“ three quarters of the inhaled insulin is basically unused and removed. This is why you have such rapid elimination of afrezza insulin from the system. Two processes are at work simultaneously. As the monomer is being both used and degraded, the equation is constantly re-equilibrating. So, on one hand, you have the receptors binding and pulling monomers out to the left, while, on the other hand, IDE is degrading all four forms with re-equilibration accordingly pulling monomers out to the right.

Lispro is a modified monomer that resists forming polymers. Once it is injected, it is not exposed to IDE in the subcutaneous tissue. It simply diffuses down its concentration gradient into the bloodstream where it either binds a receptor or is degraded. Very little is converted to more complex forms. This why you have the 4U afrezza cartridge as roughly equivalent to 1U of lispro ā€“ 3 of the afrezza insulin are simply metabolized away. It is less rapidly removed since it doesnā€™t have that right side of the equation destroying 3 inactive insulin and pulling monomers toward it.

A consequence of the rapid metabolism of afrezza insulin is that its concentration rapidly decreases below effective levels as opposed to lispro. The rapid decrease is good at preventing later hypoglycemia but, at the same time, leaves the diabetic exposed to hyperglycemia from late digesting food.

Another consequence might be noted as well. During the trials, in type 1s, afrezza appeared to require increasing doses over time to maintain adequate glucose control as opposed to lispro. Some afrezza users also have reported requiring more afrezza over the weeks subsequent to starting it. Enzymes such as IDE are susceptible to a phenomena known as ā€œinduction.ā€ If an enzyme is used frequently ā€“ as would be the case with IDE with the very high concentrations of insulin achieved after dosing afrezza ā€“ cells sometimes are induced to make more of the enzyme. In effect, the cell adapts by cranking up its internal factory to increase output of the enzyme to meet the perceived need. Of course, the more IDE available, the more rapidly insulin is degraded. This is likely what is happening in patients who exhibit a need for increased afrezza dosing. Lispro, of course, is subcutaneous and not exposed to IDE there, so it would not exert the same effect.

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Everyone is different. I would test your correction factor on Afrezza (if you havenā€™t already) by drinking a juice and artificially bringing blood sugar up to 250. Then try a 4 unit Afrezza to see what the drop is. My DD is 105 lbs. small frame. Her correction factor on Apidra is 1 to 70. A four unit cartridge of Afrezza drops her 80 to 90 points. A four unit cartridge of Afrezza covers 20 to 30 grams of carbs for meals. An 8 unit covers 45 to 60 grams of carbs for meals. Afrezza covers a broader range of carbs than injected insulin. You do not have to be precise. You do have to be within a precise RANGE though. In her case there seems to be a ten to fifteen gram range leeway. The drawback for us is we need more of the four unit cartridges and they are packaged together with the eight units in one box. We need a lot more of the four units than we do of the eight units. Four units are used for both small meals and corrections. If she is going to have under 25 grams for a snack, she cannot use Afrezza. So you do have to match your meals to the dose given. And because Afrezza is so fast you may have to take a four unit a half hour after a pasta meal, and the rest when your blood sugar rises thee hours after the pasta. Afrezza often needs two doses for a meal. And four and four would really be ideal for a lot of the meals she eats, not one dose of the 8 unit cartridge. In short, we need the fours packaged separately than the eights as we use so much more of them.

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This puzzles me, @Julia61, since I buy Affrezza in boxes of 90 each 4-unit doses. Thatā€™s all I order is 4-unit doses. That ordering scheme would seem to well match your needs and dosing flexibility desired.